record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10024335,Distinct and combined vascular effects of ACE blockade and HMG-CoA reductase inhibition in hypertensive subjects.,P Nazzaro; M Manzari; M Merlo; R Triggiani; A Scarano; L Ciancio; A Pirrelli,"Hypercholesterolemia and hypertension are frequently associated with elevated sympathetic activity. Both are independent cardiovascular risk factors and both affect endothelium-mediated vasodilation. To identify the effects of cholesterol-lowering and antihypertensive treatments on vascular reactivity and vasodilative capacity, we studied 30 hypercholesterolemic hypertensive subjects. They received placebo for 4 weeks, either enalapril or simvastatin for 14 weeks, and, finally, both medications for an additional 14 weeks. Postischemic forearm blood flow (MFBF) and minimal vascular resistance (mFVR) were used as indices of vasodilative capacity and structural vascular damage, respectively. Total (resting-stress-recovery phases) cardiovascular (blood pressure [BP] and heart rate [HR]) and regional hemodynamic (FBF and FVR) reactivity to stressful stimuli were calculated as area-under-the-curve (auc) (valuextime). Compared with baseline levels, simvastatin reduced total (TOT-C) and LDL cholesterol (LDL-C) (1.27 mmol/L, P<0.001 and 1.33 mmol/L, P<0.001, respectively). Enalapril also reduced TOT-C and LDL-C (0.6 mmol/L, P<0.001 and 0.58 mmol/L, P<0.05, respectively). MFBF was increased substantially by both treatments (P<0.001). Enalapril had a greater effect (-1.7 arbitrary units (AU), P<0.001) than simvastatin (-0.6 AU, P<0.05) on mFVR. During stress, FBF increased more with enalapril (4.4 FBFxminutes, P<0.001) than with simvastatin (1.8 FBFxminutes, P<0.01). Conversely, FVR stress response was reduced more with enalapril (9.1 FVRxminutes, P<0.001) than with simvastatin (2.9 FVRxminutes, P<0.01). During combination treatment, a significant (0.001>P<0.05) additive effect on hypercholesterolemia, structural vascular damage, BP, and FVR was shown. The findings suggest that angiotensin-converting enzyme (ACE) inhibition induces a larger reduction than HMG-CoA reductase blockade in vascular reactivity and structural damage in hypercholesterolemic hypertensive subjects.",1999.0,0,0
2,10027665,Computerized surveillance of adverse drug reactions in hospital: implementation.,M Levy; T Azaz-Livshits; B Sadan; M Shalit; G Geisslinger; K Brune,"To implement and measure the effects of automatic computerized laboratory signals (ALS) as a detection support tool of adverse drug reactions (ADRs) in hospital. This was a prospective observational study of a total of 192 patients (199 sequential medical admissions) during a 2-month period in a 34-bed medical ward at the Hadassah University Hospital, Jerusalem, Israel. The study involved the routine (daily) distribution to staff physicians of lists of automatic signals generated from computerized laboratory data as potential indicators of ADRs. Patient charts were reviewed by the clinical pharmacology team for ADRs and to see whether these were recognized by the staff physicians. Seventy-one ADRs were detected in 64 of the 199 (32%) admissions. Twenty-seven per cent of the ADRs were serious, 9% of the admissions were due to ADRs. Two hundred and ninety-five ALS were generated involving 69% of the admissions. Sixty-one per cent of the ADRs were identified by ALS. ALS were present in 58% of the ADR negative admissions. Eighty-five per cent of the ADRs were recognized as such and 19% of the ALS-positive ADRs were not recognized by the staff physicians. The routine implementation of ALS doubled the number of ADRs recognized by the physicians while patients were hospitalized in the medical ward. The use of the system appeared valid, simple and potentially cost-effective.",1999.0,0,0
3,10027935,Glomerular size-selective dysfunction in NIDDM is not ameliorated by ACE inhibition or by calcium channel blockade.,P Ruggenenti; L Mosconi; F Sangalli; F Casiraghi; V Gambara; G Remuzzi; A Remuzzi,"In patients with insulin-dependent diabetes mellitus (IDDM) and overt nephropathy glomerular barrier size-selectivity progressively deteriorates with time and is effectively improved by angiotensin converting enzyme (ACE) inhibition. Whether similar glomerular functional changes develop in proteinuric patients with non-insulin-dependent diabetes mellitus (NIDDM), and whether antihypertensive agents can favorably affect glomerular filtration of macromolecules in these patients, has not been documented yet. We investigated renal hemodynamics and fractional clearance of neutral dextrans of graded sizes, in nine proteinuric patients with NIDDM and renal biopsy findings of typical diabetic glomerulopathy. Six healthy volunteers served as controls. We also investigated the effects of an ACE inhibitor and of a calcium channel blocker, both given in doses targeted to achieve a comparable level of systemic blood pressure control, on glomerular hemodynamics and sieving function. Theoretical analysis of glomerular macromolecule transport was adopted to evaluate intrinsic glomerular membrane permeability properties. Fractional clearance of large macromolecules (42 to 66 A in radius) was significantly higher in diabetic patients than in controls, and the distribution of membrane pore radii was calculated to be shifted towards larger pore sizes in diabetics (mean radius increased from 55 to 60 A). Despite effective blood pressure control, neither antihypertensive affected glomerular hemodynamics to any significant extent. Fractional clearance of dextrans, as well as of albumin and IgG, and total urinary proteins were not modified by either treatments. These data indicate that patients with NIDDM and overt nephropathy develop abnormalities in size-selective function of the glomerular barrier and, at variance to IDDM, such changes were not ameliorated either by ACE inhibition or calcium channel blockade.",1999.0,0,0
4,10028936,Total arterial compliance in ambulatory hypertension during selective beta1-adrenergic receptor blockade and angiotensin-converting enzyme inhibition.,J Soma; S Aakhus; K Dahl; T E Widerøe; T Skjaerpe,"Aortic root flow and pressure estimates were obtained noninvasively with Doppler echocardiography and calibrated subclavian artery pulse tracing in 30 subjects with ambulatory hypertension in a randomized, crossover study with 4 weeks' treatment and washout periods. Total arterial compliance, assessed by use of a three-element Windkessel model of the arterial tree, increased 42% with atenolol (50-100 mg once daily), and 7% (p = NS) with captopril (25-50 mg twice daily). Atenolol reduced mean arterial pressure by 15%, heart rate by 22%, and cardiac output by 14%, and increased acceleration time of aortic root flow by 17% and stroke volume and ejection time each by 11%. Captopril reduced mean arterial pressure and total peripheral resistance each by 7%. Acceleration time of aortic root flow, ejection time, heart rate, stroke volume, and cardiac output were not significantly changed by captopril. We conclude that total arterial compliance, at the operational blood pressure, increases during selective beta1-adrenergic receptor blockade in subjects with ambulatory hypertension. Although the main mechanism may be a reduction in mean arterial pressure, it should be considered whether reduced heart rate may play an additional role. The nonsignificant increase in total arterial compliance during angiotensin-converting enzyme inhibition may primarily be a consequence of a modest reduction of the mean arterial pressure.",1999.0,0,0
5,10029645,Racial differences in the outcome of left ventricular dysfunction.,D L Dries; D V Exner; B J Gersh; H A Cooper; P E Carson; M J Domanski,"Population-based studies have found that black patients with congestive heart failure have a higher mortality rate than whites with the same condition. This finding has been attributed to differences in the severity, causes, and management of heart failure, the prevalence of coexisting conditions, and socioeconomic factors. Although these factors probably account for some of the higher mortality due to congestive heart failure among blacks, we hypothesized that racial differences in the natural history of left ventricular dysfunction might also have a role. Using data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, in which all patients received standardized therapy and follow-up, we conducted a retrospective analysis of the outcomes of asymptomatic and symptomatic left ventricular systolic dysfunction among black and white participants. The mean (+/-SD) follow-up was 34.2+/-14.0 months in the prevention trial and 32.3+/-14.8 months in the treatment trial among the black and white participants. The overall mortality rates in the prevention trial were 8.1 per 100 person-years for blacks and 5.1 per 100 person years for whites. In the treatment trial, the rates were 16.7 per 100 person-years and 13.4 per 100 person-years, respectively. After adjustment for age, coexisting conditions, severity and causes of heart failure, and use of medications, blacks had a higher risk of death from all causes in both the SOLVD prevention trial (relative risk, 1.36; 95 percent confidence interval, 1.06 to 1.74; P=0.02) and the treatment trial (relative risk, 1.25; 95 percent confidence interval, 1.04 to 1.50; P=0.02). In both trials blacks were also at higher risk for death due to pump failure and for the combined end point of death from any cause or hospitalization for heart failure, our two predefined indicators of the progression of left ventricular systolic dysfunction. Blacks with mild-to-moderate left ventricular systolic dysfunction appear to be at higher risk for progression of heart failure and death from any cause than similarly treated whites. These results suggest that there may be racial differences in the outcome of asymptomatic and symptomatic left ventricular systolic dysfunction.",1999.0,0,1
6,10029788,Exfoliative dermatitis.,G Karakayli; G Beckham; I Orengo; T Rosen,"Exfoliative dermatitis, also known as erythroderma, is an uncommon but serious skin disorder that family physicians must be able to recognize and treat appropriately. Although the etiology is often unknown, exfoliative dermatitis may be the result of a drug reaction or an underlying malignancy. The approach to treatment should include discontinuation of any potentially causative medications and a search for any underlying malignancy. One of the most common malignancies associated with exfoliative dermatitis is cutaneous T-cell lymphoma, which may not manifest for months or even years after the onset of the skin condition. Hospitalization is usually necessary for initial evaluation and treatment. In the hospital, special attention must be given to maintaining temperature control, replacing lost fluids and electrolytes, and preventing and treating infection. The long-term prognosis is good in patients with drug-induced disease, although the course tends to be remitting and relapsing in idiopathic cases. The prognosis of cases associated with malignancy typically depends on the outcome of the underlying malignancy.",1999.0,0,0
7,10030325,Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial.,L Hansson; L H Lindholm; L Niskanen; J Lanke; T Hedner; A Niklason; K Luomanmäki; B Dahlöf; U de Faire; C Mörlin; B E Karlberg; P O Wester; J E Björck,"Angiotensin-converting-enzyme (ACE) inhibitors have been used for more than a decade to treat high blood pressure, despite the lack of data from randomised intervention trials to show that such treatment affects cardiovascular morbidity and mortality. The Captopril Prevention Project (CAPPP) is a randomised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension. CAPPP was a prospective, randomised, open trial with blinded endpoint evaluation. 10,985 patients were enrolled at 536 health centres in Sweden and Finland. Patients aged 25-66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were randomly assigned captopril or conventional antihypertensive treatment (diuretics, beta-blockers). Analysis was by intention-to-treat. The primary endpoint was a composite of fatal and non-fatal myocardial infarction, stroke, and other cardiovascular deaths. Of 5492 patients assigned captopril and 5493 assigned conventional therapy, 14 and 13, respectively, were lost to follow-up. Primary endpoint events occurred in 363 patients in the captopril group (11.1 per 1000 patient-years) and 335 in the conventional-treatment group (10.2 per 1000 patient-years; relative risk 1.05 [95% CI 0.90-1.22], p=0-52). Cardiovascular mortality was lower with captopril than with conventional treatment (76 vs 95 events; relative risk 0.77 [0.57-1-04], p=0.092), the rate of fatal and non-fatal myocardial infarction was similar (162 vs 161), but fatal and non-fatal stroke was more common with captopril (189 vs 148; 1.25 [1-01-1-55]. p=0.044). Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality. The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients randomised to conventional therapy.",2000.0,0,0
8,10047639,Effects of short-acting and long-acting loop diuretics on heart rate variability in patients with chronic compensated congestive heart failure.,H Tomiyama; T Nakayama; G Watanabe; K Shiojima; Y Sakuma; A Yamamoto; Y Imai; H Yoshida; N Doba,"We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in patients with mild to moderate chronic congestive heart failure. Nineteen patients with mild to moderate chronic congestive heart failure received furosemide (40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We performed time-domain and frequency-domain analyses of 24-hour Holter electrocardiographic recordings to assess heart rate variability. The 24-hour urinary sodium excretion was similar during the furosemide and azosemide treatment periods but was significantly greater in the first 2 hours after drug administration during furosemide treatment. Plasma renin activity and the hematocrit level increased and high-frequency power significantly decreased 2 hours after the administration of furosemide only. The standard deviation of all normal R-R intervals and the root mean square of successive differences in the R-R interval were lower with furosemide than with azosemide (P <.05). Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate chronic congestive heart failure.",1999.0,0,0
9,10049657,Capillary blood cell velocity in finger nailfold: effect of enalapril and mibefradil in patients with mild to moderate hypertension.,B Martina; B Frach; C Surber; J Drewe; E Battegay; P Gasser,"Outpatients with essential hypertension were randomized to receive antihypertensive treatment with either mibefradil or enalapril. Ambulatory blood pressure measurement (ABPM) and video capillary microscopy of the finger nailfold were performed at baseline and after 12 weeks of treatment. In the enalapril group (n = 21) baseline ABP was 156 +/- 12/100 +/- 9 mm Hg and decreased to 140 +/- 17/89 +/- 10 mm Hg after 12 weeks. In the mibefradil group (n = 22) mean 24-h ABP decreased from 159 +/- 14/102 +/- 7 to 140 +/- 10/89 +/- 7 mm Hg. Capillary blood cell velocity (CBV) without treatment was 0.90 +/- 0.58 mm/s (mean +/- SD) and 0.83 +/- 0.46 mm/s at rest and 0.30 +/- 0.22 and 0.21 +/- 0.20 mm/s immediately after local finger cooling in the mibefradil and the enalapril group, respectively. In the Enalapril group CBV at week 12 was 0.99 +/- 0. 60 mm/s (n.s.) at rest and 0.40 +/- 0.28 mm/s immediately after local cooling (P = 0.005 compared to 0.21 +/- 0.20 mm/s without treatment). Twelve weeks after initiation of treatment CBV was 0.76 +/- 0.48 mm/s (n.s.) at rest and 0.31 +/- 0.28 mm/s (n.s.) immediately after local cooling in the mibefradil group. Finger nailfold CBV immediately after local finger cooling was increased by enalapril compared to baseline. The T-channel-inhibiting calcium antagonist mibefradil did not change CBV in finger nailfold capillaries.",1999.0,0,0
10,10051289,Addition of angiotensin II receptor blockade to maximal angiotensin-converting enzyme inhibition improves exercise capacity in patients with severe congestive heart failure.,G Hamroff; S D Katz; D Mancini; I Blaufarb; R Bijou; R Patel; G Jondeau; M T Olivari; S Thomas; T H Le Jemtel,"Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT1) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT1 receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown. Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V(O2)) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V(O2) at baseline and after 3 and 6 months were 13.5+/-0.6, 15.1+/-1.0, and 15.7+/-1.1 mL. kg-1. min-1, respectively, in patients receiving losartan and 14.1+/-0.6, 14.3+/-0.9, and 13.6+/-1.1 mL. kg-1. min-1, respectively, in patients receiving placebo (P<0.02 for treatment group-by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo. Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.",1999.0,0,0
11,10053176,Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.,J Tuomilehto; D Rastenyte; W H Birkenhäger; L Thijs; R Antikainen; C J Bulpitt; A E Fletcher; F Forette; A Goldhaber; P Palatini; C Sarti; R Fagard,"Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly. At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively). Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.",1999.0,0,0
12,10063787,Low-dose combination therapy as first-line hypertension treatment for blacks and nonblacks.,L M Prisant; J M Neutel; K Ferdinand; V Papademetriou; V DeQuattro; W D Hall; M R Weir,"To assess the efficacy and safety of bisoprolol/6.25-mg hydrochlorothiazide (HCTZ), amlodipine, and enalapril in black and nonblack patients, data from two comparative studies were pooled and subgroup analyses performed. Both studies had similar designs and included all three active treatments. The second study also included a placebo group. Subjects (n = 541) with a sitting diastolic blood pressure of 95-114 mmHg were titrated to achieve a diastolic blood pressure < or = 90 mmHg. The studies included 114 blacks and 427 nonblacks. Results of an intention-to-treat analysis of mean change from baseline after 12 weeks of treatment showed the following: 1) blood pressure was significantly lowered by all three active drugs compared with baseline or placebo; 2) in blacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reductions of systolic and diastolic blood pressure than enalapril or placebo, but was not significantly different from amlodipine; 3) in nonblacks, bisoprolol/6.25-mg HCTZ resulted in significantly greater reduction of diastolic blood pressure than amlodipine, enalapril, or placebo. The placebo-corrected change in blood pressure was greater for blacks than whites on the bisoprolol/6.25-mg HCTZ combination, but this was not statistically significant. Bisoprolol/6.25-mg HCTZ controlled diastolic blood pressure to < or = 90 mmHg in significantly more patients than enalapril or placebo in blacks and nonblacks. The difference in control rates was not significant versus amlodipine. The incidence of drug-related adverse events was similar between treatments; however, bisoprolol/6.25-mg HCTZ had a lower discontinuation rate due to lack of blood pressure control or adverse experiences in both blacks and nonblacks.",1999.0,0,0
13,10066961,Linear IgA bullous dermatosis in a patient with acute lymphocytic leukemia: possible involvement of granulocyte colony-stimulating factor.,Y Kano; T Kokaji; T Shiohara,"We describe a case of linear IgA bullous dermatosis (LABD) in a patient with acute lymphocytic leukemia during treatment with granulocyte colony-stimulating factor (G-CSF). After a drug eruption due to imipenem cilastatin sodium had disappeared, bullous lesions appeared on the trunk. Results of histopathological studies and direct immunofluorescence studies of the lesion were consistent with LABD. Reinstitution of G-CSF after the resolution, however, did not reproduce the bullous eruptions. This suggests that in addition to G-CSF, the presence of precipitating factors that can synergistically enhance or accelerate the outbreak of the disease is required for the development of bullous lesions. Various cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), endogenously produced from activated lymphocytes during the drug eruption might have provided a favorable milieu for the onset of G-CSF-induced LABD. We suggest that patients with LABD will need special attention with respect to the type of cytokines or combination of cytokines given as therapeutic modalities.",1999.0,0,0
14,10067800,"Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group.",B E Karlberg; L E Lins; K Hermansson,"To assess the antihypertensive efficacy and safety of the novel AT1 receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension. A 26-week, multicenter, double-blind, parallel-group, dosage titration study. A total of 278 patients aged > or = 65 years were randomized to eithertelmisartan or enalapril once a day. The telmisartan dosage was increased from 20 to 40-80 mg and that of enalapril from 5 to 10-20 mg at 4-week intervals until trough supine diastolic blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5-25 mg once a day was added to the treatment regimen of those patients not controlled on monotherapy. Both treatments lowered blood pressure in a comparable and clinically meaningful manner. The adjusted mean changes from baseline in supine diastolic blood pressure at trough were -12.8 mmHg for telmisartan and -11.4 mmHg for enalapril (P = 0.074). Mean changes in supine systolic blood pressure were -22.1 mmHg for telmisartan and -20.1 mmHg for enalapril (P = 0.350). Overall, 63 and 62% of patients responded to telmisartan and enalapril, respectively, with a supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective blood pressure lowering over the 24 h dosing interval, as determined by ambulatory blood pressure monitoring. Both regimens were well tolerated; however, patients on the enalapril regimen had more than double the incidence of treatment-related cough compared with those on the telmisartan regimen (16 versus 6.5%). These results demonstrate that telmisartan is well tolerated and is at least as effective as enalapril in treating elderly patients with mild to moderate hypertension.",1999.0,0,0
15,10069777,Meeting highlights. Highlights of the 20th congress of the European society of cardiology.,J J Ferguson,,1999.0,0,0
16,10072218,Acute anti-ischemic effects of perindoprilat in men with coronary artery disease and their relation with left ventricular function.,G L Bartels; F M van den Heuvel; D J van Veldhuisen; M van der Ent; W J Remme,"Long-term angiotensin-converting enzyme (ACE) inhibition may reduce ischemic events in patients with coronary artery disease, but whether it protects against acute ischemia or the effects of preexisting left ventricular (LV) dysfunction on potential anti-ischemic properties is unknown. We performed a double-blind trial in 25 patients with exercise-induced ischemia. The effects of perindoprilat on pacing-induced myocardial ischemia were examined. Fourteen patients received perindoprilat and 11 patients received placebo. Based on LV function, 2 subgroups were formed in the perindoprilat group: 7 patients with LV dysfunction (LV ejection fraction <0.40), and 7 patients with normal LV function. After receiving the study medication, the pacing test was repeated. During the first pacing test both groups developed ischemia. After perindoprilat administration, the increase in systemic vascular resistance and LV end-diastolic pressure were significantly blunted (p <0.05). Further, the ischemia-induced increase in arterial and cardiac uptake of norepinephrine was inhibited by perindoprilat, and the increase in atrial natriuretic peptide was less pronounced; also, ST-segment depression was reduced by 32% compared with placebo (all p <0.05). In the group with LV dysfunction, perindoprilat reduced LV end-diastolic pressure significantly by 67% and myocardial lactate production was prevented, but this did not happen in the group with normal LV function. In addition, the increase in arterial norepinephrine was reduced by 74% and 33%, respectively (p <0.05). These results indicate that perindoprilat reduced acute, pacing-induced ischemia in normotensive patients. In patients with (asymptomatic) LV dysfunction these effects were more pronounced than in patients with normal LV function.",1999.0,0,0
17,10073748,Cough and angiotensin II receptor antagonists: cause or confounding?,F J Mackay; G L Pearce; R D Mann,"Cough is one of the most frequent side effects associated with angiotensin converting enzyme inhibitors (ACEIs) but is not thought to be associated with losartan, an angiotensin II receptor antagonist (ARA). This study compares reports of cough with losartan and three ACEIs used in general practice. Studies have been conducted for losartan, and three ACEIs enalapril, lisinopril and perindopril, using the technique of Prescription-Event Monitoring. Patients were identified using dispensed prescription data. Questionnaires were sent to patients' general practitioners 6 months after the date of first prescription. Cases of cough within the first 60 days of treatment with losartan resulting in withdrawal of the drug were followed up with additional questionnaires. Incidence rates for reports of cough were calculated. In order to reduce the impact of carry-over effects, rate ratios were calculated for first reports of cough between days 8 and 60 using losartan as the index drug. The cohort for each drug exceeded 9000 patients. Age and sex distributions and indications for prescribing the four drugs were similar. Cough was the most frequent reason for discontinuation of losartan and the most frequently reported event in the first month of treatment with this drug. When reports of cough between days 1-7 were excluded, rates of cough were significantly higher for the three ACEIs when compared with losartan (rate ratios 1.5, 4.8 and 5.7, all P<0.03). 101 patients had discontinued losartan due to cough. 91% of these had previously been prescribed an ACEI and 86% had previously experienced ACEI cough. Carry-over accounted for the observed excess of reports of cough with losartan. Rates of cough between days 8 and 60 were significantly higher for the three ACEIs compared with losartan. Confounding factors associated with comparative observational cohort studies are discussed.",1999.0,0,0
18,10073783,Angiotensin-converting enzyme inhibition as antiatherosclerotic therapy: no answer yet. QUIET Investigators. QUinapril Ischemic Event Trial.,L Cashin-Hemphill; G Holmvang; R C Chan; B Pitt; R E Dinsmore; R S Lees,"Angiotensin-converting enzyme inhibitors have proven to be of clinical benefit in congestive heart failure. Whether they also provide benefit to patients with coronary artery disease in the absence of congestive heart failure via an antiatherosclerotic mechanism is a question the QUinapril Ischemic Event Trial quantitative coronary angiography (QCA) study attempted to answer: 1,750 patients with normal left ventricular function who were undergoing coronary angiography and angioplasty were randomized to 20 mg/day of quinapril versus placebo and followed for 3 years for cardiac end points. A randomly selected subgroup of the total cohort underwent follow-up angiography. The primary QCA end point was the categorical designation of progression versus nonprogression, defined either by QCA or by a cardiac event in patients selected for the QCA trial who had no usable follow-up x-ray film. Secondary end points in patients with 2 angiograms were: new stenosis development, change in minimum lumen diameter index, and change in percent diameter stenosis index. There were 119 progressors among 243 placebo-treated patients (49%) and 111 progressors among 234 quinapril-treated patients (47%) (p = NS). There were 44 patients with new stenosis development in the placebo group (19%) and 50 (22%) in the quinapril group (p = NS). Change in minimum lumen diameter index was -0.21+/-0.03 mm in the placebo group and -0.18+/-0.03 mm in the quinapril group (p = NS). Finally, change in percent diameter stenosis index was +5.1+/-1.0 in the placebo group and +3.5+/-1.0 in the quinapril group (p = NS). Potential confounders of this trial are presented and discussed.",1999.0,0,0
19,10073846,Comparison of the effects of losartan and captopril on mortality in patients after acute myocardial infarction: the OPTIMAAL trial design. Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan.,K Dickstein; J Kjekshus,"Patients with acute myocardial infarction and evidence of heart failure or left ventricular dysfunction during the acute phase have an excessive mortality risk. Therapy with angiotensin-converting enzyme inhibitors attenuates the detrimental effects of angiotensin II and has been shown to substantially reduce morbidity and mortality in this population. Selective, angiotensin type 1 receptor antagonism with losartan, which inhibits the effects of angiotensin II regardless of its source at the receptor level, may provide more complete blockade of the renin-angiotensin system. The Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist Losartan (OPTIMAAL) study is a multicenter, double-blind, randomized, parallel, captopril-controlled trial. The primary hypothesis is that, compared with captopril, losartan will decrease the risk for all-cause mortality by 20% in high-risk patients after acute myocardial infarction. The study population will consist of 5,000 patients, > or = 50 years of age, with heart failure during the acute phase or with a new Q-wave anterior infarction or reinfarction. Patients will be randomized to treatment with either losartan or captopril. All patients will be followed until 937 deaths occur (event-driven). The primary end point is total mortality (all-cause mortality). The secondary and tertiary end points are sudden death (and/or resuscitated cardiac death) and fatal/nonfatal reinfarction. Based on the assumed event rate, treatment effect and a 95% power to detect a 20% reduction in all-cause mortality at the 4.3% significance level (2-sided, adjusted for 2 interim analyses), the trial will enroll at least 5,004 patients and continue until a total number of 937 events has been reached (intention-to-treat analysis).",1999.0,0,1
20,10075143,,,,,0,0
21,10075388,Reduced bcl-2 concentrations in hypertensive patients after lisinopril or nifedipine administration.,M Buemi; A Allegra; F Corica; C Aloisi; A Ruello; M S Giacobbe; G Di Pasquale; M Senatore; N Frisina,"In 30 patients with essential hypertension and 30 healthy control subjects, we evaluated blood concentrations of B cell leukemia-2 (bcl-2), a protooncogene that can reduce apoptosis. Bcl-2 concentrations were higher in hypertensive than in normotensive subjects. The increase in pressure due to a cold pressor test caused a further increase in blood bcl-2 concentrations, in both hypertensive and normotensive subjects. Treatment of hypertensive patients with hypotensive drugs caused a reduction in bcl-2 concentrations, which was more marked after administration of lisinopril than of nifedipine. The results suggest that concentrations of bcl-2 are increased in patients with hypertension, which could be an important factor in cell proliferation underlying posthypertensive vascular remodeling. Moreover, lisinopril and nifedipine appear to be capable of reducing bcl-2 concentrations, with potentially beneficial effects on vascular modifications in patients with hypertension.",1999.0,0,0
22,10077374,Tolerance to ACE inhibitors after cardiac surgery.,A Manché; J Galea; W Busuttil,"Several studies have shown angiotensin-converting enzyme (ACE) inhibitors to confer significant mortality and morbidity benefits in heart failure. First-dose hypotension may necessitate interruption of such therapy. This is more likely to occur if the ACE inhibitor is administered early after coronary artery bypass grafting (CABG). The purpose of this study was to analyse the haemodynamic tolerance to early post-operative treatment with perindopril and enalapril in patients with impaired renal and ventricular function. Eighty one consecutive CABG patients with a previous myocardial infarction, impaired pre-operative left ventricular ejection fraction (LVEF) on ventriculography and moderately impaired renal function (serum creatinine of 115-150 micromol/l) were randomised into three groups to receive oral placebo, perindopril (4 mg) or enalapril (5 mg) once daily. Groups were subdivided into those with mild ventricular dysfunction (LVEF = 35-65%, n = 20) and significant ventricular dysfunction (LVEF < 35%, n = 7). Exclusion criteria included oliguria (<0.5 ml/kg per h) or inotrope dependance at the point of entry on the first post-operative day. Intolerance to ACE inhibitor was defined as hypotension (<95 mmHg systolic blood pressure or a decrease exceeding 25 mmHg in systolic blood pressure) leading to oliguria (<0.5 ml/kg per h) which was unresponsive to intravenous furosemide (20 mg). In such cases ACE inhibitor treatment was discontinued and patients commenced on dopamine. In the groups with mild ventricular dysfunction (LVEF = 35-65%) perindopril was discontinued in 1/20 and enalapril in 4/20 patients (P = n.s). However, in the groups with significant ventricular dysfunction (LVEF < 35%) perindopril was discontinued in 2/7 and enalapril in 7/7 patients (P = 0.02). Our results suggest that after CABG, patients with moderately impaired renal function and significant ventricular dysfunction do not tolerate ACE inhibitors well when these were commenced on the first post-operative day. However, perindopril was associated with less haemodynamic deterioration than enalapril and consequently may be advantageous in this setting. rights reserved.",1999.0,0,0
23,10078088,Quality of life in chronic heart failure: cilazapril and captopril versus placebo. Cilazapril-Captopril Multicentre Group.,C J Bulpitt; A E Fletcher; L Dössegger; A Neiss; T Nielsen; S Viergutz,"To measure quality of life (QOL) in patients with mild to moderate heart failure treated with angiotensin converting enzyme (ACE) inhibitors cilazapril or captopril. Randomised, double blind, placebo controlled, parallel groups trial. 367 patients with New York Heart Association (NYHA) heart failure class II (62%), III (36%) or IV (1%). Patients were randomised to receive cilazapril 1 mg daily (n = 191) or captopril 25 mg three times daily (n = 90) for 24 weeks, or placebo for 12 weeks followed by cilazapril 1 mg daily for a further 12 weeks (n = 86). If patients had not responded after four weeks cilazapril was increased to 2.5 mg daily and captopril to 50 mg three times daily. QOL was assessed at baseline, 12, and 24 weeks using the sickness impact profile (SIP), the profile of mood states (POMS), the Mahler index of dyspnoea-fatigue, and a health status index (HSI). The physical dimension of the SIP averaged 7 units at baseline and improved after 12 weeks by 2.24 units in the cilazapril group, 2.38 units in the captopril group, and 1.51 units in the placebo group. The difference between drug and placebo was therefore 0.73 units (95% CI -0.86 to 2.32) for cilazapril, and 0.87 units (95% CI -0.96 to 2.70) for captopril, with small non-significant effect sizes (a statistical method for estimating the importance of a treatment related change) of 0.12 and 0.14. Similar results were observed for the total POMS and HSI scores. Although QOL improved more on the ACE inhibitors than on placebo, the effect sizes were not significant (< or = 0.26). Improvements in QOL in mild to moderate heart failure were small when treated with cilazapril or captopril compared with placebo.",1999.0,0,1
24,10080414,Long-term prognostic importance of hyperkinesia following acute myocardial infarction. TRACE Study Group. TRAndolapril Cardiac Evaluation.,E Kjøller; L Køber; S Jørgensen; C Torp-Pedersen,"The long-term prognostic importance of hyperkinesia is unknown following an acute myocardial infarction (AMI). The American Society of Echocardiography recommends that hyperkinesia should not be included in calculation of wall motion index (WMI). The objective of the present study was to determine if hyperkinesia should be included in WMI when it is estimated for prognostic purposes following an AMI. Six thousand, six hundred seventy-six consecutive patients were screened 1 to 6 days after AMI in 27 Danish hospitals. WMI was measured in 6,232 patients applying the 9-segment model and the following scoring system: 3 for hyperkinesia, 2 for normokinesia, 1 for hypokinesia, 0 for akinesia, and -1 for dyskinesia. All patients were followed with respect to mortality for at least 3 years. WMI was calculated in 2 different ways: 1 including hyperkinetic segments (hyperkinetic-WMI) and the other excluding nonhyperkinetic segments (nonhyperkinetic-WMI) by converting the hyperkinetic segments to normokinetic segments. Hyperkinesia occurred in 736 patients (11.8%). WMI was an important prognostic factor (relative risk 2.49; p = 0.0001) for long-term mortality together with heart failure, history of hypertension, angina, or diabetes, previous AMI, age, thrombolytic therapy, arrhythmias, and bundle branch block. In a multivariate analysis including nonhyperkinetic-WMI, hyperkinesia was associated with a relative risk of 0.84, which was statistically significant (confidence intervals 0.74 to 0.96; p = 0.01). When hyperkinesia was included, both in WMI (hyperkinetic-WMI) and as an independent variable, no additional prognostic information (relative risk 0.93; p = 0.26) was obtained. An echocardiographic evaluation shortly after an AMI gave important prognostic information, especially if the information concerning hyperkinesia was included. If WMI is used for prognostic purposes, hyperkinesia should be included in calculation of the index.",1999.0,0,0
25,10080455,The Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET) and combination therapies.,M Pahor; P Tatti,,1999.0,0,0
26,10080457,Effect of angiotensin converting enzyme inhibition on sudden cardiac death in patients following acute myocardial infarction. A meta-analysis of randomized clinical trials.,M J Domanski; D V Exner; C B Borkowf; N L Geller; Y Rosenberg; M A Pfeffer,"Estimate the effect of angiotensin converting enzyme (ACE) inhibitors on the risk of sudden cardiac death (SCD) following myocardial infarction (MI). Trials in post-MI patients have shown that ACE inhibitor therapy reduces mortality. However, the effect on SCD as a mechanism has not been clarified. Trials of ACE inhibitor therapy following MI reported between January, 1978 and August, 1997 were identified. Studies were included if they met the following criteria: 1) randomized comparison of ACE inhibitor to placebo within 14 days of MI; 2) study duration/blinded follow-up of > or =6 weeks; 3) the number of deaths and modes of death were reported or could be obtained from the investigators. We identified 374 candidate articles, of which 15 met the inclusion criteria. The 15 trials included 15,104 patients, 2,356 of whom died. Most (87%) fatalities were cardiovascular and 900 were SCDs. A significant reduction in SCD risk or a trend towards this was observed in all of the larger (N > 500) trials. Overall, ACE inhibitor therapy resulted in significant reductions in risk of death (random effects odds ratio [OR] = 0.83; 95% confidence interval [CI] 0.71-0.97), cardiovascular death (OR = 0.82; 95% CI 0.69-0.97) and SCD (OR = 0.80; 95% CI 0.70-0.92). This analysis is consistent with prior reports showing that ACE inhibitors decrease the risk of death following a recent MI by reducing cardiovascular mortality. Moreover, this analysis suggests that a reduction in SCD risk with ACE inhibitors is an important component of this survival benefit.",1999.0,1,1
27,10082500,ACE inhibitor versus beta-blocker for the treatment of hypertension in renal allograft recipients.,M Hausberg; M Barenbrock; H Hohage; S Müller; S Heidenreich; K H Rahn,"Angiotensin-converting enzyme (ACE) inhibitors have been shown to slow the progression of chronic renal failure. However, the value of ACE inhibitors for the treatment of hypertension in renal allograft recipients has not been established. ACE inhibitors dilate the efferent glomerular arteriole, an effect that may aggravate the decrease in glomerular filtration rate resulting from cyclosporine-induced vasoconstriction at the afferent glomerular arteriole. Therefore, the goal of this double-blind, randomized study was to compare the antihypertensive and renal effects of the ACE inhibitor quinapril with those of the beta-blocker atenolol in renal allograft recipients in whom hypertension developed 6 to 12 weeks after transplantation. All patients received cyclosporine as an immunosuppressant and had stable graft function (serum creatinine concentration, <220 micromol/L) at entry into the study. Twenty-nine patients who received quinapril (daily dose titrated between 2.5 and 20 mg) and 30 patients who received atenolol (daily dose titrated between 12.5 and 100 mg) completed the 24-month study. The two groups did not differ in age, sex ratio, height, and weight before entry into the study. Quinapril decreased diastolic blood pressure from 96+/-1 to 84+/-1 mm Hg (average throughout treatment period), and atenolol decreased diastolic blood pressure from 96+/-1 to 83+/-1 mm Hg. The serum creatinine concentration did not change significantly in either group after 24 months (129+/-8 micromol/L at entry and 148+/-19 micromol/L after 24 months in the quinapril group and 131+/-6 micromol/L at entry and 152+/-15 micromol/L after 24 months in the atenolol group; P=NS for both groups). After 24 months, the change in urinary albumin excretion from baseline was -10+/-15 mg/d in the quinapril group and 52+/-32 mg/d in the atenolol group (P=0.03). These results show that quinapril and atenolol are effective antihypertensive drugs when used after renal transplantation. Moreover, compared with atenolol, quinapril has no adverse effects on graft function. The relative reduction in albuminuria observed with quinapril as compared with atenolol could indicate a beneficial effect of quinapril on long-term graft function.",1999.0,0,0
28,10083055,Value of sequential big endothelin plasma concentrations to predict rapid worsening of chronic heart failure.,B Stanek; B Frey; R Berger; E Hartter; R Pacher,,1999.0,0,0
29,10086852,In vitro release of interferon-gamma and macrophage migration inhibition factor in drug-induced urticaria and angioedema.,E Livni; M Lapidoth; S Halevy,"T-cells are involved in the pathogenesis of cutaneous drug reactions. T-cell phenotype and cytokine release pattern in rivo and in vitro might correlate with the type of immune response involved in cutaneous drug reactions. In vitro release of interferon-gamma and macrophage migration inhibition factor (MIF) from peripheral blood lymphocytes, following in vitro challenge with the suspected unmodified drugs, was studied in 12 patients with drug-induced urticaria and/or angioedema and in two group-matched controls. The occurrence of positive interferon-gamma and MIF responses was significantly higher in patients with drug-induced urticaria and/or angioedema than in controls. The sensitivity and specificity of the interferon-gamma test (50% and 92%, respectively) were similar to that of the MIF test (58% and 96%, respectively). Percentage agreement between both tests was 80.9 (kappa = 0.76). In vitro release of interferon-gamma and MIF in drug-induced urticaria and/or angioedema suggests a drug-specific immune response, and may implicate the drug as a possible inducer of the reaction.",1999.0,0,0
30,10088066,Effects of early treatment with captopril and metoprolol singly or together on six-month mortality and morbidity after acute myocardial infarction. Results of the RIMA (Rimodellamento Infarto Miocardico Acuto) study. The RIMA researchers.,C Coletta; R Ricci; V Ceci; F Seccareccia; F Rulli; V Mazzuca; R L Putini; A Salustri; G Bottero; M Pasquale,"The RIMA (Rimodellamento Infarto Miocardico Acuto) study was designed to assess the relative effects of angiotensin-converting enzyme (ACE) inhibition by captopril, beta-blocker therapy by metoprolol, and their combination in patients with a first acute myocardial infarction on: 1. echocardiographically detected left ventricular remodeling; 2. prognosis. The second goal will be the argument of the present paper. Two-hundred fifty < or = 75 years consecutive patients (mean age: 58 yrs, males = 203) with acute myocardial infarction were randomly allocated to receive for > or = 3 months captopril (up to 75 mg/day, Group 1), metoprolol (up to 200 mg/day, Group 2) or captopril + metoprolol (Group 3) starting in the first 24 hours after the onset of symptoms. Intravenous beta-blockers in the acute phase of myocardial infarction and all other cardioactive drugs were allowed. The effect of the randomized therapy at six months from admission to the coronary care unit was considered in relation to: 1. recurrence of spontaneous cardiac events and of elective revascularization procedures; 2. adverse reactions (hypotension, atrioventricular block, cough, allergy, need of beta-blockers in Group 1, need for ACE inhibition in Group 2) requiring treatment modification based on physician's decision. Definite follow-up data were available in 226 patients and 195/226 patients (86%) had a complete treatment period. In these patients (per protocol analysis), 37 spontaneous cardiac events occurred: cardiac death = 6, non-fatal reinfarction = 9, unstable angina requiring hospitalization = 16, congestive heart failure = 6. Moreover, seven patients received a coronary revascularization procedure. Events occurred in 11/67 patients from Group 1, 16/63 patients from Group 2, 10/65 patients from Group 3 (16% vs 25% vs 15%, p = 0.28). The multiple logistic regression analysis demonstrated an increased odds ratio (OR) for spontaneous cardiac events in patients from Group 2 (OR = 2.82, 95% Cl: 1.16-6.87: p < 0.05). Elective revascularization procedures were statistically less frequent in patients treated with metoprolol (Group 1 = 9%, Group 2 = 1.6%, Group 3 = 0%; Group 1 vs Groups 2 and 3; p = 0.03). The intention-to-treat analysis on the overall population (226 patients) confirmed the presence of a trend towards a higher risk in patients from Group 2 (OR = 2.1, 95% Cl: 0.96-4.59; p = 0.06). Adverse reactions were observed in 16 patients from Group 1, 6 patients from Group 2 and 15 patients from Group 3 (22% vs 10% vs 23%; Group 2 vs Groups 1 and 3; p = 0.08). At the multivariate regression analysis, a trend towards less adverse reactions in patients assigned to the beta-blocker therapy alone was confirmed (OR = 0.41, 95% Cl: 0.15-1.13; p = 0.07). In a randomized early post-infarction treatment strategy, ACE inhibition with captopril alone or in combination with metoprolol demonstrated an increased protection against spontaneous cardiac events at six months in comparison with metoprolol alone. On the other hand, the beta-blocker treatment was associated with a lower number of elective revascularization procedures and appeared better tolerated than ACE inhibition.",1999.0,0,1
31,10089936,,,,,0,0
32,10090111,Diuretics and beta-blockers do not have adverse effects at 1 year on plasma lipid and lipoprotein profiles in men with hypertension. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,M R Lakshman; D J Reda; B J Materson; W C Cushman; E D Freis,"Concern based on the reported short-term adverse effects of antihypertensive agents on plasma lipid and lipoprotein profiles (PLPPs) has complicated the therapy for hypertension. To compare the long-term (1-year) effects of 6 different antihypertensive drugs and placebo on PLPPs in a multicenter, randomized, double-blind, parallel-group clinical trial in 15 US Veterans Affairs medical centers. A total of 1292 ambulatory men, 21 years or older, with diastolic blood pressures (DBPs) ranging from 95 to 109 mm Hg taking placebo were randomized to receive placebo or 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, or prazosin. After drug titration, patients with a DBP of less than 90 mm Hg were followed up for 1 year. Plasma lipids and lipoprotein profiles were determined at baseline, after initial titration, and at 1 year. After 8 weeks on a regimen of hydrochlorothiazide, increases of 3.3 mg/dL (0.09 mmol/L) in total cholesterol and 2.7 mg/dL in apolipoprotein B were significantly different (P< or =.05) from decreases of 9.3 mg/dL in total cholesterol and 5.4 mg/dL in ApoB levels while receiving prazosin but not from placebo. Patients achieving positive DBP control using hydrochlorothiazide (responders) showed no adverse changes in PLPPs, whereas nonresponders exhibited increases in triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. Plasma lipids and lipoprotein profiles did not change significantly among treatment groups after 1 year except for minor decreases in high-density lipoprotein 2 levels using hydrochlorothiazide, clonidine, and atenolol. None of these 6 antihypertensive drugs has any long-term adverse effects on PLPPs and, therefore, may be safely prescribed. Previously reported short-term adverse effects from using hydrochlorothiazide are limited to nonresponders.",1999.0,0,0
33,10090348,Antihypertensive monotherapy with nisoldipine CC is superior to enalapril in black patients with severe hypertension.,I Radevski; D Skudicky; G Candy; S Sathekge; V Strugo; P Sareli,"A single-center, prospective double-blind randomized trial was conducted to compare the efficacy and safety of the calcium channel blocker nisoldipine in a sustained release coat-core formulation (CC), titrated from 10 mg to 40 mg daily, with the angiotensin converting enzyme inhibitor enalapril, titrated from 10 to 40 mg daily, in the treatment of black South African patients with severe hypertension (sitting diastolic blood pressure [DBP] between 115 and 140 mm Hg, confirmed by 24-h ambulatory blood pressure monitoring). Treatment target was a sitting DBP < 95 mm Hg by the 9th week of treatment. This was followed by a 4-month open phase using nisoldipine CC 10 to 60 mg daily. Ninety-six patients had complete data at baseline, and at the end of the double-blind and open phases, and were included in this analysis. In both groups, all patients required titration up to the maximal dose of double-blind medication. Monotherapy with nisoldipine CC, but not enalapril, significantly reduced both sitting and 24-h ambulatory blood pressure (BP). Twenty-four-hour BP in the nisoldipine CC group decreased from 179+/-14 / 118+/-7 to 144+/-16 / 94+/-10 mm Hg (P < .0001) versus 181+/-13 / 117+/-5 to 171+/-17 / 110+/-11 mm Hg in the enalapril group (P = ns). The profound decrease in blood pressure achieved with nisoldipine CC was accompanied by a significant reduction in left ventricular [LV] mass index, observed after only 2 months of treatment (from 146+/-40 to 129+/-35 g/m2, P = .05). In contrast, enalapril had no effect on LV mass (from 139+/-36 to 142+/-50 g/m2, P = NS). The antihypertensive effect of nisoldipine CC was further demonstrated in the open phase, during which 24-h BP decreased from 180+/-14 / 118+/-6 mm Hg (at baseline) to 142+/-16 / 92+/-10 mm Hg at the end of the 16-week open phase (P < .0001). This effect was sustained with trough-to-peak ratio of 74% for systolic and 67% for diastolic BP, with further regression in LV mass. Reduction in 24-h systolic BP to < 135 mm Hg was associated with a greater degree of regression of LV mass index in patients treated with nisoldipine CC. The incidence of adverse events in both groups was low and both nisoldipine CC and enalapril were well tolerated. The incidence of significant ventricular arrhythmia was also low and did not change with treatment. In conclusion, our findings suggest that nisoldipine CC administered once daily could be considered as a suitable first-line antihypertensive agent in black patients with severe hypertension, based on its profound and sustained blood-pressure-lowering effect, associated with significant regression of left ventricular mass and its low side effect profile.",1999.0,0,0
34,10090351,Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.,S Gasic; O F Wagner; P Fasching; C Ludwig; M Veitl; S Kapiotis; B Jilma,"Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.",1999.0,0,0
35,10091486,"Eruptions induced by the ACE inhibitor, lisinopril.",Y Horiuchi; M Matsuda,,1999.0,0,0
36,10091816,Beta-adrenergic blocking agent use and mortality in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a post hoc analysis of the Studies of Left Ventricular Dysfunction.,D V Exner; D L Dries; M A Waclawiw; B Shelton; M J Domanski,"This analysis was performed to assess whether beta-adrenergic blocking agent use is associated with reduced mortality in the Studies of Left Ventricular Dysfunction (SOLVD) and to determine if this relationship is altered by angiotensin-converting enzyme (ACE) inhibitor use. The ability of beta-blockers to alter mortality in patients with asymptomatic left ventricular dysfunction is not well defined. Furthermore, the effect of beta-blocker use, in addition to an ACE inhibitor, on these patients has not been fully addressed. This retrospective analysis evaluated the association of baseline beta-blocker use with mortality in 4,223 mostly asymptomatic Prevention trial patients, and 2,567 symptomatic Treatment trial patients. The 1,015 (24%) Prevention trial patients and 197 (8%) Treatment trial patients receiving beta-blockers had fewer symptoms, higher ejection fractions and different use of medications than patients not receiving beta-blockers. On univariate analysis, beta-blocker use was associated with significantly lower mortality than nonuse in both trials. Moreover, a synergistic reduction in mortality with use of both a beta-blocker and enalapril was suggested in the Prevention trial. After adjusting for important prognostic variables with Cox multivariate analysis, the association of beta-adrenergic blocking agent use with reduced mortality remained significant for Prevention trial patients receiving enalapril. Lower rates of arrhythmic and pump failure death and risk of death or hospitalization for heart failure were observed. The combination of a beta-blocker and enalapril was associated with a synergistic reduction in the risk of death in the SOLVD Prevention trial.",1999.0,0,0
37,10091821,Independent prognostic information provided by sphygmomanometrically determined pulse pressure and mean arterial pressure in patients with left ventricular dysfunction.,M J Domanski; G F Mitchell; J E Norman; D V Exner; B Pitt; M A Pfeffer,"The purpose of this study was to evaluate the relationship of baseline pulse pressure and mean arterial pressure to mortality in patients with left ventricular dysfunction. Increased conduit vessel stiffness increases pulse pressure and pulsatile load, potentially contributing to adverse outcomes in patients with left ventricular dysfunction. Pulse and mean arterial pressure were analyzed for their effect on mortality, adjusting for other modifiers of risk, using Cox proportional hazards regression analysis of data collected from 6,781 patients randomized into the Studies of Left Ventricular Dysfunction trials. Pulse and mean arterial pressure were related positively to each other, age, ejection fraction and prevalence of diabetes and hypertension and inversely to prior myocardial infarction and beta-adrenergic blocking agent use. Higher pulse pressure was associated with increased prevalence of female gender, greater calcium channel blocking agent, digoxin and diuretic use, lower heart rate and a higher rate of reported smoking history. Higher mean arterial pressure was associated with higher heart rate, lower calcium channel blocker and digoxin use and lower New York Heart Association functional class. Over a 61-month follow-up 1,582 deaths (1,397 cardiovascular) occurred. In a multivariate analysis adjusting for the above covariates and treatment assignment, higher pulse pressure remained an independent predictor of total and cardiovascular mortality (total mortality relative risk, 1.05 per 10 mm Hg increment; 95% confidence interval, 1.01 to 1.10; p = 0.02). Mean arterial pressure was inversely related to total and cardiovascular mortality (total mortality relative risk, 0.89; 95% confidence interval, 0.85 to 0.94; p <0.0001). One noninvasive blood pressure measurement provides two independent prognostic factors for survival. Increased conduit vessel stiffness, as assessed by pulse pressure, may contribute to increased mortality in patients with left ventricular dysfunction, independent of mean arterial pressure.",1999.0,0,0
38,10093076,Predictive value of 99Tcm-DTPA captopril scintigraphy in patients with a solitary kidney and reduced kidney function.,C Van de Wiele; B Brans; R Vanholder; H Hoeben; K Van Laere; R A Dierckx,"The aim of this study was to determine if the qualitative 99Tcm-DTPA captopril radionuclide test (CRT) can help predict the acute detrimental effect of angiotensin-converting enzyme (ACE) inhibitors on renal function in hypertensive patients with solitary kidneys and chronic renal failure. Between 1991 and 1996, eight consecutive patients (6 males, 2 females) aged 27-73 years (mean 49.8 years) with known chronic renal failure and a solitary kidney referred for ACE treatment were included. 99Tcm-DTPA renography was performed at baseline and 1 h after the administration of 25 mg captopril within 1 week of each other. The CRT was performed in accordance with the criteria of the Working Party on the Diagnostic Criteria of Renovascular Hypertension with Captopril Renography. A beneficial or detrimental effect of subsequent ACE inhibitor treatment on renal function was determined by long-term follow-up (> or = 2 years). The CRT accurately predicted outcome in all eight patients subsequently treated with ACE inhibitors. In conclusion, our results suggest a role for qualitative 99Tcm-DTPA CRT in the prediction of renal function in patients with a solitary kidney and chronic renal failure subsequently treated with ACE inhibitors.",1999.0,0,0
39,10093769,Heart failure.,M W Rich,"Heart failure is predominantly a disorder of older adults, and to a large extent the epidemiology of heart failure reflects the convergence of age-related changes in the cardiovascular system and the rising prevalence of age-related cardiovascular diseases. The diagnosis of heart failure in the elderly is often difficult because of the presence of atypical symptomatology and comorbid conditions. Similarly, optimal treatment frequently poses a therapeutic challenge because of the high prevalence of confounding medical, behavioral, psychosocial, and economic factors. In addition, there is a paucity of data on the pharmacotherapy of heart failure in the very elderly (over age 80), and in the large proportion of older patients with heart failure and preserved left ventricular systolic function. Despite these difficulties, a number of therapeutic options, including ACE inhibitors, digoxin, and possibly beta blockers and angiotensin receptor antagonists, have been shown to favorably affect the clinical course of heart failure in elderly patients. In addition, several studies have documented the efficacy of multidisciplinary heart failure disease management programs for reducing hospital admission rates, improving quality of life, and decreasing cost of care. At present, the three greatest challenges in managing older heart failure patients are: (1) to more effectively implement proven treatments, such as ACE inhibitors, disease management systems, and antihypertensive therapy; (2) to develop effective therapies for the treatment of diastolic heart failure; and (3) to develop more effective means for heart failure prevention. It is hoped that future studies will address each of these critically important issues.",1999.0,0,0
40,10095796,"Comparison of effects of quinapril and metoprolol on glycaemic control, serum lipids, blood pressure, albuminuria and quality of life in non-insulin-dependent diabetes mellitus patients with hypertension. Swedish Quinapril Group.",J Ostman; K Asplund; T Bystedt; B Dahlöf; S Jern; T Kjellström; H Lithell,"To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control, with glycosylated haemoglobin (HbA1c) as the principal variable, in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. A randomized, double-blind, double-dummy, multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period. Quinapril (20 mg) and metoprolol (100 mg, conventional tablets) were given once daily. No change was made in the treatment of diabetes (diet and hypoglycaemic agents). Seventy-two patients fulfilling the criteria were randomized and entered the double-blind period. Twelve patients did not complete the study. Sixty patients, 26 on quinapril and 34 on metoprolol, were available for the final analysis. The effect was assessed by changes in HbA1c, the fasting serum glucose and the post-load serum glucose, C-peptide and insulin levels during the oral glucose tolerance test. In the quinapril group, the fasting serum glucose, oral glucose tolerance and the C-peptide and insulin responses, determined as the incremental area under the curves (AUC), showed no change, but the mean HbA1c level increased from 6.2 +/- 1.1% to 6.5 +/- 1.3% (P < 0.05). In the metoprolol group, the rise in the mean level of HbA1c, from 6.3 +/- 1.0% to 6.8 +/- 1.3% (P < 0.01), tended to be more marked than after quinapril, although there was no significant difference between the increments. The mean fasting serum glucose showed an increase from 9.1 +/- 1.9 mM to 10.1 +/- 2.8 mM (P < 0.01) which correlated significantly with the duration of diabetes (P < 0.01) and the increase in fasting serum triglycerides (P < 0.001). Moreover, in the metoprolol group we found significant decreases in the oral glucose tolerance as well as C-peptide and insulin responses to the glucose load. Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension. Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c, increased fasting blood glucose, decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol.",1999.0,0,0
41,10097934,Effects of nisoldipine and lisinopril on left ventricular mass and function in diabetic nephropathy.,L Tarnow; A Sato; S Ali; P Rossing; F S Nielsen; H H Parving,"To compare the effects of the calcium channel blocker, nisoldipine, and the ACE inhibitor, lisinopril, on left ventricular mass (LVM) and systolic function in type 1 diabetic patients with diabetic nephropathy. M-mode echocardiography was performed in 50 hypertensive type 1 diabetic patients with diabetic nephropathy enrolled in a 1-year, randomized, double-blind, parallel study of antihypertensive treatment with nisoldipine CC (20-40 mg/day) or lisinopril (10-20 mg/day). Ambulatory 24-h blood pressure was measured with the Takeda TM 2420 device (A & D, Tokyo, Japan) every 3 months. Three patients dropped out and seven patients were excluded due to technical difficulties. The 24-h diastolic blood pressure was reduced from 83 to 80 mmHg in the nisoldipine group (P = 0.06) and from 85 to 80 mmHg in the lisinopril group (P = 0.02). The decline in systolic blood pressure was not significant with any of the two treatments, and no difference in reduction of blood pressure was seen between groups. LVM corrected for body surface area (LVMI) was comparable between groups at baseline and increased from 96 +/- 5 to 107 +/- 6 g/m2 (mean +/- SEM; P = 0.007) in the nisoldipine group and from 95 +/- 4 to 103 +/- 5 g/m2 (P = 0.03) in the lisinopril group. The mean difference between the change in LVMI in the two groups was 2.9 (95% CI 6.8 to 12.7) g/m2. The prevalence of left ventricular hypertrophy rose from 18 (95% CI 6-30) to 30% (16-44) during the study period. A multiple linear regression analysis revealed that after 1 year of treatment, LVMI increased with higher systolic blood pressure level and declining glomerular filtration rate (R2 = 0.25). Fractional shortening was within normal range at baseline, 42 +/- 1 vs. 41 +/- 1% with nisoldipine and lisinopril, respectively, and did not change during follow-up. Antihypertensive treatment with nisoldipine or lisinopril to bring diastolic blood pressure level within the normal target range does not hinder a rise in LVMI in type 1 diabetic patients with diabetic nephropathy.",1999.0,0,0
42,10099033,Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients.,D Acanfora; D T Lowenthal; G Furgi; L Trojano; C Picone; A Nicolino; G L Iannuzzi; A Papa; F Rengo,"We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.",1999.0,0,0
43,10099034,Clinical and neurohormonal effects of nicardipine hydrochloride in patients with severe chronic heart failure receiving angiotensin-converting enzyme inhibitor therapy.,D Benatar; V Hall; S Reddy; M Gheorghiade,"It has been proposed that worsening of heart failure with dihydropyridines, such as nicardipine, is related to the activation of the neuroendocrine system. To test this, we evaluated 20 patients with severe heart failure (mean age, 55 +/- 13 years; New York Heart Association functional class III; left ventricular ejection fraction, 18% +/- 8% on maintenance therapy with captopril, digoxin, and diuretics) who were randomized to nicardipine (60 or 90 mg/d) or placebo during a 4-month double-blind protocol. The following measurements were obtained at baseline, monthly, and at 4 months or last follow-up visit: rest and exercise radionuclide ventriculography, maximal treadmill time, 6-minute walking test distance, serum norepinephrine and aldosterone concentrations, and plasma renin activity. During the follow-up period, worsening of heart failure occurred in 6 patients in the nicardipine group and in 2 patients in the placebo group (p = 0.06). The maximal treadmill time for a 6-minute walking distance and exercise radionuclide ejection fraction at the last follow-up visit did not change in patients who did not deteriorate with heart failure in the placebo or nicardipine groups as compared with baseline values. In this study group of patients with severe heart failure receiving therapy with digoxin, captopril, and diuretics, nicardipine was associated with worsening heart failure without an apparent activation of the neurohormones. However, because of the small number of patients and a significant number of patients who deteriorated during the follow-up period, no definitive conclusions can be made.",1999.0,0,0
44,10099064,"Effect of benazepril on endothelial function in previously untreated hypertensive patients. The Working Group of Cardiology of the Academic Committee of Veszprém, Hungary.",L Nagy; J Tarján; M Sámóczi; I Kovács; J Takács,"The aim of this study was to determine whether angiotensin-converting enzyme inhibitor administration improves the endothelial function of patients with previously untreated essential hypertension. Using high-resolution ultrasonography, we measured the arteria brachialis diameter at rest, during reactive hyperemia (endothelium-dependent flow-mediated dilatation [FMD]), and after sublingual nitroglycerin (endothelium-independent dilatator). Twenty-one previously untreated hypertensive patients participated in the study (13 men, 8 women; mean age, 39.1 +/- 15 years). In the 21 patients, the basal FMD was 5.02% +/- 4.1%. Two hours after the first 10-mg benazepril dose, the FMD was 6.67% +/- 3.9%, and after 1 month of daily 10-mg benazepril administration, the FMD was 5.59% +/- 2.9%. These changes were not significant compared with the baseline value. Nine patients had relatively normal FMD (>5%), whereas the other 12 patients had abnormal FMD (<5%) at baseline. In the latter group, the first 10 mg benazepril produced significant improvement in FMD, from 2.4% +/- 2.5% to 5.08% +/- 2.4% (P < 0.05), but 10 mg benazepril daily for 1 month resulted in no further improvement (4.78% +/- 2.7%) compared with the acute effect. No difference was found between groups with regard to age, gender, blood pressure, blood lipids, and basal arteria brachialis diameter. The previously untreated patients with essential hypertension have endothelial dysfunction, but individual differences were found. The angiotensin-converting enzyme inhibitor treatment improves endothelial function only in those patients who had endothelial dysfunction before the treatment.",2000.0,0,0
45,10099075,"Low-dose combination treatment for hypertension versus single-drug treatment-bisoprolol/hydrochlorothiazide versus amlodipine, enalapril, and placebo: combined analysis of comparative studies.",L M Prisant; J M Neutel; V Papademetriou; V DeQuattro; W D Hall; M R Weir,"To assess the efficacy and safety of 2.5, 5, and 10 mg bisoprolol/6. 25 mg hydrochlorothiazide (HCTZ), 2.5, 5, and 10 mg amlodipine; and 5, 10, 20, and 40 mg enalapril in subjects (n = 541) with a sitting diastolic blood pressure of 95 to 114 mm Hg, data from two comparative studies were pooled. All drugs were titrated to a diastolic blood pressure 90 mm Hg or less. Both studies were double-blind, randomized, parallel dose escalation trials with similar designs and included three active treatments. The second study also had a placebo group. The mean change from baseline of systolic and diastolic blood pressure for placebo (n = 79) was -0. 1/-2.2 mm Hg; amlodipine (n = 154), -12.4/-10.3 mm Hg; enalapril (n = 155), -9.4/-8.2 mm Hg; and bisoprolol/HCTZ (n = 155), -14.0/-12.0. Overall efficacy analyses documented a statistically significant decrease in sitting diastolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo, amlodipine, and enalapril. There was a significant reduction in sitting systolic blood pressure for bisoprolol/6.25 mg HCTZ compared with placebo and enalapril but not amlodipine. Also, there was a significant decrease in sitting heart rate for bisoprolol/6.25 mg HCTZ (-6.2 beats/min) compared with placebo (+0.1 beats/min), amlodipine (+1.2 beats/min), and enalapril (+0.5 beats/min). The control rate (diastolic blood pressure < or = 90 mm Hg) for bisoprolol/6.25 mg HCTZ (66.5%) was significantly better than for placebo (21.8%) and enalapril (47.1%) but not amlodipine (58.4%). Of those patients achieving and maintaining control, 49% of the bisoprolol/6.25 mg HCTZ subjects were on the lowest two doses compared with 30% of the amlodipine and 26% of the enalapril subjects. Percentages of patients reporting at least one drug-related adverse event through week 12 were 27%, 24%, 28%, and 25% for placebo, bisoprolol/6.25 mg HCTZ, amlodipine, and enalapril (not significant). Lower doses of two drugs in fixed combination can provide as good or better blood pressure control compared with higher doses of a single drug with similar tolerability and safety.",1999.0,0,0
46,10099910,Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I.,K Swedberg; J Kjekshus; S Snapinn,"The CONSENSUS trial was the first study to show prognostic improvement by an ACE inhibitor. Patients in NYHA class IV heart failure were treated with enalapril or placebo. After study completion (average 183 days) all patients were offered open-label enalapril therapy. This paper reports on the survival at the 10-year follow up of the patients randomized in the CONSENSUS trial. All 35 participating centres in CONSENSUS I were asked to complete a questionnaire on the survival status at 1 November 1996 of patients randomized in CONSENSUS. At 10-year follow up, one patient was lost to follow-up. Five patients, all in the enalapril group, were long-term survivors (P = 0.004). Averaged over the duration of the trial (double-blind plus open-label extension) the risk reduction was 30% (P = 0.008), with a 95% confidence interval of 11% to 46%. At the end of the double-blind study period, mortality was considerably higher among patients who did not receive open ACE inhibitor therapy compared to those who did. After a treatment period of, on average, 6 months, enalapril was shown to be effective. The effect was sustained for at least 4 years i.e. for another 3.5 years. The present follow-up is the first heart failure trial where the full life-cycle has been followed from randomization. In severe heart failure, mortality is significantly reduced by enalapril. On average, the beneficial effect is maintained for several years and overall survival time is prolonged by 50% (from 521 to 781 days).",1999.0,0,1
47,10100063,"Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.",J Gasowski; J A Staessen; H Celis; R H Fagard; L Thijs; W H Birkenhäger; C J Bulpitt; A E Fletcher; G G Arabidze; P de Leeuw; C T Dollery; J Duggan; K Kawecka-Jaszcz; G Leonetti; C Nachev; M Safar; J L Rodico; J Rosenfeld; M L Seux; J Tuomilehto; J Webster; Y Yodfat,"The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.",1999.0,0,0
48,10100064,Antihypertensive drug treatment: a comparison of usual care with self blood pressure measurement.,B Bailey; S L Carney; A A Gillies; A J Smith,"Blood pressure self-measurement is increasing in most communities and yet its role in the management of hypertension is poorly understood. This study was devised to evaluate the behaviour of doctors in general practice when treating patients with poorly controlled essential hypertension who use self-measurement. Patients, most of whom were already taking antihypertensive medications were commenced on perindopril or indapamide at their doctor's discretion and were randomly allocated to self-measurement (SM) using an OMRON HEM706 oscillometric device or a continuation of their usual care (UC) over an 8-week period. This was an observational study without any specific or set treatment goals for the doctor to follow. Sixty of 62 subjects completed the study and the two groups were equally matched for age, body mass index, gender, and blood pressure (BP). While additional perindopril or indapamide produced a significant fall in BP in both groups over the study period, the systolic pressure remained significantly higher in the SM group (sitting 148 +/- 3 compared with 142 +/- 3; 145 +/- 3 compared with 138 +/- 3 mm Hg respectively; P < 0.05). Twenty-four hour and daytime ambulatory monitor systolic pressures were also significantly higher in the SM group. Differences in diastolic BP were not statistically significant. Furthermore, SM patients were less likely to have their medications increased and more likely to have them reduced or ceased. Doctors and patients found self-measurement convenient and useful. This study suggests that doctors prescribing decisions are influenced by evidence from self-measurement of BP with consequential increases in office BP related to reduced drug use. While self-BP measurement can offer reassurance about adequacy of control when away from a physicians office, our best evidence of understanding target blood pressures comes from large randomised studies using office blood pressures as an end-point. There is an urgent need for further study to provide arbitration between self-measurement and office blood pressures although each measurement must contribute to the management of hypertension.",1999.0,0,0
49,10100068,Association of arginine vasopressin and arterial blood pressure in a population-based sample.,X Zhang; H W Hense; G A Riegger; H Schunkert,"The role of arginine vasopressin (AVP) in the development and maintenance of arterial hypertension is controversial. Furthermore, it remains unclear whether chronic treatment with antihypertensive agents modulates levels of AVP, with potential secondary effects on vascular tone and fluid homeostasis. To investigate the relation between plasma AVP and arterial blood pressure in a population-based sample of 534 middle-aged subjects. Overall, levels of AVP were higher in hypertensive subjects (2.15 +/- 0.26 pg/ml; n = 289) than in normotensive subjects (1.45 +/- 0.15 pg/ml; n = 245; P < 0.05). (Hypertension was defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg, or receiving antihypertensive medication.) In untreated individuals, plasma levels of AVP were found to be correlated with both systolic (r = 0.15, P = 0.002) and diastolic (r = 0.14, P = 0.005) blood pressure. The differences between the lowest and highest quartile of AVP levels were 5.1 mmHg (P = 0.03) and 2.6 mmHg (NS) for systolic and diastolic blood pressure, respectively, after adjustment for age and sex. Moreover, it appeared that the relation between AVP and blood pressure was particularly strong in subjects with low levels of renin (< 10 mU/l; n = 118; systolic blood pressure r = 0.24, P = 0.007; diastolic blood pressure r = 0.19, P = 0.03). Specifically, patients receiving monotherapy with diuretics (n = 39) or beta-blockers (n = 54) displayed elevated plasma levels of AVP (2.93 +/- 0.98 pg/ml and 2.74 +/- 0.74 pg/ml respectively); however, only in patients taking diuretics was this finding apparently independent of confounding variables. Other monotherapies with angiotensin-converting enzyme inhibitors (n = 9) or Ca(2+)-antagonists (n = 19) were not associated with levels of AVP. The data suggest that plasma levels of AVP display a discernible relationship with arterial blood pressure and hypertension, particularly when renin levels are low. In addition, with the exception of diuretics, no modulation of AVP levels is attributable to the intake of antihypertensive agents as it occurs in a population-based sample.",1999.0,0,0
50,10100083,Controlled study of the effect of angiotensin converting enzyme inhibition versus calcium-entry blockade on insulin sensitivity in overweight hypertensive patients: Trandolapril Italian Study (TRIS).,F Galletti; P Strazzullo; B Capaldo; R Carretta; F Fabris; L A Ferrara; N Glorioso; A Semplicini; M Mancini,"The aim of this study was to evaluate the effect of trandolapril, an angiotensin converting enzyme inhibitor, on blood pressure, forearm blood flow and insulin sensitivity in comparison with nifedipine gastrointestinal therapeutic system. This is a multicentre, two-way parallel-group, open-label comparative study in 90 overweight hypertensive patients, who were randomly assigned to treatment for 8 weeks with either trandolapril or nifedipine. At baseline and after treatment, all patients underwent an oral glucose tolerance test, an evaluation of their metabolic profiles and a euglycaemic hyperinsulinaemic clamp test. In a subgroup of 18 patients, a forearm study was carried out. Blood pressure fell by the second week of treatment and remained significantly reduced compared with baseline in both treatment groups. Plasma triglyceride levels were also significantly reduced after trandolapril therapy, but no significant changes occurred in the other metabolic parameters during treatment with either drug. During the euglycaemic hyperinsulinaemic clamp, whole-body glucose use was similar in the two treatment groups at baseline, and a moderate but statistically significant increase in insulin sensitivity was observed after trandolapril treatment (trandolapril: 5.0 +/- 0.2 versus 4.5 +/- 0.2 mg/kg per min; nifedipine: 4.1 +/- 0.3 versus 4.2 +/- 0.3 mg/kg per min; P < 0.05, versus baseline and trandolapril versus nifedipine treatment). Skeletal muscle glucose uptake was significantly higher after trandolapril than after nifedipine therapy (5.0 +/- 0.7 and 3.0 +/- 0.4 mg/min, respectively; P < 0.01). As forearm blood flow was similar in the two treatment groups at baseline and was unchanged after 8 weeks of therapy, skeletal muscle glucose extraction was significantly greater in the ACE inhibitor treated-group than in the nifedipine comparative group (trandolapril: baseline 21 +/- 2, treatment 24 +/- 3 mg/dl; nifedipine: baseline 18 +/- 3, treatment 16 +/- 2 mg/dl; P < 0.05, trandolapril versus nifedipine treatment). During short-term treatment, ACE inhibition with trandolapril was able to moderately improve insulin sensitivity, in comparison with calcium blockade, and this effect appeared to be independent of the haemodynamic action of the drug.",1999.0,0,0
51,10100105,"Double-blind, randomized, multicentre comparison of the effects of amlodipine and perindopril on 24 h therapeutic coverage and beyond in patients with mild to moderate hypertension. General Physicians Investigators' Group.",F Zannad; C M Bernaud; R Fay,"To compare the therapeutic coverage and safety of amlodipine and perindopril in patients with mild to moderate hypertension (diastolic blood pressure > or = 90 mmHg and < or = 109 mmHg). A double-blind, randomized, parallel-group, multicentre study. Following a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either amlodipine at 5-10 mg once a day or perindopril at 4-8 mg once a day, for 60 days. Trough: peak ratios were calculated by two different methods (global and individualized approaches) from 24 h ambulatory blood pressure recordings made after the placebo period and after the active treatment period. Residual lowering of blood pressure after single-blind, single-dose omission was also investigated with further 24 h ambulatory blood pressure monitoring. Safety assessments were made throughout the study. The placebo-adjusted, global, diastolic blood pressure trough: peak ratio was 0.80 in the amlodipine group (n = 47) and 0.81 in the perindopril group (n = 49) in an intent-to-treat analysis. The corresponding global systolic blood pressure trough: peak ratio was 0.83 for amlodipine and 0.68 for perindopril. Individual trough: peak ratios were non-normally distributed. Mean (+/- SD) individual trough: peak ratios (intent-to-treat analysis) for diatolic blood pressure were 0.50 +/- 0.69 for amlodipine (median 0.42) and 0.15 +/- 3.27 for perindopril (median 0.33). In the per protocol analysis, the corresponding values were 0.50 +/- 0.72 (median 0.34) for amlodipine and 0.01 +/- 3.90 for perindopril (median 0.21). Both treatments produced comparable decreases in clinic systolic and diastolic blood pressure between days 0 and 60. Forty-eight hours after the last dose, both systolic and diastolic blood pressure were lower in amlodipine-treated patients than perindopril-treated patients. Amlodipine and perindopril were generally well tolerated. The most frequently reported adverse event was leg oedema in amlodipine-treated patients (19.1%), and coughing in perindopril-treated patients (14.3%). These results showed no statistically significant difference in trough: peak ratios between amlodipine and perindopril. However, the ambulatory blood pressure trough: peak ratios showed very large variations. Determination of trough: peak ratios by the conventional approach or by an individual approach can yield disparate values. After omitting one dose, a condition imitating noncompliance, blood pressure was more effectively controlled with amlodipine than with perindopril.",1999.0,0,0
52,10130617,"Development, implementation, and results of a successful multidisciplinary adverse drug reaction reporting program in a university teaching hospital.",B M Murphy; L C Frigo,"The development and implementation of an active adverse drug reaction reporting program in a university teaching hospital is described. The progression from a solely voluntary system to a multidisciplinary program consisting of both voluntary and involuntary components is discussed. A total of 1,011 adverse reactions were reported between July 1, 1988 and July 22, 1992. The most common reaction reported was rash. Antibiotics were most commonly implicated in the reactions reported. As a single agent, digoxin was involved most frequently. Voluntary reporting by physicians, nurses, and pharmacists accounted for approximately 24% of the adverse reactions reported. Occurrence screening by the Quality Assurance department produced approximately 76% of the reports.",1999.0,0,0
53,10150320,Effect of acute and long-term administration of ramipril on circadian rhythm of blood pressure in essential hypertension.,D Cavazzini; G Amadei; R Manfredini; G Musacci; D Mele; C Longhini,"Ambulatory monitoring was used to evaluate the antihypertensive efficacy and effect on circadian rhythms of blood pressure and heart rate of a single dose and long-term administration of ramipril in 20 patients with mild to moderate essential hypertension. Patients initially were randomized to receive either placebo or a single 5-mg dose of ramipril, followed 1 week later by 5 mg of ramipril daily for 6 months. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate were measured every 20 minutes for 24 hours. Single-dose ramipril reduced both SBP and DBP (P < .001) without affecting heart rate. Long-term treatment produced a small additional antihypertensive effect, again without modifying heart rate. Cosinor analysis demonstrated that both administrations of ramipril effectively lowered SBP and DBP mesors (P < .001), compared to placebo; circadian rhythms remained undisturbed. Heart rate also was not modified on any circadian parameter. A significant reduction (P < .001) of blood pressure amplitude, however, occurred after long-term treatment and may have importance in terms of preventing cardiac damage.",1994.0,0,0
54,10150325,Effect of atenolol and ramipril on regression of left ventricular hypertrophy: comparative echocardiographic assessment.,F Rosatti; M Lunardi; M Mangrella; A Filippelli; E Lampa; F Rossi,"Left ventricular hypertrophy (LVH) dramatically worsens hypertensive illness. Because the genesis of LVH appears to be multifactorial, antihypertensive treatment should aim to reduce not only pressor values but also the hypertrophic ventricular mass. This result can be obtained only when drugs able to act on both pathogenetic factors are used. To evaluate the effectiveness of antihypertensive therapy on regression of LVH, 21 patients with stage 2 essential hypertension were treated for a year with either atenolol (120 mg/d orally), a cardioselective beta-blocker without intrinsic sympathomimetic activity, or ramipril (5 mg/d orally), an angiotensin-converting enzyme inhibitor with high tissue activity. Both treatments produced significant control of hypertension and regression of LVH. No statistically significant difference between treatments was noted, except for heart rate, which was substantially unchanged by ramipril but significantly decreased by atenolol. Both drugs were well tolerated. Atenolol and ramipril have a major role in the long-term treatment of hypertension and in the regression of hypertension-associated LVH.",1995.0,0,0
55,10155301,Quality-of-Life measurements for patients taking which drugs? The clinical PCASEE perspective.,P Bech,"Of the many publications on quality of life in medicine over the last 2 decades, only a minor fraction have been devoted to drug trials. The most frequently investigated are classes of drugs within cancer disorders, hypertension and depressive illness. Health-related quality-of-life (QOL) measurements are typically applied in chronic or subchronic disorders where the balance between effectiveness (disease-modifying drug effects) and safety (adverse drug reactions) are assessed by patients in terms of subjective well-being. In this context, quality of life is an attempt to help the doctor to listen to his or her patient. The components of QOL measurements are to be found within the PCASEE model where: P = physical indicators; C = cognitive indicators; A = affective indicators; S = social indicators; E = economic-social stressors or negative life events; and E = ego function or personality problems. Most variance in QOL measurements arises through operating in the cognitive (e.g. lack of control, concentration difficulties) or affective (e.g. depressed mood or anxiety) components. The most specific component is, of course, adverse drug reactions, which are typically gastrointestinal symptoms in cancer therapies, and circulatory symptoms and sexual function with antihypertensive drugs. However, the affective and cognitive components also have different weights within subclasses of drugs, such as antihypertensive agents. Thus, angiotensin converting enzyme inhibitors act on the affective component (depression and anxiety) and calcium channel blockers on the cognitive component (neurasthenia). In general, patients with cancer or hypertension give more reliable assessments of their cognitive and affective symptoms than their doctors do, while patients with primary depression are less reliable than their doctors or relatives in measuring changes in the affective components of their illness when they are ill. Health-related QOL measurements have not only an impact on the doctor-patient relationship but also involve a holistic approach to drug treatment, by checking all the PCASEE components.",1995.0,0,0
56,10164060,Formulary management of ACE inhibitors.,K R Gerbrandt; K C Yedinak,"An increasing number of ACE inhibitors have become available in recent years. Because these agents are all similar, careful scrutiny is required in order to determine specific advantages of particular agents when making formulary decisions. Differences between agents with regard to structure and tissue specificity have been identified, but the clinical relevance of these differences is not clear. ACE inhibitors vary greatly with regard to bioconversion, distribution and elimination. Disease states such as congestive heart failure (CHF) and hepatic or renal insufficiency may affect the disposition of specific ACE inhibitors. These agents may differ substantially in duration of action, and ACE inhibitors that are given once daily may optimise patient compliance and decrease costs. ACE inhibitors have been extensively studied in patients with hypertension, CHF or nephropathy, and following myocardial infarction (MI). Differences in efficacy between agents are often a result of variations in study design, or because nonequipotent dosages were compared. It is likely that the benefits of ACE inhibitors are class effects, and it is probably reasonable to use an agent even if large scale clinical trials have not been performed with that particular drug. Few differences have been found between ACE inhibitors with regard to adverse effects or drug interactions, and these factors are of minor importance when making formulary decisions. Cost and availability may vary among agents, and will depend on geographical location and institution-specific purchasing contracts. ACE inhibitors have shown positive effects on quality of life when compared with agents of other classes. Quality-of-life studies that have directly compared ACE inhibitors have produced conflicting results. In the setting of hypertension, cost-effectiveness evaluations typically find that the newer, longer-acting ACE inhibitors provide the greatest financial benefit. Differences in cost effectiveness in the post-MI patient population are typically the result of variations in protocol design, including duration of treatment and nondrug costs. ACE inhibitors are fairly homogeneous and selection between agents can be difficult. Clinical efficacy, time course of action, and cost are the primary concerns in selecting agents for inclusion on a formulary.",1996.0,0,0
57,10169388,Economic evaluation of ACE inhibitor treatment of nephropathy in patients with insulin-dependent diabetes mellitus in Italy.,L Garattini; M Brunetti; F Salvioni; M Barosi,"Diabetic nephropathy is one of the major complications of insulin-dependent diabetes mellitus (IDDM), with proteinuria being the main clinical manifestation of diabetic nephropathy. Most patients who develop overt proteinuria progress to end-stage renal disease (ESRD), usually within 5 to 7 years; ESRD necessitates dialysis or renal transplantation. Although a relationship between blood pressure reduction and delaying of ESRD has been assumed for a long time, only recently has a controlled randomised clinical trial shown that the treatment of diabetic nephropathy with an ACE inhibitor can significantly delay the loss of renal function and, therefore, ESRD. Consistent with the clinical trial on which this economic evaluation was based, the costs and consequences of 2 alternatives were considered: (i) patients subject to blood pressure control with only antihypertensive medication, but without an ACE inhibitor (placebo group) and (ii) patients given ACE inhibitor therapy (captopril group) with similar blood pressure control to the placebo group. This cost-effectiveness analysis was performed from the perspective of the Italian National Health Service [Servizio Sanitario Nazionale (SSN)]. Accordingly, only direct costs related to publicly funded healthcare services were included. The number of dialysis-years avoided (DYA) was the clinical end-point. A 10-year time horizon was considered for the economic evaluation. Captopril therapy was dominant, being at the same time more effective and less costly. The total cost for the captopril alternative during the 10-year period was 21,901,625 Italian lire (L; 1993 values) per patient, while total cost for the placebo alternative was L30,352,590 per patient. Compared with placebo, 20.01 DYA per 100 patients treated were estimated with captopril therapy during the trial period, equivalent to 2.4 months per patient. The robustness of this result was confirmed by sensitivity analysis: for both extremes, captopril remained dominant. This economic evaluation, requested by the Italian Ministry of Health, demonstrated savings in healthcare expenditure with the use of an ACE inhibitor in patients with proteinuria.",1997.0,0,0
58,10170450,Cost effectiveness in the treatment of heart failure with ramipril. A Swedish substudy of the AIRE study. Acute Infarction Ramipril Efficacy.,L Erhardt; S Ball; F Andersson; P Bergentoft; C Martinez,"We estimated the cost effectiveness of adding the ACE inhibitor ramipril to conventional treatment in patients with heart failure after acute myocardial infarction. These estimates were based on the Acute Infarction Ramipril Efficacy (AIRE) study and on complementary Swedish healthcare resource use data for a subset of patients. The average follow-up period was 15 months (minimum 6 months, maximum 3.8 years). The perspective of the analysis was that of the county councils (third-party payers), and we focused on the cost of drugs and hospitalisation. The marginal cost effectiveness of the treatment was estimated over 3 treatment periods: 1, 2 and 3.8 years. The cost-effectiveness ratios varied between SEK14,148 and SEK33,033 per life-year gained ($US1 = SEK7.70. Pounds 1 = SEK12.40) for the 3 treatment periods. Adding ramipril to conventional treatment for heart failure after acute myocardial infarction is therefore cost effective, and compares favourably with the cost effectiveness of other common medical therapies in the cardiovascular field.",1997.0,0,0
59,10172139,Incidence of adverse drug reactions in adult medical inpatients.,L Bowman; B C Carlstedt; C D Black,"This study was a prospective observational study of ADR occurrence and evaluation in adult internal medicine inpatients conducted over a 120-day period. Clinical pharmacists screened for ADRs at a county hospital in Indianapolis, IN. Patient information was reviewed on admission, every four days during hospitalization, and at discharge. ADRs occurring after hospital admission were assessed for causality, severity, pharmacological type (i.e., augmented pharmacology versus idiosyncratic reaction) and affected organ system. Nurse and pharmacist reports, incident reports, physician consults, patient transfers to critical care units, and serum drug concentration reports were additional means of ADR identification. Overall, 23.1% of patients experienced an ADR while 2.6% of the 11,702 drug exposures resulted in an ADR. Patients aged greater than 65 years (29.6% vs. 20.5% for younger patients) and females (26.2% vs. 20% for males) were at higher risk for ADR development (p < 0.05). Length of hospital stay was longer (13.3 days vs. 6.7 days; p < 0.05) and drug exposures more frequent for patients experiencing ADRs (p < 0.001). Furosemide elicited the most ADRs with 36 in 244 patient exposures (14.7%). Diltiazem, enalapril, heparin, trimterene/hydrochlorothiazide combination and captopril were also frequently implicated. ADRs were classified as mild (35.9%), moderate (52.6%), and severe (10.2%). Organ systems most commonly affected were the metabolic/hematologic (32.9%), gastrointestinal (17.8%), genitourinary (11.8%), and cardiovascular (10.5%). Over 30% of events were idiosyncratic reactions. ADR incidence was consistent with previous literature. Many frequently implicated medications were newer agents and the severity of events was less than previously reported.",1999.0,0,0
60,10178659,Cost-effectiveness analysis of early lisinopril use in patients with acute myocardial infarction. Results from GISSI-3 trial.,M G Franzosi; A P Maggioni; E Santoro; G Tognoni; E Cavalieri,"The cost effectiveness of early treatment with lisinopril in acute myocardial infarction (MI) was estimated using survival and cost data gathered prospectively during the hospitalisation of the overall population of patients enrolled in the third study of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI-3), which assessed the efficacy of early (within 24 hours) treatment with an angiotensin-converting enzyme (ACE) inhibitor (lisinopril) for 6 weeks in a group of 19,394 relatively unselected patients with acute MI. A statistically significant reduction in 6-week mortality was achieved among patients treated with lisinopril when compared with patients allocated to the control group (absolute reduction in mortality: 7.5 +/- 3.6 lives saved per 1000 treated patients). The comparative cost-effectiveness ratio for the use of lisinopril, expressed as cost per additional survivor among patients randomised to receive lisinopril, was $US2080 per life saved (1993 values). The sensitivity analysis conducted to examine the effects of varying the estimated absolute reduction in mortality throughout its 95% confidence interval, which ranged from 14.6 to 0.4 lives saved per 1000 treated patients, showed that the cost-effectiveness ratios consequently vary from $US1121 to $US40,910 per life saved. The cost effectiveness of early treatment with lisinopril of a relatively unselected population of patients with acute MI compares very favourably with that of other therapies judged to be worthwhile by the medical community.",1998.0,0,0
61,10190395,Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation.,T H Mäkikallio; S Høiber; L Køber; C Torp-Pedersen; C K Peng; A L Goldberger; H V Huikuri,"A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.",1999.0,0,0
62,10190404,Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension.,A Ylitalo; K E Airaksinen; L Sellin; H V Huikuri,"Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.",1999.0,0,0
63,10190422,Ramipril reduces QT dispersion in patients with acute myocardial infarction and heart failure.,K S Spargias; S J Lindsay; A S Hall; J C Cowan; S G Ball,"In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we showed that ramipril therapy was associated with a significant reduction in QT dispersion over a 2-month period after acute myocardial infarction. This reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic effect and may be an important additional mechanism for the reduced all-cause mortality and sudden death incidence achieved with angiotensin-converting enzyme inhibition after acute myocardial infarction.",1999.0,0,0
64,10190653,Fosinopril reduces left ventricular mass in untreated hypertensive patients: a controlled trial.,B M Cheung; C P Lau,"Left ventricular hypertrophy is a powerful predictor of cardiovascular morbidity and mortality. We tested the hypothesis that fosinopril, an angiotensin-converting enzyme inhibitor, reduces left ventricular mass in hypertensive patients. Thirty-three patients with untreated mild essential hypertension were randomised to treatment with oral fosinopril (10 mg-20 mg daily) or placebo for 12 weeks. The primary outcome measure was the change in left ventricular mass index determined by echocardiography. Diastolic blood pressure changed from 95.5+/-2.1 mmHg at baseline to 96.6+/-2.8 mmHg at the final visit in control patients and changed from 96.6+/-2.3 mmHg to 91.5+/-3.0 mmHg in patients treated with fosinopril (P= 0.04). Systolic blood pressure changed from 147.4+/-3.2 mmHg at baseline to 152.7+/-4.4 mmHg at the final visit in control patients and changed from 157.6+/-5.1 mmHg to 149.1+/-6.1 mmHg in patients treated with fosinopril (P=0.02). Fosinopril reduced diastolic pressure by 6.3 (95%CI 0.3-12.4) mmHg and systolic pressure by 13.3 (95%CI 2.7-23.8) mmHg compared with placebo. The left ventricular mass index changed from 110.0+/-8.3 gm(-2) to 113.1+/-8.7 g m(-2) in the control patients and changed from 120.8+/-5.8 g m(-2) to 109.0+/-7.5 g m(-2) in patients treated with fosinopril (P=0.02). Fosinopril reduced left ventricular mass index by 14.9 (95%CI 2.2-27.6) g m(-2) compared with placebo. There was no significant change in the left ventricular systolic or diastolic function, nor were there any significant changes in plasma electrolytes and renal function. Treatment with fosinopril for 12 weeks reduced left ventricular mass significantly in hypertensive patients.",1999.0,0,0
65,10192229,The prevalence and etiology of impotence in 101 male hypertensive outpatients.,J Jensen; A Lendorf; H Stimpel; J Frost; H Ibsen; P Rosenkilde,"Erectile dysfunction and impotence has a high prevalence among male hypertensive patients. Whether this relates mainly to specific drug side effects or to primary pathogenic disorders is unknown. In the present study 101 male patients from our outpatient hypertension clinic answered detailed questionnaires about hypertension and sexual function. Patients with perceived impotence were offered a thorough penile evaluation and examination performed by specialists in the urology department. Twenty-seven (27%) men had impotence. The main cause of impotence was an arterial dysfunction (89%). The prevalence of impotence was related to the degree of secondary organ manifestation, reflected by World Health Organization (WHO) classification I-III (P = .01). Intermittent claudication (P = .001) and ischemic heart disease (P = .005) were the best determinants in this respect. Twelve impotent patients (44%) ascribed onset of impotence to drug initiation. A variety of drugs were incriminated in the occurrence of drug-induced impotence. In summary our results indicate that impotence in hypertensive men is caused mainly by penile arterial vascular changes, probably atherosclerosis. Drug-induced impotence could well be the result of blood pressure reduction itself and not specific drug side effects.",1999.0,0,0
66,10192233,A double blind comparison of the effects of amlodipine and enalapril on insulin sensitivity in hypertensive patients.,D Lender; C Arauz-Pacheco; L Breen; P Mora-Mora; L C Ramirez; P Raskin,"This study compares the effects of a calcium channel blocker (amlodipine) and an angiotensin converting enzyme inhibitor (enalapril) on in vivo insulin sensitivity in patients with essential hypertension. Forty-six patients with mild and moderate hypertension were studied. After a 2-week single-blind placebo phase, they were randomly assigned to double-blind therapy with either amlodipine (2.5 to 10 mg/day) or enalapril (5 to 40 mg/day) for 16 weeks. Both groups were comparable in terms of demographic characteristics, degree of obesity, metabolic parameters, and arterial blood pressure. Insulin sensitivity was measured at baseline and at week 16 during the active phase using euglycemic hyperinsulinemic clamps. Arterial blood pressure decreased similarly in both groups. Whole body glucose uptake (M-value) increased with amlodipine from 3.63 +/- 0.32 (mean +/- SEM) to 3.97 +/- 0.31 mg/kg/min (P = .02). A similar tendency was observed with enalapril: from 3.59 +/- 0.32 to 3.94 +/- 0.30 mg/kg/min (P = .09). A trend to lower steady-state insulin level during the second clamp (compared to baseline) was observed in both groups. The clamp-derived insulin sensitivity index (that corrects for steady-state insulin levels and glucose levels during the clamp) increased similarly in both groups: from 1.15 +/- 0.11 to 1.39 +/- 0.13 with amlodipine (P = .03) and from 1.25 +/- 0.13 to 1.49 +/- 0.16 with enalapril (P = .01). LDL cholesterol decreased with amlodipine (mean change, -11.3 mg/dL, P = .004). Amlodipine and enalapril were associated with increments in insulin sensitivity. Amlodipine provided an additional benefit with decreased low density lipoprotein cholesterol levels.",1999.0,0,0
67,10192973,Nebivolol versus enalapril in essential hypertension: a long-term double-blind comparative trial.,L Van Nueten; M Rishøj Nielsen; C Vertommen; A G Dupont; J I Robertson,"Nebivolol was compared in a dose of 5 mg once daily with enalapril 10 mg once daily over 7 months in a double-blind randomised trial in essential hypertension. The two drugs had very similar sustained effects in lowering both systolic and diastolic pressures; neither had an orthostatic component. Both drugs were well-tolerated. No haematological, biochemical, or urinary abnormalities were seen.",1999.0,0,0
68,10193712,Recent insight into therapy of congestive heart failure: focus on ACE inhibition and angiotensin-II antagonism.,H P Brunner-La Rocca; G Vaddadi; M D Esler,"One possible intervention to interrupt the deleterious effects of the renin-angiotensin system is suppression of angiotensin II (Ang II) formation by inhibition of angiotensin-converting enzyme (ACE). However, ACE inhibition incompletely suppresses Ang II formation and also leads to accumulation of bradykinin. Angiotensin II type 1 (AT1) receptors are believed to promote the known deleterious effects of Ang II. Therefore, AT1 receptor antagonists have been recently introduced into therapy for hypertension and congestive heart failure (CHF). Although there are significant differences between the effects of AT1 receptor antagonists and ACE inhibitors including the unopposed stimulation of angiotensin II type 2 (AT2) receptors by AT1 receptor antagonists, the discussion of whether ACE inhibitors, AT1 receptor antagonists or the combination of both are superior in the pharmacotherapy of CHF is still largely theoretical. Accordingly, AT1 receptor antagonists are still investigational. Angiotensin-converting enzyme inhibitors remain first line therapy in patients with CHF due to systolic dysfunction. However, in patients not able to tolerate ACE inhibitor induced side effects, in particular cough, AT1 receptor antagonism is a good alternative. In clinical practice, emphasis should be placed on increasing the utilization of ACE inhibitors, as more than 50% of patients with CHF do not receive ACE inhibitors. In addition, the majority of those on ACE inhibitors receive doses lower than the dosage used in the large clinical trials. Although not yet completely proved, it is likely that high doses of ACE inhibition are superior to low doses with respect to prognosis and symptoms.",1999.0,0,0
69,10193713,Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure.,E P Havranek; I Thomas; W B Smith; G A Ponce; M Bilsker; M A Munger; R A Wolf,"The primary purpose of this study was to determine the acute and long-term hemodynamic and clinical effects of irbesartan in patients with heart failure. Inhibition of angiotensin II production by angiotensin-converting enzyme (ACE) inhibitors reduces morbidity and mortality in patients with heart failure. Irbesartan is an orally active antagonist of the angiotensin II AT1 receptor subtype with potential efficacy in heart failure. Two hundred eighteen patients with symptomatic heart failure (New York Heart Association [NYHA] class II-IV) and left ventricular ejection fraction < or = 40% participated in the study. Serial hemodynamic measurements were made over 24 h following randomization to irbesartan 12.5 mg, 37.5 mg, 75 mg, 150 mg or placebo. After the first dose of study medication, patients receiving placebo were reallocated to one of the four irbesartan doses, treatment was continued for 12 weeks and hemodynamic measurements were repeated. Irbesartan induced significant dose-related decreases in pulmonary capillary wedge pressure (average change -5.9+/-0.9 mm Hg and -5.3+/-0.9 mm Hg for irbesartan 75 mg and 150 mg, respectively) after 12 weeks of therapy without causing reflex tachycardia and without increasing plasma norepinephrine. The neurohormonal effects of irbesartan were highly variable and none of the changes was statistically significant. There was a significant dose-related decrease in the percentage of patients discontinuing study medication because of worsening heart failure. Irbesartan was well tolerated without evidence of dose-related cough or azotemia. Irbesartan, at once-daily doses of 75 mg and 150 mg, induced sustained hemodynamic improvement and prevented worsening heart failure.",1999.0,0,0
70,10195086,Cardiac risks with beta agonists.,B Lindmark,,1999.0,0,0
71,10204820,Fixed low-dose perindopril 2 mg/indapamide 0.625 mg combination in very elderly hypertensives.,B Forette,,1999.0,0,0
72,10209075,Lisinopril improves arterial function in hyperlipidaemia.,A F Lee; J B Dick; C E Bonnar; A D Struthers,"Endothelial function is defective in hypercholesterolaemia, and animal models have suggested that angiotensin-converting enzyme inhibitors may prevent arterial damage. We studied the effect of 6 months treatment with lisinopril on endothelial function in a group of patients with hypercholesterolaemia. Forty patients were studied. Forearm blood flow responses to acetylcholine and sodium nitroprusside were assessed by venous occlusion plethysmography. Subjects were then randomized in a double-blind fashion to receive either lisinopril, 20 mg/day (n=20), or placebo (n=20) for 6 months. Plethysmography was then repeated. Baseline variables between groups were comparable. In the lisinopril group blood pressure fell significantly [systolic: 145+/-4 to 128+/-4 mmHg (P<0.001); diastolic: 84+/-2 to 74+/-2 mmHg (P<0.001)]. An improvement was found in the vasodilatory response (expressed as a ratio of the infused/control arm) to acetylcholine, e.g. 3.33+/-0.3 (pre) versus 4.45+/-0.48 (post) at 30 microg/ml (P<0.03), and also to nitroprusside, e.g. 3.0+/-0.2 (pre) versus 3.86+/-0.3 (post) at 3.2 microg/ml (P<0.01). In the placebo group vasodilatation did not change significantly in response to acetylcholine, and nitroprusside responses were unchanged. The data presented suggest that 6 months of lisinopril therapy have a beneficial effect on arterial function in subjects with hyperlipidaemia. Further work should now investigate whether angiotensin-converting enzyme inhibitors are beneficial in reducing mortality and morbidity in hypercholesterolaemia.",1999.0,0,0
73,10211343,ACE inhibitor use and severe angioedema.,A Murray; J Crowther,,1999.0,0,0
74,10216796,,,,,0,0
75,10218721,Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2.,M Lerch; P Weidmann; M P Ho; P Gerber; P Eckenberger; A Kaemmereit; A U Teuscher,"Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.",1999.0,0,0
76,10218737,"The effects of mibefradil and enalapril on 24-hour blood pressure control and left ventricular mass in patients with mild to moderate hypertension: double-blind, randomized trial.",B Martina; W Lorz; B Frach; T Bart; E J Battegay,"In this prospective, double-blind, monocenter drug trial, 48 primary care patients with mild to moderate essential hypertension were randomized to mibefradil, 50 mg, titrated to 100 mg, or enalapril, 20 mg, titrated to 2 x 20 mg. Ambulatory 24-h blood pressure measurements (ABPM) and echocardiography were performed at baseline and after 12 weeks' treatment. Complete data from 43 patients were analyzed. Mibefradil (n = 22; titration, 13 patients) reduced mean 24-h ABP from 159+/-14/102+/-7 mm Hg to 140+/-10/89+/-7 mm Hg after 12 weeks. Enalapril (n = 21; titration, six patients) reduced baseline ABP from 156+/-12/100+/-9 mm Hg to 140+/-17/89+/-10 mm Hg (12 weeks). Trough-to-peak ratios in DBP were 86% for mibefradil and 75% with enalapril. Left ventricular mass (LVM) decreased from 199+/-65 to 193+/-62 g [M-mode modified American Society of Echocardiography (ASE)] and from 184+/-65 to 173+/-50 g (truncated ellipsoid method) after 12 weeks in response to mibefradil (p > 0.2), and from 212+/-50 to 196+/-57 g and from 182+/-39 to 170+/-40 g (mean +/- SD, p < 0.02) with enalapril. Mibefradil matched enalapril in 24-h ABP control. Enalapril reduced LVM significantly after 12 weeks (p < 0.02). Mibefradil did not significantly reduce LVM after 12 weeks.",1999.0,0,0
77,10219067,Reduction of sympathetic hyperactivity by enalapril in patients with chronic renal failure.,G Ligtenberg; P J Blankestijn; P L Oey; I H Klein; L T Dijkhorst-Oei; F Boomsma; G H Wieneke; A C van Huffelen; H A Koomans,"Inhibition of angiotensin-converting enzyme (ACE) reduces the risk of cardiovascular problems in patients with chronic renal failure. This effect may be due in part to a decrease in sympathetic nervous activity, but no direct evidence of such an action is available. We studied muscle sympathetic-nerve activity in 14 patients with hypertension, chronic renal failure, and increased plasma renin activity before, during, and after administration of the ACE inhibitor enalapril. Ten other patients with similar clinical characteristics were studied before and during treatment with the calcium-channel blocker amlodipine. Normal subjects matched for age and weight were included in both studies. At base line, mean (+/-SD) muscle sympathetic-nerve activity was higher in the group of patients who received enalapril than in the control subjects (35+/-17 vs. 19+/-9 bursts per minute, P=0.004). The baroreflex curve, which reflects changes in muscle sympathetic-nerve activity caused by manipulations of blood pressure with sodium nitroprusside and phenylephrine, was shifted to the right in the patients, but baroreflex sensitivity was similar to that in the control subjects (-2.1+/-1.9 and -2.7+/-1.3 bursts per minute per mm Hg, respectively; P=0.36). A single dose of the sympatholytic drug clonidine caused a greater fall in blood pressure in the patients than in the control subjects. Treatment with enalapril normalized blood pressure and muscle sympathetic-nerve activity (at 23+/-10 bursts per minute) in the patients and shifted the baroreflex curve to the left, reflecting normal blood-pressure levels, without significantly changing sensitivity (-2.3+/-1.8 bursts per minute per mm Hg, P=0.96). In the patients who received amlodipine, treatment also lowered blood pressure but increased muscle sympathetic-nerve activity, from 41+/-19 to 56+/-14 bursts per minute (P=0.02). Increased sympathetic activity contributes to hypertension in patients with chronic renal disease. ACE inhibition controls hypertension and decreases sympathetic hyperactivity.",1999.0,0,0
78,10220232,An economic evaluation of the JNC hypertension guidelines using data from a randomized controlled trial. Joint National Committee.,S D Ramsey; N Neil; S D Sullivan; E Perfetto,"We wanted to determine the clinical cost of managing hypertension when following the Joint National Committee on Hypertension (JNC) guidelines, including drug therapy, the cost of monitoring for and treating side effects, compliance, and the cost of switching after therapeutic failures. The base-case analysis considers antihypertensive agents from four therapeutic classes that were recently evaluated in a large randomized trial: enalapril, amlodipine, acebutolol, and chlorthalidone. Clinical evaluation, therapy, and monitoring for hypertension are modeled with an incidence-based Markov model. Clinical inputs include agent efficacy, side effects, and compliance with dosing schedules. JNC-recommended clinical and laboratory monitoring schedules are followed for each agent. Switches between classes occur for therapeutic failures. Drug and medical care costs are valued in 1995 US dollars. Although patients whose hypertension was initially treated with amlodipine achieved control more readily than patients who were given the other agents, the initial costs to achieve and maintain hypertension control were lowest for chlorthalidone ($641), followed by acebutolol ($920), amlodipine ($946), and enalapril ($948). Maintenance costs were lowest for chlorthalidone. For all agents except chlorthalidone, drug costs were the largest component of overall costs, followed by the costs of office visits, laboratory monitoring, and switching between classes for therapeutic failures. By following JNC guidelines, a slightly higher percentage of patients will achieve hypertension control with a newer class calcium channel blocker (amlodipine) but at a substantially higher cost than with a generic diuretic (chlorthalidone).",2000.0,0,0
79,10220238,Did we learn evidence-based medicine in medical school? Some common medical mythology.,D S Paauw,"Medical myths occur for many different reasons. A common thread is that they all make some pathophysiologic sense. A good example is the concern about using oral cobalamin when treating pernicious anemia. The difficulty in absorbing vitamin B12 when intrinsic factor is not available does not make oral replacement impossible; the dose just needs to be higher. Pathophysiologic concerns have also been a key reason why physicians have avoided using beta-blockers in patients with diabetes. They fear that beta-blockers will block adrenergic symptoms, and patients will not know when they are hypoglycemic. In studies addressing this issue, there appears to be no real problem with increased severe episodes of hypoglycemia in patients on beta-blockers or increased hypoglycemic unawareness. Several studies commented on the unanticipated symptom of increased sweating associated with hypoglycemia in diabetic patients who are taking beta-blockers. Another important concept behind some medical myths is the overreliance on case reports or authoritative text. The concern about depression associated with beta-blocker use grew out of one widely referenced case report. Subsequent studies have not shown convincing evidence for a strong association with beta-blocker use and depression. The strong position taken against narcotic use in Cope's Early Diagnosis of the Acute Abdomen is probably the reason for the perpetuation of the myth of avoiding narcotics for pain relief in patients with undiagnosed acute abdominal conditions. The only two studies addressing this issue showed no problems with diagnosis caused by providing narcotic pain relief. Newer therapies usually undergo closer scrutiny before being accepted, often including placebo-controlled trials to show the efficacy of a medication. Such might not be the case with newer technologies. It is harder to evaluate the benefit of a new technology in the face of noncomparable previous technologies. Catheterization of the right side of the heart (Swan-Ganz catheter) was a technology that became widely used before any outcome studies became available. Multiple reports in the last decade have shown increased mortality and increased utilization of resources in patients who received catheterization of the right side of the heart. Most new drug therapies require randomized data to show effects before widespread use and acceptance occur. Older therapies that have been widely accepted for a long time might not have had controlled trial data behind recommendations for their use, and once practice patterns become widespread, it is hard to change. It is always good to ask the question, ""Will this help my patient live better or longer?"" when prescribing a therapy. These myths underscore the importance and utility of outcome-based research to help guide physicians in their practices.",1999.0,0,0
80,10220239,Drug-induced pancreatitis (lisinopril).,L G Miller; G Tan,,1999.0,0,0
81,10220541,beta blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study.,K S Spargias; A S Hall; D C Greenwood; S G Ball,"To examine clinical outcomes associated with optional beta blockade in a population of patients with evidence of heart failure after myocardial infarction. Data from the acute infarction ramipril efficacy (AIRE) study were analysed retrospectively. At baseline 22.3% of the patients were receiving a beta blocker. To minimise confounding, beta blocker and diuretic treatments, presence of clinical signs of heart failure, left ventricular ejection fraction, and 16 other baseline clinical variables were simultaneously entered in a multivariate Cox regression model. In addition, the same analysis was repeated separately within a high and a low risk group of patients, as defined according to the need for diuretic treatment. beta Blocker treatment was an independent predictor of reduced risk of total mortality (hazard ratio 0.66, 95% confidence interval (CI) 0. 48 to 0.90) and progression to severe heart failure (0.58, 95% CI 0.40 to 0.83) for the entire study population. There were similar findings in high risk patients requiring diuretics (0.59, 95% CI 0.40 to 0.86; and 0.58, 95% CI 0.38 to 0.89). beta Blocker treatment is associated with improved outcomes in patients with clinical evidence of mild to moderate heart failure after myocardial infarction. Most importantly, high risk patients with persistent heart failure appear to benefit at least as much as lower risk patients with transient heart failure.",1999.0,0,0
82,10221346,Effects of spironolactone and angiotensin-converting enzyme inhibitor on left ventricular hypertrophy in patients with essential hypertension.,A Sato; Y Suzuki; T Saruta,"There is increasing evidence for important cardiovascular effects of aldosterone via classical mineralocorticoid receptors in the heart. Administration of aldosterone with excess salt produces both cardiac hypertrophy and interstitial cardiac fibrosis in rats, and concomitant administration of potassium canrenoate at a dose that only modestly lowers blood pressure completely blocks the cardiac effects of aldosterone. In the present study, we examined the effect on left ventricular hypertrophy of adding a low dose of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to an angiotensin-converting enzyme inhibitor (enalapril maleate) in patients with essential hypertension. Eighteen untreated patients with moderate to severe essential hypertension based on the WHO/ISH guidelines participated in this study. Subjects were treated with either an angiotensin-converting enzyme inhibitor alone (group I: 10 patients, 4 men and 6 women, mean age 56 +/- 18 yr) or an angiotensin-converting enzyme inhibitor plus spironolactone (group II: 8 patients, 3 men and 5 women, mean age 59 +/- 14 yr) for 9 mo. Left ventricular mass index, various echocardiographic variables, mean blood pressure, plasma renin activity, and plasma aldosterone concentration before treatment were similar in the two groups. Blood pressure of both groups decreased significantly and similarly after antihypertensive treatment (group I, 136 +/- 9/82 +/- 9 mmHg; group II, 133 +/- 9/85 +/- 10 mmHg). Left ventricular mass index also decreased significantly in both groups (group I, -10.2 +/- 7.1%; group II, -18.1 +/- 6.9%). The extent of reduction was significantly greater in the spironolactone group (group II) (p < 0.05 vs. group I). In group II patients, spironolactone did not cause any side effects during the observation period. We conclude that spironolactone may have beneficial effects on left ventricular hypertrophy in patients with essential hypertension who are receiving an angiotensin-converting enzyme inhibitor.",1999.0,0,0
83,10226860,Long-term results of the Spanish trial on treatment and survival of patients with predominantly mild heart failure.,J Cosín-Aguilar; J Marrugat; G Sanz; J Massó; M Gil; R Vargas; F Pérez-Casar; E Simarro; D De Armas; J García-García; J Azpitarte; J L Diago; G Rodrigo-Trallero; I Lekuona; E Domingo; E Marin-Huerta,"A randomized open-label clinical trial was conducted to determine whether mortality, readmission, or quality of life differed between heart failure patients managed with captopril plus diuretics and those with digoxin plus diuretics. A total of 345 heart failure patients in New York Heart Association functional classes 2 and 3 without atrial fibrillation, dyspnea of bronchopulmonary origin, or hypertension not controlled with diuretics was randomized for digoxin (n = 175) or captopril (n = 170) treatment and followed up for a median of 4.5 years. Socioeconomic, demographic, electrocardiographic, echocardiographic, spirometric, and chest radiograph data were obtained at the initial examination. In a random sample of half the patients, ergometric, echocardiographic, and Holter records were obtained at entry and at 3 and 18 months. Patients were followed up for > or = 3 years. The end points were mortality, hospitalization for cardiac events, deterioration in quality of life, worsening of functional class, and need for digoxin or captopril in the captopril and digoxin groups, respectively. The trial had to be terminated prematurely owing to the difficulty in finding candidates free of angiotensin-converting enzyme (ACE)-inhibitor treatment. Baseline patient characteristics were similar in both groups. From the clinical point of view, only the 48-month mortality was relevantly lower (20.9 vs. 31.9%, respectively) among patients treated with captopril than that in those receiving digoxin (log rank test, p = 0.07). No statistically or clinically relevant differences were found in other end points or adverse effects. The results suggest but do not confirm the hypothesis that captopril treatment in mild to moderate heart failure might provide better long-term survival than digoxin.",1999.0,0,1
84,10229295,Angiotensin converting enzyme inhibition and arterial endothelial function in adults with Type 1 diabetes mellitus.,R McFarlane; R J McCredie; M A Bonney; L Molyneaux; R Zilkens; D S Celermajer; D K Yue,"Arterial endothelial dysfunction is a key early event in atherogenesis, and occurs in asymptomatic adults with Type 1 diabetes mellitus (DM). As angiotensin converting enzyme (ACE) inhibitors have been reported to reverse microvascular endothelial dysfunction acutely, we assessed the longer term effect of ACE inhibition on large vessel endothelial physiology in a randomized, crossover double-blind controlled clinical trial. Flow-mediated arterial dilatation (FMD), which is largely due to endothelial release of nitric oxide, was assessed by vascular ultrasound in 20 Type 1 DM subjects with known endothelial dysfunction. These subjects, aged 28+/-5 years, were studied before and after 12 weeks oral therapy with either the ACE inhibitor perindopril 4 mg daily or the diuretic hydrene (triamterene 50 mg with hydrochlorothiazide 25 mg) daily. Although perindopril lowered both systolic and diastolic blood pressure by 2.7/3.2 mmHg, respectively (F3,78 = 4.7, P= 0.006; F3,78 = 3.2, P = 0.03), there was no significant effect of either perindopril or hydrene on FMD (baseline FMD before perindopril 4.6+/-2.5%, after 4.1+/-3.4%, baseline FMD before hydrene 5.4+/-3.6%, after 6.0+/-3.3%; F3,78= 1.9, P=0.1). Glycaemic control deteriorated slightly on hydrene whilst lipid levels, heart rate, resting blood flow and the arterial responses to nitroglycerine, a smooth muscle dilator, were unaffected by the treatment given. ACE inhibitor therapy for 3 months did not improve arterial endothelial function in Type 1 DM subjects.",1999.0,0,0
85,10229744,Changes in arterial structure and function under trandolapril-verapamil combination in hypertension.,J Topouchian; R Asmar; F Sayegh; A Rudnicki; A Benetos; A M Bacri; M E Safar,"Converting enzyme inhibition and calcium blockade alter large arteries in hypertension. However, the heterogeneity of the response according to the site of cardiovascular measurements has never been investigated. In a double-blind study, we compared for 180 days 3 hypertensive patient groups treated with verapamil, trandolapril, or their combination. Using echo-Doppler technique and applanation tonometry, we independently measured mean pressure, local pulse pressure, arterial diameter, and distensibility at 3 arterial sites (brachial and common carotid arteries and abdominal aorta), as well as cardiac and carotid wall structure. Mean and pulse pressure decreased significantly to a greater extent with the drug combination. Regarding arterial and cardiac hemodynamics, significant and similar changes were noted in the 3 groups: decreases in abdominal aorta and carotid but not brachial diameter; increases in carotid artery, abdominal aorta, and brachial distensibility even after adjustment to mean blood pressure reduction; and more substantial regression of cardiac mass than carotid wall thickness. This study shows that both compounds and more significantly combination therapy decreased mean and pulse pressures measured independently and that the changes in diameter, thickness, and stiffness were influenced primarily by the site of cardiovascular measurements, resulting in a predominant increase in distensibility of muscular arteries, little change in carotid wall thickness, but a significant regression of cardiac hypertrophy.",1999.0,0,0
86,10232497,Use of electronic pill boxes to assess risk of poor treatment compliance: results of a large-scale trial.,L Vaur; B Vaisse; N Genes; F Elkik; C Legrand; L Poggi,"The objective of the present study was to determine the predictive factors of treatment compliance in hypertensive patients. This was an open large-scale multicenter study where mild to moderate essential hypertensive patients received trandolapril (2 mg) once daily for 30 to 60 days in addition to their usual treatment. Trandolapril was packed in electronic pill boxes that registered date and time of each opening. The main compliance parameters were the percentage of missed doses, the percentage of delayed doses, and the percentage of correct dosing periods. Predictive factors of poor compliance (correct dosing periods < 80%) were determined using a multivariate stepwise logistic regression analysis. Two thousand one hundred seventy-three patients aged 60 +/- 12 years were analyzed. Of the total patients 37% were poor compliers; 29% of patients forgot more than 10% of doses and 36% of patients delayed more than 10% of doses. Ranked predictive factors of poor compliance were: age < 60 years (odds ratio [OR], 1.80 [1.49 to 2.17], P = .0001), the Paris area (OR, 1.70 [1.32 to 2.19], P = .0001), smokers (OR, 1.65 [1.29 to 2.11], P = .0001), monotherapy (OR, 1.40 [1.14 to 1.72], P = .0012), and baseline diastolic blood pressure > or = 100 mm Hg (OR, 1.21 [1.01 to 1.46], P = .044). Therefore, we conclude that young hypertensives, large city dwellers, and smokers are more likely to be poor compliers. The presence of some of these characteristics might incite the physician either to encourage patient compliance or to prescribe antihypertensive drugs that have an effect that persists even beyond 24 h.",1999.0,0,0
87,10232685,In chronic nephropathies prolonged ACE inhibition can induce remission: dynamics of time-dependent changes in GFR. Investigators of the GISEN Group. Gruppo Italiano Studi Epidemiologici in Nefrologia.,P Ruggenenti; A Perna; R Benini; T Bertani; C Zoccali; Q Maggiore; M Salvadori; G Remuzzi,"The Ramipril Efficacy in Nephropathy Core and Follow-Up Study found that > or =36 mo of continued ramipril therapy decreased substantially the risk of end-stage renal failure (ESRF) in patients with chronic nephropathies and a urinary protein excretion rate > or =3 g/24 h. This study investigates the time-dependent changes in GFR in these patients and in control subjects who were randomized to conventional therapy during the Core period and switched to ramipril during the Follow-Up study. Analyses included 150 patients (continued ramipril: n = 74; switched to ramipril: n = 76) who had at least three GFR measurements (including baseline) during the whole observation period and a subgroup of 43 patients (continued ramipril: n = 26; switched to ramipril: n = 17) who had at least six GFR measurements, including at least three on the Core and at least three on the Follow-Up study. Ramipril (1.25 to 5 mg/d) and conventional therapy were targeted at achieving a diastolic BP below 90 mm Hg. The main efficacy variables were GFR and ESRF (need for dialysis). Analysis was by intention to treat. Throughout the study, the mean +/- SEM rate of GFR decline (deltaGFR) was significantly lower in patients continued on ramipril compared to those switched to ramipril (0.51+/-0.09 versus 0.76+/-0.10 ml/min per 1.73 m2 per mo, P<0.03). In patients on continued ramipril who had at least six GFR measured--but not in control subjects--deltaGFR progressively improved with time and, in the cohort with the longest follow-up, decreased from (in ml/min per 1.73 m2 per mo): 0.16+/-0.12 (at 18 mo) to 0.10+/-0.05 (at 60 mo). This rate was about 10-fold slower compared to patients on conventional therapy during the REIN Core study. Analyses of the individual slopes found that at the end of the follow-up, 10 of 26 patients on continued ramipril therapy had a positive deltaGFR and another 10 patients had an improvement of deltaGFR while on ramipril therapy. DeltaGFR significantly improved in parallel with a significant reduction in proteinuria. Changes in deltaGFR (P = 0.0001) and proteinuria (P = 0.04) were significantly different in the two groups. Baseline characteristics and changes in systolic and diastolic BP and 24-h urine urea and sodium excretion were comparable. The present results offer evidence that in chronic nephropathies, the tendency of GFR to decline with time can be effectively halted, even in patients with remarkably severe disease.",1999.0,0,0
88,10235696,Nebivolol in the management of essential hypertension: a review.,W McNeely; K L Goa,"Nebivolol is a lipophilic beta1-blocker. It is devoid of intrinsic sympathomimetic or membrane stabilising activity but appears to have nitric oxide-mediated vasodilatory effects. Nebivolol is administered as a racemic mixture of equal proportions of d- and l-enantiomers. The drug does not significantly influence glucose or plasma lipid metabolism and appears to have a protective effect on left ventricular function. At the recommended dosage (5 mg once daily) nebivolol reduces resting diastolic blood pressure as effectively as standard therapeutic dosages of atenolol, metoprolol, lisinopril and nifedipine, as shown in comparative trials. Nebivolol reduced blood pressure significantly more than enalapril 10 mg daily in the short but not the long term, although the enalapril dose may not have been optimal. Nebivolol has an additive effect in combination with hydrochlorothiazide. Standing blood pressure and/or mean 24-hour ambulatory blood pressure is significantly and similarly reduced with nebivolol, atenolol or nifedipine. Nebivolol tended to prevent increases in early morning blood pressure better than nifedipine. Overall response rates to nebivolol therapy (a decrease in sitting/supine diastolic blood pressure to < or = 90 mm Hg or a 10% or > or = 10 mm Hg fall in diastolic blood pressure) ranged from 58 to 81% after 4 to 52 weeks' treatment. In comparative studies, response rates were greater in nebivolol than in enalapril or metoprolol recipients, but not significantly different from those in atenolol or nifedipine recipients. Nebivolol 5 mg once daily is well tolerated in patients with hypertension. Adverse events are infrequent, transient and mild to moderate. Those reported most often include headache, fatigue, paraesthesias and dizziness. Several studies reported no signs of orthostatic hypotension with nebivolol. Comparative trials revealed no significant differences between the frequency and severity of adverse events in patients receiving nebivolol, atenolol, enalapril or placebo; however, the overall incidence of adverse events was greater with nifedipine or metoprolol. Some atenolol or enalapril, but not nebivolol, recipients reported impotence or decreased libido during therapy. Current evidence indicates that nebivolol 5 mg once daily is a well tolerated beta-blocker, which is as effective as once daily atenolol and other classes of antihypertensive agents. It may therefore be recommended as a useful alternative first-line treatment option for the management of patients with mild to moderate uncomplicated essential hypertension.",1999.0,0,0
89,10321443,Low-dose diuretic and/or dietary sodium restriction when blood pressure is resistant to ACE inhibitor.,L M Wing; L F Arnolda; P J Harvey; J Upton; D Molloy; G M Gabb; A J Bune; J P Chalmers,"To compare the efficacy of indapamide (1.25 mg daily) and low-salt diet (<100 mmol/day) separately and in combination in essential hypertensive patients with inadequate BP response to perindopril. Randomized double-blind, double-dummy, crossover design. The randomized treatments were indapamide 1.25 mg daily, sodium chloride 80 mmol daily, the combination of indapamide and sodium chloride and placebo. All patients received perindopril 4 mg daily and maintained a low-sodium diet. 19 patients entered and 17 completed the study. Prior to randomization, average clinic sitting blood pressure was 162/101 mm Hg and average 24-h urine sodium excretion was 157 mmol/day. Compared to the phase in which patients received perindopril with sodium repletion, clinic and ambulatory BPs were significantly reduced (p<0.01) in all the other phases. Indapamide had a greater effect on BP than dietary sodium restriction, and in combination their effects were additive. The effect of indapamide on ambulatory BP persisted throughout 24 h, but the effect of the low-salt diet was predominantly observed during waking hours. In hypertensives with BP resistant to the angiotensin converting enzyme (ACE) inhibitor perindopril, the diuretic indapamide had greater additional efficacy and longer duration of action than dietary sodium restriction. In combination they had additive effects on BP.",1999.0,0,0
90,10321444,Combination therapy with felodipine and metoprolol compared with captopril and hydrochlorothiazide. German MC Study Group.,G Klein,"This study compared the antihypertensive efficacy and tolerability of a combination tablet containing the vascular-selective calcium antagonist felodipine and the beta1-selective adrenergic antagonist metoprolol, with a combination tablet of captopril-hydrochlorothiazide in a randomized, double-blind trial involving 109 patients with mild to moderate hypertension. After 2 weeks on placebo, patients with a supine diastolic blood pressure of 95-115 mm Hg were randomized to felodipine-metoprolol, 5/50 mg o.d. (Logimax) or captopril-hydrochlorothiazide, 25/25 mg o.d. (Capozide). After a further 4 weeks, there was a mandatory dose increase to felodipine-metoprolol 10/100 mg o.d., and captopril-hydrochlorothiazide, 50/25 mg o.d., and treatment then continued for a another 4 weeks. At the end of the study, felodipine-metoprolol reduced supine blood pressure significantly more than captopril-hydrochlorothiazide. The mean differences in change in supine systolic and diastolic blood pressure between treatments after 8 weeks were 5.2 and 3.4 mm Hg, respectively, in favour of felodipine-metoprolol (p<0.05). Standing blood pressure also showed trends in favour of felodipine-metoprolol. The proportion of responders was similar in both groups. Both treatments were well tolerated. Two patients treated with felodipine-metoprolol and 5 with captopril-hydrochlorothiazide discontinued treatment due to adverse events. Felodipine-metoprolol combination reduced supine blood pressure significantly more than captopril-hydrochlorothiazide with maintained tolerability.",1999.0,0,0
91,10323377,Effect of chronic treatment with lacidipine or lisinopril on intracellular partitioning of glucose metabolism in type 2 diabetes mellitus.,E Bonora; G Targher; M Alberiche; R C Bonadonna; F Saggiani; M B Zenere; S Uleri; M Muggeo,"Antihypertensive treatment is frequently needed in type 2 diabetes. In this study we measured the rates of total, oxidative, and nonoxidative glucose disposal, glycogen synthesis, glycolysis, endogenous glucose production, and lipid oxidation using a 4-h euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 300 pmol/L) clamp in combination with a dual glucose tracer infusion ([3-(3)H]- and [U-14C] D-glucose) and indirect calorimetry in 40 nonobese subjects with type 2 diabetes. Subjects were studied twice: after a 4-week run-in period and after a 16-week period of double blind, randomized treatment with 4-6 mg/day lacidipine, a calcium channel blocker (n = 19), or 10-20 mg/day lisinopril, an angiotensin-converting enzyme inhibitor (n = 21). Antihypertensive treatment resulted in a significant increase in total glucose disposal during insulin clamp as well as in basal and insulin-stimulated nonoxidative glucose disposal rates. On the contrary, oxidative glucose disposal was significantly decreased by antihypertensive treatment, mainly in the basal state. The changes in glucose disposal rates were not significantly different in subjects treated with lacidipine and in those treated with lisinopril. The suppression of endogenous glucose production during insulin clamp was significantly greater after lacidipine than after lisinopril. These results suggest that treatment of subjects with type 2 diabetes with either lacidipine or lisinopril has no adverse effect on glucose metabolism. Conversely, both drugs seem to improve insulin sensitivity.",1999.0,0,0
92,10326170,Antianginal and anti-ischemic effects of nisoldipine and ramipril in patients with syndrome X.,F Ozçelik; A Altun; G Ozbay,"Syndrome X is defined as typical angina pectoris, positive treadmill exercise test, negative intravenous ergonovine test, and angiographically normal coronary arteries. In the present study, we investigated the anti-ischemic and antianginal effects of nisoldipine and ramipril in patients with syndrome X. After 2 weeks of the first wash-out period, 18 patients (7 men, 11 women, age 46 +/- 10 years) were given nisoldipine (NIS) 5 mg twice daily for 4 weeks, and after 2 weeks of the second wash-out period, the same patients were given ramipril (RAM) 2.5 mg once daily for 4 weeks. A treadmill exercise test with modified Bruce protocol was performed at the end of each period. The time to angina in exercise (607 +/- 115 s-650 +/- 117 s, p = 0.006, vs. 630 +/- 114 s-660 +/- 123 s, p = 0.02), total exercise time (612 +/- 110 s-656 +/- 114 s, p = 0.0008, vs. 630 +/- 114 s-660 +/- 123 s, p = 0.02), and maximum MET value (11.09 +/- 2.08-11.86 +/- 2.04, p = 0.0016, vs. 11.42 +/- 2.09-12.2 +/- 2.26, p = 0.01) were increased significantly with both therapy modalities. The time to 1 mm ST-segment depression (123 +/- 93 s-220 +/- 172 s, p = 0.002) was increased significantly with NIS therapy. The time to ST-segment recovery (434 +/- 268 s-330 +/- 233 s, p = 0.016 vs. 443 +/- 289 s-370 +/- 278 s, p = 0.012), the frequency of anginal attacks per week (1.27 +/- 1.4-0 +/- 0.38, p = 0.005, vs. 1 +/- 1.32-0.33 +/- 0.59, p = 0.028), and the need for sublingual nitroglycerin (1.16 +/- 1.29-0.11 +/- 0.32, p = 0.005, vs. 0.94 +/- 1.16-0.27 +/- 0.57, p = 0.012) were decreased significantly with both drugs. We observed that 10 mg daily NIS and 2.5 mg daily RAM have similar anti-ischemic and antianginal effects in patients with syndrome X.",1999.0,0,0
93,10326532,Distinguishing subacute cutaneous from other types of lupus erythematosus.,D P McCauliffe,,1999.0,0,0
94,10327128,Subglottic stenosis: an unusual presentation of ace inhibitor-induced angioedema.,D J Martin; R G Grigg; A Tomkinson; W B Coman,,2000.0,0,0
95,10329066,The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. TRACE Study group. TRAndolapril Cardiac Evalution.,O D Pedersen; H Bagger; L Køber; C Torp-Pedersen,"To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction. The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial infarction screened in 27 centres in Denmark for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study. Information about occurrence of atrial fibrillation/-flutter during hospitalization was prospectively collected for the following three periods: day 1-2, day 3-4 and from day 5 until discharge. A total of 1395 patients (21%) suffered from atrial fibrillation/-flutter in one or more of the specified periods during hospitalization. Patients with atrial fibrillation/-flutter were significantly older, a significantly greater proportion were women, left ventricular systolic dysfunction was more extensive, thrombolytic therapy was received less frequently, and anterior Q wave myocardial infarction was experienced more frequently than patients without atrial fibrillation/-flutter. History of acute myocardial infarction and/or angina pectoris was similar in patients with and without atrial fibrillation/-flutter, whereas significantly more patients with atrial fibrillation/-flutter had a history of hypertension, congestive heart failure, diabetes mellitus, pulmonary disease and stroke. The unadjusted in-hospital mortality rate was significantly higher in patients with atrial fibrillation/-flutter in one or more of the specified periods during hospitalization (18%) than in patients without atrial fibrillation/-flutter (9%), P<0.001. After adjustment for baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with increased in-hospital mortality; odds ratio=1.5 (95% Cl: 1.2-1.8), P<0.001. In patients surviving hospitalization, the unadjusted 5-year mortality rate was also significantly higher in patients suffering from atrial fibrillation/-flutter (56%) than in patients without atrial fibrillation/-flutter (34%), P<0.001. After adjustment for important prognostic baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with an increased mortality, relative risk=1.3 (95% Cl: 1.2-1.4). Subgroup analysis revealed that sustained atrial fibrillation/-flutter during hospitalization was associated with the highest risk of dying, relative risk=1.4 (95% Cl: 1.2-1.7). Atrial fibrillation/-flutter often occurs after acute myocardial infarction and our analysis demonstrated that it was an independent predictor of an increased short and long-term mortality.",1999.0,0,0
96,10333052,Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus.,S Rudberg; R Osterby; H J Bangstad; G Dahlquist; B Persson,"To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy. Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19-160) microg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36-48) months of treatment. Albumin excretion rate, blood pressure and HbA1c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26-34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods. Measurements of basement membrane thickness, mesangial and matrix volume fractions were similar among groups at baseline. Structural variables were only increased in group 3 at follow-up. Delta values in basement membrane thickness and diabetic glomerulopathy index per 24 months were lower in group 1 and 2 than in group 3 (p < 0.05). Microalbuminuria returned to normal in group 1 and 2 only. Decreased albumin excretion rate tended to inversely correlate with increased basement membrane thickness (p = 0.08) and diabetic glomerulopathy index (p = 0.05). Mean HbA1c was similar between groups. Mean diastolic blood pressure was lower in group 1 and 2 than in group 3 (p < 0.01). Mean HbA1c and mean diastolic blood pressure correlated to changes in basement membrane thickness, mesangial volume fraction and diabetic glomerulopathy index (p < 0.05). Contrary to findings in the group without antihypertensive treatment, no progression of glomerulopathy was seen in those treated with enalapril or metoprolol.",1999.0,0,0
97,10333343,"Clinical presentation and management of patients with uncontrolled, severe hypertension: results from a public teaching hospital.",R A Preston; N M Baltodano; J Cienki; B J Materson,"There is relatively little data available on the management of patients with severe, uncomplicated hypertension and severe hypertension with stable hypertensive complications. To determine the incidence, clinical features, acute management, and clinical course of severe, uncomplicated hypertension and severe hypertension with stable hypertensive complications presenting for emergency department care in a large public teaching hospital. Chart survey of consecutive emergency department visits. Ninety-one of 2898 consecutive visits to a public teaching hospital emergency department were specifically for severe, uncomplicated hypertension. Of 2898 consecutive medical emergency department visits, there were 142 (4.9%) patient visits specifically for systolic blood pressure (SBP) > or =220 mm Hg or diastolic blood pressure (DBP) > or =120 mm Hg. Ninety-one of the 142 patient visits were for severe hypertension in the absence of acute target organ impact or neuroretinopathy. Eighty-nine patients received acute drug therapy. Twenty-nine patients received two drugs, and 15 received three drugs. Sixty-eight patients (75%) received clonidine, and 15 (16.5%) received short-acting nifedipine despite widely published concerns about the safety of this practice. We found a wide variability of blood pressure response to treatment. The average decline in SBP was 50+/-31 mm Hg and the average decline of DBP was 34+/-20 mm Hg over 4.2+/-2.9 h. Forty-two patients (46%) had the SBP reduced to less than 160 mm Hg, and 46 patients (50%) the DBP to less than 100 mm Hg. Long-term management and follow-up were suboptimal. Of 74 patients discharged from the emergency room, 22 patients (30%) returned because of uncontrolled hypertension within an average of 33+/-28 days, 10 patients with hypertensive complications. Severe hypertension continues to present an important and common problem. Physicians appear to place a strong emphasis on acute lowering of the blood pressure to near-normal levels. Patients are frequently lost to follow-up and have a very high rate of recurrent emergency department visits and hypertensive complications. This study points to a need for detailed, specific practice guidelines and comprehensive disease management protocols for severe, uncomplicated hypertension.",1999.0,0,0
98,10334415,Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus.,G O'Driscoll; D Green; A Maiorana; K Stanton; F Colreavy; R Taylor,"The aim of this study was to assess the effect of angiotensin-converting enzyme (ACE) inhibition with enalapril on forearm endothelial function in subjects with type II diabetes mellitus. Endothelial function is depressed in the presence of conventional risk factors for atherosclerosis, and various therapies, such as lipid-lowering therapy in hypercholesterolemia, can improve endothelial-mediated vasodilation. ACE inhibition has improved such function in several conditions including type I diabetes, but there is no evidence for a beneficial effect in type II diabetes. The influence of enalapril (10 mg twice daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 10 type II diabetic subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gage plethysmography and graded intrabrachial infusion of acetylcholine (ACh), N(G)-monomethyl-L-arginine (LNMMA) and sodium nitroprusside (SNP). Enalapril increased the response to the endothelium-dependent vasodilator, ACh (p < 0.02) and the vasoconstrictor response to the nitric oxide (NO) synthase inhibitor, LNMMA (p < 0.002). No difference was evident in the response to SNP. In type II diabetic subjects without evidence of vascular disease, the ACE inhibitor enalapril improved stimulated and basal NO-dependent endothelial function. The study extends the spectrum of beneficial effects demonstrated to result from ACE inhibition in diabetes.",1999.0,0,0
99,10335324,Hypertensive crisis. How to tell if it's an emergency or an urgency.,A Bales,"Hypertensive crisis occurs when critically elevated blood pressure is accompanied by diastolic pressure greater than 120 to 130 mm Hg. The presence of acute or ongoing end-organ damage constitutes a hypertensive emergency, which requires reduction of blood pressure within minutes to hours to avoid catastrophic outcomes. Critically elevated blood pressure without end-organ damage is known as a hypertensive urgency, which is generally treated over 24 to 48 hours in a closely monitored outpatient setting. Although hypertensive crises are relatively rare, most primary care physicians will eventually encounter them. Thus, for optimal patient outcomes, it is important to be aware of appropriate treatment options as well as the impact of potential complications on management.",1999.0,0,0
100,10335771,Additional reduction in blood pressure after cholesterol-lowering treatment by statins (lovastatin or pravastatin) in hypercholesterolemic patients using angiotensin-converting enzyme inhibitors (enalapril or lisinopril).,A C Spósito; A P Mansur; O R Coelho; J C Nicolau; J A Ramires,"Blood pressure (BP) reduction was compared between patients receiving angiotensin-converting enzyme inhibitors alone and patients receiving these medications plus statins after 3 months of dietary intervention. Although BP was similarly reduced at week 4, the statin-treated group had a greater reduction in BP and total cholesterol levels at week 16, suggesting a synergistic effect between cholesterol lowering with statins and angiotensin-converting enzyme inhibitor treatment for hypertensive patients.",1999.0,0,0
101,10335912,"Adverse drug events in hospitalized patients. A comparison of doctors, nurses and patients as sources of reports.",P M van den Bemt; A C Egberts; A W Lenderink; J M Verzijl; K A Simons; W S van der Pol; H G Leufkens,"This study investigated the relative value of adverse drug events reported by doctors, nurses and patients. The study was conducted on a total of four wards: the paediatric and internal medicine wards (including geriatric patients) of two peripheral hospitals in The Netherlands. Adverse drug events were collected by spontaneous reporting (doctor and nurse reports) and by daily ward visits, during which the patients were interviewed by a hospital pharmacist (patient reports). Criteria for relative value of the reported adverse drug events were the number of potentially serious reactions, the number of reactions not mentioned in the patient information leaflet and the number of reactions reported to new drugs (5 years or less on the Dutch market). No formal causality assessment was applied. Over a period of 2 months in 1996 (Hospital I) and 2 months in 1997 (Hospital II) a total of 620 patients were included in the study and adverse drug events were reported in 179 (29%) of these cases. Doctors reported a statistically significant larger number of serious (26% of all doctor reports; odds ratio (OR) 3.2; confidence interval (CI) 1.2-8.7) and unknown (39%; OR 2.5; CI 1.0-6.0) adverse drug events than patients themselves during the daily ward visit. Doctors also reported more serious and unknown adverse drug events than nurses. Adverse reactions to new drugs were reported during the daily ward visit only (8% of all daily ward visit reports). This study reconfirms that doctors are the main source for reports of serious and unknown adverse drug events in hospitalized patients. However, patients themselves seem to report more adverse reactions to new drugs (during the daily ward visit). By focusing on patients using new drugs, the daily ward visit might become cost-effective. This needs to be explored in future studies.",1999.0,0,0
102,10336919,Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study.,P Di Pasquale; V Bucca; S Scalzo; S Cannizzaro; A Giubilato; S Paterna,"To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction. 99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF). Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0. 001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11) v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675 (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93) v 277 (98) pg/ml; AII 5.31 (2.25) v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan). The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.",2000.0,0,0
103,10338458,"Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition.",U Elkayam; J V Johnson; A Shotan; S Bokhari; A Solodky; M Canetti; O R Wani; I S Karaalp,"Organic nitrates are widely used in the treatment of chronic heart failure (CHF). No information, however, is available regarding their effect in patients already treated with ACE inhibitors. In a randomized, double-blind, crossover design, we studied the effects of high-dose (50 to 100 mg) transdermal nitroglycerin (NTG) and placebo given daily for 12 hours in 29 patients with CHF (NYHA functional classes II to III). Exercise time (4 hours after patch application) showed a progressive improvement during NTG administration, with an increase of 38+/-35 seconds (9+/-7%) at the end of the first month (P=NS), 76+/-28 seconds (16+/-6%) at the end of the second month (P=0.01), and 117+/-34 seconds (27+/-6%) at the end of the third month (P=0.003). No significant change was seen during placebo administration (12+/-20, 5+/-26, and 19+/-28 seconds, all P=NS). Exercise time 8 hours after NTG application measured at 3 months was also significantly longer, with a difference of 87+/-28 seconds (P=0.006), but not with placebo (23+/-36 seconds, P=0.53). Assessment of quality of life and need for additional diuretics or hospitalizations for CHF failed to demonstrate a significant difference between the 2 treatment periods. In contrast, NTG decreased left ventricular end-diastolic (-2.1+/-0.1%, P<0.05) and end-systolic (-3.2+/-1.3%, P<0.05) dimensions and augmented LV fractional shortening (24.7+/-10.5%, P<0.03). The effect of placebo on these parameters was not statistically significant. High-dose nitrate therapy significantly improves exercise tolerance and left ventricular size and systolic function in patients with chronic, mild to moderate CHF already treated with ACE inhibitors. These findings support the role of organic nitrates as an adjunctive therapy to ACE inhibitors in patients with chronic CHF.",1999.0,0,0
104,10338459,Augmented short- and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V-HeFT) Study Group.,L Baruch; I Anand; I S Cohen; S Ziesche; D Judd; J N Cohn,"ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heart failure. An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects. Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were randomly assigned to double-blind treatment with valsartan 80 mg BID, valsartan 160 mg BID, or placebo while receiving their usual ACE inhibitor therapy. Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy. A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition. Compared with placebo, the first dose of valsartan 160 mg resulted in a significantly greater reduction in pulmonary capillary wedge pressure at 3, 4, and 8 hours and during the prespecified 4- to 8-hour interval after the dose and in systolic blood pressure at 2, 3, 6, 8, and 12 hours and 4 to 8 hours after the dose. A pressure reduction from valsartan 80 mg did not achieve statistical significance. After 4 weeks of therapy, net reductions in 0-hour trough pulmonary capillary wedge pressure (-4.3 mm Hg; P=0. 16), pulmonary artery diastolic pressure (-4.7 mm Hg; P=0.013), and systolic blood pressure (-6.8 mm Hg; P=0.013) were observed in the valsartan 160 mg group compared with placebo. After 4 weeks of therapy, plasma aldosterone was reduced by valsartan 80 mg BID (-52. 1 pg/mL; P=0.001) and 160 mg BID (-47.8 pg/mL; P<0.001) compared with placebo, and there was a trend for a reduction in plasma norepinephrine (-97 pg/mL; P=0.10). Seventy-four of the 83 patients completed the trial. Physiologically active levels of angiotensin II persist during standard long-term ACE inhibitor therapy.",1999.0,0,0
105,10340259,Acute myocardial infarction. Extended review.,A Dana; M Walker,,2000.0,0,0
106,10344043,"The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group.",Y Lacourciére,"Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system. The incidence of dry cough associated with two of these therapies, the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril, was assessed in a multicentre, randomised, parallel-group, double-blind, placebo-controlled, 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough. Patients received either telmisartan 80 mg, lisinopril 20 mg, or placebo once daily. Cough incidence, measured at each visit by a self-administered symptom assessment questionnaire, was significantly higher with lisinopril (60%) than with telmisartan (15.6%) or placebo (9.7%). A visual analogue scale demonstrated a similar trend for cough frequency. Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo.",1999.0,0,0
107,10344062,First-dose response to angiotensin-converting enzyme inhibition in congestive cardiac failure: a Malaysian experience.,N T Navookarasu; A R Rahman; I Abdullah,"Despite their proven value in reducing morbidity and mortality in different grades of heart failure, angiotensin converting enzyme (ACE) inhibitors continue to be underused. One reason for this is clinicians' apprehension of first-dose hypotension. We conducted a double-blind, randomised, placebo-controlled parallel group study to investigate the effect of various ACE inhibitors on first-dose hypotension. Eighty unselected patients were randomised into five treatment groups: placebo, captopril 6.25 mg, enalapril 2.5 mg, perindopril 2 mg and lisinopril 2.5 mg. Blood pressure was measured at baseline, half hourly for two hours and hourly for three hours after drug treatment. The maximum drops in mean arterial pressure (in mmHg +/- SD) were placebo 5.89 +/- 2.65, perindopril 5.29 +/- 2.49, enalapril 13.28 +/- 3.31, lisinopril 15.04 +/- 5.74 and captopril 16.76 +/- 5.74 (all p < 0.05 vs placebo except for perindopril). Perindopril, unlike the other ACE inhibitors studied, did not produce first-dose hypotension following its initiation in patients with congestive heart failure.",1999.0,0,0
108,10347337,Differential effects of enalapril and nitrendipine on the fibrinolytic system in essential hypertension.,K Sakata; M Shirotani; H Yoshida; T Urano; Y Takada; A Takada,"Impaired fibrinolysis is associated with thromboembolic complications in hypertensive patients. It has been reported that cardiovascular morbidity and mortality rates are high even after lowering the elevated blood pressure with antihypertensive drugs. The aim of this study was to assess the effect of clinically used dosages of enalapril and nitrendipine on the fibrinolytic system. Tissue plasminogen activator antigen (tPA) and tissue plasminogen activator inhibitor-1 (PAI-1) activity were measured in 20 normotensive male subjects and 46 male patients with mild essential hypertension divided into 2 groups (22 patients treated with 5 to 10 mg enalapril once a day and 24 treated with 5 to 10 mg nitrendipine once a day) before and 3 months after drug administration. Plasma renin activity and norepinephrine concentration were also measured. There were no significant differences in basal characteristics between the 2 hypertensive groups. In both hypertensive groups, blood pressure was significantly reduced to a similar level after drug treatment. In the 2 hypertensive groups, plasma renin activity significantly increased after drug treatment; however, there were no significant changes in norepinephrine concentration. Before drug treatment, the 2 hypertensive groups had significantly higher tPA and higher PAI-1 activity than the normotensive subjects. In the enalapril group, there was no significant change in tPA although PAI-1 activity significantly decreased after drug treatment. In the nitrendipine group, there was no significant change in tPA although PAI-1 activity significantly increased after drug treatment. Thus enalapril improved impaired fibrinolysis but nitrendipine further aggravated fibrinolysis in essential hypertension. Considering the effect of antihypertensive drugs on the fibrinolytic system, more effective and beneficial treatment of hypertensives, especially at a high risk for thrombus formation might be selected.",1999.0,0,0
109,10348094,"Cyclosporin-induced hypertension: incidence, pathogenesis and management.",S J Taler; S C Textor; V J Canzanello; L Schwartz,"Blood pressure increases soon after administration of immunosuppressive regimens using cyclosporin. Characteristic vascular changes lead to systemic and renal vasoconstriction. Changes in blood pressure are commonly associated with disturbed circadian regulation and may promote the rapid development of target organ injury, including intracranial haemorrhage, left ventricular hypertrophy and microangiopathic haemolysis. The mechanisms underlying this disorder are complex and include altered vascular endothelial function. Vasodilators such as prostacyclin and nitric oxide are suppressed, whereas vasoconstrictors, including endothelin, are increased. Changes in the kidney include vasoconstriction, reduced glomerular filtration and sodium retention. Effective therapy depends upon rigorous blood pressure control by administration of vasodilating agents, with attention to potential interactions with cyclosporin.",1999.0,0,0
110,10350103,Stunned myocardium and cellular damage in patients undergoing valvular cardiac surgery and pretreated with captopril.,J A Ruíz Ros; V V Ortega; J A Martínez; I Tovar; J A Nuño; R Florenciano; M Fuentes; J A Ruipérez,"Following extracorporeal cardiac surgery, transient myocardial dysfunction (stunning) and cellular damage may develop in relation, among other mechanisms, to the production of free radicals (FR) during reperfusion. The purpose of this study is to evaluate whether captopril (CTP), an angiotensin converting enzyme inhibitor with a thiolic group, which has been shown to be useful as an antioxidant agent both in in vitro and in vivo studies, can prevent emergence of those problems when used as pretreatment within 24 hours in patients undergoing valvular cardiac surgery.  prospective and randomized study. Comparison of data pre-ischemic (pre-aortic clamping) and post-reperfusion (post-cardiac rewarming) was performed. Ejection fraction was compared pre-surgery, after surgery and after 3 months. cardiology and cardiovascular surgery services in a general hospital. thirty patients who had to undergo valvular replacement surgery were randomly allocated to two similar groups, one group pretreated with captopril (CTP group, n = 15) and the other group without it (CON group, n = 15). Exclusion criteria (left ventricular ejection fraction <40%, evidence of angiographic coronary disease or prior myocardial infarction and peroperative myocardial infarction). in CTP group, the dose of captopril administered was 12.5 mg every 8 hours orally, from 24 hours before. using electron microscopy of myocardial biopsies taken prior to aortic clamping and post-reperfusion, a semi-quantitative analysis was performed on the degree of myocytic damage (MD), mitochondrial swelling (MS), sarcoplasmic reticulum swelling (SRS) and content in glycogen granules (GLY). Left ventricular ejection fraction was evaluated isotopically at three timepoints, preoperatively (EF1), at 2-3 days (EF2) and at 3 months (EF3). Also, analytical data were collected from the coronary sinus to determine creatine phosphokinase (CPK) and activity of the angiotensin converting enzyme (ACE). We noted that, in general, cellular damage resulting from valvular surgery is low, the degree of MS and SRS being lower in the CTP group. In the CTP group, however, there is a stunning phenomenon (EF1: 54.9+/-6.9%; EF2: 50.8+/-8.5%; EF3: 57.7+/-7.7%) which does not occur in the CON group (EF1: 58.0+/-8.3%; EF2: 60.8+/-10.9%; EF3: 63.0+/-9.3%). We conclude that the cellular damage caused during valvular replacement surgery is small, and emphasize that pretreatment with CTP further minimizes both MS and SRS; however, for reasons as yet unknown, CTP pretreatment may induce myocardial stunning, an indication that at these low rates of cellular damage, CTP has no beneficial effect, either because it is ineffective as an antioxidant agent or because FR formation has little repercussion in human beings, pointing out to the likely existence of other mechanisms that may induce an appearance of postsurgical myocardial stunning.",1999.0,0,0
111,10356671,Sexual dysfunction related to antihypertensive agents: results from the animal model.,B Srilatha; P G Adaikan; S Arulkumaran; S C Ng,"The present investigation elucidates the deleterious effects of three prototypical antihypertensive drugs namely, propranolol, clonidine and captopril on the erectile physiology. In order to delineate the direct drug effects from vascular insufficiency inherent in hypertensive states, the study was conducted on a normotensive animal model. The adverse effects of these drugs were estimated as changes in sexual behaviour and intracavernous pressure response of electrical stimulation in the treated rats compared to normal age-matched controls (n = 10, each group). Copulation studies indicated significant impairment of sexual function in the groups on propranolol and clonidine. The cavernous pressure response to nerve stimulation at the end of sixteen weeks further reinforced the gross compromise on sexual function in these two treated groups. In contrast, the captopril administration produced only marginal alterations to the responses recorded. The results from this study clearly indicate that propranolol and clonidine interfere with sexual behaviour and nerve mediated response to erection whereas captopril which is devoid of significant effects on these parameters, may be a better therapeutic option.",1999.0,0,0
112,10361863,Expansion of cortical interstitium is limited by converting enzyme inhibition in type 2 diabetic patients with glomerulosclerosis. The Diabiopsies Group.,D J Cordonnier; N Pinel; C Barro; M Maynard; P Zaoui; S Halimi; B Hurault de Ligny; Y Reznic; D Simon; R W Bilous,"Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, placebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance >60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of nondiabetic nephropathy. The remaining 22 were randomized ( 11 to Perindopril [PE], 11 to placebo [PO]), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (+1562 mg/d) but declined in PE patients (-156 mg/d) (P < 0.05). Morphometric analysis was performed by light microscopy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 +/- 5.3 versus 40.2 +/- 11.1%; P = 0.001) but was unchanged in PE patients (33.8 +/- 4.9 versus 34.7 +/- 6.6%; P = 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril prevents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.",1999.0,0,0
113,10362194,"Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: a cohort study of 11,575 patients with coronary artery disease.",J Leor; H Reicher-Reiss; U Goldbourt; V Boyko; S Gottlieb; A Battler; S Behar,"The purpose of this study was to investigate the significance of the possible negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors. Several provocative reports have recently suggested that aspirin is unsafe in patients with heart failure and has negative interaction with ACE inhibitors that might attenuate their beneficial effects upon survival. We analyzed mortality data of 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention trial. A total of 1,247 patients (11%) were treated with ACE inhibitors. Of them, 618 patients (50%) used aspirin. Five-year mortality was lower among patients on ACE inhibitors and aspirin than patients on ACE inhibitors without aspirin (19% vs. 27%; p < 0.001). After adjusting for confounders, treatment with aspirin and ACE inhibitors remained associated with lower mortality risk than using ACE inhibitors only (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.56 to 0.91). Subgroup analysis of 464 patients with congestive heart failure treated with ACE inhibitors revealed 221 patients (48%) on aspirin and 243 patients not on aspirin. Although clinical characteristics and therapy were similar, patients taking aspirin experienced lower mortality than patients who did not (24% vs. 34%; p = 0.001). After adjustment, treatment with aspirin was still associated with lower mortality (RR = 0.70; 95% CI = 0.49 to 0.99). Among coronary artery disease patients with and without heart failure who are treated with ACE inhibitors, the use of aspirin was associated with lower mortality than treatment without aspirin. Our findings contradict the claim that aspirin attenuates the beneficial effect of ACE inhibitors and supports its use in patients with coronary artery disease treated with ACE inhibitors.",2000.0,0,0
114,10362195,Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol. The Heart-Muscle Disease Study Group.,A Di Lenarda; G Sabbadini; L Salvatore; G Sinagra; L Mestroni; B Pinamonti; D Gregori; F Ciani; A Muzzi; S Klugmann; F Camerini,"The purpose of this study was to analyze whether long-term treatment with the nonselective beta-adrenergic blocking agent carvedilol may have beneficial effects in patients with dilated cardiomyopathy (DCM), who are poor responders in terms of left ventricular (LV) function and exercise tolerance to chronic treatment with the selective beta-blocker metoprolol. Although metoprolol has been proven to be beneficial in the majority of patients with heart failure, a subset of the remaining patients shows long-term survival without satisfactory clinical improvement. Thirty consecutive DCM patients with persistent LV dysfunction (ejection fraction < or =40%) and reduced exercise tolerance (peak oxygen consumption <25 ml/kg/min) despite chronic (>1 year) tailored treatment with metoprolol and angiotensin-converting enzyme inhibitors were enrolled in a 12-month, open-label, parallel trial and were randomized either to continue on metoprolol (n = 16, mean dosage 142+/-44 mg/day) or to cross over to maximum tolerated dosage of carvedilol (n = 14, mean dosage 74+/-23 mg/day). At 12 months, patients on carvedilol, compared with those continuing on metoprolol, showed a decrease in LV dimensions (end-diastolic volume -8+/-7 vs. +7+/-6 ml/m2, p = 0.053; end-systolic volume -7+/-5 vs. +6+/-4 ml/m2, p = 0.047), an improvement in LV ejection fraction (+7+/-3% vs. -1+/-2%, p = 0.045), a reduction in ventricular ectopic beats (-12+/-9 vs. +62+/-50 n/h, p = 0.05) and couplets (-0.5+/-0.4 vs. +1.5+/-0.6 n/h, p = 0.048), no significant benefit on symptoms and quality of life and a negative effect on peak oxygen consumption (-0.6+/-0.6 vs. +1.3+/-0.5 ml/kg/min, p = 0.03). In DCM patients who were poor responders to chronic metoprolol, carvedilol treatment was associated with favorable effects on LV systolic function and remodeling as well as on ventricular arrhythmias, whereas it had a negative effect on peak oxygen consumption.",1999.0,0,0
115,10362383,Treatment of chronic heart failure with perindopril in ethnic Sri Lankan patients.,P N Thenabadu; J Bulumulle; G R Constantine,,1999.0,0,1
116,10367600,Blood pressure response to the first 36 hours of heart failure therapy with perindopril versus captopril. French General Hospitals National College of Cardiologists.,R Haïat; O Piot; H Gallois; G Hanania,"An open randomized hospital study conducted in 169 centers in France compared the blood pressure response to the first 36 h of treatment with perindopril (PER), 2 mg once daily, with that to captopril (CAP), 6.25 mg t.i.d., in 725 patients (mean age, 70 years; men, 67%) with echocardiographic left ventricular systolic dysfunction (fractional shortening, < or = 28%) due to ischemia (56.7%) or hypertension (34.5%) and a systolic blood pressure (SBP) > or = 120 mm Hg. Each dose of CAP induced a sharp and rapid decrease in blood pressure (maximum, 1.5-2 h); with PER, the decrease was gradual (maximum, 6 h) and variation was less marked. However, at 36 h, the decrease in blood pressure versus baseline was similar on both treatments. Over the 36-h period, there were 22 (3%) dropouts due to marked orthostatic hypotension (SBP, <90 mm Hg), and they were fewer with PER than with CAP: 16 cases in the CAP group versus six in the PER group (p = 0.036). At 36 h, heart rate was lower with CAP than with PER: 75.2 versus 77.5 beats/min, respectively (p = 0.039). As initial therapy for stabilized left ventricular systolic dysfunction, the first dose of PER (2 mg) induced a significantly smaller decrease in blood pressure than the first dose of CAP (6.25 mg); dropouts due to orthostatic hypotension were also significantly fewer with PER than with CAP.",1999.0,0,0
117,10368114,Effects of acute angiotensin II type 1 receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic parameters in patients with heart failure.,N E Goodfield; D E Newby; C A Ludlam; A D Flapan,"Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure. Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05). Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.",1999.0,0,0
118,10369535,Diffuse hair loss.,R Sinclair,,1999.0,0,0
119,10369612,Fosinopril and hydrochlorothiazide combination versus individual components: lack of a pharmacokinetic interaction.,H D Uderman; D R Much; J Brennan; C L Delaney; E A Morgenthien; J Weaver; B C Stouffer; S Y Chang; D VanHarken; W Liao,"To evaluate the pharmacokinetic interaction and bioequivalence of a combination formulation of the angiotensin-converting enzyme inhibitor fosinopril and the diuretic hydrochlorothiazide (HCTZ). In an open-label, balanced, randomized incomplete block, three-way crossover fashion, healthy men received single doses of three of four regimens in one of two independent studies. Regimens for study A (36 subjects): (1) fosinopril 10-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 10 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 10 mg and HCTZ 12.5 mg. Study B (40 subjects) received: (1) fosinopril 20-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 20 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 20 mg and HCTZ 12.5 mg. There was no evidence of any significant effect of HCTZ on the pharmacokinetics of fosinoprilat, based on maximum concentration value, AUC, or cumulative urinary recovery over 24 hours. Fosinoprilat had no clinically important effect on the pharmacokinetics of HCTZ only slightly decreasing its AUC by 14% in study A. Coadministration was well tolerated; no new adverse events were reported with the combination tablet. Fosinopril and HCTZ in a combination tablet display pharmacokinetic profiles similar to those achieved when either drug is administered alone or when coadministered in separate tablets. When used with HCTZ, the favorable pharmacokinetic feature of fosinopril, dual and compensatory pathways of renal and hepatic elimination, is preserved.",1999.0,0,0
120,10371365,"Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.",G R Norton; A J Woodiwiss; C Hartford; B Trifunovic; S Middlemost; A Lee; M J Allen,"Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.",1999.0,0,0
121,10373219,Angiotensin-converting enzyme inhibition restores hepatocyte growth factor production in patients with congestive heart failure.,S Yasuda; Y Goto; H Sumida; T Noguchi; T Baba; S Miyazaki; H Nonogi,"Endothelium-dependent vasodilation is impaired in patients with congestive heart failure. For vascular endothelium, hepatocyte growth factor (HGF) is one of the most potent and specific growth factors, which acts protectively against endothelial dysfunction. HGF production is downregulated by angiotensin II (Ang II) in vitro. We hypothesized that HGF production is impaired as the result of increased Ang II in patients with congestive heart failure, and that if so, the impaired production should be restored with angiotensin-converting enzyme inhibitors (ACE-I). We studied 16 patients with congestive heart failure caused by previous anterior myocardial infarction in whom left ventricular ejection fraction was 35+/-8% (mean+/-SD). Before and approximately 4 weeks after the treatment with ACE-I, blood samples were collected to measure the levels of HGF, Ang II, and brain natriuretic peptide as a biochemical marker for severity of heart failure. We also studied 5 control subjects, in whom heparin increased HGF production to 48+/-5-fold. However, in patients with heart failure, HGF response to heparin was significantly attenuated (24+/-5-fold, P<0.05 vs control). Therapy with ACE-I decreased the levels of Ang II and brain natriuretic peptide and restored HGF production in response to heparin by 43+/-7-fold, comparable to the control response. In conclusion, impaired HGF production was restored after the treatment with ACE-I probably by the mechanism of Ang II suppression. This novel effect of ACE-I may contribute to the clinical improvement in patients with heart failure and thereby may have an important therapeutic implication.",1999.0,0,0
122,10374374,Cardiac protection by long-term treatment with captopril in patients with acute myocardial infarction.,W Shen; M Li; H Hu; X Zhang; L Gong,"To assess the effects of long-term angiotensin-converting enzyme (ACE) inhibitor treatment with captopril on cardiac function in acute myocardial infarction (AMI). One hundred and one patients with AMI who were admitted to hospital within 72 hours of the onset of symptoms with no cardiogenic shock were randomly allocated to captopril (n = 52; group I) and conventional treatment (n = 49; group II). Left ventricular (LV) systolic performance and diastolic transmitral flow velocity profiles were assessed by Doppler echocardiography at admission (1.2 +/- 1.1 days), before discharge (27 +/- 10 days) and during follow-up (363 +/- 31 days). At one year follow-up, in group I LV end-diastolic volume decreased, and ejection fraction increased due to a disproportionate decrease in end-systolic volume. The incidence of cardiac dilatation was reduced. LV early diastolic filling velocity (E) increased and late atrial filling velocity (A) decreased, resulting in an elevation of E/A ratio. However, the mean values of LV systolic and diastolic functional parameters were unchanged in group II. Long-term treatment with captopril exerts a beneficial effect on cardiac protection for patients with AMI.",1999.0,1,1
123,10376178,The effects of metoprolol and captopril on heart rate variability in patients with idiopathic dilated cardiomyopathy.,K Jansson; I Hagerman; R Ostlund; K E Karlberg; E Nylander; O Nyquist; U Dahlström,"The effects of treatment with captopril or metoprolol on heart rate variability (HRV) were investigated in 38 patients (29 men and 9 women) with mild to moderate symptoms of heart failure due to idiopathic dilated cardiomyopathy (DCM). The aim of the study was to investigate and compare the effects of the angiotensin-converting enzyme inhibitor captopril with those of the selective beta-adrenergic receptor blocker metoprolol on HRV in patients with idiopathic DCM. Heart rate variability was analyzed in the time and frequency domains from 18th of Holter monitoring before randomized treatment was started, after 6 months of therapy, and 1 month after therapy was stopped. Captopril treatment increased HRV expressed as total power and low-frequency power in the frequency domain. There was no change in the time domain. In the metoprolol group, there was a pronounced increase in both time- and frequency-domain indices of HRV. The increase in total power was partly maintained 1 month after therapy was stopped in both treatment groups. Treatment with captopril and metoprolol increases HRV in patients with DCM. This effect seems to be maintained for at least 1 month after therapy is stopped. The increase in HRV seems to be more pronounced with metoprolol, and the two different pharmacologic approaches may have additive effects that are of prognostic importance in patients with heart failure.",1999.0,0,0
124,10376615,Optimisation of antihypertensive treatment by crossover rotation of four major classes.,J E Dickerson; A D Hingorani; M J Ashby; C R Palmer; M J Brown,"Most comparisons of antihypertensive drugs are undertaken in parallel groups. We undertook a crossover rotation of the four main classes of antihypertensive drugs, in untreated young hypertensive patients, to assess the response rate with monotherapy achieved by a systematic rotation. 56 patients, mean blood pressure 161/98 mm Hg, entered the rotation, of whom 36 received all four monthly cycles of treatment with an angiotensin-converting-enzyme (ACE) inhibitor (A), beta-blocker (B), calcium-channel blocker (C), and diuretic (D). Each patient's best drug was then repeated to assess repeatability. Two measures of individual variability in response were used. First, the value of rotation was measured by the increased proportion of patients reaching target blood pressure on their best drug versus their first drug. Second, we assessed whether the responses to each drug were correlated with each other. Significant variability in response was found. 20 of the 41 patients reaching target blood pressure (< or =140/90 mm Hg) failed to achieve this target on their first drug. Rotation increased from 22/56 (39%) to 41/56 (73%) the success of monotherapy (p=0.0001); in half the patients, blood-pressure on the best treatment was 135/85 mm Hg or less. There were significant correlations between the blood pressure responses to A and B (r=0.5, p<0.01), and C and D (r=0.6, p<0.001), but not between the other four pairings of treatments. The responses to the AB pair were, on average, at least 50% higher than those to the CD pair; this difference was highly significant by multivariate repeated-measures ANOVA. There is a marked variability in hypertensive patients' response to different antihypertensive drugs. The basis may be underlying variability in types of essential hypertension. Optimisation of treatment requires systematic rotation through several therapies; however, an ""AB/CD"" rule is proposed in which one of each of the two pairs of treatments is initially selected to abbreviate the rotation in routine practice.",1999.0,0,0
125,10376852,Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women.,B Koch; S Oparil; M Stimpel,"Co-administration of antihypertensive drug therapy and hormonal replacement therapy (HRT) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy. The present study was designed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive, postmenopausal women on HRT. After a 4-week placebo run-in phase, 95 postmenopausal women (35-74 years of age) who had a sitting diastolic blood pressure (BP) of 95-114 mm Hg and were treated with HRT were randomised to a 12-week treatment with moexipril 15 mg or placebo. Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose. Adverse events were recorded continuously. After 12 weeks of treatment, moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo (-12.2/-9.9 mm Hg vs -1.6/-4.3 mm Hg, P < 0.001). Metabolic parameters were not affected by treatment with moexipril: mean levels of triglycerides, total cholesterol, HDL, LDL, total cholesterol/HDL ratio and glucose remained unchanged throughout the study. Fibrinogen, an independent cardiovascular risk factor, increased after placebo (+35.0 mg/dl) and decreased after treatment with moexipril (-33.6 mg/dl), the difference, however, was not statistically significant. Moexipril was well-tolerated by postmenopausal women using HRT. The most frequent adverse events included headache (21.3%), cough (12.8%) and rhinitis (10.6%) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups. This study indicates that moexipril is effective and well tolerated in the treatment of hypertensive, postmenopausal women and can safely be co-administered to HRT.",1999.0,0,0
126,10377929,Should all Pima Indians with type 2 diabetes mellitus be prescribed routine angiotensin-converting enzyme inhibition therapy to prevent renal failure?,B A Kiberd; K K Jindal,"To determine how effective angiotensin-converting enzyme (ACE) inhibitors must be in preventing diabetic nephropathy to warrant early and routine therapy in all Pima Indians with type 2 diabetes mellitus. A computerized medical decision analysis model was used to compare strategy 1, screening for microalbuminuria and treatment of incipient nephropathy as currently recommended with ACE inhibitor therapy, with strategy 2, a protocol wherein all patients were routinely administered an ACE inhibitor 1 year after diagnosis of type 2 diabetes mellitus. The model assumed that ACE inhibitors can block, at least in part, the pathogenic mechanisms responsible for early diabetic nephropathy (microalbuminuria). The model predicted that strategy 2 would produce more life-years at less cost than strategy 1, if routine drug therapy reduced the rate of development of microalbuminuria by 21% in all patients. Only a 9% reduction in the rate of development of microalbuminuria was cost-effective at $15,000 per additional life-year gained, and only a 2.4% reduction was cost-effective at $75,000 per additional life-year gained for strategy 2 over strategy 1. Routine ACE inhibitor therapy in Pima Indians with type 2 diabetes mellitus could prove more effective and even cost saving than the currently recommended approach of microalbuminuria screening. A prospective trial examining this goal should be considered.",1999.0,0,0
127,10379633,Efficacy and tolerability of moexipril and nitrendipine in postmenopausal women with hypertension. MADAM study group. Moexipril as Antihypertensive Drug After Menopause.,E Agabiti-Rosei; E Ambrosioni; A Pirelli; M Stimpel; A Zanchetti,"The aim of this study was to compare the efficacy and tolerability of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and the calcium antagonist nitrendipine in postmenopausal women with mild to moderate hypertension. After a 4-week placebo run-in period, 93 postmenopausal women (age range 44-70 years) with primary hypertension were randomized to receive moexipril 15 mg once daily or nitrendipine 20 mg once daily for 8 weeks. The mean sitting systolic (SSBP) and sitting diastolic blood pressures (SDBP) at baseline were 161.3/103.0 mmHg in the moexipril group, and 162.2/102.3 mmHg in the nitrendipine group. After the 8 weeks of treatment, the SSBP/SDBP reductions were -21.2/-15.2 mmHg in the moexipril group and -18.2/-13.6 mmHg in the nitrendipine group. Blood pressure responses were adequate in 82.2% of the moexipril-treated patients and in 80.9% in the nitrendipine-treated group. Adverse events were more frequent with nitrendipine than with moexipril. The most common adverse events in the nitrendipine group were headache (23.4%), flushing (21.3%) and ankle oedema (14.9%). In the moexipril group the most common adverse event was cough (8.9%). The results of the study suggest that moexipril and nitrendipine are equieffective in the given dosages. In the patient population of postmenopausal women, the ACE inhibitor moexipril appears to have an advantage over the calcium antagonist nitrendipine with regard to tolerability.",1999.0,0,0
128,10379634,The effect of four different antihypertensive medications on cardiovascular regulation in hypertensive sleep apneic patients--assessment by spectral analysis of heart rate and blood pressure variability.,T M Salo; I Kantola; L M Voipio-Pulkki; L Pelttari; J S Viikari,"To study the effect of antihypertensive medications on autonomic nervous system in patients with hypertension and sleep apnea syndrome using frequency domain measures of heart rate and blood pressure variabilities. The beta-receptor blocking agent atenolol (50 mg), the calcium antagonist isradipine SRO (2.5 mg), the diuretic hydrochlorothiazide (25 mg) and the ACE inhibitor spirapril (6 mg) once daily were given in a double-blind crossover schedule for 8 weeks. Cardiovascular autonomic control was assessed using frequency domain measures of heart rate variability during the spontaneous and controlled breathing tests. During orthostatic maneuver and cold pressor test the blood pressure variability analysis also was performed. In general, the responses of heart rate and blood pressure variabilities were abnormal in the patients with arterial hypertension and sleep apnea syndrome compared to reference data. Of the four drugs, only atenolol effected heart rate and blood pressure variabilities as it shifted the autonomic regulation to the vagal direction. Other antihypertensive drugs did not change any parameter of heart rate or blood pressure variabilities. The short-term treatment with atenolol in patients with arterial hypertension and sleep apnea syndrome is associated with normalization of autonomic nervous control judged by heart rate and blood pressure variability. Thus, beta-receptor blockade may have adjunctive beneficial effects beyond blood pressure reduction in these patients. However, the long-term effects of blood pressure reduction on autonomic nervous control remain to be studied.",1999.0,0,0
129,10386477,The effect of ACE inhibitors on cardiovascular morbidity and mortality.,D Hachey; R W Force,,1999.0,0,0
130,10386557,A 75-year-old man with congestive heart failure.,G Guyatt,,2000.0,0,0
131,10390455,Randomised controlled trial of long term efficacy of captopril on preservation of kidney function in normotensive patients with insulin dependent diabetes and microalbuminuria.,E R Mathiesen; E Hommel; H P Hansen; U M Smidt; H H Parving,,1999.0,0,1
132,10391114,The effect of captopril on histamine release from purified rat mast cells.,M Wawrocka-Pawlak; R Dabrowski,"Captopril as inhibitor of angiotensin-converting enzyme is widely used in cardiovascular therapy, however, in some patients this drug causes allergic side effects. This fact suggests that captopril may release histamine from mast cells. Peritoneal mast cells were obtained from rats. The cells were purified by Percoll. Aliquots of mast cells were incubated with captopril or with vehicle. Histamine was determined by the spectrofluorimetric assay. The results were analyzed with the Kruskall-Wallis (ANOVA) test. The study has shown that captopril releases histamine from mast cells. The process depends on Ca2+ presence in the incubation environment. Sodium cromoglycate, as mast cell membrane stabilizer, inhibits the effect of captopril. Our results suggest that allergic side effects of captopril may be linked to histamine release from mast cells.",1999.0,0,0
133,10391389,Small is beautiful - but too cheap.,S A Amiel,,1999.0,0,0
134,10391396,Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double-blind crossover study.,S J Hunter; M I Wiggam; C N Ennis; H M Whitehead; B Sheridan; A B Atkinson; P M Bell,"It has been suggested that the adverse metabolic effects of antihypertensive therapy offset some of the benefits of blood pressure reduction. It has also been suggested that angiotensin converting enzyme (ACE) inhibitors reduce insulin resistance and that, if used together with thiazide diuretics, the adverse effects of thiazides on insulin sensitivity may be eliminated. We examined the effects on insulin sensitivity of captopril either alone or in combination with bendrofluazide in 11 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomized, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendrofluazide (CB) (2.5 mg). Blood pressure was lower following CB compared to C (128/82 vs. 144/ 88 mmHg; P<0.005) and both were lower than baseline (162/101 mmHg; P < 0.001). CB resulted in a significant increase in fasting plasma glucose compared to C (9.7+/-0.8 vs. 8.5+/-0.6 mmol/; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (22.3+/-2.4 vs. 27.4+/-4.2 mol x kg(-1) x min(-1); P < 0.05). Suppression of endogenous glucose production was reduced after CB compared to baseline (4.0+/-0.6 vs. 2.4+/-0.5 mol x kg(-1) x min(-1); P< 0.05). Combination of bendrofluazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.",1999.0,0,0
135,10393392,Effect of isosorbide-5-mononitrate on exercise performance and clinical status in patients with congestive heart failure. Results of the Nitrates in Congestive Heart Failure (NICE) Study.,B S Lewis; B Rabinowitz; Z Schlesinger; A Caspi; W Markiewicz; T Rosenfeld; S Sclarovsky; W Ermer,"Nitrate therapy improves hemodynamics in patients with heart failure, but the chronic effects of oral nitrates on exercise performance and clinical status have not been well studied. Oral isosorbide-5-mononitrate (ISMN) (50 mg once daily) or placebo was administered to 136 patients (NYHA Class 2-3) treated for heart failure, all receiving captopril and most also furosemide. Endpoints were treadmill exercise time at 12 weeks by modified Naughton protocol (primary), with an additional 12-week follow-up period. Secondary endpoints included left ventricular dimensions, ejection fraction, cardiothoracic ratio, functional class, quality of life, hospitalizations and plasma norepinephrine and atrial natriuretic peptide in a four-center substudy. Intention-to-treat analysis showed that mean change in treadmill exercise duration tended to be greater in patients receiving ISMN than placebo (treatment difference +42 s, 95% CI -5, +90 s at 12 weeks and +21 s, 95% CI -25, +74 s after 24 weeks) (NS). Treatment difference was greater in the prespecified subgroup with ejection fraction 31-40% (+55 s, 95% CI -11, +136 s at 12 weeks and +65 s, 95% CI +3, +147 s) (p = 0.035) at 24 weeks. No deleterious effects (i.e. hypotension) were observed with ISMN, although headache was reported in 19% of the active treatment group (p = 0.0001). ISMN added to captopril increased treadmill exercise time in patients with heart failure and a lesser reduction in baseline ejection fraction, although for the group as a whole, the increase in treadmill time was not significant.",1999.0,0,0
136,10393397,Bolus versus continuous low dose of enalaprilat in congestive heart failure with acute refractory decompensation.,M Podbregar; G Voga; M Horvat; I Zuran; B Krivec; R Skale; R Pareznik,"The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.",1999.0,0,0
137,10399995,Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group.,I Gustafsson; C Torp-Pedersen; L Køber; F Gustafsson; P Hildebrandt,"This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of trandolapril in 1,749 patients with AMI and ejection fraction < or =35%. The mean follow-up time was 26 months. A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.",1999.0,1,1
138,10400007,Effect of aspirin and ifetroban on skeletal muscle blood flow in patients with congestive heart failure treated with Enalapril. Ifetroban Study Group.,S D Katz; M Radin; T Graves; C Hauck; A Block; T H LeJemtel,"The purpose of this study was to determine the acute and chronic effects of cyclooxygenase inhibition with aspirin and thromboxane A2 receptor blockade with ifetroban on the chronic vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure. Angiotensin-converting enzyme inhibition and antiplatelet therapy with aspirin independently reduce the risk for subsequent nonfatal coronary events in survivors of myocardial infarction. The safety of the combined administration of angiotensin-converting enzyme inhibitors and aspirin has been questioned due to their divergent effects on the vascular synthesis of vasodilating prostaglandins. Forearm blood flow (ml/min/100 ml) at rest and during rhythmic handgrip exercise and after transient arterial occlusion was determined by strain gauge plethysmography before and 4 h and six weeks after combined administration of enalapril with either aspirin, ifetroban or placebo in a multicenter, double-blind, randomized trial of 62 patients with mild to moderate heart failure. Before randomization, forearm hemodynamics were similar in the three treatment groups except for increased resting forearm blood flow and decreased resting forearm vascular resistance in the aspirin group when compared with the placebo group. After combined administration of enalapril and study drug for 4 h and six weeks, changes from prerandomization values of mean arterial pressure, forearm blood flow and forearm vascular resistance at rest, during handgrip exercise and after transient arterial occlusion did not differ among the three treatment groups. These findings demonstrate that the vasodilating effects of enalapril in the skeletal muscle circulation of patients with heart failure are not critically dependent on prostaglandin pathways.",1999.0,0,0
139,10404354,"Effects of losartan versus captopril on mortality in patients with symptomatic heart failure: rationale, design, and baseline characteristics of patients in the Losartan Heart Failure Survival Study--ELITE II.",B Pitt; P Poole-Wilson; R Segal; F A Martinez; K Dickstein; A J Camm; M A Konstam; G Riegger; G H Klinger; J Neaton; D Sharma; B Thiyagarajan,"In the Evaluation of Losartan in the Elderly (ELITE) heart failure study, a survival benefit (primarily because of a reduction in sudden deaths) was observed in symptomatic patients treated with losartan compared with captopril. The Losartan Heart Failure Survival Study--ELITE II (currently ongoing) is a double-blind, randomized clinical trial being conducted in 45 countries at 288 sites. ELITE II formally tests the hypotheses that losartan, compared with captopril, will reduce all-cause mortality (primary end point) and sudden cardiac death and/or resuscitated cardiac arrest (secondary end point). In addition, all-cause mortality and/or hospitalizations and cardiovascular mortality and/or hospitalizations will be evaluated. The trial has 90% power to detect a 25% treatment difference in all-cause mortality (event driven, 510 deaths). Substudies are examining quality of life, health care resource utilization, and mechanisms related to the reduction in sudden death. During recruitment (June 1997 to May 1998), 3,152 patients aged 60 years or older (mean age, 71.6 years), with New York Heart Association classes II (51%), III (44%), and IV (5%), and left ventricular ejection fraction of 40% or less (mean, 31%) were randomized to receive either 12.5 mg of losartan, titrated as tolerated to 50 mg once daily, or 12.5 mg of captopril, titrated as tolerated to 50 mg thrice daily. Randomization was stratified by clinical site and for baseline beta-blocker use. The ELITE II study will further define the role of losartan in the treatment of patients with symptomatic heart failure relative to the angiotensin-converting enzyme inhibitor captopril, an agent from a class currently considered standard treatment for this disease.",1999.0,0,1
140,10406358,Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left-ventricular function after acute myocardial infarction. TRACE Study Group. Trandolapril Cardiac Evaluation.,C Torp-Pedersen; L Køber,"The survival benefit from the use of inhibitors of angiotensin-converting enzyme (ACE) in patients with acute myocardial infarction is usually presented in terms of risk ratios and lives saved per 1000 people treated. A more relevant way to present the extent of benefit would be in terms of an increase in life expectancy, but this approach has not previously been possible because of limited data on long-term outcome. We aimed to calculate the effect of trandolapril on life expectancy with follow-up data from the Trandolapril Cardiac Evaluation (TRACE) Study. The TRACE study previously showed a significant survival benefit with trandolapril in patients with reduced left-ventricular function after an acute myocardial infarction who were treated for at least 2 years. We ascertained the survival status of all patients in the TRACE study in June, 1998, at which time they had been followed up for a minimum of 6 years. We estimated life expectancy as median lifetime, which was the time for 50% of the patients to have died. Change in life expectancy is expressed as change in median lifetime. Analysis was by intention to treat. The life expectancy of patients was 4.6 years for those given placebo versus 6.2 years for those on trandolapril. Thus, for patients on trandolapril, median lifetime was increased by 15.3 months or 27% (95% CI 7 to 51). Analysis of follow-up after the end of the study indicated no decrease of this benefit during the course of double-blind treatment; continued use of trandolapril was recommended at study closure. In patients with severely reduced left-ventricular function, long-term treatment with an ACE inhibitor during the critical period after myocardial infarction is associated with a substantial increase in life expectancy.",1999.0,1,1
141,10408591,Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring.,M Diamant; H H Vincent,"In 34 out-patients with essential hypertension, the antihypertensive effect and the trough-to-peak ratios of once-daily enalapril or lisinopril were compared by ambulatory blood pressure monitoring (ABPM) according to a crossover design. The drug dose was titrated and a thiazide diuretic was added if necessary to attain a target office BP of less than 140/90 mm Hg. Both drugs significantly lowered BP but the effect of lisinopril was greater (P < 0.009): day- and night-time mean BP fell from 152/98 and 135/84 mm Hg, respectively to 133/85 and 118/74 mm Hg with enalapril and to 129/83 and 116/70 mm Hg with lisinopril. BP goal was reached with an average dose of 18 mg enalapril with 8 mg hydrochlorothiazide and with 17 mg lisinopril combined with 6 mg diuretic. Trough:peak ratio values, which were calculated after Fourier analysis of ABPM data in individual patients, were independent of drug dose. The combination with the diuretic resulted in slightly higher trough:peak ratios than with ACE inhibitor monotherapy, but the difference was not significant. The median trough:peak ratio in patients when using enalapril-based therapy was 0.48 and, when taking lisinopril-based treatment, it was 0.65 (n = 28, P < 0.005). A significant correlation was found between trough:peak ratio and changes in daytime mean arterial pressure (MAP; Spearman r= 0.43) and night-time MAP (r= 0.66). When 24-h ABPM was performed starting 24 h after last drug intake, both ACE inhibitors still had a significant antihypertensive effect (P < 0.001), which was similar for both drugs. Eleven patients reported minor side effects. Four patients stopped ACE-inhibitor treatment because of cough. The data show that lisinopril has a longer duration of action than enalapril.",1999.0,0,0
142,10408592,Double-blind comparison of eprosartan and enalapril on cough and blood pressure in unselected hypertensive patients. Eprosartan Study Group.,W J Elliott,"The effects of a new angiotensin receptor antagonist, eprosartan (200 or 300 mg b.i.d.) and enalapril (5-20 mg u.i.d.) on cough and blood pressure were compared in a 26-week, double-blind, randomised, parallel-group, multicentre, international study involving 528 patients with hypertension. Uptitration of doses was based on clinic blood pressure measurements during the first 12 weeks, after which hydrochlorothiazide (12.5-25 mg/day) could be added. The frequency and intensity of cough was assessed by a standardised questionnaire administered at each clinic visit. The primary end-point was the incidence of persistent, dry cough not due to upper respiratory infection; change in sitting diastolic blood pressure and overall incidence of cough were secondary end-points. During the first 12 weeks of double-blind therapy, enalapril treatment was associated with a 3.45-fold higher risk of definite cough (14/261 vs 4/259, P = 0.018). Overall cough incidence (from spontaneous reports from patients, or investigator's observation) was also more frequent with enalapril, as compared to eprosartan. Both agents reduced blood pressure significantly compared to baseline, although the eprosartan-treated group had a slightly higher response rate (defined as sitting diastolic blood pressure <90 mm Hg, or at least a 10 mm Hg reduction from baseline), both at end of titration (70.3% vs 62.6%, P < 0.05) and after 26 weeks (81.7% vs 73.5%, P= 0.018). These data suggest that, in unselected hypertensive patients, eprosartan is associated with less cough and a somewhat higher responder rate than enalapril.",1999.0,0,0
143,10411363,Effects of the administration of an angiotensin-converting enzyme inhibitor during the acute phase of myocardial infarction in patients with arterial hypertension. SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.,C Borghi; S Bacchelli; D D Esposti; A Bignamini; B Magnani; E Ambrosioni,"A positive history of arterial hypertension (HBP) is present in as many as 30% of patients with acute myocardial infarction (AMI) and their clinical outcome could be greatly improved by drugs enhancing blood pressure control and preserving ventricular function. The aim of the present study was to evaluate the importance of a history of HBP on the clinical efficacy of early treatment with the angiotensin-converting enzyme (ACE) inhibitor zofenopril in patients with anterior AMI. We summarize the results of a post-hoc analysis of data from the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study, which randomly evaluated the efficacy of zofenopril given within 24 h of symptom onset to patients with anterior AMI not undergoing thrombolysis. Of 1441 patients who entered the study, 565 (39.2%) had a history of HBP. The mean follow-up time was 12 months and the main outcome measures were 6-week combined occurrence of death and severe congestive heart failure (CHF) and 1-year mortality. After 6-week of treatment with zofenopril the relative risk of death or severe CHF was 0.60 (95% confidence interval [CI]: 0.45-0.81; 2P < .05) in the hypertensive group and 0.89 (0.74-1.08; 2P = .62) for normotensive patients, whereas the 1-year risk of death was 0.61 (95% CI: 0.23,0.89; 2P < .05) and 0.77 (95% CI: 0.52-1.17; 2P = .22), respectively. The 6-week prevalence of mild-to-moderate CHF was also significantly reduced by zofenopril in the hypertensive population (14.1% v 9.4%; 2P < .05). The present data suggest that treatment with zofenopril started within 24 h of the onset of anterior AMI could be highly beneficial in patients with a history of HBP.",1999.0,1,1
144,10411366,Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group.,W J Elliott; R Montoro; D Smith; M Leibowitz; C Hwang; A H Gradman; M Schleman; M Klibaner,"To compare two popular strategies for intensifying treatment for hypertension, a double-blind, randomized, prospective, parallel-group, and partial crossover study was done. After 2 weeks of placebo run-in (baseline) and 3 weeks of 5 mg enalapril once daily, 217 patients were randomized to 6 weeks of treatment with either a low-dose combination therapy (5 mg enalapril + 5 mg felodipine ER once daily, Lexxel, Astra Merck, Inc.), or a higher dose of monotherapy (10 mg enalapril once daily, Vasotec, Merck & Co., Inc.). The group randomized to the combination had significantly greater reductions in sitting systolic/diastolic blood pressure (BP)--14.2/10.6 mm Hg compared with baseline versus 9.6/7.4 mm Hg (P < .05/.01)--as well as a greater percentage of patients having achieved either diastolic BP < 90 mm Hg or a decline of at least 10 mm Hg (responders), 59% v 41% (P < .01). When patients originally taking 10 mg enalapril were crossed over to the combination therapy for a further 6 weeks, there was a further BP reduction and increase in response rate, with loss of significant differences compared with those treated continuously with the combination for the entire 12 weeks. The greater BP-lowering efficacy of the combination was independent of age, gender, and race. There were no significant differences in tolerability between the regimens. These data support the hypothesis that in patients who do not achieve goal BP reduction with a low dose of an antihypertensive agent, a combination of two drugs with complementary mechanisms of action is more effective than increasing the dose of the first agent.",1999.0,0,0
145,10411851,Role of bradykinin in the vasodilator effects of losartan and enalapril in patients with heart failure.,A P Davie; H J Dargie; J J McMurray,"ACE inhibitors have been shown to potentiate the effects of exogenous bradykinin by inhibition of its breakdown. Despite this, there is little evidence that inhibition of endogenous bradykinin breakdown actually contributes to the effects of ACE inhibitors, or indeed, other inhibitors of the renin-angiotensin system, such as angiotensin II type I receptor (AT(1)) antagonists, and no evidence at all that it does so in patients with heart failure. Twelve patients with heart failure (11 male, 1 female, ages 59 to 81 years) were randomized to double-blind crossover treatment with enalapril 10 mg BID followed by losartan 25 mg BID, or the reverse, each for 5 weeks. At the end of each treatment period, forearm blood flow was measured by venous occlusion plethysmography during an intrabrachial infusion of bradykinin before and after an intrabrachial infusion of Hoe-140 (a potent, selective, and long-acting bradykinin antagonist). Bradykinin caused profound vasodilatation after enalapril (peak, 357+/-67%) and less after losartan (peak, 230+/-46%). Despite this, Hoe-140 had no discernible effects after enalapril or losartan. Similarly, this was despite the finding that Hoe-140 significantly reduced vasodilatation to bradykinin after enalapril (peak, 192+/-35%) and losartan (peak, 66+/-13%). Inhibition of endogenous bradykinin breakdown does not appear to contribute to the effects of ACE inhibition or AT(1) antagonism in the forearm of patients with heart failure at rest, despite the very obvious effects of ACE inhibition compared with AT(1) antagonism on exogenous bradykinin.",1999.0,0,0
146,10412878,Skeletal muscle angiotensin-converting enzyme and its relationship to blood pressure in primary hypertension and healthy elderly men.,R Reneland; A Haenni; P E Andersson; B Andrén; H Lithell,"The aim of this study was to investigate the relationships between angiotensin-converting enzyme (ACE) activity in serum and skeletal muscle to blood pressure and the long-term antihypertensive effects of fosinopril and atenolol. We examined 50 hypertensive patients randomized to receive 20 mg fosinopril or 50 mg atenolol daily for 16 weeks. ACE activity was measured in biopsy specimens from skeletal muscle. Measurements of office and ambulatory blood pressure, serum ACE, and left ventricular wall thickness were also performed. The same investigations were performed in a cross-sectional study of 50 healthy elderly men. Muscle ACE correlated inversely to blood pressure in cross-sectional analyses in both populations (p < 0.05). During atenolol treatment muscle ACE activity tended to increase (14%, p = 0.059), and this increase correlated inversely to the changes in standing systolic and diastolic blood pressure (r = -0.62, p = 0.0044, and r = 0.54, p = 0.016, respectively). Muscle ACE was also inversely correlated to left ventricular wall thickness when the two populations were pooled (r =-0.29, p = 0.0053). In the fosinopril group, muscle ACE activity was not different during treatment than at baseline (-2. 1%, p = 0.68). The inverse relationship between blood pressure and muscle ACE levels in this study indicate that muscle tissue ACE levels are influenced by haemodynamic factors in humans.",1999.0,0,0
147,10417028,Treatment of ACE inhibitor-induced cough.,C A Luque; M Vazquez Ortiz,"Angiotensin-converting enzyme (ACE) inhibitors are widely administered to treat numerous medical conditions. Although they are generally well tolerated, they are associated with a dry cough that can lead to discontinuation of treatment. Data concerning the frequency, onset, and clinical effects vary among the agents. When discontinuing the ACE inhibitor is not an ideal option, pharmacologic treatment of the cough may be considered, such as cromolyn, baclofen, theophylline, sulindac, and local anesthetics.",1999.0,0,0
148,10417484,Drug-induced hyponatraemia in elderly patients.,M Schwab; F Röder; K Mörike; K P Thon; U Klotz,,1999.0,0,0
149,10417487,,,,,0,0
150,10417501,"Cohort study on calcium channel blockers, other cardiovascular agents, and the prevalence of depression.",N R Dunn; S N Freemantle; R D Mann,"Some reports have suggested that calcium channel blockers may be associated with an increased incidence of depression or suicide. There is a paucity of evidence from large scale studies. The aim of this study was to assess rates of depression with calcium channel antagonists using data from prescription event monitoring studies. Observational studies on large cohorts of patients using lisinopril, enalapril (ACE inhibitors), nicardipine (type 2 calcium channel blocker) and diltiazem (type 3 calcium channel blocker) were conducted, using prescription-event monitoring. Rates of depression in the different drugs and rate ratios (95% CI) were computed. The crude overall rates of depression during treatment were 1.89, 1.92 and 1.62 per 1000 patient months for the ACE inhibitors, diltiazem and nicardipine, respectively. Using the ACE inhibitors as the reference group, the rate ratios for depression were 1.07 (0. 82-1.40) and 0.86 (0.69-1.08) for diltiazem and nicardipine, respectively. This study does not support the hypothesis that calcium channel blockers are associated with depression, when considering patients treated in general practice in the UK.",1999.0,0,0
151,10419072,Interaction between lifetime captopril treatment and NaCI-sensitive hypertension in spontaneously hypertensive rats and Wistar-Kyoto rats.,Z Fang; W Sripairojthikoon; D A Calhoun; S Zhu; K H Berecek; J M Wyss,"Previous studies that were based on daytime arterial pressure recordings indicate that lifetime treatment with captopril exacerbates the hypertensive response to a high NaCl diet in spontaneously hypertensive rats (SHR) but has no such effect in normotensive Wistar-Kyoto (WKY) rats. The present study used 24-h recording methods to examine the hypothesis that during the normal waking hours of rats (night-time) the hypertensive response to a high NaCl diet is exacerbated in SHR and induced in WKY rats treated with lifetime captopril. SHR and WKY rats were (1) untreated, (2), lifetime captopril treated or (3) lifetime captopril treated but removed from the treatment 2 weeks prior to exposure to a high (8%) NaCl diet Compared to untreated SHR, in SHR that were continuously treated with captopril, the high NaCl diet caused a more rapid and greater rise in arterial pressure. Discontinuation of the captopril treatment did not significantly diminish this NaCl-sensitivity. In untreated WKY rats, the high NaCl diet did not alter mean arterial pressure, but in the lifetime captopril-treated WKY rats the high NaCl diet induced a rapid rise in arterial pressure. In WKY rats, discontinuation of the lifetime captopril treatment did not diminish this NaCl-induced rise in arterial pressure, even though baseline mean arterial pressure in this group is similar to that in untreated WKY rats. Lifetime captopril treatment accelerates the hypertensive response to a high NaCl diet in SHR, and it induces a similar response in WKY rats. In both strains, the lifetime captopril treatment causes a change in the response that is not dependent on concurrent administration of the drug. This finding further suggests that lifetime captopril treatment causes a long-term resetting of cardiovascular response mechanisms.",1999.0,0,0
152,10421597,Trandolapril reduces the incidence of atrial fibrillation after acute myocardial infarction in patients with left ventricular dysfunction.,O D Pedersen; H Bagger; L Kober; C Torp-Pedersen,"Studies have suggested that ACE inhibitors have an antiarrhythmic effect on ventricular arrhythmias. Whether they have an effect on atrial fibrillation is unknown. We investigated the effect of ACE inhibition with trandolapril on the incidence of atrial fibrillation in patients with reduced left ventricular function secondary to acute myocardial infarction. The patients in this study were those who qualified for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study, a randomized double-blind placebo-controlled study and who had sinus rhythm on the ECG obtained at randomization. Patients who fulfilled the criteria for inclusion were randomized to treatment with the ACE inhibitor trandolapril or placebo and were followed up for 2 to 4 years. Development and time to occurrence of atrial fibrillation in one 12-lead ECG recorded at the outpatient visits was the primary end point of this investigation. Of the 1749 patients included in the TRACE study, 1577 had sinus rhythm on the ECG recorded at randomization. Of these patients, 790 were randomized to trandolapril treatment and 787 to placebo treatment. The groups differed only slightly with respect to baseline characteristics. A total of 64 patients developed atrial fibrillation during the 2- to 4-year follow-up period. Significantly more patients developed atrial fibrillation in the placebo group than in the trandolapril group, 5.3% (n=42) versus 2.8% (n=22), respectively, P<0.05. Cox multivariable regression analysis, adjusting for important baseline characteristics, revealed that trandolapril treatment significantly reduced the risk of developing atrial fibrillation (RR, 0.45; 95% CI, 0.26 to 0.76; P<0.01). The results from the present study demonstrate that trandolapril treatment reduces the incidence of atrial fibrillation in patients with left ventricular dysfunction after acute myocardial infarction.",1999.0,0,0
153,10423601,Usefulness of moexipril and hydrochlorothiazide in moderately severe essential hypertension.,W B White; B Koch; M Stimpel,"The purpose of this study was to assess the efficacy and tolerability of the angiotensin-converting enzyme inhibitor moexipril alone and in combination with hydrochlorothiazide versus hydrochlorothiazide monotherapy in patients with stage II and III essential hypertension. This was a double-blind, randomized, multicenter trial that evaluated moexipril (15 and 30 mg once daily), hydrochlorothiazide (25 and 50 mg once daily), and combinations of the drugs (15 mg moexipril/25 mg hydrochlorothiazide and 30 mg moexipril/50 mg hydrochlorothiazide) in 272 hypertensive patients whose seated diastolic blood pressure (BP) was 100 to 114 mm Hg. The primary efficacy variable was the mean change from baseline in seated diastolic BP at the end of the dosing period. Secondary efficacy measures included changes in systolic BP and standing BP. The lower doses of moexipril and hydrochlorothiazide reduced diastolic BP similarly (-8.0 +/- 1.4 versus -8.1 +/- 1.4 mm Hg; p = NS) as did higher doses of the monotherapeutic regimens (moexipril, -9.7 +/- 1.2 mm Hg versus hydrochlorothiazide, -11.0 +/- 1.2 mm Hg, p = NS). Combinations of moexipril and hydrochlorothiazide reduced diastolic BP significantly more than either monotherapy (lower doses, -16.0 +/- 1.4 mm Hg; p < 0.001; higher doses, -17.9 +/- 1.2 mm Hg; p < 0.001). Similar trends were observed for the systolic BP. Discontinuation rates due to adverse events were 0% for the moexipril monotherapy patients and 3% to 5% in patients on diuretic or combination treatment. These data demonstrate that 15 and 30 mg moexipril once daily lower BP similarly to hydrochlorothiazide in patients with stage II and III hypertension. There is also an additive effect when combining the two agents that lowers BP more significantly than either monotherapy.",2000.0,0,0
154,10423609,Quinapril in patients with congestive heart failure: controlled trial versus captopril.,D Acanfora; G Furgi; L Trojano; C Picone; G L Iannuzzi; M Rossi; A Papa; C Rengo; F Rengo,"After two weeks of a wash-out run-in period with placebo, 131 patients with congestive heart failure (New York Heart Association [NYHA] class II to III) and left ventricular ejection fraction </=40% were randomly assigned to a treatment period of 4 weeks with 10 mg quinapril once daily or 12.5 mg captopril twice daily. At the end of this period, doses were titrated to 20 mg quinapril once daily or 25 mg captopril twice daily on the basis of physician judgment if there were no major adverse reactions and if blood pressure was not below 110/70 mm Hg. Clinical symptoms of heart failure were significantly relieved by both drugs at the end of a 12-week treatment period. At the beginning of the study, 23 (35%) of the 65 patients taking quinapril and 27 (41%) of the 66 patients taking captopril were in NYHA functional class III, whereas, at the end of the trial, only 4 (6%) of the patients in the quinapril group and 14 (22%; p < 0.05 versus quinapril) patients in the captopril group were classified as NYHA class III. Both drugs had a positive effect on echocardiographic parameters. There was a statistically significant increase in exercise duration in both treatment groups (quinapril, 6.2 +/- 1.8 versus 7.8 +/- 1.9 minutes, p < 0.001; captopril, 5.9 +/- 1.9 versus 7.1 +/- 2.3 minutes, p < 0.001). One patient in the quinapril group died suddenly during the study and two patients in the captopril group dropped out of the study due to persistent dry cough. No patient in the quinapril group reported side effects. Three patients in the captopril group suffered from moderate dry cough, one from taste-blindness, and another from unstable angina. The safety of the tested drugs was confirmed by laboratory tests. Quinapril was as effective as captopril in reducing signs and symptoms of heart failure and in improving the left ventricular function and the exercise capacity with few side effects.",2000.0,1,1
155,10423659,Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension.,J M Neutel; W H Frishman; S Oparil; V Papademitriou; G Guthrie,"In this study, telmisartan, a new angiotensin AT ( 1 ) receptor antagonist given as monotherapy and in combination with hydrochlorothiazide (HCTZ), was compared with lisinopril as monotherapy and in combination with HCTZ. This 52-week, randomized, multicenter, double-blind, double-dummy, parallel-group, dose-titration study of 578 patients with mild-to-moderate essential hypertension (mean diastolic blood pressure [DBP], >/=95 mm Hg), compared the efficacy and safety of telmisartan (n = 385) with lisinopril (n = 193). Dosage could be increased for both telmisartan (40 --> 80 --> 160 mg) and lisinopril (10 --> 20 --> 40 mg) at each of the first 2 monthly visits if DBP control (<90 mm Hg) had not been established. Once DBP control was established, patients entered the 48-week maintenance period. During this period, the dose of the study drug was fixed, although open-label HCTZ at 12.5 mg or 25 mg was added, when needed, to regain DBP control. At the end of the titration period, DBP control was achieved on monotherapy by 67% and 63% of the telmisartan and lisinopril patients, respectively. At the end of the maintenance period, supine DBP was controlled in 83% and 87% of the telmisartan and lisinopril patients, respectively, with systolic blood pressure over DBP reductions of 23.8/16.6 mm Hg for telmisartan and 19.9/15.6 mm Hg for lisinopril. Treatment-related side effects occurred in fewer telmisartan-treated patients (28%) than in lisinopril-treated patients (40%; P =.001). Significantly fewer patients (P =.018) receiving telmisartan experienced treatment-related cough (3% v 7%), and cough led to discontinuation significantly less often (P =.007) with telmisartan treatment than with lisinopril treatment (0.3% v 3.1%). In addition, two cases of angioedema were observed, both in the lisinopril group. The selective AT (1) receptor antagonist, telmisartan, is extremely effective in the treatment of mild-to-moderate hypertension both as monotherapy and in combination with HCTZ and is at least comparable in efficacy to lisinopril, with a tolerability profile that may offer advantages in terms of a reduced incidence of adverse events.",1999.0,0,0
156,10424316,Effects of captopril and enalapril on electroencephalogram and cognitive performance in healthy volunteers.,U Ebert; W Kirch,"Captopril and enalapril have been reported to influence cognitive functions and quality of life in hypertensive patients. The effects of captopril (12.5 mg and 25 mg) and enalapril (5 mg and 10 mg) administered during 7-day periods on electroencephalogram (EEG), cognitive functions, and subjective assessments were investigated in healthy males. Neither captopril nor enalapril influenced EEG and cognitive functions compared with placebo. Captopril 12.5 mg decreased subjective activity compared with placebo. Enalapril did not alter subjective ratings. Both systolic and diastolic blood pressure were significantly lower after administration of captopril 25 mg, whereas blood pressure was unaffected by enalapril compared with placebo. Our results suggest that central effects of captopril and enalapril were minor and not constant in young healthy men.",1999.0,0,0
157,10426836,Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors.,M Guazzi; G Pontone; P Agostoni,"Pulmonary function abnormalities participate in causing exercise disability in patients with congestive heart failure (CHF). Impaired pulmonary gas transfer is one of these abnormalities. Angiotensin-converting enzyme (ACE) inhibitors improve diffusion for carbon monoxide and exercise capacity, an effect that is seemingly mediated through prostaglandin activation because it is inhibited by cyclooxygenase blockade with aspirin. This suggests the possibility that aspirin may disturb the pulmonary function and exercise ability in CHF, at least in those patients who are taking ACE inhibitors. This study was aimed at probing this hypothesis. A dose of 325 mg aspirin was given daily for 8 weeks to 26 consecutive patients with primary dilated cardiomyopathy (New York Heart Association class II or III) whose current outpatient antifailure therapy included (group 1, 18 cases) or did not include (group 2, 8 cases) an ACE inhibitor in addition to digoxin and furosemide. During the study ACE inhibition was continued in group 1 by giving enalapril 20 mg daily. Tests repeated at 8 weeks proved that aspirin was deleterious in group 1. Compared with run-in, rest carbon dioxide, peak exercise oxygen uptake (peak VO(2 )), and tidal volume levels were diminished in this group; the ratio of exercise minute ventilation to carbon dioxide production (VE/VCO(2)) was augmented and its variations were inversely related to those of peak VO(2). Similar results were not observed in group 2; however, once this part of the study was completed and enalapril was included in the current therapeutic regimen, an inhibitory effect of aspirin on carbon dioxide, peak VO(2), peak tidal volume, and VE/VCO(2) at 1 L levels became evident and was similar to that observed in group 1. Aspirin does not affect ventilation efficiency and peak VO(2 ) in patients with CHF not taking ACE inhibitors, but it worsens the pulmonary diffusion for carbon monoxide, VO(2 ), and the ventilatory response to exercise in the presence of ACE inhibition. This may be relevant in patients with CHF from ischemic heart disease. Whether the same may be true of smaller aspirin doses was not investigated in this study.",1999.0,0,0
158,10436357,"Intrahepatic cholestatic syndromes: pathogenesis, clinical features and management.",W A Qureshi,"Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin's disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.",1999.0,0,0
159,10437863,Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria.,P Ruggenenti; A Perna; G Gherardi; G Garini; C Zoccali; M Salvadori; F Scolari; F P Schena; G Remuzzi,"Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h. In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (> or =53 g/24 h). Median follow-up was 31 months. The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05] mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2. In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.",2000.0,0,1
160,10437875,Effects of losartan and captopril on QT dispersion in elderly patients with heart failure. ELITE study group.,P Brooksby; P J Robinson; R Segal; G Klinger; B Pitt; A J Cowley,"Differences in QT dispersion (a predictor for sudden death) were observed in a subgroup of patients in the ELITE heart failure study of losartan compared with captopril, and may explain improved survival with losartan.",1999.0,0,0
161,10438689,Mania in the geriatric patient population: a review of the literature.,M W Van Gerpen; J E Johnson; D K Winstead,"The diagnosis of mania in the geriatric population is uncommon. However, it comprises significant healthcare utilization and cost requirements, which are expected to increase in the near future with the projected increase in the geriatric population. The authors review literature pertaining to geriatric mania and discuss epidemiology, psychopathology, neuropathology, differential diagnosis, evaluation, treatment, and outcomes. Literature searches were performed by GratefulMed for the years 1960-1997, with secondary- and tertiary-source follow-up. It is clear from this review that geriatric mania is a complex illness with many possible etiologies and treatments. Much more research needs to be conducted in all of the areas reviewed.",1999.0,0,0
162,10439497,"Treatment of hypertensive and hypercholesterolaemic patients in general practice. The effect of captopril, atenolol and pravastatin combined with life style intervention.",O P Foss; S Graff-Iversen; H Istad; E Søyland; L Tjeldflaat; B Graving,"To elucidate the effect on blood pressure and blood lipids of an angiotensin converting enzyme inhibitor (captopril), and a beta-receptor blocking agent (atenolol), given alone or in combination with a cholesterol reducing drug, the beta-hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin, in patients who were also encouraged to improve their lifestyle. A longitudinal study consisting of three phases. I: Lifestyle intervention alone. II: Continued lifestyle intervention combined with captopril or atenolol. III: Continued lifestyle intervention combined with the same drugs as in phase II and in addition pravastatin or placebo. Fifty-four general practice surgeries in Norway. Hypertensive patients, 210 females and 160 males, treated or untreated with antihypertensive drugs with a sitting diastolic blood pressure between 95 and 115 mmHg and a serum total cholesterol between 6.5 mmol/l (7.0 for those age 60-67 years) and 9.0 mmol/l. The antihypertensive effect of captopril and atenolol was not influenced by concurrent administration of pravastatin. The effect of pravastatin was not limited by concurrent medication with captopril or atenolol. Improvement in lifestyle seemed to reduce the need for supplementary treatment with diuretics. Pravastatin can be used in combination with captopril or atenolol in the treatment of hypertensive and hypercholesterolaemic patients.",1999.0,0,0
163,10445870,Special considerations in the therapy of diabetic hypertension.,C B Guzmán; J R Sowers,"Patients with diabetes mellitus have an increased prevalence of hypertension and associated cardiovascular disease (CVD), including coronary and cerebrovascular disease. The risk of an individual of developing CVD is much greater when both diseases coexist and is further magnified by their frequent association with dyslipidemia, coagulation, platelet, and endothelial abnormalities. Metabolic abnormalities frequently associated with hypertension are insulin resistance, enhanced coagulation, and decreased fibrinolytic activity. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including altered efficacy of medications, possible side effects, worsening of glycemic control, and impairment of lipid metabolism. Because hypertension is a major contributor to morbidity and mortality in diabetes, it should be recognized and treated early and aggressively despite these difficulties. This article reviews the efficacy and side effects of the various classes of antihypertensive agents in patients with diabetes mellitus.",1999.0,0,0
164,10446945,The long-term outcome of patients with IgA nephropathy treated with fish oil in a controlled trial. Mayo Nephrology Collaborative Group.,J V Donadio; J P Grande; E J Bergstralh; R A Dart; T S Larson; D C Spencer,"It was reported previously that dietary fish oil supplementation retarded the progression of renal disease in patients with IgA nephropathy in a multicenter, placebo-controlled, randomized, 2-yr clinical trial. The aim of this study was to determine the long-term influence of fish oil treatment on renal progression in observations on the study cohort of 106 patients extending beyond the 2-yr trial. Renal function was assessed by serial serum creatinine and 24-h urine protein measurements. Vital, end-stage renal disease (ESRD), and BP status and treatment beyond completion of the 2-yr trial were determined. As in the trial, the primary end point was an increase of 50% or more in the serum creatinine, and the secondary end point was ESRD. After a mean follow-up of 6.4 yr, 46 patients-17 in the fish oil group versus 29 in the placebo group-reached the primary end point (P = 0.002), and 27 patients-eight in the fish oil group versus 19 in the placebo group-developed ESRD (P = 0.009). At the end of the 2-yr trial, 75 patients (45 fish oil, 30 placebo) remained at risk for the primary end point. This is also when the double-blind part of the trial ended, allowing physicians to stop supplements, switch original placebo-assigned patients to fish oil, and continue fish oil in original fish oil-assigned patients. A significantly greater number of nonsupplemented placebo patients developed the primary end point (P = 0.02) and ESRD (P = 0.003) compared with long-term supplemented fish oil patients. Conversely, more fish oil-supplemented patients had stable renal function than nonsupplemented patients (P = 0.02). By intention, BP control, primarily treated with angiotensin-converting enzyme inhibition, was equal in the fish oil and placebo groups. Proteinuria was modestly reduced in both groups. It is concluded that early and prolonged treatment with fish oil slows renal progression for high-risk patients with IgA nephropathy.",2001.0,0,0
165,10449213,Fixed-dose combination vs monotherapy in hypertension: a meta-analysis evaluation.,D E Hilleman; K L Ryschon; S M Mohiuddin; R L Wurdeman,"Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug discontinuance. The fixed-dose combination of amlodipine/benazepril achieves its goal of effective BP lowering with a minimum of significant side effects.",1999.0,0,0
166,10449940,In vivo enalapril-induced acantholysis.,A Lo Schiavo; V Guerrera; E Cozzani; A Aurilia; E Ruocco; F Pinto,"Enalapril is a widely used antihypertensive drug with a very powerful in vitro acantholytic effect. It has been known to potentially induce pemphigus in genetically predisposed subjects. The action mechanism is complex and still only partially understood. We describe the case of a 66-year-old man, affected with intermediary basal cell carcinoma, in whom the histological examination showed suprabasal acantholytic clefts in the perilesional epidermis. Surprisingly a second biopsy taken from the apparently healthy skin of his back confirmed the presence of acantholytic changes. Clinical signs of pemphigus were absent. The patient's history did not reveal any relevant data but a mild arterial hypertension that had been treated for 1 year with 10 mg enalapril. Taking into account the patient's history (enalapril long-term administration), the absence of any bullous or erosive lesions and the histological findings, a diagnosis was made of in vivo enalapril-induced acantholysis.",1999.0,0,0
167,10450715,Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.,J A Staessen; L Thijs; R Fagard; E T O'Brien; D Clement; P W de Leeuw; G Mancia; C Nachev; P Palatini; G Parati; J Tuomilehto; J Webster,"The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. Family practices and outpatient clinics at primary and secondary referral hospitals. A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.",2000.0,0,0
168,10451039,Efficacy and safety of eprosartan in severe hypertension. Eprosartan Multinational Study Group.,R Sega,"The efficacy of eprosartan, a highly selective, orally-active non-biphenyl, non-tetrazole, type 1 angiotensin II (AT1) receptor antagonist, was compared with that of the angiotensin-converting enzyme (ACE) inhibitor, enalapril, with the addition of hydrochlorothiazide (HCTZ) when necessary in patients with severe hypertension (sitting diastolic blood pressure [sitDBP] > or = 115 mmHg and < or = 125 mmHg). Patients (n = 118) were randomized into an 8-week, double-blind titration phase and were started on oral eprosartan 400 mg total daily dose, given b.i.d., or oral enalapril 10 mg total daily dose, given o.d. The dose of eprosartan was increased to 600 and 800 mg daily, given b.i.d., and that of enalapril to 20 and 40 mg daily, given o.d., at weeks 2 and 4 if sitDBP was > or = 90 mmHg. If blood pressure remained uncontrolled on maximum doses of eprosartan or enalapril at week 6, HCTZ 25 mg o.d. was added to the treatment regimen. Patients whose blood pressure was deemed medically acceptable by the investigator at week 8 entered a 2-week maintenance phase on the final dose used in the titration phase. The primary efficacy measure was the difference between treatments of the mean reduction from baseline in sitDBP at the end of the study. Eprosartan and enalapril caused a similar reduction in sitDBP at study endpoint. The mean change in sitDBP at the end of the study for the eprosartan group was -20.1 mmHg vs -16.2 mmHg for the enalapril group. However, eprosartan produced significantly greater decreases in both sitting and standing systolic blood pressure (sitSBP and staSBP, respectively) than enalapril. The mean decrease in sitSBP was 29.1 mmHg for eprosartan compared with 21.1 mmHg for enalapril (p = 0.025). The mean reduction in staSBP was 27.8 mmHg for eprosartan compared with 20.0 mmHg for enalapril (p = 0.032). At the end of the study, the response rate (sitDBP < 90 mmHg or decreased from baseline by at least 15 mmHg) was 69.5% in the eprosartan group and 54.2% in the enalapril group. The proportion of patients in each treatment group who required addition of HCTZ was similar. Eprosartan was well tolerated; the overall incidence of adverse events was comparable to that in the enalapril group. These results demonstrate that in patients with severe hypertension, eprosartan is well tolerated and may be more effective than enalapril in reducing systolic blood pressure.",1999.0,0,0
169,10453590,A clinical trial of tang shen ning for treatment of diabetic nephropathy.,Y Gao; R Lü; X Wang; J Geng; K Ren; Y Wang; J Zhao; X Yu; D Chen,"This paper reports the clinical trial of Tang Shen Ning ([symbol: see text], TSN) for treating diabetic nephropathy (incipient and clinical, as divided by Mogensen). The results showed that the total effective rate in treatment group (TSN + western medicine) was 90.0%, and that in the control group (simply with western medicine), 56.7%. TSN plays important roles in decreasing proteinuria and improving renal functions.",1999.0,0,0
170,10455471,The prognostic significance of a history of systemic hypertension in patients randomised to either placebo or ramipril following acute myocardial infarction: evidence from the AIRE study. Acute Infarction Ramipril Efficacy.,K Spargias; S Ball; A Hall,"After acute myocardial infarction (AMI), patients with a history of arterial hypertension (AH) have a worse prognosis than normotensives. Whether this adverse risk is beneficially modulated by treatment with angiotensin-converting enzyme (ACE) inhibitors is unknown. We evaluated the prognostic value of antecedent hypertension in post-AMI patients given ACE inhibitor therapy. We analysed retrospectively data from the AIRE study (randomised, placebo-controlled trial of ramipril in 2006 post-AMI patients with clinical heart failure). A history of AH was present in 28% of the patients. We examined the prognostic value of antecedent hypertension separately among placebo and ramipril treated patients and also the effect of ramipril on clinical outcomes according to whether or not a history of AH was present. Antecedent hypertension was a significant indicator of adverse prognosis in the placebo (P) treated patients (Hazard Ratio 1.49, 95% Confidence Intervals 1.13 to 1.97, P = 0.005) but not in the ramipril (R) treated patients (1.17, 0.84 to 1.61, P = 0.34). A similar pattern was observed for the risks of sudden death (P: 1.75, 1.21 to 2.54, P = 0.003; R: 1.34, 0.86 to 2.07, P = 0.18) and severe/resistant heart failure (P: 1.48, 1.08 to 2.03, P = 0.014; R: 1.18, 0.83 to 1.68, P = 0.37). Treatment with ramipril reduced the all-cause mortality risk in both hypertensive (0.63, 0.44 to 0.89, P = 0.009) and normotensive patients (0.78, 0.61 to 0.99, P = 0.041). Antecedent hypertension is not a significant prognosticator in patients with AMI and clinical heart failure given ACE inhibitor therapy.",1999.0,0,0
171,10456379,"Drug-induced cognition disorders in the elderly: incidence, prevention and management.",S L Gray; K V Lai; E B Larson,"The aetiology of cognitive impairment is multifactorial; however, drugs are an important cause of delirium and dementia. Several factors may increase the risk of drug-induced cognition disorders in the elderly including imbalances in neurotransmitters (e.g. acetylcholine), age-related alterations in pharmacokinetics and pharmacodynamics, and high levels of medication use. Nearly any drug can cause cognitive impairment in susceptible individuals; however, certain classes are more commonly implicated. Benzodiazepines, opioids, anticholinergics, and tricyclic antidepressants are probably the worst offenders. Older antihypertensive agents (reserpine, clonidine) have negative effects on cognition; however, large clinical trials in the elderly indicate that commonly used agents [e.g. thiazide diuretics, calcium antagonists (amiodipine, diltiazem), ACE inhibitors (captopril, enalapril) and beta-blockers (atenolol)] have minimal effects on cognition. Newer antidepressants such as selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and reversible inhibitors of monoamine oxidase A have not been shown to have negative effects on cognition. Although some drugs have shown low risk for causing cognition disorders in research studies, risk may be increased in frail older adults taking several medications and each case should be reviewed carefully. Identification of drug-induced cognitive impairment is crucial to early detection and resolution of symptoms. Preventive strategies directed at avoiding high risk medications when possible, appropriately adjusting doses based on age-related changes and close follow-up may prevent these conditions.",1999.0,0,0
172,10460512,Nephrotic syndrome at 5 months: no definitive treatment or complications for 12 years.,M B Garza; M Guttenberg; B S Kaplan,"We describe a patient who developed nephrotic syndrome at 5 months, with extensive glomerular and tubular damage on biopsy. The patient was treated with diuretics and was asymptomatic for a decade despite unremitting proteinuria. A repeat biopsy at 13 years of age showed remarkable healing with histopathological features consistent with ""minimal change"" nephrotic syndrome. This patient illustrates a favorable clinical outcome, without specific treatment, of nephrotic syndrome of long duration.",1999.0,0,0
173,10460781,Hypertension and diabetic retinopathy--what's the story?,J T Gillow; J M Gibson; P M Dodson,,1999.0,0,0
174,10466921,ACE inhibitor switch in an indigent community clinic.,M R Knight; M A Gales,,1999.0,0,0
175,10467219,,,,,0,0
176,10469854,Higher levels of antioxidant defenses in enalapril-treated versus non-enalapril-treated hemodialysis patients.,E M de Cavanagh; L Ferder; F Carrasquedo; D Scrivo; A Wassermann; C G Fraga; F Inserra,"We previously reported chronic treatment with angiotensin-converting enzyme inhibitors (ACEis) increases antioxidant defenses in mice. In the present study, however, we examined various antioxidant defenses in chronic hemodialysis (HD) patients either treated with enalapril (10 mg/d) for at least 6 months (+ACEi; n = 11) or untreated (-ACEi; n = 11). The relationship between antioxidant status and HD was investigated by determining oxidative stress markers and antioxidant defenses in a group of chronic HD patients (n = 33) and a group of age-matched controls (n = 29). The effect of a single HD session on those parameters was also evaluated. Before an HD session (pre-HD), HD patients had significantly lower levels of red blood cell (RBC) glutathione (GSH), selenium-dependent glutathione peroxidase activity (RBC-Se-GPx), plasma ubiquinol-10, and alpha-tocopherol than controls. In a randomly selected group of patients (n = 19), a single HD session caused an additional decrease in RBC-GSH and plasma ubiquinol-10 levels. Plasma thiobarbituric acid reactive substance (TBARS) levels were significantly greater in pre-HD patients than controls. Post-HD plasma TBARS levels were similar to control values. The cohort of +ACEi HD patients had greater pre-HD RBC-GSH content, RBC-Se-GPx activity, and plasma beta-carotene concentrations than -ACEi patients (RBC-GSH: +ACEi, 3.1 +/- 0.9 micromol/mL packed RBCs [PRBCs]; -ACEi, 1.2 +/- 0.3 micromol/mL PRBCs [P < 0.05 v +ACEi]; RBC-Se-GPx: +ACEi, 5.8 +/- 0.7 U/mL PRBCs; -ACEi, 4.3 +/- 0.2 U/mL PRBCs [P < 0.05 v +ACEi]; plasma beta-carotene: +ACEi, 0.54 +/- 0.16 micromol/L plasma; -ACEi, 0.19 +/- 0.05 micromol/L plasma [P < 0.05 v +ACEi]). Results show profound alterations in the circulating antioxidant systems of chronic HD patients and that additional oxidative stress occurs during the HD procedure. In addition, in +ACEi HD patients, the levels of several antioxidant defenses are greater than in those in -ACEi HD patients.",1999.0,0,0
177,10471456,The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.,B Pitt; F Zannad; W J Remme; R Cody; A Castaigne; A Perez; J Palensky; J Wittes,"Aldosterone is important in the pathophysiology of heart failure. In a doubleblind study, we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic, and in most cases digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily, and 841 to receive placebo. The primary end point was death from all causes. The trial was discontinued early, after a mean follow-up period of 24 months, because an interim analysis determined that spironolactone was efficacious. There were 386 deaths in the placebo group (46 percent) and 284 in the spironolactone group (35 percent; relative risk of death, 0.70; 95 percent confidence interval, 0.60 to 0.82; P<0.001). This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes. The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group (relative risk of hospitalization, 0.65; 95 percent confidence interval, 0.54 to 0.77; P<0.001). In addition, patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients. Blockade of aldosterone receptors by spironolactone, in addition to standard therapy, substantially reduces the risk of both morbidity and death among patients with severe heart failure.",2000.0,0,0
178,10473021,Perindopril 2mg/indapamide 0.625mg. Fixed low-dose combination.,K J McClellan; A Markham,"Low-dose drug combinations have been proposed in International Guidelines for use in patients with hypertension. The fixed low-dose combination of perindopril 2mg with indapamide 0.625mg combines an angiotensin converting enzyme (ACE) inhibitor with a non-thiazide diuretic. Coadministration of perindopril and indapamide did not have any clinically significant effects on the pharmacokinetic profile of either agent in healthy volunteers. In experimental models of hypertension, perindopril/indapamide restored endothelial function, improved microvascular density, reduced left ventricular and aortic hypertrophy, and reversed renal end-organ damage. Once daily oral perindopril 2mg/indapamide 0.625mg normalised blood pressure (BP) in 83.6% of elderly patients with essential hypertension (diastolic BP was reduced to < or =90mm Hg) and 81.7% of those with isolated systolic hypertension (systolic BP was reduced to <160mm Hg) after approximately 1 year of treatment. BP normalisation was sustained in 79.8% of patients throughout the study. Fixed low-dose perindopril/indapamide had a tolerability profile similar to that of placebo in clinical trials; most adverse events were of mild to moderate severity. Coadministration of the 2 agents reduced the incidence of hypokalaemia seen with indapamide alone.",1999.0,0,0
179,10475875,Drug-induced agranulocytosis in older people. A case series of 25 patients.,J E Kurtz; E Andres; F Maloisel; V Kurtz-Illig; D Heitz; J Sibilia; M Imler; P Dufour,,1999.0,0,0
180,10477530,,,,,0,0
181,10480471,Effect of aspirin on blood pressure in hypertensive patients taking enalapril or losartan.,J J Nawarskas; R R Townsend; M D Cirigliano; S A Spinler,"The ability of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure may in part be due to the formation of vasodilatory prostaglandins. Inhibition of prostaglandin synthesis with aspirin may therefore theoretically attenuate the antihypertensive effect of ACE inhibitors. This trial studied the interaction between aspirin (ASA) and enalapril, an ACE inhibitor, and ASA and losartan, an angiotensin subtype 1 receptor antagonist. Seventeen essential hypertensive patients were studied, maintained on a stable dose of either enalapril (n = 7) or losartan (n = 10) monotherapy for > or =12 weeks before and throughout the study. Each patient received a 2-week course of placebo, 81 mg/day ASA, and 325 mg/day ASA, each treatment separated by a 2-week washout period. Blood pressure (BP) and serum thromboxane B2 (TXB2) samples were obtained at the end of each treatment period. Placebo was compared with each dose of ASA for each group. In both the enalapril and losartan groups, mean, systolic, and diastolic BP were unchanged with the addition of ASA. Concentrations of TXB2 were suppressed to <10% in both groups with ASA. This study demonstrates that 81 to 325 mg/day ASA exerts no significant effect on BP in essential hypertensives taking enalapril or losartan.",1999.0,0,0
182,10480522,ACE inhibitors improve endothelial function in type 1 diabetic patients with normal arterial pressure and microalbuminuria.,G Arcaro; B M Zenere; F Saggiani; M G Zenti; T Monauni; A Lechi; M Muggeo; R C Bonadonna,"The purpose of this study was to test whether a short-course treatment with ACE inhibitors may restore endothelium-dependent and/or -independent vasodilation in the femoral artery of microalbuminuric patients with type 1 diabetes and normal arterial pressure. We studied nine normotensive microalbuminuric type 1 diabetic patients and two groups of control subjects matched for femoral artery diameter to type 1 diabetic patients after placebo (control group A, n = 17) and ACE inhibitor (control group B, n = 18) treatment, respectively. The patients were enrolled in a double-blind cross-over study with a 1-week trial of either placebo, captopril (25 mg t.i.d.), or enalapril (10 mg/day) in randomized order to ascertain whether short-term ACE inhibition obtained with (captopril) or without (enalapril) a sulfhydryl donor molecule ameliorates vessel wall function. Endothelium-mediated flow-dependent vasodilation and endothelium-independent vasodilation were evaluated in the right common femoral artery by echo Doppler. Both captopril and enalapril normalized (control group B 22.9+/-3.2% per 8 min) endothelium-dependent response (19.6+/-7.5 and 18.0+/-5.3 vs. -10.4+/-4.1% per 8 min, P < 0.01, for both captopril and enalapril versus placebo, respectively) in the type 1 diabetic patients. Captopril (28.4+/-3.5 vs. 17.1+/-3.5% per 5 min during placebo, P < 0.05) but not enalapril (20.1+/-3.0 vs. 31.7+/-2.8% per 5 min, P < 0.05 for enalapril versus control group B, and NS for captopril vs. control group B) ameliorated endothelium-independent vasodilation in type 1 diabetic patients. ACE inhibition improves endothelium-dependent vasodilation in the femoral artery of normotensive microalbuminuric type 1 diabetic patients. Captopril also ameliorates endothelium-independent vasodilation, possibly through its sulfhydryl donor properties. These results may be of pathophysiological relevance to prevent cardiovascular complications in these patients.",1999.0,0,0
183,10482155,Relations of diastolic left ventricular filling to systolic chamber and myocardial contractility in hypertensive patients with left ventricular hypertrophy (The PRESERVE Study).,V Palmieri; J N Bella; V DeQuattro; M J Roman; R T Hahn; B Dahlof; N Sharpe; C P Lau; W C Chen; E Paran; G de Simone; R B Devereux,"Abnormalities of left ventricular (LV) diastolic filling and stress-corrected midwall shortening (MWS) have been described in hypertensive patients with normal ejection fraction (EF). However, whether stress-corrected MWS parallels LV diastolic filling better than EF does remains uncertain. Blood pressure, body mass index, echocardiographic LV mass and LV geometry, EF and stress-corrected MWS, LV diastolic filling (peak E- and A-wave velocities, E-wave deceleration time, and atrial filling fraction) were evaluated in 212 hypertensive patients with LV hypertrophy enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement study. LV structure, geometry, as well as LV diastolic filling, were compared between patients with reduced EF (<55%, n = 39, 18%) and those with normal EF (>55%) as well as between patients with reduced stress-corrected MWS (<89.2%, n = 31, 15%) and those with normal stress-corrected MWS (>89.2%). Patients with reduced EF had higher LV mass, eccentric LV geometry, and higher heart rate than those with normal EF, although they did not differ in age, blood pressure, or body mass index. LV filling pattern was also similar in those 2 groups. Patients with reduced stress-corrected MWS had higher atrial filling fraction, body mass index, heart rate, LV mass, and concentric geometry than those with normal stress-corrected MWS. Atrial filling fraction was negatively associated with stress-corrected MWS, but not with EF in multivariate models, independently of age, gender, heart rate, and body mass index. Thus, in hypertensive patients with LV hypertrophy, abnormal LV diastolic filling is more closely related to impaired myocardial contractility than to LV chamber EF.",1999.0,0,0
184,10484002,Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in The Netherlands.,I A Eland; E P van Puijenbroek; M J Sturkenboom; J H Wilson; B H Stricker,"Drugs are considered a rare cause of acute pancreatitis. We conducted a descriptive study to assess which drugs have been associated with acute pancreatitis in spontaneous adverse drug reaction reports in The Netherlands. Our study is based on reports of drug-associated acute pancreatitis reported to the Netherlands Center for Monitoring of Adverse Reactions to Drugs and The Netherlands Pharmacovigilance Foundation LAREB between 1 January 1977 and 1 January 1998. We used an algorithm to validate the diagnosis and to assess the causal relationship between acute pancreatitis and use of the suspected drug. A total of 55 cases were available for review. We excluded 11 (20.0%) reports, as we could not confirm the diagnosis of acute pancreatitis. Another 10 (18%) cases were excluded, as the causal relationship with the suspected drug was unlikely. In the remaining 34 reports, acute pancreatitis was labeled as definite in 11 (32%) and as probable in 23 (68%). The age of the patients ranged from 17 to 84 yr with a median of 41; 24 (71%) patients were female. Of the 34 cases, 27 (79%) recovered, five (15%) died, and in two (6%) the outcome is unknown. Azathioprine, cimetidine, interferon-alpha, methyldopa, metronidazole, olsalazine, and oxyphenbutazon all had a definite causal relationship with acute pancreatitis. Doxycycline, enalapril, famotidine, ibuprofen, maprotiline, mesalazine, and sulindac had a probable causal relationship with acute pancreatitis. A variety of drugs was associated with acute pancreatitis in Dutch adverse drug reaction reports. Quantitative information about drug-induced pancreatitis is scanty. Epidemiological studies to assess the risk of drug-induced acute pancreas, therefore, are needed.",1999.0,0,0
185,10485510,Association between antihypertensive drug use and hypoglycemia: a case-control study of diabetic users of insulin or sulfonylureas.,M Thamer; N F Ray; T Taylor,"Antihypertensive drugs are commonly prescribed for the treatment of patients with both diabetes and hypertension. However, the role of selected agents in the development of hypoglycemia remains controversial. The main objective of this study was to evaluate the effect of antihypertensive agents on the risk of hypoglycemia in diabetic patients receiving insulin or sulfonylurea therapy. A matched case-control study was conducted using Pennsylvania Medicaid data. Five control subjects, matched for sex and age, with no reported medical condition of hypoglycemia, were randomly selected for each case patient admitted for hypoglycemia in 1993, resulting in a total of 404 cases and 1375 controls. With these sample sizes, we were able to detect a difference of 10% (P < 0.05) for our primary outcome measure, hospitalization for hypoglycemia. The relative risk of hypoglycemia was estimated using an unconditional logistic regression. The risk of hypoglycemia was 5.5 times greater (95% confidence interval [CI], 4.0 to 7.6) in insulin versus sulfonylurea users and was not influenced by use of angiotensin-converting enzyme (ACE) inhibitors overall. However, use of the ACE inhibitor enalapril was associated with an increased risk of hypoglycemia (odds ratio, 2.4; 95% CI, 1.1 to 5.3) in sulfonylurea users, suggesting that analyzing the unintended side effects of a class of drugs can sometimes mask the adverse effects of individual drugs. Use of beta-blockers was not associated with an increased risk of hypoglycemia, providing further empiric evidence that beta-blockers are an appropriate treatment for persons with concomitant diabetes and hypertension. Per capita health care costs were approximately 3 times higher in patients hospitalized for hypoglycemia compared with controls (P < 0.05). Hospitalization for hypoglycemia is expensive and may be prevented with appropriate monitoring of diabetic patients taking selected antihypertensive agents such as enalapril.",1999.0,0,0
186,10494273,Ways to minimize adverse drug reactions. Individualized doses and common sense are key.,J S Cohen,"The great majority of adverse drug reactions are dose-related and occur in patients taking standard doses of medications. These facts suggest that for many patients, standard drug doses may be excessive. The principle of variability among individuals, which requires tailoring the dose to the patient, needs to be reasserted in clinical medicine to reduce the incidence of side effects. Physicians should obtain patients' histories of drug reactions and have at hand information on the full range of effective drug doses, including data on low doses gathered in prerelease and postrelease drug studies. Whenever possible, manufacturers should provide a range of doses and breakable tablets to facilitate flexible dosing.",2000.0,0,0
187,10495761,Therapy for cardiac failure: treatments old and new.,S V Pavia; A J Galbraith,,1999.0,0,0
188,10496190,Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group.,P Carson; S Ziesche; G Johnson; J N Cohn,"Heart failure in blacks has been associated with a poorer prognosis than in whites. In such diseases as hypertension, blacks show pathophysiological differences and respond differently to some therapies than whites. The aim of this study is to evaluate the clinical characteristics and response to therapy of black compared with white patients with heart failure. In the first Vasodilator-Heart Failure Trial (V-HeFT I), 180 black male patients were compared with 450 white male patients for baseline characteristics, prognosis, and response to therapy. In V-HeFT II, the same comparisons were made for 215 black and 574 white male patients, including an analysis stratified by the presence or absence of a history of hypertension. In both trials, black patients had a lower incidence of coronary artery disease, greater incidence of previous hypertension, and a greater cardiothoracic ratio (P < .05) than white patients. In V-HeFT II, plasma norepinephrine levels were significantly less in blacks; plasma renin activity was less only in blacks with a history of hypertension. Overall mortality or hospitalization for congestive heart failure did not differ between blacks and whites in the placebo group in V-HeFT I. However, the mortality of black patients receiving hydralazine plus isosorbide dinitrate (H-I) was reduced (P = .04) in V-HeFT I, whereas white patients showed no difference from placebo. In V-HeFT II, only white patients showed a mortality reduction from enalapril therapy compared with H-I therapy (P = .02). Whites also showed evidence of greater blood pressure reduction and enhanced regression of cardiac size in response to enalapril. When stratified by history of hypertension in V-HeFT II, only whites with a history of hypertension, who had greater renin levels, showed significant mortality reduction with enalapril compared with H-I therapy. Hospitalization rates did not differ between treatment groups in either study. Whites and blacks showed differences in cause, neurohormonal stimulation, and pharmacological response in heart failure. This retrospective analysis suggests angiotensin-converting enzyme inhibitors are particularly effective in whites, and the H-I combination can be equally effective in blacks. Prospective trials involving large numbers of black patients are needed to further clarify their response to therapy.",1999.0,0,0
189,10496201,Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators.,K Swedberg; M Pfeffer; C Granger; P Held; J McMurray; G Ohlin; B Olofsson; J Ostergren; S Yusuf,"Chronic heart failure (CHF) is an increasing burden to health care. Pharmacological treatment with angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalizations in patients with low left ventricular ejection fraction (LVEF). Despite these therapies, morbidity and mortality remains problematic. Furthermore, 30% to 50% of patients with CHF have a preserved LVEF. It is not known if treatments are of benefit in this group. Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure. Patients with systolic dysfunction, tolerant or intolerant to an ACE-inhibitor, and patients with preserved systolic function are included. Specifically, the CHARM program consists of 3 independent, parallel, placebo-controlled studies in patients with (1) LVEF less than or equal to 40%, ACE-inhibitor treated (n = 2,300); (2) LVEF less than or equal to 40%, ACE-inhibitor intolerant (n = 1,700); (3) LVEF greater than 40%, not treated with ACE inhibitors (n = 2,500). The 3 studies will be combined to evaluate the effect of candesartan cilexetil on all-cause mortality in the broad spectrum of symptomatic heart failure. The primary objective in each trial is to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization. Other endpoints include the effects on myocardial infarction, all-cause hospitalization, and resource utilization. CHARM is intended to randomize 6,500 patients with symptomatic heart failure from 26 countries in Europe, the United States, Canada, South Africa, and Australia. The CHARM program started to enroll patients in March 1999. The follow-up period is a minimum of 2 years. The study is expected to end in the third quarter of 2002.",1999.0,0,0
190,10496437,Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.,S Oparil; J H Levine; C A Zuschke; A H Gradman; E Ripley; D W Jones; J D Hardison; D J Cushing; R Prasad; E L Michelson,"The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.",1999.0,0,0
191,10498172,Captopril-induced toxic epidermal necrolysis and agranulocytosis successfully treated with granulocyte colony-stimulating factor.,R I Winfred; S Nanda; G Horvath; M Elnicki,"Captopril-induced bone marrow suppression is rare, except in certain high-risk patient populations. Severe exfoliative rashes have also been associated with captopril, but a combined presentation of toxic epidermal necrolysis and agranulocytosis has not been previously described. We report an unusual case of captopril-induced toxic epidermal necrolysis with agranulocytosis in a patient with no known risk factors. The bone marrow suppression was successfully treated using granulocyte colony-stimulating factor (G-CSF), and the white blood cell (WBC) count recovered within 3 days after starting therapy. This case underscores the early experience with captopril, which showed a strong correlation between high doses used to treat hypertension and bone marrow suppression.",1999.0,0,0
192,10501269,Blood pressure lowering for the primary and secondary prevention of stroke: treatment of hypertension reduces the risk of stroke.,A A O'Brien; C Rajkumar; C J Bulpitt,"Hypertension is the most important risk factor in the development of stroke. It is also the risk factor most amenable to treatment. The results from 18 controlled trials show a reduction in relative risk of stroke of 25-47% among treated hypertensive patients. This reduction applies both to the elderly and to younger patients, but the absolute reductions are greater among the elderly and the number of patients with hypertension that need to be treated to prevent a stroke is lower in the elderly because they have a higher risk of stroke. The reductions in relative but not absolute risk appear to be similar for both isolated systolic hypertension and combined systolic and diastolic hypertension in the elderly. The case for antihypertensive treatment in the secondary prevention of stroke is less clear but the results of four clinical trials of antihypertensive treatment among patients with and without hypertension and a history of cerebrovascular disease point to a probable benefit. The results of the PROGRESS trial will elucidate this further.",1999.0,0,0
193,10502210,Within-patient comparison of effects of different dosages of enalapril on functional capacity and neurohormone levels in patients with chronic heart failure.,H P Brunner-La Rocca; D Weilenmann; W Kiowski; F E Maly; R Candinas; F Follath,"Angiotensin-converting enzyme (ACE) inhibitors are established as first-line therapy in chronic heart failure (CHF). However, conflicting results exist regarding the dose-effect relation of ACE inhibitors. We investigated 45 patients (age 55 +/- 10 years) with stable CHF who presented with a maintenance dosage of enalapril of either 5 mg given twice daily (E10; n = 16), 10 mg given twice daily (E20; n = 18), or 20 mg given twice daily (E40; n = 11). This dosage was changed 3 times to treat all patients with lower, higher, and the initial dosages for 4 weeks each. Neurohormones (atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and norepinephrine) and enalaprilat trough levels were measured, and ergospirometry was performed. Changes in enalapril dose and enalaprilat level were concordant in 82% of patients, indicating good compliance. After augmentation of enalapril to 40 mg daily, patients in the E10 group showed an increase in maximal oxygen consumption and a decrease in neurohormonal stimulation, whereas the opposite changes were observed after reduction of enalapril to 10 mg daily in patients in the E20 and E40 groups (maximal oxygen consumption: Delta1.1 +/- 2.0 vs -1.0 +/- 1.9 mL. kg(-1). min(-1), P <.01; ANP: Delta-63 +/- 106 vs 19 +/- 54 pg/mL, P <.01; BNP: Delta-62 +/- 104 vs 18 +/- 89 pg/mL, P <.05; norepinephrine: Delta-1.3 +/- 2.9 vs 0.6 +/- 1.8, P <.05). Within-patient comparison showed that neurohormone levels were higher and exercise capacity lower while patients were receiving 10 mg of enalapril per day than when they were receiving 40 mg per day (ANP: 172 +/- 148 vs 139 +/- 122 pg/mL, P <.01; BNP: 193 +/- 244 vs 152 +/- 225 pg/mL, P <.005; norepinephrine: 4.2 +/- 2.2 vs 3.5 +/- 1. 6 nmol/L, P <.05; maximal oxygen consumption 22.0 +/- 4.4 vs 21.3 +/- 4.3 mL. kg(-1). min(-1) P <.05). Similar differences were observed when comparing these variables, and patients had lowest and highest enalaprilat trough levels. High doses of enalapril resulted in an improvement of exercise capacity and reduction of neurohumoral stimulation, whereas these parameters worsened after reduction of enalapril dose. Thus patients with congestive heart failure may benefit from increasing dosage of ACE inhibitors.",1999.0,0,0
194,10502535,Are there environmental forms of systemic autoimmune diseases?,E V Hess,A large number of drugs and an increasing number of environmental agents reportedly result in the appearance of a number of autoantibodies and in many instances in the appearance of a range of autoimmune clinical syndromes. The major disorders so recognized have marked resemblances to the autoimmune disease systemic lupus erythematosus. The commonly used term is drug-induced lupus; a better term is drug-related lupus. There is considerable interest at the present time in an increasing number of environmental agents. There have been two epidemics in recent years--one in Spain to a contaminant of rapeseed oil and one in the United States to a contaminant of l-tryptophan that caused an eosinophilic myositis. It is important for physicians and others involved in health care to recognize the potential associations of these diseases of unknown cause or causes.,2000.0,0,0
195,10503655,Etiology and mechanisms of drug-induced lupus.,R L Rubin,"Systemic rheumatic symptoms occur with widely different frequencies as a side effect of long-term therapy with some 39 medications currently in use. Because symptoms are nonspecific, subjective, and protean, diagnosis of drug-induced lupus (DIL) requires awareness of this risk of chronic medication. However, laboratory features and the characteristic of full recovery after discontinuing treatment are helpful in differentiating drug-induced from spontaneous lupus or other syndromes. Drug-induced lupus is probably mediated by reactive drug metabolites, not the ingested medications, and susceptibility to neutrophil-mediated oxidative transformation is a property of ten lupus-inducing drugs reported so far. Mechanisms for DIL modeled after drug hypersensitivity reactions are unsupported experimentally and inconsistent with the features of DIL. However, several new lines of investigation using mouse models have opened up promising leads into the origin of autoreactive T cells and disease development in DIL.",1999.0,0,0
196,10506854,"Effects of prostaglandin E1, dobutamine and placebo on hemodynamic, renal and neurohumoral variables in patients with advanced heart failure.",A Wimmer; B Stanek; L Kubecova; J Vitovec; J Spinar; N Yilmaz; T Kos; E Hartter; B Frey; R Pacher,"Excessive neurohumoral activity remains a major burden to the circulation of patients with advanced heart failure. Prostaglandin E1 (PGE1), a balanced i.v. vasodilator, was shown to elicit favorable hemodynamic and clinical effects in this cohort. A prospective randomized parallel group trial was performed to evaluate acute, intermediate and chronic changes in hemodynamic, neurohumoral and renal variables in response to PGE1, dobutamine and placebo. Thirty patients with class III and IV heart failure and low cardiac index (mean 1.9 l/min/m2) two hours after oral drugs including high dose enalapril were included. A 7-day-infusion of PGE1 (16.5 +/- 5 ng/kg/min, range 10 to 20 ng/kg/min, group A n = 10), dobutamine (4.5 +/- 1 micrograms/kg/min, range 2.5 to 5 micrograms/kg/min, group B n = 10) or placebo (saline, group C n = 10) was administered via a central venous access line after stepwise titration until intolerable side effects developed with PGE1 or a 20% increase in cardiac index occurred with dobutamine, which was continued on this dose throughout while PGE1 was maintained on 50% peak dose. Hemodynamic data were collected at baseline, at peak dosages, after 12 hours and after 7 days. Of neurohumoral variables plasma norepinephrine, big endothelin (Big ET) and atrial natriuretic peptide (ANP) were simultaneously evaluated using RIA methods. Renal plasma flow (by paraaminohippurate clearance) and glomerular filtration rate (by iothalamate clearance) was measured prior to and during the infusions (after 12 hours and after 7 days). At peak dose and at 12 hours significant drops from baseline of mean pulmonary artery pressure, pulmonary capillary wedge pressure and systemic vascular resistance were observed which were accompanied by a rise in cardiac output with both PGE1 and dobutamine. These changes were maintained through 7 days when pulmonary vascular resistance levels also fell with both active drugs. Blood pressure did not change throughout, but PGE1 increased heart rate slightly at 12 hrs. Both PGE1 and dobutamine enhanced renal plasma flow after 7 days, but only PGE1 decreased glomerular filtration fraction significantly. Glomerular filtration rate did not change with either drug. PGE1 decreased ANP levels at 12 hrs, and dobutamine increased big ET levels at peak, but decreased big ET at 7 days. Norepinephrine levels were unaffected throughout. Except a slight decrease in right atrial pressure after 7 days placebo did not change any measured variable significantly. Taken together, these data suggest that treatment with PGE1 is as efficacious as low-dose dobutamine in improving cardiac performance and renal perfusion in advanced heart failure. Of importance, no deleterious neurohumoral counterregulation was observed with PGE1.",1999.0,0,0
197,10507742,Antihypertensive treatment and CHD in the elderly.,K S Fink; A Ellsworth,,2000.0,0,0
198,10507744,Evaluation of asymptomatic microscopic hematuria in adults.,T R Thaller; L P Wang,"In patients without significant urologic symptoms, microscopic hematuria is occasionally detected on routine urinalysis. At present, routine screening of all adults for microscopic hematuria with dipstick testing is not recommended because of the intermittent occurrence of this finding and the low incidence of significant associated urologic disease. However, once asymptomatic microscopic hematuria is discovered, its cause should be investigated with a thorough medical history (including a review of current medications) and a focused physical examination. Laboratory and imaging studies, such as intravenous pyelography, renal ultrasonography or retrograde pyelography, may be required to determine the degree and location of the associated disease process. Cystourethroscopy is performed to complete the evaluation of the lower urinary tract. Microscopic hematuria associated with anticoagulation therapy is frequently precipitated by significant urologic pathology and therefore requires prompt evaluation.",1999.0,0,0
199,10507747,Angiotensin II receptor antagonists in the treatment of hypertension.,N M Kaplan,"The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) includes recommendations for the assessment of overall cardiovascular risk and the need for active antihypertensive drug therapy. Once the decision to initiate antihypertensive drug therapy has been made, JNC-VI recommends one of three paths for the choice of initial therapy: one path for patients with uncomplicated hypertension, another for those with well-defined indications for certain drugs and a third path for patients with various concomitant conditions in which one or another drug has favorable effects. At this time, the place for the newest class of antihypertensive drugs, the angiotensin II receptor antagonists, remains uncertain. Currently, they are considered reasonable alternatives for patients who have a compelling need for an angiotensin-converting enzyme (ACE) inhibitor but develop a cough while taking this medication. When data from ongoing trials become available, angiotensin II receptor antagonists may prove to be a good choice for initial therapy in many patients because of the favorable side effect profile of this class of drugs.",1999.0,0,0
200,10509550,Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy?,B Waeber; J M Detry; B Dahlöf; J G Puig; T Gundersen; J Hosie; W Januszewicz; C J Lindström; D Magometschnigg; M Safar; P Tanser; P Toutouzas,"The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo. Patients with uncomplicated essential hypertension (diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period) were randomly allocated to a double-blind, 12-week treatment with either a combination tablet of felodipine and metoprolol (Logimax), 5/50 mg daily (n = 321), enalapril, 10 mg daily (n = 321), or placebo (n = 304), with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed (diastolic blood pressure remaining >90 mm Hg). The combined felodipine-metoprolol treatment controlled blood pressure (diastolic < or =90 mm Hg 24 h after dose) in 72% of patients after 12 weeks, as compared with 49% for enalapril and 30% for placebo. A dose adjustment was required in 38% of patients receiving the combination, in 63% of patients allocated to placebo, and 61% of enalapril-treated patients. The overall incidence of adverse events was 54.5% during felodipine-metoprolol treatment; the corresponding values for enalapril and placebo were 51.7% and 47.4%, respectively. Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination, in 10 patients on enalapril, and 12 patients on placebo. No significant change in patients' well-being was observed in either of the three study groups. These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone. This improved efficacy is obtained without impairing the tolerability. The fixed-dose combination of felodipine and metoprolol, therefore, may become a valuable option to initiate antihypertensive treatment.",1999.0,0,0
201,10509552,Antihypertensive effect of the combination of fosinopril and HCTZ is resistant to interference by nonsteroidal antiinflammatory drugs.,V Thakur; M E Cook; J D Wallin,"Nonsteroidal antiinflammatory drugs (NSAID) are frequently reported to interfere with the blood pressure lowering actions of various antihypertensive medications. We studied 17 women with arthritis and hypertension who were receiving fosinopril and HCTZ, and administered sequentially in random order ibuprofen, sulindac, and nabumetone for 1 month each, with an intervening 2-week washout period between each treatment period. During the washout period, subjects received acetaminophen. Blood pressure at the end of 2 weeks of acetaminophen was compared with blood pressure after 1 month of treatment with each of the NSAID. Mean blood pressure was unchanged before and after all NSAID: 108 +/- 7 v 107 +/- 9 for nabumetone, 108 +/-9 v 108 +/- 9 for sulindac, and 108 +/- 8 v 107 +/- 9 for ibuprofen. The 24-h urinary sodium excretion was not significantly different. We conclude that the three NSAID did not neutralize the antihypertensive effect of the combination of fosinopril and HCTZ, and hence the blood pressure lowering action of the combination may not be prostaglandin dependent.",1999.0,0,0
202,10510149,Fosinopril/hydrochlorothiazide: single dose and steady-state pharmacokinetics and pharmacodynamics.,P O'Grady; K F Yee; R Lins; B Mangold,"Fosinoprilat, the active product of fosinopril, is eliminated by an hepatic pathway in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors (ACEIs). This study aimed to determine whether impaired renal function affects the pharmacokinetics and pharmacodynamics of a combination of fosinopril and hydrochlorothiazide (HCTZ). The study had a parallel-group design comparing patients with renal impairment and body-mass-index-matched normal controls. The study was done in a University clinic in 13 patients with renal impairment (mean creatinine clearance 55.7+/-15.6 ml min-1 1.73 m-2 ) and 13 age-, sex-, and body-mass-index-matched normal controls (mean creatinine clearance 102.4+/-8.9 ml min-1 1.73 m-2 ). All patients and normal controls received fosinopril sodium 20 mg and HCTZ 12.5 mg as a daily oral administration on days 1-5. Non-compartmental pharmacokinetic parameters of fosinoprilat and HCTZ were determined from blood and urine samples obtained over 48 h starting on Day 1 (single dose) and Day 5 (steady state): maximum serum concentration (Cmax ), time to maximum serum concentration (tmax ), area under the serum concentration-time curve during the dosing interval (AUC), cumulative urinary excretion (CUE) and the accumulation index (AI; ratio of AUC-day 5/AUC-day 1). Pharmacodynamic parameters were also measured over 24 h on day 1 and over 48 h on day 5: serum ACE activity and arterial blood pressure. Fosinoprilat pharmacokinetic parameters on day 1 in renally impaired vs normal patients: Cmax=387+/-0.19 vs 324+/-0.25 ng ml-1 (P=0.07); tmax=3.5 vs 3.0 h (P=0.58); AUC=3510+/-0.29 vs 2701+/-0.35 ng ml-1 h (P=0. 072); CUE=5.08+/-2.70 vs 7.40+/-2.56% (P=0.009). Fosinoprilat parameters on day 5: Cmax=517+/-0.40 vs 357+/-0.19 ng ml-1 (P=0. 007); tmax=3.0 vs 3.0 h (P >0.99); AUC=4098+/-0.43 vs 2872+/-0.30 ng ml-1 h (P=0.027); CUE=6.81+/-3.53 vs 8.10+/-2.80% (P=0.068). AI=1. 17+/-0.33 vs 1.06+/-0.23 (P=0.29). In both groups ACE inhibition and blood pressure response were similar over 24 h and slightly greater 48 h after last dosing. In renally impaired subjects fosinopril and HCTZ can be coadministered without undue increases in fosinoprilat concentrations or any clinically significant pharmacodynamic effects. This is probably due to the dual excretory pathways for fosinoprilat.",1999.0,0,0
203,10512511,Penile angioedema possibly related to lisinopril.,E B Henson; D T Bess; L Abraham; J P Bracikowski,,1999.0,0,0
204,10513043,Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room.,M Gus; A G Andrighetto; V R Balle; M B Pilla,"To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.",1999.0,0,0
205,10515442,Difference in the incidence of cough induced by angiotensin converting enzyme inhibitors: a comparative study using imidapril hydrochloride and enalapril maleate.,T Saruta; K Arakawa; O Iimura; K Abe; H Matsuoka; T Nakano; M Nakagawa; T Ogihara; G Kajiyama; K Hiwada; M Fujishima; M Nakajima,"To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12 wk (Period I) followed by enalapril for 12 wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p < 0.001). During Period I, decrease in blood pressure was observed in 63.9% (115/180) of Group IE and 64.6% (115/178) of Group EI patients. In approximately half of the patients in Group EI who developed cough during Period I and in whom the treatment was subsequently switched to imidapril, cough subsequently disappeared. It was concluded that the incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects of the two ACE inhibitors.",1999.0,0,1
206,10516413,The cost-effectiveness of losartan versus captopril in patients with symptomatic heart failure.,E J Dasbach; M W Rich; R Segal; W C Gerth; G W Carides; J R Cook; J F Murray; D B Snavely; B Pitt,"The Losartan Heart Failure ELITE Study recently found that in patients with symptomatic heart failure and a left ventricular ejection fraction of </=0.40, losartan compared to captopril improved survival with better tolerability. The objective of this study was to perform an economic evaluation of losartan versus captopril based on the results of the Losartan Heart Failure ELITE Study. The Losartan Heart Failure ELITE Study was a multinational, double-blind, randomized 48-week study comparing the safety and efficacy of losartan to captopril in angiotensin-converting enzyme-inhibitor-naive patients >/=65 years with symptomatic heart failure. Data on health care resource utilization were collected as part of the trial. We conducted a cost-effectiveness analysis to estimate the lifetime benefits of treatment and the associated costs. We observed no differences between treatments in the number of hospitalizations, hospital days, and emergency room visits per patient over the trial period. We estimated the total cost of losartan to be USD 54 (95% CI: USD -1,717, USD 1,755) less per patient than captopril over this time frame. We also estimated that over the projected remaining lifetime of the study population, losartan compared to captopril would increase survival by 0.20 years (undiscounted) at an average cost of USD 769 (discounted) more per patient. This cost increase translated into a cost-effectiveness ratio of USD 4,047 per year of life gained for losartan relative to captopril. In patients with symptomatic heart failure, losartan compared to captopril increased survival with better tolerability at a cost well within the range accepted as cost-effective.",1999.0,0,1
207,10516734,ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.,J Mallion; J Siche; Y Lacourcière,"The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and </=114 mm Hg, clinic systolic blood pressure (SBP) >/=140 and </=200 mm Hg, and 24-h ambulatory DBP >/=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.",1999.0,0,0
208,10516744,Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction.,K Ray; S Dorman; R Watson,We report two cases of hyperkalaemia related to the use of the salt substitute 'Lo Salt' in hypertensive patients on treatment with ACE inhibitors. In each case serum potassium returned to the normal range after cessation of the salt substitute. Without vigilance the contribution of the salt substitute to hyperkalaemia would have been overlooked and an ACE inhibitor erroneously withdrawn.,1999.0,0,0
209,10516865,Verapamil in acute myocardial infarction. The rationales of the VAMI and DAVIT III trials.,C M Jespersen,"Verapamil is well tolerated in patients with stable and unstable angina pectoris, as well as in patients with threatened infarction. No data exist documenting verapamil to be inferior to beta-blockers in these stages of coronary heart diseases. In the prethrombolytic era i.v. intervention with verapamil did not add any benefit in the early phase of AMI. However, a retrospective analysis suggests the hypothesis that i.v. verapamil given in combination with thrombolysis may improve the prognosis, and an ongoing study (VAMI trial) examines this hypothesis. When given in the late in-hospital phase of AMI to patients without heart failure verapamil significantly reduces mortality and morbidity. When given in the late in-hospital phase to patients with heart failure verapamil did not cause the course or prognosis to deteriorate and might even improve it in patients with residual ischaemia, especially when given in combination with an ACE-inhibitors. A planned study (DAVIT III study) has to confirm these preliminary data.",1999.0,0,0
210,10520779,Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction.,H Soejima; H Ogawa; H Yasue; K Kaikita; K Takazoe; K Nishiyama; K Misumi; S Miyamoto; M Yoshimura; K Kugiyama; S Nakamura; I Tsuji,"We investigated the effects of enalapril therapy on plasma tissue factor (TF), tissue factor pathway inhibitor (TFPI) and monocyte chemoattractant protein-1 (MCP-1) levels in patients with acute myocardial infarction. Macrophages express TF in human coronary atherosclerotic plaques. Both TF and TFPI are major regulators of coagulation and thrombosis. Monocyte chemoattractant protein-1 is a monocyte and macrophage chemotactic and activating factor. In a randomized, double-blind, placebo-controlled study beginning about two weeks after myocardial infarction, 16 patients received four weeks of placebo (placebo group) and another 16 patients received four weeks of enalapril 5 mg daily therapy (enalapril group). We performed blood sampling after administration of the doses. There were no significant differences in the serum angiotensin-converting enzyme (ACE) activity, plasma TF, free TFPI or MCP-1 levels before administration between the enalapril and placebo groups. In the enalapril group, ACE activity (IU/liter) (14.0 before, 5.2 on day 3, 5.8 on day 7, 6.3 on day 28), TF levels (pg/ml) (223, 203, 182, 178) and MCP-1 levels (pg/ml) (919, 789, 790, 803) significantly decreased by day 28. However, the free TFPI levels (ng/ml) (28.2, 26.5, 26.8, 28.4) did not change. These four variables were unchanged during the study period in the placebo group. This study demonstrated that administration of enalapril reduces the increased procoagulant activity in patients with myocardial infarction associated with inhibition of the activation and accumulation of macrophages and monocytes.",1999.0,0,0
211,10521887,Depressogenic medication as an aetiological factor in major depression: an analysis in a clinical population of depressed elderly people.,T Dhondt; P Derksen; C Hooijer; B Van Heycop Ten Ham; P P Van Gent; T Heeren,"To study the role of depressogenic medication in the aetiology of major depression in the elderly. Depression can be caused, provoked or sustained by drugs prescribed for other reasons. The evidence for this statement is based on case-reports, not on investigations in relevant populations. In the geriatric wards of three Dutch psychiatric hospitals, 195 patients with a DSM-III-R diagnosis of major depression (MDD) were studied. In the first week after admission the following data were recorded: age, gender, personal psychiatric history, family psychiatric history, Montgomery-Asberg Depression Rating Scale, Mini-Mental State Examination, history of stroke, use of medication and number of different medications used. Subjects using depressogenic medication were contrasted with subjects not using depressogenic medication on all variables. There was a significant negative relationship, adjusted for the other variables, between the use of depressogenic medication and a previous admission for depression. No other significant relationships between the use of depressogenic medication and aetiological variables were found. Patients with a first-time admission for MDD use depressogenic medication 2.44 times more often than patients with previous admissions for depression. The use of depressogenic medication is an independent and clinically relevant aetiological factor in MDD.",1999.0,0,0
212,10535718,Daytime-selective antihypertensive activity of celiprolol.,T J Cleophas; J van der Meulen; L van de Luit; A H Zwinderman,"Day-activity rhythms of heart rate and blood pressure are thought to be mediated mainly through the sympathetic nervous system and may have greater amplitudes in patients with hypertension owing to increased daytime and largely normal nighttime values. Drug-induced nighttime hypotension in patients with chronic hypertension has been associated with the precipitation of cardiac failure and a fall in cerebral flow. The authors examined the effects of a single dose and of a 4-week treatment with different classes of antihypertensive drugs on ambulatory blood pressure (ABP) in 10 patients with mild hypertension. Data were assessed by polynomial analysis (Harvard Graphics 3). A single oral dose of enalapril 10 mg, amlodipine 5 mg, carvedilol 25 mg, and celiprolol 200 mg produced a mean reduction of 24-hour ABP compared to placebo of, respectively, 24/11, 11/5, 13/6, and 12/5 mm Hg (p values between <0.02 and <0.001). With enalapril, amlodipine, and carvedilol, between-subject variability contributed significantly to the overall variability in the measurements (p values between 0.05 and 0.01 versus zero), whereas with celiprolol this was not so. Although the beta blockers reduced daytime blood pressures similarly to the ACE inhibitor or the calcium channel blocker, they did not reduce nighttime blood pressures. These results were confirmed by an 8-week crossover trial comparing enalapril 10 mg daily with celiprolol 200 mg daily in the same group of patients. The authors conclude (1) that beta blockers produce a more stable reduction of blood pressure in patients with mild hypertension less affected by pressor effects through the sympathetic nervous system; (2) that beta blockers, unlike ACE inhibitors and calcium channel blockers, do not give rise to nighttime hypotension in this category of patients; and (3) that the selective beta blocker celiprolol may even perform better in these respects than the nonselective beta blocker carvedilol.",1999.0,0,0
213,10535720,Pharmacogenetic analysis of the effect of angiotensin-converting enzyme inhibitor on restenosis after percutaneous transluminal coronary angioplasty.,A Okamura; M Ohishi; H Rakugi; T Katsuya; Y Yanagitani; S Takiuchi; Y Taniyama; K Moriguchi; H Ito; Y Higashino; K Fujii; J Higaki; T Ogihara,"Angiotensin-converting enzyme (ACE) inhibitors are reported to prevent neointimal formation after balloon injury in animal models, but in most prospective studies in humans, ACE inhibitors failed to prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA). The ACE genotype assigned by an insertion/deletion (I/D) polymorphism is known to affect the potency of ACE inhibitors in several renal diseases. The authors attempted to clarify whether the effect of ACE inhibitors on restenosis might be modified by the ACE genotype. A total of 126 patients was randomly and prospectively assigned to the control group and the imidapril group. In the imidapril group, patients received 5 mg imidapril daily, starting 1 day before PTCA and continuing for 3 to 6 months. Forty-six control (65 vessels) and 32 imidapril patients (43 vessels) completed the study. The minimal lumen diameter before and after the procedure did not differ significantly among the groups with the three genotypes (II, ID, and DD) in both the control and imidapril groups. Late luminal loss during the follow-up period was not related to the ACE genotype in the control group but was significantly related in the imidapril group (II, 0.63+/- 0.19 mm; ID + DD, 1.12+/-0.14 mm, p<0.05). Furthermore, in the II genotype, imidapril significantly reduced late loss and restenosis rate as defined by most of the frequently used definitions. In conclusion the ACE I/D polymorphism may influence the effect of ACE inhibitors in preventing restenosis after PTCA.",1999.0,0,0
214,10539807,Concern for azotemia with angiotensin-converting enzyme inhibitors: public health implications and clinical relevance.,B A Bart,,1999.0,0,0
215,10539815,Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD),E L Knight; R J Glynn; K M McIntyre; H Mogun; J Avorn,"Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.",1999.0,0,1
216,10543928,ACE inhibition with ramipril improves left ventricular function at rest and post exercise in patients with stable ischaemic heart disease and preserved left ventricular systolic function.,R Willenheimer; E Rydberg; L Oberg; S Juul-Möller; L Erhardt,"To assess the effects of 6 months intervention with +ramipril on resting and post exercise left ventricular function in patients with stable ischaemic heart disease and preserved left ventricular systolic function. Patients (n=98, age 65+/-9 years, 37% women) were randomized to double-blind treatment with ramipril 5 mg. day(-1)(n=32), ramipril 1.25 mg. day(-1)(n=34), or placebo (n=32). Resting and post maximum exercise echocardiography/Doppler examinations were performed at baseline and after 6 months. Changes over 6 months in resting transmitral E-wave deceleration time (Edt) and Edt adjusted for heart rate (Edt/RR) differed between the ramipril 5 mg, ramipril 1.25 mg, and placebo groups: Edt 24+/-82, -1+/-69, and -29+/-64 ms, respectively, P=0. 012; Edt/RR 30+/-105, 2+/-61, and -28+/-69 ms, respectively, P=0.015. Changes in the difference between resting and post exercise Edt/RR also varied between groups: -53+/-137, -28+/-118, and 35+/-101 ms, respectively, P=0.029. No differences in E/A indices were noted. Resting atrioventricular plane displacement improved in the combined ramipril groups vs the placebo group: 0.2+/-0.8 vs -0.2+/-1.3 mm, P<0.05.Conclusion Six months ramipril treatment in patients with stable ischaemic heart disease and preserved left ventricular systolic function improved resting left ventricular function and reduced the exercise induced diastolic filling abnormalities usually seen in these patients.",1999.0,0,0
217,10547180,Drug-associated agranulocytosis: experience at Strasbourg Teaching Hospital.,A Emmanuel; F Maloisel,,1999.0,0,0
218,10551431,"How to use calcium antagonists in hypertension: putting the JNC-VI guidelines into practice. Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure.",V Singh; J Christiana; W H Frishman,"The prevention and treatment of hypertension remain as major challenges for clinicians all over the world. The recently published Sixth Report of the Joint National Committee for the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-VI) uses evidence-based medicine in providing guidelines to aid clinicians in the prevention, detection and treatment of high blood pressure, including pharmacological approaches. Calcium antagonists are used widely for the treatment of hypertension, and JNC-VI focuses on specific situations where calcium antagonists could be considered as preferred treatments. There are a large number of calcium antagonists available, with a variety of pharmacodynamic and pharmacokinetic actions. Several sustained-release formulations of these drugs are also available. In terms of blood pressure control, calcium antagonists are more effective as antihypertensive treatments than beta-blockers, ACE inhibitors and angiotensin II receptor blockers in Black patients. The dihydropyridine calcium antagonists have been shown to reduce morbidity and mortality in elderly patients with isolated systolic hypertension. The rate-lowering calcium antagonists can be used as alternatives to beta-blockers in patients with coronary artery disease and hypertension. Calcium antagonists can be used as alternatives to ACE inhibitors in patients with hypertension and concomitant diabetes mellitus and/or renal disease. Some dihydropyridine calcium antagonists may be useful as alternatives to ACE inhibitors in patients with hypertension and systolic heart failure. Calcium antagonists appear to be extremely useful in patients with cyclosporin-induced hypertension, and in patients with hypertension and concomitant Raynaud's phenomenon and/or migraine. The rate-lowering agents can be used in patients with atrial tachyarrhythmias and hypertension. Clinicians should be aware of drug-drug interactions involving calcium antagonists, especially after the recent problems with mibefradil. Although retrospective studies have caused controversy regarding the safety of calcium antagonists in patients with hypertension, recent prospective studies have revealed no major safety concerns with these drugs.",1999.0,0,0
219,10558453,Antihypertensive drugs: diuretics and betablockers are the best assessed.,,"(1) In trials involving hypertensive non diabetic patients under 65, some diuretics and betablockers have prevented strokes, without conferring protection from coronary events or death.  In one trial captopril had an effect comparable to that of diuretics or betablockers in terms of overall cardiovascular prevention, but was a little less effective in preventing strokes.  (2) In trials involving hypertensive subjects over 65, some diuretics and betablockers have reduced the risk of stroke, coronary events, heart failure, and death.  In one trial a diuretic was superior to a betablocker in terms of preventive efficacy and adverse effects.  Nitrendipine, in combination with other antihypertensive drugs, prevented strokes in one trial.  (3) In a trial involving hypertensive diabetic patients, captopril and atenolol reduced the risk of stroke, heart failure and worsening of retinal disease, without preventing coronary events or death.  In two trials coronary events were more frequent on dihydropyridine than on an angiotensin-coverting-enzyme (ACE) inhibitor.  (4) In one trial a diuretic reduced the risk of relapse after stroke, even in patients without severe hypertension.",1999.0,0,0
220,10561135,Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group.,J B Lewis; T Berl; R P Bain; R D Rohde; E J Lewis,"Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.",1999.0,0,1
221,10561136,Captopril-induced reduction of serum levels of transforming growth factor-beta1 correlates with long-term renoprotection in insulin-dependent diabetic patients.,K Sharma; B O Eltayeb; T A McGowan; S R Dunn; B Alzahabi; R Rohde; F N Ziyadeh; E J Lewis,"The renoprotective effect of captopril on progression of diabetic nephropathy was demonstrated by the Collaborative Study Group Captopril Trial and might be independent of blood pressure. Because angiotensin II is known to stimulate the prosclerotic cytokine, transforming growth factor-beta (TGF-beta), we postulated that the renoprotective effect may be due to inhibition of TGF-beta1 production. TGF-beta1 levels were measured in serum at baseline and 6 months from patients in the captopril trial. TGF-beta1 analyses were performed on all available patient sera. Analysis was performed between the percent change in TGF-beta1 levels during the first 6 months versus the percent change in glomerular filtration rate (GFR) in the subsequent 2 years. TGF-beta1 levels increased by 11% (P = 0. 003) in the placebo group (n = 24), whereas there was a decrease of 14% (P = 0.01) in the captopril group (n = 34). There was an inverse correlation between the percent change in TGF-beta1 levels during the first 6 months and the percent change in GFR over the ensuing 2-year period in patients from both the placebo (r = -0.55, P = 0. 005) and captopril groups (r = -0.45, P = 0.008). In patients with initial GFR below 75 mL/min, there was an even stronger correlation in percent change in TGF-beta1 levels and percent change in GFR in both placebo (n = 9, r = -0.69, P = 0.03) and captopril groups (n = 21, r = -0.73, P = 0.0001). Our data suggest that captopril decreases TGF-beta1 levels in diabetic nephropathy and that changes in TGF-beta1 levels may predict the course of diabetic nephropathy.",1999.0,0,0
222,10563064,Is trough:peak ratio a guide to clinical efficacy?,E B Wu; A Ferro; J B Chambers,,1999.0,0,0
223,10563070,A comparison of valsartan and captopril in patients with essential hypertension in Indonesia.,P Prabowo; A Arwanto; D Soemantri; E Sukandar; H Suprihadi; I Parsudi; M S Markum; P Kabo; R Atmoko; W Prodjosudjadi,"Adult Indonesian outpatients were randomised to receive either valsartan 80 mg once daily or captopril 25 mg twice daily for 8 weeks. The main criterion for tolerability was the incidence of adverse events. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to endpoint. No valsartan patients experienced dry cough, which was reported by 22 captopril patients (21.6%). Both drugs reduced mean SDBP and SSBP, with a trend in favour of valsartan. The percentage of valsartan patients whose BP normalised was higher than in captopril patients at week 4 (37% and 22%) and week 8 (45% and 34%), the difference being statistically significant at week 4 (p < 0.05). Valsartan 80 mg once daily is as effective as captopril 25 mg twice daily in reducing blood pressure in Indonesian patients, and has a better tolerability profile in respect of dry cough.",1999.0,0,0
224,10563072,Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring.,K Yusoff; T A Razak; N Yusof; N M Rafee,"ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run-in, double blind, crossover study, using 24-hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4-8 mg and enalapril 10-20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo-corrected peak (P) reduction of blood pressure (BP) of -6.4 +/- 1.3 mmHg vs its placebo-corrected trough (T) of -5.2 +/- 1.7 mmHg. Enalapril had a reduction in DBP of -8.5 +/- 1.3 mmHg (P) and -5.7 +/- 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of -7.5 +/- 1.6 mmHg (P) vs -7.3 +/- 2.2 mmHg (T) compared to enalapril with -10.8 +/- 1.6 mmHg (P) vs -8.3 +/- 2.3 mmHg (T). Placebo-corrected trough-to-peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24-hour mean BP, area under the curve or post-dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24-hour cover for the patient without excessive peak effect or poor trough effect.",1999.0,0,0
225,10569324,Effect of quinapril or metoprolol on circadian sympathetic and parasympathetic modulation after acute myocardial infarction.,A G Kontopoulos; V G Athyros; A A Papageorgiou; H Boudoulas,"Abnormal autonomic nervous system impairment in patients with acute myocardial infarction (AMI) has a circadian pattern with the greatest manifestation in the morning hours; it probably plays an important role in the pathogenesis of cardiac arrhythmias and acute ischemic syndromes. Angiotensin-converting enzyme inhibitors improve autonomic function in patients with AMI, but the circadian pattern of this effect has not been studied. Heart rate variability-normalized frequency domain indexes were assessed 5 days (baseline) after the onset of uncomplicated AMI and 30 days after therapy with quinapril (n = 30), metoprolol (n = 30), or placebo (n = 30) with a solid-state digital Holter monitor. Normal subjects (n = 30) were used as controls. Quinapril increased parasympathetic and decreased sympathetic modulation, and improved sympathovagal interactions manifested by an increase in normalized high-frequency power (HFP), and a decrease in normalized low-frequency power (LFP), and their ratio (LFP/HFP) during the entire 24-hour period (p<0.001), with maximal effect on the ratio (p<0.0001) between 02.00 to 04.00 A.M., 08.00 to 11.00 A.M., and 19.00 to 22.00 P.M. (delta% ratio -30%, -32%, and -26%, respectively). Metoprolol increased HFP and decreased LFP and the LFP/HFP ratio mainly between 08.00 A.M. to 12.00 noon, and 19.00 to 22.00 P.M. (delta% ratio -21%, and -12% respectively, p<0.001). Heart rate variability indexes in the placebo group and controls remained unchanged 30 days after the baseline study. In conclusion, quinapril increased parasympathetic, and decreased sympathetic and partially restored sympathovagal interaction in patients with uncomplicated AMI during the entire 24-hour period, with peak effect in the early and late morning and evening hours. Metoprolol had a similar effect during the late morning and evening hours, but at a lower level. These effects may prove beneficial in reducing cardiac arrhythmias and acute ischemic syndromes in past-AMI patients.",1999.0,0,0
226,10569660,Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure.,M Guazzi; P Palermo; G Pontone; F Susini; P Agostoni,"Oxygen consumption at peak exercise (peak VO2) is a strong independent predictor of the outcome in congestive heart failure (CHF). Renin-angiotensin system inhibition with either ACE or AT1 receptor blockers is effective on peak VO2. We evaluated whether mechanisms are similar for the 2 categories of drugs and whether their combination is able to produce a synergistic effect. Twenty CHF patients were randomized to receive, in a double-blind fashion, placebo + placebo (P+P), enalapril (20 mg/day) + placebo (E+P), losartan (50 mg/day) + placebo (L+P), and enalapril + losartan (E+L) or the same preparations in a reverse order, each for 8 weeks. Two patients did not complete the trial. Pulmonary function, cardiopulmonary exercise test, plasma neurohormones, and quality of life were assessed at the end of each treatment. Compared with P+P, E+P, and L+P similarly (16% and 15%, respectively) and significantly (p <0.01) augmented peak VO2. Enalapril improved lung function (reduced slope of ventilation vs carbon dioxide production and dead space to tidal volume ratio, and increased alveolar membrane conductance and tidal volume). Losartan likely activated the exercising muscle perfusion (raised delta VO2/delta work rate, which is a measure of aerobic work efficiency). In combination, they further increased peak VO2, 10% from E+P (p <0.05) and 11% from L+P (p <0.05). Compared with run-in, E+P and L+P significantly reduced plasma norepinephrine by 70 +/- 14 pg/ml and 100 +/- 16 pg/ml and aldosterone by 1.6 +/- 0.7 ng/dl and 1.6 +/- 0.8 ng/dl. These changes were significantly greater when the drugs were combined (140 +/- 20 pg/ml for norepinephrine, and 5.6 +/- 0.9 ng/dl for aldosterone). Quality-of-life score did not improve significantly at each treatment step. Thus, lorsartan and enalapril similarly increased peak VO2 in CHF patients, but mediators of this effect were, at least in part, different therapeutic targets that may be synergistic when the 2 drugs are combined.",1999.0,0,0
227,10569679,Is captopril useful in decreasing pleural drainage in children after modified Fontan operation?,N Heragu; L Mahony,We performed a retrospective cohort study to assess the relation between administration of angiotensin-converting enzyme inhibitors and duration of pleural drainage in the early postoperative period in patients who underwent a modified Fontan operation at our institution from 1990 through 1996. This study failed to show that administration of captopril decreased the duration of pleural drainage in patients after a modified Fontan operation.,1999.0,0,0
228,10576791,Blood pressure and renin angiotensin system responses to initiation of treatment with captopril or losartan in heart failure.,I B Squire; S Robb; G Brennan; K P O'Kane; H J Dargie; J L Reid,,1999.0,0,0
229,10577103,Association between actinic keratoses and potentially photosensitizing drugs.,M Placzek; B Eberlein-König; B Przybilla,,1999.0,0,0
230,10577635,Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study.,L Hansson; L H Lindholm; T Ekbom; B Dahlöf; J Lanke; B Scherstén; P O Wester; T Hedner; U de Faire,"The efficacy of new antihypertensive drugs has been questioned. We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients. We did a prospective, randomised trial in 6614 patients aged 70-84 years with hypertension (blood pressure > or = 180 mm Hg systolic, > or = 105 mm Hg diastolic, or both). Patients were randomly assigned conventional antihypertensive drugs (atenolol 50 mg, metoprolol 100 mg, pindolol 5 mg, or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily) or newer drugs (enalapril 10 mg or lisinopril 10 mg, or felodipine 2.5 mg or isradipine 2-5 mg daily). We assessed fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease. Analysis was by intention to treat. Blood pressure was decreased similarly in all treatment groups. The primary combined endpoint of fatal stroke, fatal myocardial infarction, and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group (19.8 events per 1000 patient-years) and in 438 of 4401 in the newer drugs group (19.8 per 1000; relative risk 0.99 [95% CI 0.84-1.16], p=0.89). The combined endpoint of fatal and non-fatal stroke, fatal and non-fatal myocardial infarction, and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs (0.96 [0.86-1.08], p=0.49). Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events. Decrease in blood pressure was of major importance for the prevention of cardiovascular events.",2000.0,0,0
231,10577651,ACE inhibitors still the drug of choice for heart failure--and more.,E Topol,,1999.0,0,0
232,10578225,Effectiveness and metabolic effects of perindopril and diuretics combination in primary hypertension.,M S Elisaf; J Theodorou; H Pappas; N Papagalanis; K Katopodis; R Kalaitzidis; K C Siamopoulos,"The effectiveness as well as the metabolic effects of the combination of diuretics [hydrochlorothiazide (HCT) vs indapamide (IND)] and perindopril (P) in 14 patients (7 male, 7 female) aged 37-62 years with mild idiopathic hypertension were studied. Following a 4-week wash-out period and a 4-week period of monotherapy with P (4 mg/daily), IND (2.5 mg/daily) or HCT (25 mg/daily) was added for 4 weeks. Selection of the diuretic agent was random. Following a 4-week wash-out period from the diuretic, in which only P was given, the alternative diuretic was administered for another period of 4 weeks. P decreased blood pressure levels significantly. However, the drug was more efficacious in patients with higher plasma renin activity (PRA). Combination treatment induced an additional decrease in the blood pressure levels, mainly in patients with lower PRA. The combination of P + HCT was more effective than the combination P + IND. The addition of either HCT or IND evoked a small but statistically significant increase in serum glucose levels while fasting as well as during the 75 g oral glucose challenge. However, insulin levels did not change significantly during the study. Small but not statistically significant changes in serum electrolytes and lipid parameters were observed during the various phases of the study, while a statistically significant increase in the serum uric acid was noticed when the combination P + HCT was given. We conclude: (1) P in small doses is an effective and safe antihypertensive agent, (2) PRA has a predictive value in determining the effectiveness of P treatment, (3) the combination of P with small doses of HCT or IND is more efficacious than P alone, (4) the combination treatment has adverse effects in the carbohydrate tolerance, while there are not significant changes in serum electrolyte and lipid parameters.",1999.0,0,0
233,10583036,,,,,0,0
234,10583137,Bullous pemphigoid induced by fluoxetine.,S Rault; C Grosieux-Dauger; S Verraes; K Bernardeau; A Durlach; P Bernard,,2000.0,0,0
235,10583451,Capillary permeability is increased in normo- and microalbuminuric type 1 diabetic patients: amelioration by ACE-inhibition.,P H Oomen; J Jager; K Hoogenberg; R P Dullaart; W D Reitsma; A J Smit,"Capillary leakage of sodium-fluorescein (NaF) in the skin reflects capillary permeability and may be a marker of diabetes-associated microcirculatory abnormalities. We evaluated transcapillary skin NaF leakage by fluorescence videodensitometry in 10 normoalbuminuric, 10 microalbuminuric Type 1 diabetic men (diabetes duration > 10 years) and 10 healthy subjects. The microalbuminuric patients were restudied after 6 weeks treatment with the ACE-inhibitor enalapril, 10 mg once daily. All measurements were performed at a blood glucose level of 5 mmol L-1. Transcapillary NaF leakage was strongly increased in normoalbuminuric Type 1 diabetic patients compared to healthy subjects (P < 0.001) and was still further increased in microalbuminuric Type 1 diabetic patients (P < 0.01 compared to normoalbuminuric patients). Enalapril reduced NaF leakage (P < 0.05), mean arterial blood pressure (P < 0.05) and microalbuminuria (P < 0. 05). After treatment, NaF leakage was not different from that in normoalbuminuric patients. Capillary permeability, as determined by NaF leakage, is elevated in normoalbuminuric Type 1 diabetic patients with long-standing disease, and the excess elevation in microalbuminuric Type 1 diabetic patients is ameliorated by ACE-inhibition. Skin NaF videodensitometry seems a useful tool to document capillary permeability in intervention studies.",1999.0,0,0
236,10583613,Linear IgA bullous dermatosis.,C A Egan; J J Zone,,1999.0,0,0
237,10585130,"Angiotensin-II, renal anemia and hyporesponsiveness to recombinant human erythropoietin.",H Schiffl; A Bergner,,1999.0,0,0
238,10587334,"Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group.",M Packer; P A Poole-Wilson; P W Armstrong; J G Cleland; J D Horowitz; B M Massie; L Rydén; K Thygesen; B F Uretsky,"Angiotensin-converting enzyme (ACE) inhibitors are generally prescribed by physicians in doses lower than the large doses that have been shown to reduce morbidity and mortality in patients with heart failure. It is unclear, however, if low doses and high doses of ACE inhibitors have similar benefits. We randomly assigned 3164 patients with New York Heart Association class II to IV heart failure and an ejection fraction < or = 30% to double-blind treatment with either low doses (2.5 to 5.0 mg daily, n=1596) or high doses (32.5 to 35 mg daily, n=1568) of the ACE inhibitor, lisinopril, for 39 to 58 months, while background therapy for heart failure was continued. When compared with the low-dose group, patients in the high-dose group had a nonsignificant 8% lower risk of death (P=0.128) but a significant 12% lower risk of death or hospitalization for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002). Dizziness and renal insufficiency was observed more frequently in the high-dose group, but the 2 groups were similar in the number of patients requiring discontinuation of the study medication. Conclusions-These findings indicate that patients with heart failure should not generally be maintained on very low doses of an ACE inhibitor (unless these are the only doses that can be tolerated) and suggest that the difference in efficacy between intermediate and high doses of an ACE inhibitor (if any) is likely to be very small.",1999.0,0,0
239,10588224,Effect of high- versus low-dose angiotensin converting enzyme inhibition on cytokine levels in chronic heart failure.,L Gullestad; P Aukrust; T Ueland; T Espevik; G Yee; R Vagelos; S S Frøland; M Fowler,"We examined the effect of long-term treatment with two doses of the angiotensin converting enzyme (ACE) inhibitor enalapril on various immunological variables in patients with chronic congestive heart failure (CHF). Immunological mediators are increasingly recognized to play a pathogenic role in the pathophysiology of CHF. Whether ACE inhibitor therapy modifies immunological variables has not previously been investigated. Seventy-five patients (mean age 52 +/- 11 years) with CHF were randomized between low-(5 m g daily) and high-dose (40 mg daily) enalapril in a double-blind trial. Circulating levels of immunological parameters (i.e., proinflammatory cytokines, chemokines and adhesion molecules) were measured at baseline, at 10 weeks and at the end of the study (34 weeks). All immunological parameters, except soluble interleukin (IL)-6 receptor, were increased in CHF compared with 21 healthy controls. During the study immunoreactive IL-6 levels decreased (p < 0.05) and soluble IL-6 receptor increased (p < 0.05) during high-dose but not during low-dose enalapril therapy. Furthermore, IL-6 bioactivity decreased only during the high-dose (p < 0.001), resulting in a significant difference in change during treatment between the two dosage groups (p < 0.001). This decrease in IL-6 bioactivity was significantly associated with decreased interventricular septum thickness as assessed by echocardiography (r = 0.56, p = 0.013). No other variables changed during treatment. In patients with severe CHF, high-dose enalapril therapy is associated with a significant decrease in IL-6 activity. However, despite treatment with a high-dose ACE inhibitor, a persistent immune activation exists in these patients which may be of importance for the progression of CHF.",1999.0,0,0
240,10588226,Nonadherence with angiotensin-converting enzyme inhibitor therapy: a comparison of different ways of measuring it in patients with chronic heart failure.,A D Struthers; R MacFadyen; C Fraser; J Robson; J J Morton; C Junot; E Ezan,"This study was designed to compare different proposed methods of assessing adherence with angiotensin-converting enzyme (ACE) inhibitor (ACEI) therapy in chronic heart failure. The use of ACEIs in chronic heart failure gives us a unique opportunity to assess a patient's adherence by measuring whether the expected biochemical effect of an ACEI is present in the patient's bloodstream. In fact, there are several different ways of assessing ACE in vivo: these are serum ACE activity itself, plasma N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), urine AcSDKP, plasma angiotensin I (AI), plasma angiotensin II (AII), or the AII/AI ratio. Patients with chronic heart failure (n = 39) were randomized to regimens of ACEI nonadherence for one week, ACEI adherence for one week or two versions of partial adherence for one week, after which the above six tests were performed. All six tests significantly distinguished between full nonadherence for one week and full or partial adherence. Only plasma AcSDKP produced a significantly different result between partial adherence and either full adherence or full nonadherence for one week. In terms of their ability to distinguish full nonadherence from full adherence, plasma AcSDKP was 89% sensitive and 100% specific with an area under its ROC of 0.95. Corresponding figures for urine AcSDKP were 92%, 97% and 0.95 and for serum ACE they were 86%, 95% and 0.90. All six tests distinguished full nonadherence from all other forms of adherence. The rank order of performance was plasma AcSDKP, urine AcSDKP, serum ACE, AII/AI ratio and plasma AII followed by plasma AI.",1999.0,0,0
241,10588789,Transient myocardial dysfunction associated with angiotensin-converting enzyme inhibitor-induced angioedema: recognition by serial echocardiographic studies.,P J Blomberg; H K Surks; A Long; E Rebeiz; Y Mochizuki; N Pandian,We report a case of a 58-year-old woman who had angiotensin converting enzyme inhibitor-induced angioedema after she underwent a biopsy of a hypopharyngeal mass. The angioedema was associated with severe transient myocardial dysfunction documented on echocardiography. She did not have anaphylaxis or coronary artery disease. To our knowledge this is the first reported case of transient myocardial dysfunction in the setting of angiotensin converting enzyme inhibitor-induced angioedema without anaphylaxis.,1999.0,0,0
242,10594488,Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions.,L Naldi; A Conforti; M Venegoni; M G Troncon; A Caputi; E Ghiotto; A Cocci; U Moretti; G Velo; R Leone,"Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs). All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day. A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics. Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.",1999.0,0,0
243,10594491,Angioedema due to ACE inhibitors: increased risk in patients of African origin.,C R Gibbs; G Y Lip; D G Beevers,"To determine patterns in presentation, risk factors, management and outcome of patients with ACE inhibitor associated angioedema in one British teaching hospital. Cases of ACE inhibitor associated angioedema in patients presenting to the City Hospital, Birmingham between 1993 and 1999 were collected and entered prospectively onto a computerised register. A total of 20 cases (mean age 60 years, range 42-82 years) of ACE inhibitor associated angioedema were reported (11 female and 9 male) with 65% (n=13) of patients being black/Afro-Caribbean. In 70% of cases (n=14), angioedema occurred within 4 weeks of starting therapy, although three patients presented following long-term treatment (24-48 months). ACE inhibitors were continued in 50% (n=10) patients, despite at least one documented episode of angioedema. Admission to hospital was necessary in 40% (n=8) patients, with three of these admitted to the intensive care unit, and one of these died as a result of severe laryngeal obstruction. ACE inhibitor related angioedema is a serious and potentially fatal complication which is relatively rare in the general population, but is more common amongst black/Afro-Caribbean patients. ACE inhibitors are frequently continued following an episode of angioedema and it is important that these episodes are minimised by prompt cessation of the drug, careful patient counselling and heightened awareness in all clinicians who prescribe this common group of drugs.",1999.0,0,0
244,10596866,Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema.,C Blais; J L Rouleau; N J Brown; Y Lepage; D Spence; C Munoz; J Friborg; D Geadah; N Gervais; A Adam,"Angioedema (AE) associated with angiotensin-converting enzyme inhibitors (ACEi) is a rare, but potentially life-threatening adverse reaction. Several studies have suggested that bradykinin (BK) is responsible for ACEi-induced AE, but the mechanism remains unclear. We investigated the metabolism of BK and des-Arg9-BK in the serum of 20 patients with a history of ACEi-associated AE and 21 control (C) subjects. Synthetic BK was incubated with the sera for various periods of time and residual BK and generated des-Arg9-BK were quantified by specific and sensitive enzyme immunoassays. No significant difference of half-life (t1/2) of both BK and des-Arg9-BK could be measured between C subjects and patients with AE (AE) in absence of ACEi. However, an analysis according to the prolonged (+) or not (-) t1/2 of des-Arg9-BK allowed a new stratification of C subjects and AE patients in four subgroups. The preincubation of sera with enalaprilat at a concentration inhibiting ACE significantly prevented the rapid degradation of BK and des-Arg9-BK in these four subgroups. In presence of ACEi, a subgroup (50%) of AE patients (AE + ) had a particularly significant rise of the t1/2 of des-Arg9-BK. Once ACE was inhibited, the concentration or the nature of the ACEi had no significant effect on the t1/2 of des-Arg9-BK. However, a test dilution of AE + sera with a control (C) serum showed that an enzyme defect rather than a circulating inhibitor could be responsible for the abnormal metabolism of des-Arg9-BK when ACE is inhibited. In conclusion, half of the patients with ACEi-associated AE present in serum had an enzyme defect involved in the des-Arg9-BK metabolism leading to its accumulation. The B1 agonist could be responsible, at least in part, for the local inflammatory reaction associated with the AE.",2001.0,0,0
245,10601132,Step-down of enalapril treatment for arterial hypertension.,J R González-Juanatey; A P Reino; J M García-Acuña; C González-Juanatey; L Valdes; J Cabezas-Cerrato,"Enalapril treatment (20 mg every 12 hours) of 24 patients with essential hypertension and left ventricular (LV) hypertrophy established normal blood pressures after 8 weeks, and after 5 years, it had reduced LV mass index by 39% (from 148+/-34 to 90+/-16 g/m(2)) and had normalized LV structure and function and QT dispersion. Stepwise reduction of the enalapril dosage from 40 to 30, 20, 10, and 5 mg/d during the eighth year caused no significant change in blood pressure, LV structure, LV systolic function, or QT dispersion, which all likewise remained unaltered during an additional 2-year period of the 5-mg/d regimen. We conclude that for hypertensive patients in whom prolonged treatment with high doses of enalapril has normalized blood pressure, LV structure, LV function, and QT dispersion, the dose may be reduced as much as 8-fold without detriment to cardiovascular control. The use of smaller doses is evidently advantageous from the point of view of health costs.",1999.0,0,0
246,10603148,Angiotensin converting enzyme inhibitor-induced angioedema: a report of two cases.,F K Assadi; H E Wang; S Lawless; C P McKay; L Hopp; D Fattori,"Angioedema is a rare but potentially fatal side effect of angiotensin converting enzyme (ACE) inhibitors. We report for the first time, two children with systemic lupus erythematosus who developed acute angioedema after the long-term use of enalapril. Prompt recognition and appropriate management of ACE-induced angioedema prevented life-threatening complications. This report highlights the potential risks of angioedema associated with the use of ACE inhibitors in children. Patients should be advised to seek medical treatment immediately if they experience swelling of the face, neck, or tongue, and especially if they have trouble breathing, speaking, or swallowing.",1999.0,0,0
247,10604167,Life-threatening perioperative angioedema related to angiotensin-converting enzyme inhibitor therapy.,N Sadeghi; W R Panje,,1999.0,0,0
248,10604482,Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension.,Y Erdem; C Usalan; I C Haznedaroğlu; B Altun; M Arici; U Yasavul; C Turgan; S Cağlar,"Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.",1999.0,0,0
249,10604523,Therapeutic advantage of angiotensin converting enzyme inhibitors in chronic glomerulonephritis.,K Omata; T Saito; H Sato; T Sato; F Abe; M Yamada; H Yaoita; Y Endo; S Ito; M Kanazawa; K Abe,"Hypertension in chronic progressive renal disease is a major clinical problem leading to renal function loss. We studied the influence of ambulatory blood pressure (ABP) and the effect of hypertension therapy on renal function in 116 patients with chronic glomerulonephritis. Patients were subdivided as hypertensive, normotensive and hypotensive according to the level of ABP and age. Hypotensive subjects showed improvement of renal function and normotensive subjects showed slower rate of progression of renal function loss than hypertensives, suggesting the adequate level of ABP was 100-125/55-75 mm Hg in patients less than 40 years old, 100-135/60-80 mm Hg in patients 40-60 years old, and 105-140/60-85 mm Hg in patients over 60 years, respectively. The renal protection of calcium antagonists was associated with achieving lower blood pressure levels, whereas the blood pressure level did not affect progression of renal function in patient treated with angiotensin converting enzyme (ACE) inhibitor. ACE inhibitor, but not calcium antagonists, showed a reduction of urinary protein excretion. Thus, the mechanisms of renal protection were different between ACE inhibitors and calcium antagonists.",2000.0,0,0
250,10606834,Comparison of the pharmacokinetics of fosinoprilat with enalaprilat and lisinopril in patients with congestive heart failure and chronic renal insufficiency.,R Greenbaum; P Zucchelli; A Caspi; H Nouriel; R Paz; S Sclarovsky; P O'Grady; K F Yee; W C Liao; B Mangold,"To compare the serum pharmacokinetics of fosinoprilat with enalaprilat and lisinopril after 1 and 10 days of dosing with fosinopril, enalapril and lisinopril. Patients with congestive heart failure (CHF, NYHA Class II-IV) and chronic renal insufficiency (creatinine clearance </=30 ml min-1 ) were randomized to receive fosinopril, enalapril or lisinopril in two parallel-group studies. In the first study 24 patients were treated with 10 mg fosinopril (n=12 patients) or 2.5 mg enalapril (n=12) every morning for 10 consecutive days. In the second study 31 patients were treated with 10 mg fosinopril (n=16 patients) or 5 mg lisinopril (n=15) every morning for 10 consecutive days. Samples of blood were collected for determination of pharmacokinetic parameters. The area under the curve (AUC) between the first and last days of treatment and the accumulation index (AI) were the primary outcome measures. All three angiotensin converting enzyme (ACE) inhibitors exhibited a significant increase in AUC between the first and last days of treatment in both studies. The difference between the AI for fosinoprilat (1.41) and enalaprilat (1.96) was statistically significant (95% CI: 1.05, 1.84). Similarly, the difference between the AI for fosinoprilat (1.21) and lisinopril (2.76) was statistically significant (95% CI: 1.85, 2.69). All three ACE inhibitors completely inhibited serum ACE for 24 h. All treatments were well tolerated. Fosinoprilat exhibits significantly less accumulation than enalaprilat or lisinopril in patients with CHF and renal insufficiency, most probably because fosinoprilat is eliminated by both the kidney and liver, and increased hepatic elimination can compensate for reduced renal clearance in patients with kidney dysfunction.",2000.0,0,1
251,10608477,A comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient compliance.,B Girvin; B J McDermott; G D Johnston,"To compare enalapril 20 mg once daily with 10 mg twice daily in terms of blood pressure reduction and patient compliance. Cross-over study of patients randomly assigned to a sequence of enalapril 20 mg once daily or 10 mg twice daily in three 4-week periods following a 4-week placebo run-in. General practices in the greater Belfast and Lisburn area in Northern Ireland. Twenty-five hypertensive patients who had a mean diastolic blood pressure of between 90 and 110 mm Hg after receiving placebo for 4 weeks. Reduction in blood pressure and estimation of patient compliance. Patient compliance was superior on the once daily regimen. However, the twice daily regimen was associated with a greater blood pressure reduction which almost reached statistical significance at the 5% level. Enalapril 20 mg should be prescribed as 10 mg twice daily and measures taken to improve patient compliance.",1999.0,0,0
252,10608480,PROGRESS - Perindopril Protection Against Recurrent Stroke Study: characteristics of the study population at baseline. Progress Management Committee.,,"The primary aim of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) is to determine the effects of a long-term angiotensin converting enzyme (ACE)-inhibitor-based blood-pressure-lowering regimen on the risk of stroke among patients with a history of stroke or transient ischaemic attack (TIA). Secondary aims include investigation of the effects of treatment on total cardiovascular events, dementia and disability. PROGRESS is a double-blind, placebo-controlled randomized trial. Patients were randomly assigned to treatment with the ACE inhibitor perindopril (and the diuretic indapamide for those with no definite indication or contraindication to treatment with a diuretic) versus matching placebo(s). Both hypertensive and non-hypertensive patients were eligible for inclusion. Follow-up is scheduled for completion in 2001. The study is being conducted in 172 centres in 10 countries (Australia, Belgium, China, France, Italy, Ireland, Japan, New Zealand, Sweden and the United Kingdom). Recruitment was completed in November 1997, with 6105 patients randomized. Mean age of participants at study entry was 64 years, 30% of whom were female, 84% had an entry diagnosis of stroke, and the remainder had an entry diagnosis of TIA alone. Mean baseline blood pressure was 147/86 mm Hg, with about half the patients reporting current drug treatment for hypertension. At randomization, 58% of patients were assigned to combination treatment with both study drugs versus placebos, and 42% were assigned to perindopril alone versus placebo. The successful completion of recruitment, together with current indicators of statistical power, suggest that PROGRESS should achieve its primary aim on schedule.",1999.0,0,1
253,10610242,Ambulatory blood pressure monitoring in the assessment of antihypertensive therapy.,M G Myers,"Before an antihypertensive drug is approved for use in clinical practice it must undergo rigorous clinical testing. Basic pharmacokinetic data are usually first obtained in healthy, normal individuals and thereafter in patients with renal or hepatic disease or in sub-groups such as the young or elderly. Acute dosing studies over a wide dosage range are then required prior to initiating longer-term studies. After one or more dosage levels have been selected and the appropriate dosing interval established, investigators may proceed with studies of four to twelve weeks duration, comparing the new drug with placebo or other standard therapies such as a thiazide diuretic or a beta-blocker. A key element in the evaluation process is the assessment of the drug",1999.0,0,0
254,10616844,Chronic proteinuric nephropathies. II. Outcomes and response to treatment in a prospective cohort of 352 patients: differences between women and men in relation to the ACE gene polymorphism. Gruppo Italiano di Studi Epidemologici in Nefrologia (Gisen),P Ruggenenti; A Perna; C Zoccali; G Gherardi; R Benini; A Testa; G Remuzzi,"In the Ramipril Efficacy in Nephropathy study, ramipril decreased the rate of GFR decline (deltaGFR) and progression to end-stage renal disease (ESRD) in 352 patients with proteinuric chronic nephropathies. This study investigated whether in these patients disease outcome and response to treatment were affected by gender or insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene. deltaGFR (0.43 +/- 0.05 versus 0.48 +/- 0.08 ml/min per 1.73 m2) and incidence of ESRD (23 and 22%, respectively) were comparable in male and female patients. However, compared to conventional treatment, ramipril decreased deltaGFR (-52% versus -19%) and progression to ESRD (-74% versus -40%) more effectively in women than in men. Thus, the relative risk (95% confidence interval [CI]) of events (ESRD) between conventional and ramipril treatment was 5.52 (1.59 to 19.17, P = 0.003) in women, but only 1.80 (1.08 to 2.97, P = 0.02) in men. This gender-related effect of ramipril was associated with more reduction in proteinuria (-7.8 +/- 4.2% versus -21.9 +/- 5.7%, P = 0.05) and was still evident even after correction for potentially confounding factors such as baseline GFR, daily sodium intake, ramipril dose, BP control, and concomitant treatment with diuretics or dihydropyridinic calcium channel blockers (adjusted RR [95% CI]: women, 5.07 [1.26 to 20.38], P = 0.02; men, 1.44 [0.85 to 2.44], P = 0.17). Ramipril uniformly decreased deltaGFR and incidence of ESRD in women with either DD (-39% and - 100%) or II + ID (-71% and -82%) genotype, and in men (-25% and -50%) with the DD genotype, but had no beneficial effect in men with the II + ID genotype (+18% and +34%). Thus, the relative risk of events (ESRD) between conventional and ramipril-treated men was higher in subjects with the DD genotype (1.85; 0.69 to 4.94) and lower in those with the II +/- ID genotype (0.71; 0.28 to 1.80). Again, in parallel with deltaGFR and events, proteinuria decreased in women with DD (-23.3 +/-8.0%) or II + ID (-16.0 +/- 9.5%) genotype and in men with the DD genotype (-14.8 +/- 7.0%), but did not change in men with II + ID genotype (+ 1.0 +/- 7.8%). Of note, the ACE genotype-related effect of ramipril was still evident even after correction for the above potentially confounding factors (adjusted RR [95% CI]: DD, 2.52 [0.83 to 7.63], P = 0.10; II + ID, 0.35 [0.12 to 1.01], P = 0.05). Thus, among patients with chronic proteinuric nephropathies, men are at increased risk of progression due to their lower response to ACE inhibitor treatment. ACE inhibition is uniformly renoprotective in women regardless of the ACE polymorphism, and in men with the DD genotype, but is virtually devoid of beneficial effects in men with the II or ID genotype. This information may help to guide therapeutic interventions in clinical practice and to interpret the results of prospective trials in chronic renal disease.",2000.0,0,0
255,10619579,The effect of weight loss intervention on antihypertensive medication requirements in the hypertension Optimal Treatment (HOT) study.,D W Jones; M E Miller; M R Wofford; D C Anderson; M E Cameron; D L Willoughby; C T Adair; N S King,"Obesity is a significant risk factor for hypertension and the cardiovascular sequelae of hypertension. Weight loss has been shown to be effective in lowering blood pressure in overweight individuals. The purpose of this study was to show the impact of a weight loss intervention on overall medication requirements for obese, hypertensive patients. This was a substudy of the Hypertension Optimal Treatment (HOT) study. HOT study patients who had a body mass index > or =27 kg/m2 were randomized to receive either the weight loss intervention, which included dietary counseling and group support, or to serve as the control group. Patients' weights and number of medication steps (per HOT protocol) required to achieve target diastolic blood pressure were measured at 3, 6, 12, 18, 24, and 30 months. Patients in the weight loss group lost significantly more weight than the control group only at 6 months (-3.2+/-4.3 v. -1.8+/-2.7 kg [mean +/- SD] for weight loss group versus control, respectively, P = .05). The weight loss group tended to regain weight after the first 6 months of the study. However, patients in the weight loss group used a significantly fewer number of medication steps than the control group at all time intervals except 3 months. Weight loss appears to be a useful tool in blood pressure management in patients who require medication to control their blood pressure.",2001.0,0,0
256,10619581,The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension.,T Kahan; K Eliasson,"The objective of the study was to examine the influence of angiotensin converting enzyme (ACE) inhibition on circulatory responses to standardized stress tests in primary mild to moderate hypertension. Patients (n = 28) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design, followed by 6 months of open ramipril treatment. Mental stress (a 20-min Stroop's color word conflict test) and a cold pressor test were performed at the end of each of the three study periods. Noninvasive blood pressure and heart rate were recorded. Ramipril reduced systolic and diastolic blood pressure levels at rest (from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks, and 136+/-4/91+/-3 mm Hg at 6 months, in the laboratory) and during mental stress. Resting heart rates were unchanged by ramipril. Ramipril reduced systolic blood pressure and heart rate responses during mental stress; diastolic blood pressure responses were unchanged. Ramipril reduced cardiac workload (systolic blood pressure x heart rate) levels and responses. Treatment effects at 6 months were generally greater than at 6 weeks. During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril, but responses were unchanged. Heart rate responses, however, were reduced. Thus, ramipril reduced cardiac workload levels and responses also during the cold pressor test. These findings show that ACE inhibitors can reduce cardiac workload during stressful situations. If confirmed, this would seem to offer an advantage in the treatment of hypertension.",2000.0,0,0
257,10620209,ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1.,A Perna; P Ruggenenti; A Testa; B Spoto; R Benini; V Misefari; G Remuzzi; C Zoccali,"ACE genotype and ACE induced renoprotection in chronic proteinuric nephropathies. Whether angiotensin-converting enzyme (ACE) gene polymorphism affects disease progression and response to ACE inhibitor therapy in nondiabetic proteinuric nephropathies is not clearly established. The relationship between insertion/deletion (I/D) genotypes and proteinuria, rate of glomerular filtration rate decline (DeltaGFR)-centrally evaluated by repeated measures of iohexol plasma clearance-and incidence of end-stage renal disease (ESRD) was prospectively evaluated in 212 patients with nondiabetic proteinuric chronic nephropathies enrolled in the Ramipril Efficacy in Nephropathy (REIN) trial, where patients were randomly assigned to ramipril or conventional treatment. The DeltaGFR +/- SEM (-0.38 +/- 0.09 vs. -0.50 +/- 0.08 vs. -0.36 +/- 0.06 mL/min/1.73 m2 per month) and incidence of ESRD (19 vs. 22 vs. 25%) in the three subgroups with the II, ID, and DD genotypes, respectively, were comparable. Of note, DeltaGFR (-0.28 +/- 0.07 vs. -0.43 +/- 0.09 mL/min/1.73 m2 per month) and incidence of ESRD [14% vs. 36%, P = 0.04, RR (95% CI), 2.62 (1.02 to 6.71)] were lower in ramipril than in conventionally treated patients in the DD genotype, but not in the II and ID genotype. Either at univariate (P = 0.04) or at multivariate (P = 0.01) analysis, ramipril significantly predicted a lower incidence of events in DD, but not in II and ID patients. At three months, ramipril decreased proteinuria more effectively in DD (-38.2%) than in the II (-26.7%) or ID (-19.2%) genotype. In DD (but not in II or ID) ramipril-treated patients, a short-term reduction in proteinuria correlated with DeltaGFR over the entire follow-up period (P = 0.02, r = -0.41). In nondiabetic proteinuric nephropathies, the ACE I/D polymorphism does not predict disease progression, but is a strong predictor of ACE inhibition-associated renoprotection in that proteinuria, DeltaGFR, and progression to ESRD are effectively reduced in patients with the DD, but not in those with the II or ID genotype.",2000.0,0,0
258,10620219,Renoprotective therapy: how good can it get?,L A Hebert,,2000.0,0,0
259,10620545,ACE inhibitors and angiotensin II antagonists in renal transplantation: an analysis of safety and efficacy.,C E Stigant; J Cohen; M Vivera; J S Zaltzman,"Angiotensin-converting enzyme inhibitors (ACEi) are a class of antihypertensive agents that decrease mortality in congestive heart failure and have established efficacy in the treatment of hypertension and the slowing of established diabetic nephropathy and other proteinuria-associated glomerulonephritides. These drugs have not gained wide acceptance in the treatment of hypertension in renal transplant recipients (RTRs) because of a potential for decreased renal blood flow and glomerular filtration rate associated with a single kidney and concomitant cyclosporine use. Experimental animal models suggest that ACEi may be of benefit in slowing the progression of chronic renal allograft rejection. We undertook a retrospective chart analysis of all RTRs in our institution who had been treated with an ACEi or an angiotensin II (AT II) antagonist, with the objectives of determining the safety, efficacy, and side effect profile of these medications. The minimum follow-up period was 6 months. One hundred seventy-seven of 642 RTRs were prescribed an ACEi or AT II antagonist. Forty-seven patients discontinued therapy, with the most common causes of discontinuation being cough (8 patients) and hyperkalemia (6 patients). The mean arterial blood pressure at each follow-up period was lower than that at the time of initiation of ACEi or AT II antagonist therapy, with a decrease from 92 +/- 12 mm Hg to 86 +/- 9 mm Hg (P < 0.05) after 3 years of treatment. The serum creatinine concentrations did not change throughout the follow-up period. There was a nonsustained increase from the baseline serum potassium of 4.4 +/- 0.5 to 4.6 +/- 0.6 mEq/L at 3 months (P < 0.05), but no further increases in potassium beyond this time. The mean hemoglobin concentration for the cohort did not change, but 13 RTRs given an ACEi for posttransplantation erythrocytosis (PTE) had a decrease in hemoglobin from 17.1 +/- 1.0 g/dL at the start of ACEi therapy to 14.8 +/- 2.2 g/dL at 3 years (P < 0.05). ACEi and AT II antagonists were generally effective antihypertensives, and were safe and well-tolerated agents in this cohort of RTRs. ACEi were also effective in the treatment of PTE.",2000.0,0,0
260,10630728,Metabolic coronary-flow regulation and exogenous nitric oxide in human coronary artery disease: assessment by intravenous administration of nitroglycerin.,J E Kal; H B Van Wezel; M Porsius; I Vergroesen; J A Spaan,"We sought to evaluate the effect of intravenous administration of the nitric oxide--donor substance nitroglycerin (NTG) on metabolic coronary-flow regulation in patients with coronary artery disease (CAD). In 12 patients with stable CAD, we measured coronary sinus blood flow and myocardial oxygen supply and consumption (MVO2) at sinus rhythm and during atrial pacing (30 beats/min above sinus rate), both at control and during infusion of NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min. To study metabolic coronary vasodilation, changes in myocardial oxygen supply were related to pacing-induced changes in MVO2, by using standard regression analysis. The myocardial oxygen supply/consumption ratio (i.e., the slope of the regression line at control, characterizing physiological metabolic coronary flow regulation) was compared with the ratios obtained during infusion of NTG. Compared with control measurements, NTG, 1 microg/kg/min, and NTG, 2 microg/kg/min, attenuated pacing-induced increases in MVO2 by 29 and 60%, respectively, whereas coronary blood flow during pacing remained unchanged. At control, normal metabolic coronary-flow regulation resulted in a myocardial oxygen supply/demand ratio of 1.39 (95% CI, 1.29-1.49). This ratio did not change during NTG, 1 microg/kg/min: 1.44 (95% CI, 1.33-1.56). However, during NTG, 2 microg/kg/min, this ratio significantly increased to 1.84 (95% CI, 1.63-2.05; p<0.01). Intravenous administration of high-dose NTG, a donor of exogenous NO, blunts pacing-induced increases in MVO2 and may increase metabolic coronary vasodilation in patients with CAD.",2000.0,0,0
261,10632767,Erythroderma: a comparison between HIV positive and negative patients.,N Morar; N Dlova; A K Gupta; D K Naidoo; J Aboobaker; P K Ramdial,"Background Erythroderma has protean underlying causes. There have been isolated case reports suggesting an association between erythroderma and the human immunodeficiency virus (HIV). To describe and characterize further the prevalence, etiology, and metabolic sequelae of erythroderma in HIV positive and negative patients. In a subset of patients, clinicopathologic correlation was performed. One hundred and thirty-eight consecutive patients were prospectively recruited over a one and a half year period at the skin clinic of King Edward VIII Hospital. Demographic, clinical, biochemical, and histologic data were recorded. Seventy-five per cent of the patients were black, 22.5% Indian, and 2.5% white. The men to women ratio was 1.9 : 1. The mean age was 34. 7 years (range, 1 month to 85 years). Forty-three per cent of patients were HIV positive, of whom 90% were black. The commonest causes of erythroderma in the total sample were atopic dermatitis (23.9%), psoriasis (23.9%), and drug reactions (22.5%). The commonest cause in the HIV positive group was drug reactions (40.6%), the commonest being ethambutol (30.8%). HIV positive patients had a significantly lower (P < 0.05) white cell count (7.6 vs. 10.5 x 109 /L), hemoglobin (11.1 vs. 12.6 g/dL), platelets (278.3 vs. 378.0 x 109 /L), and albumin (25.4 vs. 28.7 g/L) and significantly higher serum urates (0.6 vs. 0.4 mM/L) than HIV negative patients. HIV positive patients did not have a significant increase in the number of episodes of erythroderma. Clinicopathologic correlation was greatest with psoriasis in the HIV negative group and with psoriasis and drug reactions in the HIV positive group. A large proportion of erythrodermic patients in this study were HIV positive. Inflammatory dermatoses were the commonest cause of erythroderma in all the patients studied. Drug reactions were the commonest cause in HIV positive patients. In the young black patient, erythroderma may be a marker for HIV infection.",2000.0,0,0
262,10634670,Beneficial effects of long-term treatment with enalapril on cardiac function and heart rate variability in patients with old myocardial infarction.,T Ooie; T Saikawa; M Hara; T Takakura; Y Sato; T Sakata,"The beneficial effects of the early use of angiotensin-converting enzyme inhibitors (ACEis) in patients with acute myocardial infarction (MI) are well documented. However, the effects of ACEis in patients with an old MI and preserved cardiac function have not yet been studied. We examined the effects of 12 months of enalapril treatment in patients with previous MI. Thirteen patients with an old MI and no overt congestive heart failure (CHF), aged 70 +/- 2 years, were treated with enalapril for 12 months. We also included 13 age- and sex-matched control patients who had a similar clinical background but were not treated with enalapril. Holter electrocardiography and echocardiography were performed at entry and after 12 months of treatment. Heart rate variability, low- and high-frequency powers (LF and HF), and the ratio between LF and HF (LF/HF) were analyzed. Changes from baseline to 12 months in HF, LF/HF, left ventricular end-diastolic dimension (LVEDD), and end-systolic dimension (LVESD) were significantly different in the enalapril group (HF, 8.1 +/- 0.9 to 9.3 +/- 0.9 milliseconds: LF/HF, 1.65 +/- 0.11 to 1.53 +/- 0.16; LVEDD, 57.2 +/- 1.6 to 54.7 +/- 1.6 mm; LVESD, 40.0 +/- 2.4 to 36.3 +/- 1.9 mm) compared with the control group (HF, 8.9 +/- 0.9 to 8.5 +/- 0.7 milliseconds; LF/HF, 1.78 +/- 0.18 to 1.88 +/- 0.15; LVEDD, 52.3 +/- 2.5 to 55.9 +/- 2.2 mm; LVESD, 32.5 +/- 2.6 to 36.1 +/- 2.6 mm; P < .05). The delta change (delta) in LVESD between the end and the start of study correlated inversely with deltaHF (r = -0.56; P < .05) and positively with deltaLF/HF (r = 0.65; P < .01). Our results suggest possible ongoing structural changes in patients with old MI even in the absence of overt CHF. Enalapril seemed to prevent such changes and to restore cardiac autonomic tone toward normal. Further prospective studies using a larger sample size are warranted to confirm potential beneficial effects of ACEis in patients with previous MI and preserved left ventricular function.",2000.0,0,0
263,10635443,Pharmacokinetics and pharmacodynamics of zofenopril in healthy volunteers.,A Marzo; L Dal Bo; P Mazzucchelli; N C Monti; R A Tettamanti; F Crivelli; M R Uhr; S Ismaili; A Giusti,"This study was carried out to investigate the pharmacokinetics of zofenopril (CAS 81938-43-4) and zofenoprilat, the behaviour of the angiotensin converting enzyme (ACE) (pharmacodynamics) following the administration of zofenopril calcium at the single oral dose of 60 mg in eighteen healthy volunteers. This open label, one-way study was carried out in a single centre on 18 healthy volunteers. The volunteers received an oral single 60 mg dose of zofenopril calcium following an overnight fast. The tablet was swallowed with 250 ml of water. Fasting continued for additional 4 h after dosing and no other liquid intake was allowed from 1 h before to 2 h after administration. Plasma concentrations of zofenopril and its active metabolite zofenoprilat as well as serum ACE activity were measured before drug intake (baseline) and on timed samples over a 36 h period after dosing by LC-MS-MS, a highly sensitive, validated method for active moiety concentrations. Peak plasma concentration was reached on average at 1.19 h with zofenopril and at 1.36 h with zofenoprilat. Concentrations then decreased reaching values under or close to the limit of quantitation (1 ng.ml-1 for zofenopril, 2 ng.ml-1 for zofenoprilat) from 8 to 16 h after dosing. Complete inhibition of ACE was seen at the first blood sampling time (1 h) and lasted on average up to 9.44 h. ACE activity then slowly reactivated, but enzyme inhibition continued and was estimated to be 74% and 56% at 24 and 36 h following drug administration, respectively. From these data a complete or almost complete enzyme inhibition is expected with zofenopril given in repeated dose regimen.",2000.0,0,0
264,10636260,"Comparative study of ACE-inhibition, angiotensin II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF study)",T J Anderson; E Elstein; H Haber; F Charbonneau,"To determine the effect of angiotensin-converting enzyme (ACE) inhibition on brachial flow-mediated vasodilation. Quinapril, an ACE inhibitor with high affinity, has been shown to improve coronary endothelial dysfunction in patients with coronary artery disease. The effectiveness of different vasoactive agents to improve human endothelial function is unknown. High resolution ultrasound was used to assess endothelium-dependent brachial artery flow-mediated vasodilation (FMD) in patients with coronary disease. We studied 80 patients (mean age 58 +/- 0.9 years) in a partial-block, cross-over design trial. Patients were randomized to one of four different drug sequences to receive quinapril 20 mg, enalapril 10 mg, losartan 50 mg or amlodipine 5 mg daily. Each patient received three drugs with a two-week washout period between treatments. The primary end point was the absolute difference in FMD after eight weeks of each study drug compared with their respective baselines analyzed in a blinded fashion. There was mild impairment of FMD at baseline (7.3 +/- 0.6%). The change in FMD from baseline was significant only for quinapril (1.8 +/- 1%, p < 0.02). No change was seen with losartan (0.8 +/- 1.1%, p = 0.57), amlodipine (0.3 +/- 0.9%, p = 0.97) or enalapril (-0.2 +/- 0.8%, p = 0.84). No significant change in nitroglycerin-induced dilation occurred with drug therapy. The improvement in quinapril response was not seen in those with the DD ACE genotype (0.5 +/- 2.1%) but was seen in those with the ID and II genotype (3.3 +/- 1.2 and 3.2 +/- 1.9%, respectively, p = 0.03). Only quinapril was associated with significant improvement in FMD, and this response is related to the presence of the insertion allele of the ACE genotype.",2000.0,0,0
265,10636261,Endothelium: a new target for cardiovascular therapeutics.,P C Deedwania,,2000.0,0,0
266,10638131,Comparative study of nifedipine CD retard 30 tablets vs enalapril in patients of uncomplicated essential hypertension.,S A Kamat; P Modi; P P Walwaikar,,2000.0,0,0
267,10639539,"Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.",Heart Outcomes Prevention Evaluation Study Investigators; S Yusuf; P Sleight; J Pogue; J Bosch; R Davies; G Dagenais,"Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction, whether or not they have heart failure. We assessed the role of an angiotensin-converting-enzyme inhibitor, ramipril, in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure. A total of 9297 high-risk patients (55 years of age or older) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were randomly assigned to receive ramipril (10 mg once per day orally) or matching placebo for a mean of five years. The primary outcome was a composite of myocardial infarction, stroke, or death from cardiovascular causes. The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper. A total of 651 patients who were assigned to receive ramipril (14.0 percent) reached the primary end point, as compared with 826 patients who were assigned to receive placebo (17.8 percent) (relative risk, 0.78; 95 percent confidence interval, 0.70 to 0.86; P<0.001). Treatment with ramipril reduced the rates of death from cardiovascular causes (6.1 percent, as compared with 8.1 percent in the placebo group; relative risk, 0.74; P<0.001), myocardial infarction (9.9 percent vs. 12.3 percent; relative risk, 0.80; P<0.001), stroke (3.4 percent vs. 4.9 percent; relative risk, 0.68; P<0.001), death from any cause (10.4 percent vs. 12.2 percent; relative risk, 0.84; P=0.005), revascularization procedures (16.3 percent vs. 18.8 percent; relative risk, 0.85; P<0.001), cardiac arrest (0.8 percent vs. 1.3 percent; relative risk, 0.62; P=0.02), [corrected] heart failure (9.1 percent vs. 11.6 percent; relative risk, 0.77; P<0.001), and complications related to diabetes (6.4 percent vs. 7.6 percent; relative risk, 0.84; P=0.03). Ramipril significantly reduces the rates of death, myocardial infarction, and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure.",2000.0,0,1
268,10639540,Vitamin E supplementation and cardiovascular events in high-risk patients.,Heart Outcomes Prevention Evaluation Study Investigators; S Yusuf; G Dagenais; J Pogue; J Bosch; P Sleight,"Observational and experimental studies suggest that the amount of vitamin E ingested in food and in supplements is associated with a lower risk of coronary heart disease and atherosclerosis. We enrolled a total of 2545 women and 6996 men 55 years of age or older who were at high risk for cardiovascular events because they had cardiovascular disease or diabetes in addition to one other risk factor. These patients were randomly assigned according to a two-by-two factorial design to receive either 400 IU of vitamin E daily from natural sources or matching placebo and either an angiotensin-converting-enzyme inhibitor (ramipril) or matching placebo for a mean of 4.5 years (the results of the comparison of ramipril and placebo are reported in a companion article). The primary outcome was a composite of myocardial infarction, stroke, and death from cardiovascular causes. The secondary outcomes included unstable angina, congestive heart failure, revascularization or amputation, death from any cause, complications of diabetes, and cancer. A total of 772 of the 4761 patients assigned to vitamin E (16.2 percent) and 739 of the 4780 assigned to placebo (15.5 percent) had a primary outcome event (relative risk, 1.05; 95 percent confidence interval, 0.95 to 1.16; P=0.33). There were no significant differences in the numbers of deaths from cardiovascular causes (342 of those assigned to vitamin E vs. 328 of those assigned to placebo; relative risk, 1.05; 95 percent confidence interval, 0.90 to 1.22), myocardial infarction (532 vs. 524; relative risk, 1.02; 95 percent confidence interval, 0.90 to 1.15), or stroke (209 vs. 180; relative risk, 1.17; 95 percent confidence interval, 0.95 to 1.42). There were also no significant differences in the incidence of secondary cardiovascular outcomes or in death from any cause. There were no significant adverse effects of vitamin E. In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes.",2000.0,0,0
269,10644922,Cough is common in children prescribed converting enzyme inhibitors.,R O von Vigier; S Mozzettini; A C Truttmann; P Meregalli; G P Ramelli; M G Bianchetti,,2000.0,0,0
270,10647760,Chinese trial on isolated systolic hypertension in the elderly. Systolic Hypertension in China (Syst-China) Collaborative Group.,J G Wang; J A Staessen; L Gong; L Liu,"In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group initiated the placebo-controlled Syst-China trial to investigate whether antihypertensive drug treatment could reduce the incidence of fatal and nonfatal stroke in older Chinese patients with isolated systolic hypertension. To explore (1) whether the benefits of active treatment were evenly distributed across 4 strata, prospectively defined according to sex and previous cardiovascular complications, and (2) whether the morbidity and mortality results were influenced by age, level of systolic or diastolic blood pressure (BP), smoking or drinking habits, or diabetes mellitus at enrollment. Eligible patients had to be 60 years or older with a sitting systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg. After stratification for center, sex, and previous cardiovascular complications, 1253 patients were assigned to active treatment starting with nitrendipine (10-40 mg/d), with the possible addition of captopril (12.5-50.0 mg/d), and/or hydrochlorothiazide (12.5-50 mg/d). In the 1141 control patients, matching placebos were used similarly. Male sex, previous cardiovascular complications, older age, higher systolic BP or lower diastolic BP, living in northern China, smoking, and diabetes mellitus significantly and independently increased the risk of 1 or more of the following end points: total or cardiovascular mortality, all fatal and nonfatal cardiovascular end points, all strokes, and all cardiac end points. In the placebo-control group diabetes raised the risk of all end points 2- to 3-fold (P< or =.05). However, active treatment reduced the excess risk associated with diabetes to a nonsignificant level (P values ranging from .12-.86) except for cardiovascular mortality (P = .04). Cox regression with adjustments applied for significant covariates suggested that active treatment may reduce total mortality more (P = .06) in women and stroke more (P = .07) in men and that it may provide better protection against cardiac end points in nonsmokers than smokers (P = .04). Otherwise, the benefits of active treatment were equally manifest, regardless of the enrollment characteristics of the patients, and regardless of whether active treatment consisted of only nitrendipine or of nitrendipine associated with other active drugs. In elderly Chinese patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improved prognosis. The benefit was particularly evident in diabetic patients; for cardiac end points it tended to be larger in nonsmokers. Otherwise, the benefit of active treatment was not significantly influenced by the characteristics of the patients at enrollment in the trial.",2000.0,0,0
271,10652036,Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients.,J C Chan; G T Ko; D H Leung; R C Cheung; M Y Cheung; W Y So; R Swaminathan; M G Nicholls; J A Critchley; C S Cockram,"Long-term effects of angiotensin-converting enzyme inhibition and metabolic control in hypertensive type 2 diabetic patients. In hypertensive type 2 diabetic patients, treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with a lower incidence of cardiovascular events than those treated with calcium channel-blocking agents. However, the long-term renal effects of ACE inhibitors in these patients remain inconclusive. In 1989, we commenced a placebo-controlled, double-blind, randomized study to examine the anti-albuminuric effects of enalapril versus nifedipine (slow release) in 102 hypertensive, type 2 diabetic patients. These patients have been followed up for a mean trial duration of 5.5 +/- 2.2 years. We examined the determinants, including the effect of ACE inhibition on clinical outcomes in these patients. After a six-week placebo-controlled, run-in period, 52 patients were randomized double-blind to receive nifedipine (slow release) and 50 patients to receive enalapril. After the one-year analysis, which confirmed the superior anti-albuminuric effects of enalapril (-54%) over nifedipine (+11%), all patients were continued on their previously assigned treatment with informed consent. They were subdivided into normoalbuminuric (N = 43), microalbuminuric (N = 34), and macroalbuminuric (N = 25) groups based on two of three 24-hour urinary albumin excretion (UAE) measurements during the run-in period. Renal function was shown by the 24-hour UAE, creatinine clearance (CCr), and the regression coefficient of the yearly plasma creatinine reciprocal (beta-1/Cr). Clinical endpoints were defined as death, cardiovascular events, and/or renal events (need for renal replacement therapy or doubling of baseline plasma creatinine). In the whole group, patients treated with enalapril were more likely to revert to being normoalbuminuric (23.8 vs. 15.4%), and fewer of them developed macroalbuminuria (19.1 vs. 30.8%) compared with the nifedipine-treated patients (P < 0.05). In the microalbuminuric group, treatment with enalapril (N = 21) was associated with a 13.0% (P < 0.01) reduction in 24-hour UAE compared with a 17.3% increase in the nifedipine group (N = 13). In the macroalbuminuric patients, enalapril treatment (N = 11) was associated with stabilization compared with a decline in renal function in the nifedipine group, as shown by the beta-1/Cr (0.65 +/- 4.29 vs. -1.93 +/- 2.35 1/micromol x 10-3, P < 0.05) after adjustment for baseline values. Compared with the normoalbuminuric and microalbuminuric patients, those with macroalbuminuria had the lowest mean CCr (75.5 +/- 24.1 vs. 63.5 +/- 21.3 vs. 41.9 +/- 18.5 mL/min, P < 0.001) and the highest frequency of clinical events (4.7 vs. 5.9 vs. 52%, P < 0. 001). On multivariate analysis, beta-1/Cr (R2 = 0.195, P < 0.001) was independently associated with baseline HbA1c (beta = -0.285, P = 0.004), whereas clinical outcomes (R2 = 0.176, P < 0.001) were independently related to the mean low-density lipoprotein cholesterol (beta = 2.426, P = 0.018), high-density lipoprotein cholesterol (beta = -8.797, P = 0.03), baseline UAE (beta = 0.002, P = 0.04), and mean CCr during treatment (beta = -0.211, P = 0.006). In this prospective cohort analysis involving 102 hypertensive, type 2 diabetic patients with varying degrees of albuminuria followed up for a mean duration of five years, we observed the importance of good metabolic and blood pressure control on the progression of albuminuria and renal function. Treatment with enalapril was associated with a greater reduction in albuminuria than with nifedipine in the entire patient group, and especially in those with microalbuminuria. In the macroalbuminuric patients, the rate of deterioration in renal function was also attenuated by treatment with enalapril.",2000.0,0,0
272,10652037,Renoprotective effects of angiotensin II receptor blockade in type 1 diabetic patients with diabetic nephropathy.,S Andersen; L Tarnow; P Rossing; B V Hansen; H H Parving,"Angiotensin I-converting enzyme (ACE) inhibitors reduce angiotensin II formation and induce bradykinin accumulation. Animal studies suggest that bradykinin may play a role for the effects of ACE inhibition on blood pressure and kidney function. Therefore, we compared the renal and hemodynamic effects of specific intervention in the renin-angiotensin system by blockade of the angiotensin II subtype-1 receptor to the effect of ACE inhibition. A randomized, double-blind, cross-over trial was performed in 16 type 1 diabetic patients (10 men), age 42 +/- 2 years (mean +/- SEM). The study consisted of five periods, each lasting two months. The patients received losartan 50 mg, losartan 100 mg, enalapril 10 mg, enalapril 20 mg, and placebo in random order. At the end of each period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were determined. Both doses of losartan and enalapril reduced albuminuria (P < 0.05) and mean arterial blood pressure (MABP; P < 0.05), whereas GFR remained stable. Albuminuria was reduced by 33% (95% CI, 12 to 51) on losartan 50 mg, 44% (95% CI, 26 to 57) on losartan 100 mg, 45% (95% CI, 23 to 61) on enalapril 10 mg, and 59% (95% CI, 39 to 72) on enalapril 20 mg, and MABP fell by 9 +/- 2, 8 +/- 2, 6 +/- 3, and 11 +/- 3 mm Hg (mean +/- SEM), respectively. No significant differences were found between the effects of losartan 100 mg and enalapril 20 mg. HbA1C and sodium intake remained unchanged throughout the study, whereas a significant rise in serum potassium occurred during ACE inhibition. The angiotensin II subtype 1 receptor antagonist, losartan, reduces albuminuria and MABP similar to the effect of ACE inhibition. These results indicate that the reduction in albuminuria and blood pressure during ACE inhibition is primarily caused by interference in the renin-angiotensin system. Our study suggest that losartan represents a valuable new drug in the treatment of hypertension and proteinuria in type 1 diabetic patients with diabetic nephropathy.",2000.0,0,0
273,10652967,Progression from hypertension to heart failure. Mechanisms and management.,J G Cleland,"Patients with hypertension are at increased risk of developing heart failure (HF), but the mechanisms by which hypertension leads to HF have not been clarified [although left ventricular hypertrophy (LVH) is clearly a predictor of an increased risk of HF]. Similarly, although antihypertensive therapy has been shown to reduce the risk of HF in hypertensive patients, it is not known how this benefit is produced and, currently, there is no clear evidence that any class of antihypertensive agent is more effective than any other in this respect. On theoretical grounds, beta-blockers would be expected to be ideal agents for the prevention of HF in hypertensive patients. In addition to control of blood pressure and regression of LVH, they have clear benefits on morbidity and mortality after myocardial infarction (MI), which probably plays a major role in the development of HF in hypertensive patients, and on the prognosis of HF itself. A reduction in long-term mortality after MI has been demonstrated only for non-selective beta-blockers. Carvedilol, a non-selective beta-blocker which also has other ancillary properties including alpha-1-receptor blockade and antioxidant effects and a favourable metabolic profile, may be an appropriate choice for the prevention of HF in hypertensive patients. This is reinforced by the salutary benefits of carvedilol for the reduction in the morbidity and mortality of HF itself.",2000.0,0,0
274,10658293,The ATLAS study: low-dose versus high-dose lisinopril in heart failure.,J D Horowitz,,2000.0,0,1
275,10658295,Causes of death in the ATLAS study: effects of high-dose ACE inhibitors.,J G Cleland,,2000.0,0,1
276,10658943,Effects of valsartan on left ventricular diastolic function in patients with mild or moderate essential hypertension: comparison with enalapril.,A Cuocolo; G Storto; R Izzo; G L Iovino; M Damiano; F Bertocchi; J Mann; B Trimarco,"This study compares the effects of an AT1 angiotensin II receptor antagonist (valsartan) with those of an ACE inhibitor (enalapril) on left ventricular (LV) diastolic function in patients with mild or moderate essential hypertension and no evidence of LV hypertrophy at echocardiography. A total of 24 patients (16 men, mean age 47 +/- 8 years) underwent radionuclide ambulatory monitoring (Vest) of LV function at rest and during upright bicycle exercise testing before and after two 4-week treatment periods with valsartan (80-160 mg/day orally) and enalapril (20-40 mg/day orally) according to a double-blind, crossover randomization scheme. In the overall population no differences between the two treatments were found in LV peak filling rate (PFR) either at rest or at peak exercise. In a subgroup analysis it was found that baseline PFR was normal (= 2.5 EDV/sec) in 12 patients (subgroup A) and impaired (< 2.5 EDV/sec) in the remaining 12 (subgroup B). In both subgroups, valsartan and enalapril induced a significant and comparable reduction of systolic and diastolic blood pressure. In subgroup A, valsartan and enalapril did not induce significant changes in PFR. In subgroup B, valsartan increased PFR both at rest (from 2.0 +/- 0.3 to 2.4 +/- 0.3 EDV/sec, P < 0.01) and at peak exercise (from 4.1 +/- 1.1 to 4.4 +/- 1.0 EDV/s, P < 0.05), whereas enalapril did not change PFR either at rest (2.0 +/- 0.4 EDV/s, P < 0.01 versus valsartan) or at peak exercise (3.7 +/- 1.1 EDV/sec, P < 0.05 versus valsartan). Valsartan-induced renin-angiotensin system blockade is able to improve LV filling in patients with mild or moderate essential hypertension and impaired diastolic function. These findings support the hypothesis of a contribution of the renin-angiotensin system in the control of LV diastolic function in these patients.",2000.0,0,0
277,10664901,Cardiac drug and psychotropic drug interactions: significance and recommendations.,J J Strain; G Caliendo; J D Alexis; R S Lowe; A Karim; M Loigman,"Understanding cardiac drug interactions with concurrent psychotropic prescriptions is essential for the practicing cardiologist and primary care physician, as well as for the psychiatrist. There has been an explosive use of new drugs in both psychiatry and cardiology without widespread knowledge of their potential interactions. The increasing tendency toward poly-pharmacy, the use of psychotropic medications by cardiologists and primary care physicians caring for cardiac patients, and the growth of the aging population present major challenges for the practitioner. Finally, there is a need to have models/paradigms for predicting potential drug interactions--e.g., the Cytochrome p450 schema. This paper describes a method to identify, understand, and codify the interactions between psychotropic and cardiac drugs, a systematic approach for updating this key database and specific cardiac-psychotropic drug interactions. Specifically, this paper 1) details the interactions, 2) addresses the level of their clinical significance, 3) describes the potential mechanism(s) of the interactions, and 4) offers recommendations to the clinician. Since the majority of the original clinical trials, either for cardiac medications or psychotropic drugs, do not include studies comparing these two drug domains contemporaneously, their interactions often become known only with their combined use in the clinical arena, using the patient as ""guinea pig,"" and through subsequent reporting.",2000.0,0,0
278,10665127,,,,,0,0
279,10668225,Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring.,O Kohlmann Júnior; P C Jardim; W Oigman,"A double-blind, placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of trandolapril, an angiotensin I converting enzyme inhibitor, in the treatment of mild-to-moderate systemic arterial hypertension. Of 262 patients enrolled in this study, 127 were treated with trandolapril 2 mg/day for 8 consecutive weeks, and the remaining 135 patients received placebo for the same period of time. Reduction in blood pressure (BP) and the occurrence of adverse events during this period were evaluated in both groups. Significantly reductions in both systolic and diastolic pressures were observed in patients treated with trandolapril when compared with those on placebo. Antihypertensive efficacy was achieved in 57.5% of the patients on trandolapril and in 42% of these normal values of BP were obtained. The efficacy of trandolapril was similar in all centers, regardless of the area of the country. In a subset of 30 patients who underwent ABPM, responders showed a significant hypotensive effect to trandolapril throughout the 24 hour day. The adverse event profile was similar in both trandolapril and placebo groups. Our results demonstrate, for the first time in a large group of hypertensive patients from different regions in Brazil, good efficacy and tolerability of trando-lapril during treatment of mild-to-moderate essential systemic hypertension.",2000.0,0,1
280,10668837,"Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer.",C R Meier; L E Derby; S S Jick; H Jick,"The use of angiotensin-converting enzyme (ACE) inhibitors has been linked to a decreased risk of developing cancer, and longer-term use of calcium channel blockers (CCBs) has been associated with an increased risk of developing cancer in general and breast cancer in particular. Using data from the General Practice Research Database, we conducted a large case-control analysis. Previous exposure to ACE inhibitors, CCBs, and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women. Compared with nonusers of antihypertensive drugs, women who used ACE inhibitors (odds ratio [OR], 1.0; 95% confidence interval [CI], 0.7-1.5), CCBs (OR, 0.9; 95% CI, 0.7-1.2), or beta-blockers (OR, 1.0; 95% CI, 0.8-1.2) for 5 or more years were not at an increased or decreased risk of developing breast cancer (adjusted for smoking and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs (dihydropyridines, diltiazem hydrochloride, and verapamil hydrochloride) or between users of short-acting (OR, 1.0; 95% CI, 0.7-1.4) or sustained-release (OR, 1.0; 95% CI, 0.8-1.3) nifedipine preparations. The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer.",2000.0,0,0
281,10669450,"ABC of heart failure. Management: diuretics, ACE inhibitors, and nitrates.",M K Davies; C R Gibbs; G Y Lip,,2000.0,0,0
282,10670508,Smell and taste disorders: a primary care approach.,S M Bromley,"Smell and taste disorders are common in the general population, with loss of smell occurring more frequently. Although these disorders can have a substantial impact on quality of life and may represent significant underlying disease, they are often overlooked by the medical community. Patients may have difficulty recognizing smell versus taste dysfunction and frequently confuse the concepts of ""flavor"" and ""taste."" While the most common causes of smell disturbance are nasal and sinus disease, upper respiratory infection and head trauma, frequent causes of taste disturbance include oral infections, oral appliances (e.g., dentures), dental procedures and Bell's palsy. Medications can interfere with smell and taste, and should be reviewed in all patients with reported dysfunction. In addition, advancing age has been associated with a natural impairment of smell and taste ability. A focused history and a physical examination of the nose and mouth are usually sufficient to screen for underlying pathology. Computed tomographic scanning or magnetic resonance imaging of affected areas, as well as commercially available standardized tests, may be useful in selected patients. The causes of olfactory dysfunction that are most amenable to treatment include obstructing polyps or other masses (treated by excision) and inflammation (treated with steroids). Enhancement of food flavor and appearance can improve quality of life in patients with irreversible dysfunction.",2000.0,0,0
283,10673735,Does the Dundee Step Test predict outcome in treated hypertension? A sub-study protocol for the ASCOT trial. Anglo-Scandinavian Cardiac Outcome Trial.,P O Lim; P T Donnan; T M MacDonald,"Treated hypertensive subjects may remain five times more likely to die of cardiac and cerebrovascular diseases than normotensive subjects with equivalent resting blood pressure (BP) levels. Research evidence suggests that exercise BP is a better predictor of end-organ damage and mortality than resting BP, and data from our centre show that a significant proportion of treated hypertensives have uncontrolled BP during a 5-min Dundee Step Test. The prognostic usefulness of exercise BP has yet to be translated into clinical practice because of the lack of a suitable technique. The Dundee Step Test is being evaluated in the ASCOT (Anglo-Scandinavian Cardiac Outcome Trial) study, a 5-year follow-up multicentre, multinational trial comparing the effect of newer (amlodipine and perindopril) and older (bendroflumethiazide and atenolol) antihypertensive agents stratified according to cholesterol levels on cardiac outcome. If the value of the Dundee Step Test is proven, then it may be adopted into routine clinical practice for the assessment of exercise BP. This may result in the improved management of hypertension with a subsequent reduction in morbidity and mortality. The publication of this study protocol is meant to be a statement of on-going research which may stimulate interest among those with an interest in this area of research. Journal of Human Hypertension (2000) 14, 75-78.",2000.0,0,0
284,10675071,Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.,,"Diabetes mellitus is a strong risk factor for cardiovascular and renal disease. We investigated whether the angiotensin-converting-enzyme (ACE) inhibitor ramipril can lower these risks in patients with diabetes. 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study, aged 55 years or older, who had a previous cardiovascular event or at least one other cardiovascular risk factor, no clinical proteinuria, heart failure, or low ejection fraction, and who were not taking ACE inhibitors, were randomly assigned ramipril (10 mg/day) or placebo, and vitamin E or placebo, according to a two-by-two factorial design. The combined primary outcome was myocardial infarction, stroke, or cardiovascular death. Overt nephropathy was a main outcome in a substudy. The study was stopped 6 months early (after 4.5 years) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo. Ramipril lowered the risk of the combined primary outcome by 25% (95% CI 12-36, p=0.0004), myocardial infarction by 22% (6-36), stroke by 33% (10-50), cardiovascular death by 37% (21-51), total mortality by 24% (8-37), revascularisation by 17% (2-30), and overt nephropathy by 24% (3-40, p=0.027). After adjustment for the changes in systolic (2.4 mm Hg) and diastolic (1.0 mm Hg) blood pressures, ramipril still lowered the risk of the combined primary outcome by 25% (12-36, p=0.0004). Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes. The cardiovascular benefit was greater than that attributable to the decrease in blood pressure. This treatment represents a vasculoprotective and renoprotective effect for people with diabetes.",2000.0,0,0
285,10676602,The effect of amlodipine and enalapril on blood pressure and neurohumoral activation in hypertensive patients with Ribbing's disease (multiple epiphysal dystrophy).,G Cocco; T Ettlin; H R Baumeler,"In patients with Ribbing's disease (RD)--a form of multiple epiphysal dystrophy--hypertension is frequent, often severe, and accompanied by a relevant cardiac dysfunction. This study was undertaken to evaluate the contribution of the calcium antagonist amlodipine and of the angiotensin-converting-enzyme inhibitor enalapril to blood pressure regulation by studying their effect on neurohormonal activation. Fifty hypertensive patients with RD were studied. After a placebo run-in period of 4 to 6 weeks, patients were randomly assigned to receive either amlodipine (10 mg once daily) or enalapril (20 mg once daily) for 6 months. Both drugs significantly lowered blood pressure. Enalapril did not result in activation of the sympathetic system (as determined by measurement of the plasma norepinephrine level). On the other hand, the hypotensive effect of amlodipine occurred with an increase in heart rate and in the levels of plasma norepinephrine and angiotensin II. It is unclear whether amlodipine may reduce cardiac dysfunction in patients with RD.",2000.0,0,0
286,10676671,"A comparison of angiotensin-converting enzyme inhibitors, calcium antagonists, beta-blockers and diuretic agents on reactive hyperemia in patients with essential hypertension: a multicenter study.",Y Higashi; S Sasaki; K Nakagawa; T Ueda; A Yoshimizu; S Kurisu; H Matsuura; G Kajiyama; T Oshima,"The purpose of this study was to compare the effect of different antihypertensive agents, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and diuretic agents on endothelial function. Endothelial dysfunction is a component of essential hypertension, and various antihypertensive drugs may be able to restore normal function. Forearm blood flow (FBF) was measured in 296 patients with essential hypertension, including 46 untreated subjects using strain-gauge plethysmography during reactive hyperemia and after sublingual administration of nitroglycerin (NTG). Forty-seven normotensive subjects were similarly evaluated as control subjects. The FBF during reactive hyperemia in the 296 hypertensive patients was significantly less than that in age-matched normotensive subjects. The increase in FBF after administration of sublingual NTG was similar in both groups. Systolic and diastolic blood pressures and forearm vascular resistance were greater in the untreated group than in the four treated groups and did not differ with respect to the antihypertensive agent used. The maximal FBF response from reactive hyperemia was significantly greater in the ACE inhibitor-treated group than in the group treated with calcium antagonists, beta-blockers, diuretic agents, or nothing (40.5 +/- 5.2 vs. 32.9 +/- 5.8, 34.0 +/- 5.6, 32.1 +/- 5.9, and 31.9 +/- 5.8 ml/min per 100 ml tissue, p < 0.05, respectively). Reactive hyperemia was similar in the calcium antagonist, beta-blocker, diuretic and untreated groups, and changes in FBF after sublingual NTG administration were similar in all groups. The infusion of NG-monomethyl-L-arginine, a nitric oxide (NO) synthase inhibitor, abolished the enhancement of reactive hyperemia in hypertensive patients treated with ACE inhibitors. These findings suggest that ACE inhibitors augment reactive hyperemia, an index of endothelium-dependent vasorelaxation, in patients with essential hypertension. This augmentation may be due to increases in NO.",2000.0,0,0
287,10676825,Syndrome of inappropriate antidiuretic hormone secretion associated with lisinopril.,Z H Shaikh; H C Taylor; P V Maroo; L A Llerena,"To describe a case of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with lisinopril therapy. A 76-year-old white woman who was being treated with lisinopril and metoprolol for hypertension presented with headaches accompanied by nausea and a tingling sensation in her arms. Her serum sodium was 109 mEq/L, with a serum osmolality of 225 mOsm/kg, urine osmolality of 414 mOsm/kg, and spot urine sodium of 122 mEq/L. Diclofenac 75 mg qd for osteoarthritic pain and lisinopril 10 mg qd for hypertension was begun in 1990. Lisinopril was increased to 20 mg qd in August 1994 and to 20 mg bid pm in August 1996 for increasing blood pressure; metoprolol 50 mg qd was added in July 1996. A diagnosis of SIADH was postulated and further evaluation was undertaken to exclude thyroid and adrenal causes. After lisinopril was discontinued and the patient restricted to 1000 mL/d of fluid, serum sodium gradually corrected to 143 mEq/L. The patient was discharged taking metoprolol alone for her hypertension; serum sodium has remained > or =138 mEq/L through April 1999, 32 months after discharge, despite daily use of diclofenac. Angiotensin-converting enzyme (ACE) inhibitors in antihypertensive doses may block conversion of angiotensin I to angiotensin II in the peripheral circulation, but not in the brain. Increased circulating angiotensin I enters the brain and is converted to angiotensin II, which may stimulate thirst and release of antidiuretic hormone from the hypothalamus, eventually leading to hyponatremia. SIADH should be considered a rare, but possible, complication of therapy with lisinopril and other ACE inhibitors.",2000.0,0,0
288,10677399,Is there a role for renin profiling in selecting chronic heart failure patients for ACE inhibitor treatment?,P O Lim; R J MacFadyen; A D Struthers,"It remains uncertain whether angiotensin converting enzyme (ACE) inhibitors benefit all heart failure patients or just those with renin-angiotensin-aldosterone system (RAAS) activation. To determine whether the response to an ACE inhibitor, assessed by urine sodium excretion, was different in patients with low renin versus those with high renin. Plasma renin activity (PRA) was measured in 38 patients with stable chronic heart failure (21 male, 17 female; mean (SD) age 71 (6) years, range 59-82 years) on chronic diuretic treatment alone. They were divided into three groups: low (PRA </= 1.5 ng/ml/h, n = 11); normal (1.5 < PRA < 5, n = 14); and high (PRA > 5, n = 13). The effect of ACE inhibition was then assessed on diuretic induced natriuresis with respect to renin status. There were no significant differences in age and sex distribution between the groups. Plasma angiotensin II and aldosterone increased serially from low to high renin groups, while 24 h urinary sodium concentrations fell from low to high renin groups (low PRA, 96.7 (39.5); normal PRA, 90.4 (26.7); high PRA, 66. 3 (18.9) mmol/l; p = 0.033), despite a higher diuretic dose in the high renin group. This blunted natriuretic effect of loop diuretics was caused by RAAS activation, which could partly be reversed by ACE inhibition. ACE inhibitors increased natriuresis by 22% in the high renin group (p = 0.029), but had no effect in the normal and low renin groups. Within the low renin group, five of the 11 patients had persistently low renin levels despite ACE inhibition. There was a non-significant reduction in natriuresis (-9.6%, p = 0.335) following ACE inhibition in this subgroup of patients. About one third of heart failure patients in our study had low renin status and a non-activated RAAS, despite diuretic treatment. ACE inhibitors did not alter natriuresis significantly in this subgroup of patients, and enhanced natriuresis only in patients with high renin. There is thus tentative support for renin profiling in targeting ACE inhibitors to the most deserving, by showing that short term sodium retention does not occur in low renin patients if ACE inhibitors are withdrawn.",2000.0,0,0
289,10678274,"Peroxisome proliferator-activated receptor (PPAR)-gamma expression in human vascular smooth muscle cells: inhibition of growth, migration, and c-fos expression by the peroxisome proliferator-activated receptor (PPAR)-gamma activator troglitazone.",S Benson; J Wu; S Padmanabhan; T W Kurtz; H A Pershadsingh,"This study was conducted to determine whether cultured human coronary artery and aorta vascular smooth muscle (VSM) cells express the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma); whether the thiazolidinedione troglitazone, a ligand for PPARgamma, would inhibit c-fos expression by these cells; and whether troglitazone would inhibit proliferation and migration induced in these cells by mitogenic growth factors. Using immunoblotting and reverse-transcriptase polymerase chain reaction (RT-PCR) techniques, we show that both human aorta and coronary artery VSM cell lines expressed PPARgamma protein and mRNA for both PPARgamma isoforms, PPARgamma1 and PPARgamma2. Immunocytochemical staining localized the PPARgamma protein primarily within the nucleus. Troglitazone inhibited basic fibroblast growth factor and platelet-derived growth factor-BB induced DNA synthesis in a dose-dependent manner and downregulated the growth-factor-induced expression of c-fos. Troglitazone also inhibited the migration of coronary artery VSM cells along a platelet-derived growth factor-BB concentration gradient. These findings demonstrate for the first time the expression and nuclear localization of PPARgamma in human coronary artery and aorta VSM cells. The data also suggest that the downregulation of c-fos expression, growth-factor-induced proliferation, and migration by VSM may, in part, be mediated by activation of the PPARgamma receptor.",2000.0,0,0
290,10678548,Safety of the combination of valsartan and benazepril in patients with chronic renal disease. European Group for the Investigation of Valsartan in Chronic Renal Disease.,L M Ruilope; J C Aldigier; C Ponticelli; P Oddou-Stock; F Botteri; J F Mann,"Several experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin system than either agent alone. Such enhanced suppression might be of benefit for patients exhibiting a progressive decline in renal function because of chronic renal disease. A pilot multinational, multicentre, randomized, active-controlled, parallel group open-label study has been conducted in a group of patients with progressive chronic renal failure (creatinine clearance 20-45 ml/min) either with or without proteinuria and hypertension. The primary aim of the study was to investigate the safety and tolerability of the combination of valsartan and benazepril. Patients were randomly assigned to one of three groups: group 1 received valsartan 160 mg once daily (n = 22); group 2 received valsartan 80 mg once daily plus benazepril 5 or 10 mg once daily (n = 42); group 3 received valsartan 160 mg once daily plus benazepril 5 or 10 mg once daily (n = 44). The study lasted for 5 weeks, and in groups 2 and 3 benazepril was added on top of valsartan after the first week of therapy with the angiotensin receptor blocker. Serum creatinine increased in all three groups (mean change within a group: 11 micromol/l in group 1, P= 0.045; 9 micromol/l in group 2, P= 0.030; 15 micromol/l in group 3, P= 0.0006). Serum potassium also increased in all three groups of patients (mean change within a group: 0.28 mmol/l in group 1, P= 0.28; 0.48 mmol/l in group 2, P= 0.0008; 0.36 mmol/l in group 3, P= 0.02). After 5 weeks of treatment, the largest decrease in blood pressure was observed in group 3 (the mean change from baseline in seated diastolic blood pressure (SDBP) and seated systolic blood pressure (SSBP), respectively, were: -2.0 and -11.5 mmHg in group 1; -7.6 and -15.4 mmHg in group 2; -12.6 and -21.6 mmHg in group 3). In addition, both combination treatments resulted in the reduction of proteinuria. The total number of patients with adverse experiences were 10 (45.5%), 14 (33.3%) and 11 (25%) in groups 1,2 and 3, respectively. In six patients (5.6%) therapy was discontinued as a result of adverse experiences. Only one patient in each of the combined therapy groups withdrew from the study because of hyperkalaemia and no patients were forced to withdraw because of an increase in serum creatinine, acute renal failure or hospitalization. These results indicate that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure.",2000.0,0,0
291,10679507,"Amlodipine, enalapril, and dependent leg edema in essential hypertension.",R Pedrinelli; G Dell'Omo; E Melillo; M Mariani,"Calcium channel blockers (CCBs) blunt postural skin vasoconstriction, an autoregulatory mechanism that minimizes gravitational increases in capillary pressure and avoids fluid extravasation when standing. To evaluate the dose-response relation between this pharmacological interference and dependent edema, a frequent side effect of CCBs during antihypertensive treatment, skin blood flow (laser Doppler flowmetry) at the dorsum of the foot, both supine and with the limb passively placed 50 cm below the heart level, and leg weight (Archimedes principle) were measured at baseline, during increasing doses of the dihydropyridine amlodipine (5 and 10 mg UID each for 2 weeks), and after drug withdrawal in 10 hypertensive men. Because angiotensin-converting enzyme inhibitors may attenuate ankle swelling by CCBs, those parameters were evaluated according to a similar design during amlodipine (10 mg UID) and enalapril (20 mg UID) combined (n=10). As a control, the effect of enalapril monotherapy (10 and 20 mg UID for 2 weeks each) was evaluated in a third series of patients (n=8). Amlodipine (5 mg UID) increased leg weight without modifying postural vasoconstriction (the percent skin blood flow decrease from horizontal to dependent position), which indicates that extravascular fluid shift was independent of postural skin vasoconstriction. At 10 mg UID, however, amlodipine blunted postural vasoconstriction and increased leg weight further, which suggests that skin blood flow autoregulation limited additional fluid transfer. Both parameters normalized after drug withdrawal. Enalapril per se did not affect cutaneous vasomotion or leg weight but reduced the amount of dependent fluid extravasation by the CCB despite a persistent antagonism for postural vasoconstrictor responses.",2000.0,0,0
292,10692268,Effect of antihypertensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease.,T Ecder; A B Chapman; G M Brosnahan; C L Edelstein; A M Johnson; R W Schrier,"Hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) have a faster progression to end-stage renal disease (ESRD) than their normotensive counterparts. The aim of this prospective, randomized study is to compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor enalapril as first-line therapy on blood pressure, renal function, and urinary albumin excretion in hypertensive patients with ADPKD. Twenty-four patients with ADPKD with hypertension with creatinine clearances (Ccrs) greater than 50 mL/min/1.73 m(2) were included in the study. Twelve patients received amlodipine (mean dose, 9 mg/d), and 12 patients received enalapril (mean dose, 17 mg/d). The patients were followed up for 5 years. Baseline mean arterial pressures, which were 109 +/- 3 mm Hg in the amlodipine group and 108 +/- 3 mm Hg in the enalapril group, decreased significantly after 1 year of follow-up (amlodipine, 96 +/- 3 mm Hg; P < 0.005; enalapril, 89 +/- 2 mm Hg; P < 0.0005) and remained stable at year 5 (amlodipine, 97 +/- 3 mm Hg; P < 0.0005 versus baseline; enalapril, 94 +/- 3 mm Hg; P < 0.005 versus baseline). Ccrs, which were 83 +/- 5 mL/min/1.73 m(2) in the amlodipine group and 77 +/- 6 mL/min/1.73 m(2) in the enalapril group, remained stable after 1 year of follow-up and decreased significantly at year 3 in both groups (amlodipine, 67 +/- 5 mL/min/1.73 m(2); P < 0.01 versus year 1 and baseline; enalapril, 58 +/- 4 mL/min/1.73 m(2); P < 0.05 versus year 1 and P < 0.0005 versus baseline) with no significant change thereafter. No change was observed in urinary albumin-creatinine ratio in the amlodipine group (baseline, 68 +/- 21 mg/g; year 1, 52 +/- 21 mg/g; year 5, 148 +/- 74 mg/g), whereas it decreased significantly in the enalapril group at year 1 (baseline, 23 +/- 4 mg/g; year 1, 13 +/- 3 mg/g; P < 0.05) and remained stable until the end of the study at year 5 (14 +/- 6 mg/g). The investigators concluded that blood pressure was similar in both groups but only enalapril had a significant effect to sustain decreased urinary albumin excretion for a 5-year follow-up. Although proteinuria has been considered a surrogate of renal disease progression, further studies will be necessary to confirm this hypothesis in ADPKD, because after 5 years, no differences in renal function were observed between the enalapril and amlodipine groups. In comparison with patients with ADPKD with uncontrolled hypertension, effective control of blood pressure, as undertaken in the present study, should delay the onset of ESRD by approximately 15 years.",2000.0,0,0
293,10692751,The effect of valsartan and captopril on lipid parameters in patients with type II diabetes mellitus and nephropathy.,R Cheung; R Z Lewanczuk; N W Rodger; M W Huff; P Oddou-Stock; F Botteri; E Pecher; N Muirhead,"The study compared valsartan 80 mg or 160 mg o.d. with captopril 25 mg t.i.d. or placebo on plasma lipids in normotensive and treated hypertensive patients with type II diabetes and microalbuminuria. One hundred and twenty-two adult outpatients were randomised to receive either valsartan 80 mg or 160 mg, captopril 25 mg or placebo for 360 days. Changes from baseline to endpoint in plasma lipid parameters were measured. The primary criterion for tolerability was the incidence of adverse events. All treatment groups showed minor changes in lipid parameters. Triglyceride increased by 2.7% (valsartan 160 mg) to 9.1% (placebo). Total cholesterol decreased under valsartan 80 mg, while other groups showed increases of up to 0.031 mmol/l. Decreases in total cholesterol (p = 0.018), apolipoprotein B (p = 0.042) and apolipoprotein A1 (p = 0.025), were significant for the comparison of 80 mg valsartan and captopril. Valsartan 80 mg or 160 mg o.d. does not cause deleterious changes in the diabetic lipid profile and, unlike captopril, is not associated with dry cough.",2000.0,0,0
294,10694829,Does Chinese ethnicity affect the pharmacokinetics and pharmacodynamics of angiotensin-converting enzyme inhibitors?,P Y Ding; O Y Hu; P E Pool; W Liao,"Information from clinical and pharmacokinetic studies of angiotensin-converting enzyme inhibitors (ACEIs) has come from subjects who are mostly male and Caucasian, but the use of ACEIs extends to populations worldwide. Significant differences between Chinese in general and male Caucasians have been demonstrated in the pharmacokinetics/dynamics of other drug classes that could have implications for the use of ACEIs in the Chinese population. These include: significant Chinese/Caucasian genetic variation in the renin-angiotensin system based on an insertion/deletion (O/D) polymorphism of the ACE gene; the genetic determination of plasma ACE activity in the Chinese population; and genetic factors involving the disease substrate which may also influence the response to treatment. Oral and IV pharmacokinetic data from various studies of Chinese and Caucasian subjects are available for cilazapril, fosinopril, and perindopril, and pharmacodynamic data are available for eight different ACEIs. Based on these data, there are few differences among the pharmacokinetics of ACEIs between Chinese and Caucasians. Most ACEIs showed good blood pressure lowering efficacy in Chinese (benazepril, enalapril, fosinopril and spirapril), with perhaps less blood pressure lowering with cilazapril or a relatively shorter-term effect with cilazapril or perindopril compared to Caucasions. Chinese experience more cough from ACEIs (captopril and enalapril) than Caucasians. Data suggest that fosinopril may not induce cough in as many subjects as other ACEIs, and this seems to be true of Chinese as well. The mechanism, currently unknown, could involve fosinopril's dual elimination pathway (hepatic and renal). Pharmacokinetic data also support the use of fosinopril in congestive heart failure where elimination pathways may be impaired. In conclusion, ethnic differences between Chinese and Caucasians with respect to ACE and AGT gene polymorphism, which might be expected to differentially affect the action of ACEIs in these two ethnic groups, do not, in fact, have such an effect. Rather, differences among the ACEIs appear to be more important. Journal of Human Hypertension (2000) 14, 163-170.",2000.0,0,0
295,10694831,Induction of insulin resistance by beta-blockade but not ACE-inhibition: long-term treatment with atenolol or trandolapril.,R Reneland; E Alvarez; P E Andersson; A Haenni; L Byberg; H Lithell,"The effects on glucose metabolism by the beta-blocker atenolol and the angiotensin-converting enzyme (ACE)-inhibitor trandolapril were investigated in a randomised double-blind parallel group study of patients with primary hypertension. Twenty-six patients were treated with 50-100 mg atenolol and 27 patients with 2-4 mg trandolapril o.d. Intravenous glucose tolerance tests, euglycaemic hyperinsulinaemic clamps and serum lipid measurements were performed after 8 and 48 weeks of active treatment. After 48 weeks insulin sensitivity was reduced by 23% by atenolol while it remained unchanged during trandolapril treatment (+0.5%, P = 0.0010 for difference between treatments, ANCOVA). The effect on triglycerides (+22% vs -8.5%) and high-density lipoprotein cholesterol (-13% vs +0.7%) also differed significantly between atenolol and trandolapril. Results after 8 weeks were similar. Glucose tolerance was not affected by either drug. Atenolol reduced diastolic blood pressure (DBP) better than trandolapril (-15.3 mm Hg vs -6.6 mm Hg for supine DBP after 48 weeks, P = 0.012). The difference in effect on insulin sensitivity between the drugs corresponded to 25% of the baseline values of insulin sensitivity, and persisted over 48 weeks of treatment. The choice of antihypertensive treatment could influence the risk of diabetes associated with treated hypertension. Journal of Human Hypertension (2000) 14, 175-180.",2000.0,0,0
296,10696996,Angiotensin II receptor antagonists.,M Burnier; H R Brunner,"Blockade of the renin-angiotensin system began as a way of studying the pathogenesis of cardiovascular disease with specific pharmacological probes. Oral activity, achieved by shortening the original peptide structures, transformed the probes into therapeutic agents, the angiotensin-converting enzyme (ACE) inhibitors. However, ACE is a non-specific target for blocking the renin-angiotensin enzymatic cascade. The availability of orally active drugs turned ACE inhibition into a therapeutic breakthrough but more specific blockade always seemed desirable. This goal has now been achieved with the orally active angiotensin II receptor antagonists; six are on the market and more are under development. This new class of drugs is equal in efficacy to ACE inhibitors, at least in hypertensive patients. Trials now underway will demonstrate whether angiotensin II receptor antagonists can prevent target-organ damage and reduce cardiovascular morbidity and mortality. If they do, these compounds might one day replace ACE inhibitors.",2000.0,0,0
297,10698231,Angiotensin-converting enzyme inhibitor therapy affects myocardial fatty acid metabolism after acute myocardial infarction.,S Fukuzawa; S Ozawa; M Inagaki; J Sugioka; M Daimon; S Kushida,"Angiotensin-converting enzyme (ACE) inhibitor therapy has an early mortality benefit in unselected patients with acute myocardial infarction (AMI). However, the effects of ACE inhibition on myocardial fatty acid metabolism in this patient population have not been studied. We tested the hypothesis that ACE inhibitor therapy improves myocardial fatty acid metabolism and decreases mortality rate in patients after AMI. Forty-two patients after first anterior AMI and primary angioplasty were randomly assigned to titrated oral enalapril (n = 24) or placebo therapy (n = 18). Iodine 123-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) single photon emission computed tomography imaging was performed an average of 4.8 days after AMI and 1 month after AMI. BMIPP abnormalities were quantified as a severity index by a polar map. There were no significant changes in baseline characteristics, cardiac function, and angiographic findings between patients in the enalapril group and patients in the placebo group. However, BMIPP severity index from acute phase to chronic phase was significantly decreased in the enalapril-treated group (118+/-48 to 82+/-36, P<.05), but not in the placebo group (123+/-65 to 115+/-58, P not significant). ACE inhibition therapy improved myocardial fatty acid metabolism and regional left ventricular function in patients after anterior AMI. BMIPP single photon emission computed tomography findings imply that this better outcome may be attributable to an improvement of cellular function with ACE inhibitors.",2000.0,0,0
298,10698886,ABC of heart failure: Heart failure in general practice.,F D Hobbs; R C Davis; G Y Lip,,2000.0,0,0
299,10701819,Electronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimen.,M Andrejak; N Genes; L Vaur; P Poncelet; P Clerson; A Carré,"The objective was to compare the compliance of hypertensive patients treated with captopril twice daily or trandolapril once daily. After a 2-week placebo period, hypertensive patients (diastolic BP 95-115 mm Hg) were randomly allocated to trandolapril 2 mg once daily or to captopril 25 mg twice daily for 6 months. Trandolapril and captopril were packed in electronic pill-boxes equipped with a microprocessor that recorded date and time of each opening (MEMS). Patients' compliance was assessed both by standard pill-count and by electronic monitoring. Blood pressure was measured using a validated semi-automatic device at the end of the placebo period and of the treatment period. One hundred sixty-two patients entered the study. Compliance data were evaluable for 133 patients (62 in the captopril group and 71 in the trandolapril group). Treatment groups were comparable at baseline except for age (P = .046). Using electronic pill-box, overall compliance was 98.9% in the trandolapril group and 97.5% in the captopril group (P = .002). The percentage of missed doses was 2.6% in the trandolapril group and 3.3% in the captopril group (P = .06). The percentage of delayed doses was 1.8% in the trandolapril group and 11.7% in the captopril group (P = .0001). The percentage of correct dosing periods, ie, a period with only one correct recorded opening, was 94.0% in the trandolapril group and 78.1% in the captopril group (P = .0001). Results were unchanged when adjusted for age. At the end of the study, 41% of patients in the trandolapril group and 27% in the captopril group (NS) had their blood pressure normalized (systolic BP <140 and diastolic BP <90 mm Hg). In this 6-month study, the electronic pill-box allowed refined analysis of compliance of hypertensive patients. Patients' compliance with once daily trandolapril was higher than with twice daily captopril. The between-group difference is mainly explained by an increase in delayed doses in the twice daily group.",2000.0,0,0
300,10701823,Candesartan cilexetil is not associated with cough in hypertensive patients with enalapril-induced cough. Multicentre Cough Study Group.,P H Tanser; L M Campbell; J Carranza; J Karrash; P Toutouzas; R Watts,"The aim of this study was to evaluate the occurrence of dry cough during treatment with candesartan cilexetil, enalapril, or placebo in patients with hypertension and a history of angiotensin converting enzyme (ACE)-inhibitor-related cough. Patients with confirmed cough during an enalapril (10 mg) challenge period, followed by no cough during a placebo dechallenge period were randomized to 8 weeks of double-blind treatment with candesartan cilexetil (8 mg) (n = 62), enalapril (10 mg) (n = 66), or placebo (n = 26). Incidence and severity of dry cough was evaluated by the symptom assessment questionnaire, frequency of dry cough by a visual analog scale, and the possible impact on quality of life by the minor symptom evaluation (MSE) profile. The percentage of patients with cough was significantly lower with candesartan cilexetil (35.5%) than with enalapril (68.2%, P < .001), and did not differ between candesartan cilexetil and placebo (26.9%, P > .20). Patients coughed less frequently and with less severe cough with candesartan cilexetil than with enalapril, and similarly with candesartan cilexetil and placebo. Changes in the MSE profile were minor, although candesartan cilexetil had better scores for contentment than placebo (P = .03), and also tended to be associated with better sleep than enalapril (P = .08). In hypertensive patients with ACE-inhibitor-induced cough, the incidence, frequency, and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril, and no different from that found with placebo.",2000.0,0,1
301,10703873,Use of computerized neuropsychological tests (CANTAB) to assess cognitive effects of antihypertensive drugs in the elderly. Cambridge Neuropsychological Test Automated Battery.,W J Louis; A G Mander; M Dawson; C O'Callaghan; E L Conway,"To establish reliability and ease of use of the Cambridge Neuropsychological Test Automated Battery (CANTAB) in assessing changes in cognitive function induced by antihypertensive drugs. Standard neuropsychological testing was combined with CANTAB in a double-blind 18-week cross-over study in elderly hypertensives taking perindopril or hydrochlorothiazide/triamterene (HT). Cognitive effects were assessed by employing tests of attention, visuospatial and verbal memory, learning, reasoning, planning, problem solving, speed and coordination. Affect was assessed using two different depression-rating scales. Perindopril and the diuretic had no adverse effects on the various aspects of cognitive function. Mood, as assessed by the Hamilton Depression Rating Scale and the Beck Depression Inventory, was improved on Perindopril, and the error rate in the motor screening test was lower. Ambulatory blood pressure monitoring showed both drugs achieved effective 24-h control. The ease of use and the ability to adjust the level of testing to the requirements of individual patients, together with the reliability of longitudinal test/re-test results, indicates that CANTAB is an important addition to the methods available to quantitate adverse central nervous system drug effects. The other purpose of the study was to assess any adverse cognitive effects of perindopril against a drug HT believed to have no adverse central nervous system effects. In this context, perindopril was free of adverse effects in all the objective tests employed. In addition, there was a benefit seen in two independent assessments of depression (the Hamilton and the Beck rating scales).",2000.0,0,0
302,10703890,Prospective comparison of therapeutical attitudes in hypertensive type 2 diabetic patients uncontrolled on monotherapy. A randomized trial: the EDICTA study.,L M Ruilope; A de la Sierra; E Moreno; R Fernández; J Garrido; M de la Figuera; A G de la Cámara; A Coca; M Luque-Otero,"To compare the anti-hypertensive effect of combination therapy versus a single drug regimen schedule (dose-titration or switching to a different drug class) in type 2 diabetic hypertensive patients with inadequate blood pressure (BP) control on monotherapy. Prospective, randomized, open-fashion, parallel study of two therapeutic strategies during an 8-week period. Primary care centers in Spain. A total of 898 men and women with type 2 diabetes mellitus and hypertension, receiving antihypertensive treatment with one single drug and whose BP was > 140 and/or 90 mmHg. Patients were randomized to a fixed combination therapy (verapamil 180 mg plus trandolapril 2 mg; Knoll AG, Ludwigshafen, Germany) or continued on a single drug regimen, either increasing the dose of the current drug or switching to a different drug class. Absolute BP reduction in the two groups of treatment, and the percentage of normalized patients (< 140/90 mmHg) in each group. The diastolic BP (DBP) decrease (5.6 mmHg) was significantly greater in patients treated with combination therapy, compared to patients on monotherapy (2.9 mmHg). The decrease in systolic BP (SBP) was not significantly different (11.1 versus 10.0 mmHg). In addition, a significantly higher number of patients treated with combination therapy (82% versus 74%) reached diastolic BP normalization (< 90 mmHg). In type 2 hypertensive patients with uncontrolled BP despite anti-hypertensive monotherapy, the change to combination therapy was more effective in attaining DBP control than any monotherapy schedule (either increasing the dose or switching to another different drug class).",2000.0,0,0
303,10707752,Long-term effects of clinical outcome with low and high dose in the Captopril in Heart Insufficient Patients Study (CHIPS).,D L Clement; M De Buyzere; M Tomas; G Vanavermaete,"Although angiotensin-converting enzyme inhibitors are recommended as first line therapy in patients with chronic heart failure, the target doses proven to be effective in major morbidity and mortality trials (e.g. captopril 50 mg b.i.d), are generally not used in daily practice in Belgium. The objective of this study (CHIPS, Captopril in Heart Insufficient Patients Study) was to compare the long-term effects of a low dose (25 mg b.i.d.) and a high dose (50 mg b.i.d.) of captopril in mild to moderate heart failure. After a titration period of at least 10 days, patients who tolerated 50 mg b.i.d., were randomly assigned to receive either the low dose or the high dose of captopril and followed up to 2 years. 298 patients were included and were followed up for a mean of 12 months. Progression in heart failure seems to be favourably influenced by therapy with high dose in comparison to low dose; a relative difference of 29% in the rates of heart failure worsening was observed between the two doses, 31.5% and 22.4% for low and high dose (p = 0.088), respectively. Treatment with high dose showed also a trend to benefit as compared to low dose in reducing the number of hospitalizations for all causes from 22.4 to 14.5% (p = 0.1) and for congestive heart failure from 14.7 to 7.2% (p = 0.06); moreover, the incidence of fatal and nonfatal cardiac events showed a trend in favour of the high dose of 22% (p = 0.142). The total number of adverse events was comparable for both doses, but dizziness and hypotension were a little more frequently reported in the high-dose group. Serum creatinine values showed no significant changes either in the low-dose or in the high-dose group. In the CHIPS-study, in comparison to a low dose, therapy with a high dose of captopril tends to improve the long-term clinical outcome of patients with mild to moderate heart failure without significantly more toxicity.",2000.0,0,0
304,10711307,Avoiding adverse reactions. Effective lower-dose drug therapies for older patients.,J S Cohen,"Adverse drug reactions (ADRs) are a leading cause of morbidity and mortality, with the highest incidence occurring in patients age 60 and older. Prescribing the lowest effective doses of medications to older patients can help avoid ADRs, minimize bothersome side effects, and increase rates of compliance. For many drugs, clinical experience and published studies demonstrate the effectiveness of doses substantially lower than those recommended in standard references. This article examines the problem of ADRs in older patients, discusses pharmacokinetic data regarding older versus younger adults, and provides effective lower doses for many common drugs.",2000.0,0,0
305,10713875,Profound bradycardia and hypotension following spinal anaesthesia in a patient receiving an ACE inhibitor: an important 'drug' interaction?,N E Williams,"An 86-year-old man on whom a transurethral resection of prostate was performed under spinal anaesthesia developed profound bradycardia and hypotension with disturbance of consciousness during transfer to the recovery room. Initial treatment with atropine produced rapid improvement in cardiovascular and cerebral function. A further hypotensive episode (without bradycardia) occurred approximately 1 h later but responded rapidly to methoxamine. The patient made a full recovery during an overnight stay on the High Dependency Unit. Possible mechanisms for this event are discussed, with the proposal that the concomitant administration of captopril and the relative unavailability of Angiotensin II may have significantly contributed to the problem.",2000.0,0,0
306,10715761,ACE inhibitors and heart failure in hospital: any difference between cardiologists and general physicians?,A P Davie; J J McMurray,"Cardiologists and generalists have been reported to diverge in terms of their self-reported use of angiotensin-converting enzyme (ACE) inhibitors, but information on their actual use of ACE inhibitors has been lacking. In order to assess ACE inhibitor use in patients with heart failure in a teaching hospital and any differences between specialties we studied all patients in the Western Infirmary of Glasgow between 1 April and 1 October 1996 with an echocardiogram showing moderate or severe left ventricular systolic dysfunction (n = 236). We found that most patients were on an ACE inhibitor (66%), 12% had been tried but found to be intolerant, 10% had not been tried because of a contraindication, but 12% had not been tried despite no contraindication. Of those on treatment, 58% were on a dose used in a major survival study (38% of all patients). Most patients were treated by a cardiologist (64%). Of these, more were on an ACE inhibitor (77% vs 53%, p < 0.01), fewer had been tried but found intolerant (11% vs 18%), and fewer had never been tried (11% vs 29%, p < 0.01), irrespective of whether they had a contraindication (5% vs 18%, p < 0.01) or not (6% vs 12%). More were on a dose used in a major survival study (48% vs 31%, p < 0.05). We conclude that, despite improvements over time, ACE inhibitors are still under-used, sometimes without good reason. There are also differences in the use of ACE inhibitors between cardiologists and generalists which may affect outcome, and could affect resource utilisation.",2000.0,0,0
307,10716135,Efficacy and safety of valsartan compared with enalapril at different altitudes.,R Botero; H Matiz; E María; H Orejarena; M Blanco; J R Velez; H Del Portillo,"To compare the safety, tolerability, and antihypertensive efficacy of valsartan with enalapril at different altitudes. A total of 142 adult Colombian outpatients with mild to moderate essential hypertension were recruited in 3 cities at different altitudes (Bogotá at 2600 m, Medellin at 1538 m and Barranquilla at 100 m) and randomized in an open label fashion to receive either valsartan 80 mg once daily or enalapril 20 mg once daily for 8 weeks. Those patients not responding at 4 weeks received additional 1.25 mg indapamide daily during the remaining trial period. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to 4 weeks. Secondary efficacy variables included the change in mean sitting systolic blood pressure (SSBP). The primary criterion for tolerability was the incidence of adverse experiences. Both valsartan and enalapril reduced mean SDBP and SSBP with similar efficacy, independent of altitude. Adverse events irrespective of relationship to trial drug were reported by 12 patients (18.8%) on valsartan and by 15 (23.4%) patients on enalapril. Enalapril was associated with a significantly (P<0.05) higher rate of dry cough and more cases of headache than valsartan. Valsartan 80 mg once daily is as effective as enalapril 20 mg once daily in reducing blood pressure, with tolerability profile at least as good as enalapril's.",2000.0,0,0
308,10716471,The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction.,D L Dries; D V Exner; M J Domanski; B Greenberg; L W Stevenson,"The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction. Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function. This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation. In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (RR 1.41; p = 0.001), also largely explained by an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001). Even moderate degrees of renal insufficiency are independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression.",2000.0,0,0
309,10716520,Effect of beta-blocker therapy on severe ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy.,S Inoue; Y Yokota; H Takaoka; H Kawai; M Yokoyama,"Beta-blocker therapy has been shown to improve cardiac function and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). However, whether beta-blockers reduce severe ventricular arrhythmias and sudden cardiac death has not been clarified. The present study was designed to investigate the effects of beta-blockers on non-sustained ventricular tachycardia (VT) and sudden cardiac death in patients with DCM. Sixty-five patients with DCM treated with diuretics, digitalis and angiotensin-converting enzyme inhibitors were assigned to receive beta-blockers (n = 33) or not (n = 32). Mean follow-up was 53+/-30 months. The echocardiographic indices of cardiac function, the incidence of non-sustained VT on Holter monitoring electrocardiograms, and sudden cardiac death rate were compared between the 2 groups. Comparable improvement in cardiac function on echocardiograms was found in the 2 treatment groups. The patient group treated with beta-blockers showed a significant reduction in the prevalence of VT (from 43 to 15%, p<0.05) and the development of new episodes of VT (5 vs. 16%) compared to the group without beta-blockers. The sudden cardiac death rate did not differ between the 2 groups. The results of the present study suggest that beta-blockers are effective in reducing severe ventricular arrhythmias in patients with DCM.",2000.0,0,0
310,10716552,Taste effects of lingual application of cardiovascular medications.,J Zervakis; B G Graham; S S Schiffman,"Medications used to treat cardiovascular diseases such as congestive heart failure, high blood pressure, and arrhythmia, are prescribed extensively in Western countries. However, taste complaints are common side effects of many of these cardiovascular medications. Although clinical observations are helpful in determining potential taste problems from a medication, experimental studies are necessary to obtain quantitative data on taste. In the studies performed here, nine cardiovascular medications (labetalol HCl, captopril, diltiazem HCl, enalapril maleate, hydrochlorothiazide, propranolol HCl, mexiletine HCl, procainamide HCl, and propafenone HCl) were applied to the tongue in human volunteers to measure the direct effect of these drugs on taste receptors. The medications were applied topically to the tongue surface of both young and elderly subjects to mimic the situation in which the drug is secreted into the saliva. Detection thresholds ranged from 0.048 mM (propafenone) to 0.438 mM (procainamide). The detection thresholds of healthy elderly subjects did not significantly differ from young controls. The compounds tested had a predominantly bitter taste with other qualities as well. In addition, topical application of the medications to the tongue affected the taste of one or more taste stimuli, with medications differing in the pattern of taste effects exhibited. The mechanism of taste effects is not fully known, but the results of this study suggest one route may be due to medications' effect on peripheral taste receptors.",2000.0,0,0
311,10719438,Treatment of arterial hypertension in the elderly using enalapril.,R Terranova; S Luca; A Calanna,"Arterial pressure increases with age and is the most common chronic disease in the elderly, men and women alike. At present arterial hypertension is considered a social disease as it poses great health, economic and social problems. A group of 50 patients of both sexes, between 66 and 83 years of age, suffering from essential arterial hypertension and treated with Enalapril administered at doses varying from 10 to 20 mg/day, for a period of 18 months, has been studied. The results of this study showed that blood pressure values of almost all the patients treated normalised and left ventricular hypertrophy decreased in all patients with this complication.",2000.0,0,0
312,10721643,Captopril for prevention of contrast-induced nephropathy in diabetic patients: a randomised study.,R K Gupta; A Kapoor; S Tewari; N Sinha; R K Sharma,"Contrast-induced nephrotoxicity is an important cause of hospital-acquired acute renal insufficiency. Different modalities have been used to prevent contrast induced-nephrotoxicity namely saline infusion, mannitol, furosemide, calcium channel blockers, atrial natriuretic factor and dopamine infusion with variable success. The possible role of medullary ischaemia mediated by renin angiotensin system in genesis of contrast-induced nephrotoxicity prompted us to investigate the role of captopril (a sulfhydryl group containing angiotensin-converting enzyme inhibitor) in its prevention. Seventy-one patients of diabetes mellitus undergoing coronary angiography were included in the study. Patients randomised to receive captopril, received the drug in a dose of 25 mg thrice a day for three days, starting one hour prior to angiography while the patients in the control group underwent angiography in a routine manner without receiving captopril. Following angiography, patients in the control group developed a significant increase in serum creatinine and blood urea nitrogen levels, as compared to those who received captopril. Contrast-induced nephrotoxicity (i.e. a rise of 0.5 mg/dL in serum creatinine) developed in 29 percent of the control group. Administration of captopril reduced the risk of development of contrast-induced nephrotoxicity by 79 percent. Glomerular filtration rate as measured by Tc DTPA renal scanning prior to and 24-72 hours following angiography demonstrated a mean fall of 9.6 ml/min in the control group while those in the captopril group had a mean increase of 13 ml/min in glomerular filtration rate. We conclude that abnormalities of renal perfusion possibly mediated by renin angiotensin system are responsible for development of contrast-induced nephrotoxicity. Administration of the angiotensin-converting enzyme inhibitor, captopril, offers protection against development of contrast-induced nephrotoxicity.",2000.0,0,0
313,10723978,Management of patients with hypertension and diabetes mellitus: advances in the evidence for intensive treatment.,W B White; L M Prisant; J T Wright,"Diabetes mellitus is common in patients with hypertension, and greatly increases the risk of cardiovascular disease, including myocardial infarction, stroke, and peripheral vascular disease. ""The pharmacologic therapy of patients with hypertension and diabetes has been surrounded by controversy because of concerns about the metabolic effects of several antihypertensive agents, as well as concerns about the safety of calcium antagonists. The objective of this review is to re-evaluate the management of diabetic patients with hypertension in light of the latest clinical trials. We also review the importance of intensive blood pressure control in these patients.",2000.0,0,0
314,10724055,Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?,G L Bakris; M R Weir,"Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACEIs) slows nephropathy progression in patients with or without diabetes. Post hoc analyses of many ACEI-based clinical trials demonstrate the greatest slowing of renal disease progression in patients with the greatest degree of renal insufficiency at study initiation. However, many physicians fail to use ACEIs or angiotensin receptor blockers in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise. To determine if limited initial reduction in either glomerular filtration rate (GFR) or elevation in serum creatinine levels, associated with ACEI or angiotensin receptor blocker use, results in long-term protection against decline in renal function in patients with renal insufficiency. We reviewed 12 randomized clinical trials that evaluated renal disease progression among patients with preexisting renal insufficiency. Six of these studies were multicenter, double-blinded, and placebo controlled, with the remainder being smaller randomized studies with a minimum 2-year follow-up on renal function. These investigations evaluated patients with and without diabetes or systolic heart failure. Average duration of follow-up for all studies was 3 years. Trials were examined in the context of changes in either serum creatinine levels or GFR in the group randomized to an ACEI (N = 1,102). Sixty-four percent of these individuals (705/1,102) had renal function data at both less than 6 months and at the end of the study. Most trials demonstrated that patients with preexisting renal insufficiency manifested an acute fall in GFR, a rise in serum creatinine, or both. Those randomized to an ACEI with a serum creatinine level of 124 pmol/L or greater (> or =1.4 mg/dL) demonstrated a 55% to 75% risk reduction in renal disease progression compared with those with normal renal function randomized to an ACEI. An inverse correlation was observed between the amount of renal function loss at baseline and the subsequent rate of annual decline in renal function following randomization to an antihypertensive regimen that contained an ACEI. A strong association exists between acute increases in serum creatinine of up to 30% that stabilize within the first 2 months of ACEI therapy and long-term preservation of renal function. This relationship holds for persons with creatinine values of greater than 124 pmol/L (>1.4 mg/dL). Thus, withdrawal of an ACEI in such patients should occur only when the rise in creatinine exceeds 30% above baseline within the first 2 months of ACEI initiation, or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.",2000.0,0,0
315,10726719,Fixed low-dose combination therapy in hypertension--a dose response study of perindopril and indapamide.,M G Myers; R Asmar; F H Leenen; M Safar,"To establish the optimal dose of the perindopril/indapamide combination (Per/Ind) in the treatment of mild or moderate hypertension. This was a randomized, double-blind, placebo-controlled, seven-way parallel-group, dose-ranging study, set in multicenter, outpatient offices/clinics in Europe and Canada. A total of 438 patients aged between 18 and 75 years whose supine diastolic blood pressure was between 95 and 114 mmHg were randomly assigned to an 8-week double-blind treatment with either placebo, Per 2/Ind 0.625, Per 4/Ind 1.25, Per 8/Ind 2.5, Per 0/Ind 1.25, Per 2/Ind 1.25 or Per 8/Ind 1.25 mg. Systolic and diastolic blood pressure measured in the clinic approximately 24 h after dosing. There was a linear dose-response relationship (P<0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in supine diastolic blood pressure (-9.3 to -15.0 mmHg). Combining 1.25 mg Ind with increasing doses of Per (0, 2, 4 and 8 mg) also showed a linear dose-response relationship (P<0.001), with supine diastolic blood pressure falling by -8.0 to -12.0 mmHg compared with a fall of -5.2 mmHg for the placebo group. Similar findings were noted for supine systolic blood pressure, standing blood pressure and ambulatory blood pressure. Hypokalemia was more common (9.7%) in the Per 8/Ind 2.5 mg group than in the groups receiving other doses (0-4.6%). The combinations of Per 2/Ind 0.625 mg and Per 4/Ind 1.25 mg were effective in reducing blood pressure without producing clinically important side effects.",2000.0,0,0
316,10726720,"Long-term efficacy of a new, fixed, very-low-dose angiotensin-converting enzyme-inhibitor/diuretic combination as first-line therapy in elderly hypertensive patients.",J Chalmers; A Castaigne; T Morgan; C Chastang,"To determine the long-term efficacy and safety of a fixed, very-low-dose tablet combining one-half the standard dose of perindopril with one-quarter the standard dose of indapamide as first-line treatment in elderly patients. Double-blind, randomized, placebo-controlled study in an outpatient setting. Following a single-blind, placebo run-in period of 4 weeks, patients [65-85 years, with mild-to-moderate essential hypertension or isolated systolic hypertension (ISH)] were randomized to receive one tablet of perindopril 2 mg/indapamide 0.625 mg (Per/ Ind) (n=193) or placebo (n=190), daily for 12 weeks. After this first 12-week period, all patients on Per/Ind (n=138) and patients responding to placebo (n=61) were maintained on their previous regimen for a further 48 weeks. Patients in the placebo group whose blood pressure was not normalized, were switched to Per/Ind (n=60). The primary endpoint was the proportion of patients with blood pressure that normalized between weeks 0 and 60. After 1 year of treatment (intention-to-treat) supine systolic and diastolic blood pressure decreased by 23.0 +/- 15.3 mmHg and 13.3 +/- 94 mmHg with Per/Ind (n=253: 193 from randomized Per/Ind group and 60 from the placebo group switched at week 12). The mean decreases in systolic blood pressure were similar in essential hypertension and ISH (systolic blood pressure 23.2 versus 22.7 mmHg, respectively). Per/Ind treatment (n=253) achieved an initial normalization of blood pressure in 96.2% [95% confidence interval (CI) 93.6-98.9%; Kaplan-Meier estimate] of Per/Ind-treated patients; 79.8% (95% CI 74.1-85.5%) of these maintained a normalized blood pressure throughout the 1 -year follow-up. The incidence of adverse events was similarly low in the placebo and active therapy groups. Efficacy and safety results for the over 75 years subgroup were similar to those for the younger elderly subjects The fixed, very low-dose combination of perindopril 2 mg/indapamide 0.625 mg results in sustained blood pressure control when used as first line treatment of elderly hypertensive patients over 1-year, and is well-tolerated.",2000.0,0,0
317,10730685,Evaluation and management of drug-induced thrombocytopenia in the acutely ill patient.,L D Wazny; R E Ariano,"The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug-induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug-induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune-mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.",2000.0,0,0
318,10731402,New Q waves on the presenting electrocardiogram independently predict increased cardiac mortality following a first ST-elevation myocardial infarction.,J Andrews; J K French; S O Manda; H D White,"The prognostic significance of pathological Q waves appearing in the acute phase of myocardial infarction has not been determined. We investigated whether new Q waves on the presenting electrocardiogram of patients with acute ST-segment elevation were independently associated with a worse outcome after a first myocardial infarction. The presence or absence of new Q waves on the presenting electrocardiogram was assessed in 481 patients who presented within 4 h of symptom onset and were randomized to receive either captopril or placebo within 2 h of streptokinase therapy for myocardial infarction. Ventriculography was performed at 22+/-6 days and mortality status was obtained at a median follow-up of 5.6 years. New Q waves were associated with a lower ejection fraction (51+/-13% vs 61+/-12%, P<0.0001), a larger end-systolic volume index (37 ml vs 28 ml, P<0.001), and increased cardiac mortality at 30 days (7% vs 2%, P=0.01) and at follow-up (17% vs 7%, P=0.002). On multivariate analysis, age (P<0.01), new Q waves at presentation (P<0.01) and a history of angina (P=0.046) were independent predictors of cardiac mortality, whereas randomization to captopril and the time from symptom onset to streptokinase administration were not. New Q waves at presentation are independently associated with a worse outcome after a first myocardial infarction. The presence of new Q waves on the presenting electrocardiogram allows very early identification of patients at risk of increased cardiac mortality.",2000.0,0,0
319,10732883,The Angiotensin-converting Enzyme Inhibition Post Revascularization Study (APRES).,L Kjøller-Hansen; R Steffensen; P Grande,"This study was performed to assess the effect of treatment with ramipril on the incidence of cardiac events after invasive revascularization in patients with asymptomatic moderate left ventricular dysfunction. In patients with angina pectoris and left ventricular dysfunction, both invasive revascularization and treatment with angiotensin-converting enzyme inhibitors reduce cardiac mortality and morbidity. Whether there is a benefit from combining the two treatment strategies has never been evaluated prospectively. After invasive revascularization, 159 patients with preoperative chronic stable angina pectoris, left ventricular ejection fraction between 0.30 and 0.50 and no clinical heart failure were randomly assigned to receive double-blind treatment with either ramipril or placebo and subsequently followed for a median of 33 months. Ramipril reduced the incidence of the triple-composite end point of cardiac death, acute myocardial infarction or clinical heart failure (risk reduction 58%; 95% confidence interval 7% to 80%, p = 0.031). The incidence of the quadruple-composite end point of cardiac death, acute myocardial infarction, clinical heart failure or recurrent angina pectoris was not altered with ramipril. These findings were consistent across subgroups with respect to left ventricular ejection fraction below or above 0.40, and whether coronary artery bypass grafting or percutaneous transluminal coronary angioplasty was performed. In patients with angina pectoris and asymptomatic moderate left ventricular dysfunction, long-term treatment with ramipril after invasive revascularization significantly reduced the incidence of the composite end point of cardiac death, acute myocardial infarction or clinical heart failure, indicating that the beneficial effects of angiotensin-converting enzyme inhibitor treatment may be extended to include treatment of this patient group.",2000.0,0,0
320,10737282,Regional and racial differences in response to antihypertensive medication use in a randomized controlled trial of men with hypertension in the United States. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,W C Cushman; D J Reda; H M Perry; D Williams; M Abdellatif; B J Materson,"Stroke incidence and mortality rates are higher in the southeastern region of the United States, which is called the ""Stroke Belt."" We compared the response to antihypertensive medication use in patients from different US regions. The short-term and 1-year efficacy of the antihypertensive medications hydrochlorothiazide, atenolol, diltiazem hydrochloride (sustained release), captopril, prazosin hydrochloride, and clonidine was compared by US region in a randomized controlled trial of 1,105 men with hypertension from 15 US Veterans Affairs medical centers. Compared with patients outside the Stroke Belt, patients inside the Stroke Belt achieved significantly lower treatment success rates of diastolic blood pressure control at 1 year with hydrochlorothiazide (63% vs 41%), atenolol (62% vs 46%), captopril (60% vs 30%), and clonidine (69% vs 43%); there were no differences in treatment success rates with diltiazem (70% vs 71%) or prazosin (54% vs 53%). When controlling for race, patients inside the Stroke Belt had significantly lower treatment success rates with hydrochlorothiazide (P = .003) and clonidine (P = .003), and the lower success rate with atenolol approached significance (P = .15). Regardless of region, blacks were less likely than whites to achieve treatment success with atenolol (P = .02) or prazosin (P = .03) and more likely with diltiazem (P = .05). There was a trend for blacks residing inside the Stroke Belt to have a lower treatment success rate than other race-region groups when treated with captopril (P = .07). Many regional and racial differences in diet, lifestyle, and other characteristics were observed. After adjustment for these characteristics by regression analysis, the effect of residing inside the Stroke Belt remained for captopril (P = .01) and clonidine (P = .01) and approached significance for hydrochlorothiazide (P = .10). Hypertension in patients residing inside the Stroke Belt responded less to the use of several antihypertensive medications and important differences were shown in a number of characteristics that may affect the control of blood pressure, compared with patients residing outside the Stroke Belt.",2000.0,0,0
321,10738847,"Drug-induced oesophageal disorders: pathogenesis, incidence, prevention and management.",D Jaspersen,"Drug-induced injury of the oesophagus is a common cause of oesophageal complaints. 'Pill-induced' oesophagitis is associated with the ingestion of certain drugs and accounts for many cases of erosive oesophagitis. To date, more than 70 drugs have been reported to induce oesophageal disorders. Antibacterials such as doxycycline, tetracycline and clindamycin are the offending agents in more than 50% of cases. Other commonly prescribed drugs that cause oesophageal injury include aspirin (acetylsalicylic acid), potassium chloride, ferrous sulfate, quinidine, alprenolol and various steroidal and nonsteroidal anti-inflammatory agents. However, many physicians and even more patients are not aware of this problem. Capsules or tablets are commonly delayed in their passage through the oesophagus. Highly caustic coatings, direct medication injury and poor oesophageal clearance of pills can lead to acute inflammation. Oesophageal damage occurs when the caustic contents of a drug remain in the oesophagus long enough to produce mucosal lesions. Taking medications at bedtime or without fluids is a common cause of oesophagitis. The possibility of drug-related damage should be suspected in all cases of oesophagitis, chest pain and dysphagia. History and gastrointestinal endoscopy will confirm the diagnosis. Treatment is supportive, although acid reduction is used frequently as an adjunct. This review reflects the current state of knowledge in this field.",2000.0,0,0
322,10739792,Effect of ACE inhibitors in diabetic and nondiabetic chronic renal disease: a systematic overview of randomized placebo-controlled trials.,A V Kshirsagar; M S Joy; S L Hogan; R J Falk; R E Colindres,"Clinical trials have shown the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in delaying the progression of diabetic renal disease. There is less evidence from primary clinical trials of nondiabetic renal disease. We performed an updated meta-analysis to determine the efficacy of ACE inhibitors in slowing the progression of renal disease over a broad range of functional renal impairment. We included published and unpublished randomized, placebo-controlled, parallel trials with at least 1 year of follow-up available from January 1970 to June 1999. In nine trials of subjects with diabetic nephropathy and microalbuminuria, the relative risk for developing macroalbuminuria was 0.35 (95% confidence interval [CI], 0.24 to 0.53) for individuals treated with an ACE inhibitor compared with placebo. In seven trials of subjects with overt proteinuria and renal insufficiency from a variety of causes (30% diabetes, 70% nondiabetes), the relative risk for doubling of serum creatinine concentration or developing end-stage renal disease was 0.60 (95% CI, 0.49 to 0.73) for individuals treated with an ACE inhibitor compared with placebo. Treatment of individuals with chronic renal insufficiency with ACE inhibitors delays the progression of disease compared with placebo across a spectrum of disease causes and renal dysfunction.",2000.0,0,1
323,10740141,Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.,C B Granger; G Ertl; J Kuch; A P Maggioni; J McMurray; J L Rouleau; L W Stevenson; K Swedberg; J Young; S Yusuf; R M Califf; B A Bart; P Held; E L Michelson; M A Sellers; G Ohlin; R Sparapani; M A Pfeffer,"Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.",2000.0,0,0
324,10742708,A comparison of intervention with losartan or captopril in acute myocardial infarction.,J Spinar; J Vitovec; L Spinarova; L Pluhacek; B Fischerova; J Toman,"Angiotensin-converting enzyme (ACE) inhibitors prolong life, lower the progression of heart failure, and decrease the need for hospitalizations in patients after myocardial infarctions. It is still unclear whether these effects could also be achieved by blocking the angiotensin II (ATII) type 1 receptor. We randomized 201 patients with acute myocardial infarction treated with either direct angioplasty, thrombolysis, or heparin alone to the ACE inhibitor captopril or the ATII antagonist losartan. The primary endpoints were safety, tolerability, and left ventricular parameters. The patients were followed for at least 15 days. The incidence of severe adverse events was similar in both groups, although cough presented less often in the losartan group. Captopril failed to prevent an increase in end-diastolic volume and did not influence left ventricular end-systolic volume. This effect led to an increase in the left ventricular ejection fraction (P<0. 001) without a change in wall-motion index. Losartan did not affect end-diastolic volume but decreased end-systolic volume (P<0.001), resulting in a significant increase in left ventricular ejection fraction (P<0.001) and a decrease in wall-motion index (P<0.001). This study suggests that losartan is safe and well tolerated in patients after myocardial infarction. ATII antagonists seem to have a more pronounced effect on left ventricular remodeling than ACE inhibitors.",2000.0,0,0
325,10746484,Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril.,J P New; R W Bilous; M Walker,"The aims of this study were to examine the effects of trandolapril, a long acting angiotensin converting enzyme (ACE) inhibitor with high tissue uptake, on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus. Insulin sensitivity was assessed after an acute dose (day 3) and 19 days continuous treatment (days 3-21) using the isoglycaemic, hyperinsulinaemic glucose clamp with D[3-3H] labelled glucose, a variable D[3-3H] priming dose and a 'hot' glucose infusion. Rates of glucose appearance (Ra) and glucose disappearance (Rd) were isotopically determined during the basal and insulin stimulated periods of the clamp. Twenty-four (5 female) hypertensive (blood pressure >75th centile for age and sex) patients with Type 2 diabetes mellitus were studied. Patients were randomized, in a double-blind manner, to either trandolapril 4 mg daily (T) or placebo (P). Baseline (day 1) systolic (mean +/- SD; P 164+/-14 and T 168+/-13 mm Hg) and diastolic (P 93+/-6, and T 98+/-10 mm Hg) blood pressures were comparable. On days 3 and 21, significant reductions were observed in both groups (P<0.001). In the trandolapril-treated group, serum trandolapril concentrations were >200 pg/ml on days 3 and 21, in all patients apart from one subject at a single visit, while trandolapril was undetectable in the placebo group. Body mass index (BMI) was greater in T compared with P (32.2+/-5.4 v. 28.3+/-4.6, P = 0.07). After correcting for BMI, basal hepatic glucose output (HGO) P 2.6 (95% CI 2.23-3.13) and T 1.91 (1.33-2.51) mg x kg(-1) x min(-1) and clamped HGO P 0.32 (-0.44-1.09) and T 0.87 (0.40-1.34) mg x kg(-1) x min(-1) were similar in both groups. The insulin sensitivity index was comparable in both groups on all days. Total cholesterol concentrations were similar in both groups throughout the study. Triglyceride concentrations were significantly lower in group P 1.38 (1.07-1.68); T 2.14 (1.70-2.58) mmol/l, P<0.01), no significant treatment effect being observed. An acute dose and 19 days' continuous treatment with trandolapril resulted in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension. These data support the metabolic neutrality of trandolapril in patients with Type 2 diabetes mellitus and hypertension.",2000.0,0,0
326,10746814,Effects of carvedilol on left ventricular regional wall motion in patients with heart failure caused by ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.,R N Doughty; G A Whalley; G Gamble; S MacMahon; N Sharpe,"Beta-blocker therapy has been shown to improve left ventricular (LV) ejection fraction and reduce LV volumes in patients with heart failure caused by ischemic heart disease. However, the possible mechanisms of this improvement and the effects of such treatment on regional wall motion have not been established. In a substudy of the Australia-New Zealand trial of carvedilol in patients with heart failure caused by ischemic heart disease, the effects of treatment on LV regional wall motion were assessed using 2-dimensional echocardiography. One hundred nineteen patients from 10 centers were included on this substudy. Patients were randomly assigned to treatment with carvedilol or placebo. Echocardiography was performed before randomization and after 6 and 12 months of treatment. LV regional wall motion was assessed using a semiquantitative scoring system. LV wall motion score index (WMSI) was reduced from 2.40 to 2.29 after 6 and 12 months in the carvedilol group and remained unchanged in the placebo group (2-tailed P = .005, carvedilol vs placebo). The percentage of myocardium with normal function also significantly improved with carvedilol treatment. Carvedilol improved LV regional WMSI in patients with heart failure caused by ischemic heart disease. These results indicate a mechanism by which beta-blocker therapy may benefit patients with heart failure and are consistent with an intrinsic improvement in LV function after treatment with carvedilol.",2000.0,0,0
327,10746815,Felodipine improves left ventricular emptying in patients with chronic heart failure: V-HeFT III echocardiographic substudy of multicenter reproducibility and detecting functional change.,M Wong; T Germanson; W R Taylor; I S Cohen; G Perry; L Baruch; P Deedwania; B Lopez; J N Cohn,"The echocardiographic substudy of the Vasodilator-Heart Failure Trial III (V-HeFT III) aimed to determine if felodipine treatment in patients with heart failure who were taking an angiotensin-converting enzyme inhibitor had a favorable effect on left ventricular (LV) structure and function. Earlier V-HeFT trials showed that hydralazine-isosorbide dinitrate improved ejection fraction (EF) and survival, whereas enalapril achieved greater survival with smaller increases in EF. Would the combination of a potent vasodilator and enalapril produce greater improvements in function and survival? Doppler-echocardiographic data were collected from 260 males with heart failure who were randomized to felodipine or a placebo. Mean intrasubject differences between baseline, at 3 months, and at 12 months were compared. Intersite and intrareader reproducibilities were measured from duplicate recordings and readings. At 3 months, no changes in ultrasound variables from baseline occurred in either group. At 12 months, felodipine patients achieved greater increases in EF, shortening of LV end-systolic length, and increases in stroke volume index. Reproducibility coefficients of variation were 7.4% (EF), 6.0% (end-diastolic length), and 13.0% (stroke volume index). The echocardiographic substudy showed that felodipine, added to heart failure therapy, increased EF, shortened end-systolic length, and increased stroke volume index. The changes were small and confirmed that reproducibility from multiple laboratories can be coordinated into a useful research tool.",2000.0,0,0
328,10750252,"A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group.",M Tonkon; N Awan; I Niazi; P Hanley; L Baruch; R A Wolf; A J Block,"Because heart failure therapy with angiotensin-converting enzyme (ACE) inhibitors may not be optimal, owing to persistent levels of angiotensin II occurring through incomplete blockade and alternate pathways, the benefit of adding irbesartan, an angiotensin receptor antagonist, to conventional therapy, including ACE inhibitors, was examined. In this multicentre, randomised, double-blind, placebo-controlled study, 109 patients with heart failure (New York Heart Association functional class II and III) and left ventricular ejection fraction (LVEF) < or = 40% received stable doses of ACE inhibitors and diuretics before and throughout the study. Irbesartan was titrated as tolerated to 150 mg once daily in all patients. Exercise tolerance time (ETT), LVEF and clinical status were assessed at baseline and after 12 weeks. Compared with placebo, irbesartan in combination with conventional therapy, including ACE inhibitors, produced favourable trends in ETT and LVEF and was well tolerated in patients with mild to moderate heart failure.",2000.0,0,0
329,10752019,,,,,0,0
330,10757440,"Effect of medical therapy on progressive nephropathy: influence of pregnancy, diabetes and hypertension.",G Leguizamon; E A Reece,"Nephropathy is a complication of diabetes mellitus that can affect women in their reproductive years. This article reviews the effects on treatment on the main factors associated with short- and long-term complications in pregnant women with diabetic nephropathy. Tight glycemic control, adequate treatment of elevated blood pressure, and renal function in early pregnancy are the most significant predictors of maternal and perinatal outcomes. Contemporary methods of perinatal care and adequate treatment of blood pressure allow fetal survival rates of 95%. Furthermore, pregnancy per se does not appear to worsen the natural progression to end-stage renal disease for most women with renal insufficiency. However, patients with moderate to severe renal impairment may experience acceleration of renal disease.",2000.0,0,0
331,10768275,Long-term safety of an early ACE-inhibitor treatment of patients with acute myocardial infarction: results of the 3 year follow-up period on 696 Swiss patients randomized to the ISIS-4 trial. ISIS-Switzerland Study Group.,M Genoni; R Malacrida; F Sessa; P Siegrist; A P Maggioni; T Moccetti,"Several large scale clinical trials showed that early ACE inhibitor treatment in patients with acute myocardial infarction reduced 30-day mortality. While the short-term evidence of benefit and risks appears to be consistent among trials, scarce data are available with respect to the long-term effects of short-term treatments. This study shows that the early reduction in mortality rate observed among patients treated with captopril persists for up to 3 years. This suggests that the benefit achieved in the acute phase in not lost even after a long period of time.",2000.0,0,1
332,10772593,"Diuretics, ACE inhibitors and NSAIDs--the triple whammy.",M C Thomas,,2000.0,0,0
333,10773514,Postoperative fatal intestinal necrosis after enalapril treatment in a patient with rheumatoid arthritis.,A Schweizer; L Hohn; D R Morel; A Spiliopoulos; M Licker,The inappropriate use of antihypertensive medications may cause hypotensive responses associated with organ failure. We describe a patient who developed nonocclusive splanchnic ischemia leading to death following the administration of enalapril to treat postoperative hypertension. The mechanisms and consequences of refractory hypotension induced by angiotensin-converting enzyme inhibitors are discussed.,2000.0,0,0
334,10773617,Acute tubular necrosis due to captopril.,S Al Shohaib; E Raweily,"Angiotensin-converting enzyme (ACE) inhibitors are standard therapy for congestive cardiac failure. ACE inhibitors have been used worldwide and are usually safe and have relatively few side effects. Hypotension can develop with the first dose of captopril and can lead to symptomatic renal hypoperfusion with subsequent acute renal failure (ARF). The case of a 65-year-old patient with congestive heart failure who developed acute renal failure following the first dose of captopril is described. He required hemodialysis for 8 weeks for the improvement of his renal function and urinary output. The renal biopsy confirmed the presence of acute tubular necrosis. The reversibility of captopril-induced ARF is confirmed and the patient made an uneventful recovery. An immunoallergic mechanism is not thought to have been responsible for this adverse effect. It is advised that caution should be exerted in giving ACE inhibitors to elderly patients with congestive heart failure, particularly if they are on diuretics. Routine biochemical monitoring is suggested before and during captopril therapy.",2000.0,0,0
335,10778687,,,,,0,0
336,10780101,"The HOPE study. Ramipril lowered cardiovascular risk, but vitamin E did not.",B J Hoogwerf; J B Young,"The Heart Outcomes Prevention Evaluation (HOPE) study found that the ACE inhibitor ramipril can lower the risk of atherosclerotic disease events and death in patients without heart failure but with known atherosclerosis or with diabetes plus at least one cardiovascular risk factor. This benefit was independent of ramipril's effect on blood pressure. Additional benefits were a reduced risk of diabetic nephropathy in diabetic patients, and a lower likelihood of newly diagnosed diabetes. On the other hand, vitamin E in the doses and duration studied (400 IU/day for 4.5 years) did not lower risk significantly.",2000.0,0,0
337,10784227,Angiotensin-converting enzyme inhibition by quinapril blocks the albuminuric effect of atrial natriuretic peptide in Type 1 diabetes and microalbuminuria.,K McKenna; D Smith; P Barrett; A Glenn; C M Kesson; J Connell; C J Thompson,"This study examined the effect of angiotensin-converting enzyme inhibition, administered at doses with no effect on systemic blood pressure, on the albuminuric action of atrial natriuretic peptide (ANP). Seven Type 1 diabetic patients with established microalbuminuria participated in a two limb, single-blind, placebo controlled study. Subjects were administered quinapril 10 mg daily or placebo for 7 days prior to study. On the study day, subjects were euglycaemic clamped and subsequently fluid loaded (20 ml/kg tap water orally plus urinary losses). At steady state diuresis, a 1 h intravenous infusion of ANP 0.05 mg.kg(-1) x min(-1) was administered. Urine was collected at 15-min intervals for estimation of albumin-creatinine ratio (ACR). Results were analysed by ANOVA. Baseline mean arterial pressure was similar after pre-treatment with quinapril and placebo (98.7 +/- 3.8 vs. 100 +/- 4.5 mmHg, mean +/- SD, P > 0.5), and was unaltered by ANP infusion on either study day. Baseline ACR was similar on quinapril and placebo (P = 0.13). ANP infusion induced a rise in urine ACR with placebo (58.4 +/- 40.2 to 393.6 +/- 262.9 mg/mmol, P = 0.006), but not with quinapril (29.3 +/- 10.7 to 81.5 +/- 43 mg/mmol, P = 0.15). The urine ACR response to ANP infusion was higher with placebo than with quinapril (P = 0.02). Quinapril blocks the albuminuric effect of intravenous infusion of ANP in subjects with Type 1 diabetes mellitus and established microalbuminuria. This action is independent of changes in mean arterial pressure and creatinine clearance.",2000.0,0,0
338,10784546,Drug treatment in heart failure.,E Lonn; R McKelvie,,2000.0,0,0
339,10785875,Rilmenidine in the hypertensive type-2 diabetic: a controlled pilot study versus captopril.,B Bauduceau; H Mayaudon; O Dupuy,"Rilmenidine is an innovative antihypertensive agent that binds specifically to I1 imidazoline receptors. The antihypertensive efficacy of rilmenidine in treating type-2 diabetics has been demonstrated, and is associated with very good clinical and laboratory tolerance. This was a 6-month, double-blind, randomized, controlled study comparing the effects of rilmenidine and captopril on the progression of microalbuminuria in a population of patients with mild-to-moderate hypertension [90 mmHg < diastolic blood pressure (DBP) < 110 mmHg], type-2 diabetes, and microalbuminuria (30 mg/24 h < urine albumin excretion < or = 300 mg/24 h). Between month 0 and month 6, the mean supine blood pressure was reduced in a similar manner by rilmenidine (systolic blood pressure from 159 to 141 mmHg and diastolic blood pressure from 98 to 84 mmHg) and captopril (systolic blood pressure from 157 to 144 mmHg and diastolic blood pressure from 101 to 82 mmHg). The median value for microalbuminuria was reduced from 160 (90-260) to 56 (27-87) mg per 24 h by rilmenidine and from 144 (51-200) to 54 (41-123) mg per 24 h by captopril. Rate of clearance of creatinine was not significantly changed during the study by either treatment (with rilmenidine it varied from 95.2 to 95.6 ml/min; with captopril it varied from 86.2 to 90.4 ml/min). There was no statistical difference between the changes in levels of glycosylated hemoglobin for the groups treated with rilmenidine and captopril. Clinical and laboratory acceptabilities were good, and those for the two groups were comparable. Rilmenidine exerts similar antihypertensive effects to those of captopril on the hypertensive with type-2 diabetes. Decreases in microalbuminuria elicited by the two treatments do not differ. That administration of rilmenidine decreases microalbuminuria suggests that it could exert nephroprotective effects.",2000.0,0,0
340,10786260,Community pharmacist outreach program directed at physicians treating congestive heart failure.,C J Turner; P Parfrey; K Ryan; R Miller; A Brown,"The predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for congestive heart failure (CHF), the use of angiotensin-converting-enzyme (ACE) inhibitors in this population, and the ability of a pharmacist outreach program to address underutilization of ACE inhibitors were studied. All physicians and owner-managers of community pharmacies on Newfoundland's Avalon Peninsula were asked to participate in the study. Pharmacists who agreed to participate were asked to list patients of the participating physicians with prescriptions for (1) furosemide and digoxin with and without an ACE inhibitor or angiotensin II-receptor inhibitor and (2) an ACE inhibitor. Physicians were visited by a pharmacist and asked whether each of their patients receiving digoxin and furosemide was being treated for CHF and to identify further cases of CHF among their patients receiving an ACE inhibitor. Intervention-group physicians received academic detailing on the use and dosage of ACE inhibitors and angiotensin II-receptor inhibitors for CHF. Both groups were reinterviewed after three months to establish what if any changes in therapy had occurred for each patient discussed during the first visit. The positive predictive value of digoxin and furosemide treatment for identifying patients receiving treatment for CHF was 94%. Seventy-six percent of patients identified by physicians as CHF patients who were taking digoxin and furosemide were treated with an ACE inhibitor. Thirty-six percent of patients treated with an ACE inhibitor for CHF received the targeted dosage. Four physicians stated that the outreach visit influenced their prescribing, but there was no significant difference in ACE inhibitor prescribing between the intervention and control groups. A pharmacist outreach program involving the use of prescription records and academic detailing did not affect prescribing or dosages of ACE inhibitors but demonstrated value as a quality assurance tool.",2000.0,0,0
341,10789664,Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group.,,"Hypertension is associated with a significantly increased risk of morbidity and mortality. Only diuretics and beta-blockers have been shown to reduce this risk in long-term clinical trials. Whether newer antihypertensive agents reduce the incidence of cardiovascular disease (CVD) is unknown. To compare the effect of doxazosin, an alpha-blocker, with chlorthalidone, a diuretic, on incidence of CVD in patients with hypertension as part of a study of 4 types of antihypertensive drugs: chlorthalidone, doxazosin, amlodipine, and lisinopril. Randomized, double-blind, active-controlled clinical trial, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, initiated in February 1994. In January 2000, after an interim analysis, an independent data review committee recommended discontinuing the doxazosin treatment arm based on comparisons with chlorthalidone. Therefore, outcomes data presented herein reflect follow-up through December 1999. A total of 625 centers in the United States and Canada. A total of 24,335 patients (aged > or = 55 years) with hypertension and at least 1 other coronary heart disease (CHD) risk factor who received either doxazosin or chlorthalidone. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,268), or doxazosin, 2 to 8 mg/d (n=9067), for a planned follow-up of 4 to 8 years. The primary outcome measure was fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; secondary outcome measures included all-cause mortality, stroke, and combined CVD (CHD death, nonfatal MI, stroke, angina, coronary revascularization, congestive heart failure [CHF], and peripheral arterial disease); compared by the chlorthalidone group vs the doxazosin group. Median follow-up was 3.3 years. A total of 365 patients in the doxazosin group and 608 in the chlorthalidone group had fatal CHD or nonfatal MI, with no difference in risk between the groups (relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.17; P=.71). Total mortality did not differ between the doxazosin and chlorthalidone arms (4-year rates, 9.62% and 9.08%, respectively; RR, 1.03; 95% CI, 0.90-1.15; P=.56.) The doxazosin arm, compared with the chlorthalidone arm, had a higher risk of stroke (RR, 1.19; 95% CI, 1.01-1.40; P=.04) and combined CVD (4-year rates, 25.45% vs 21.76%; RR, 1.25; 95% CI, 1.17-1.33; P<.001). Considered separately, CHF risk was doubled (4-year rates, 8.13% vs 4.45%; RR, 2.04; 95% CI, 1.79-2.32; P<.001); RRs for angina, coronary revascularization, and peripheral arterial disease were 1.16 (P<.001), 1.15 (P=.05), and 1.07 (P=.50), respectively. Our data indicate that compared with doxazosin, chlorthalidone yields essentially equal risk of CHD death/nonfatal MI but significantly reduces the risk of combined CVD events, particularly CHF, in high-risk hypertensive patients.",2000.0,0,0
342,10790814,Don't keep that ACE (inhibitor) up your sleeve! Is ramipril effective for secondary prevention of cardiovascular disease and stroke?,D C Hammett; J C MacFadyen,,2000.0,0,0
343,10791374,Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations.,R W Troughton; C M Frampton; T G Yandle; E A Espiner; M G Nicholls; A M Richards,"There is currently no objective practical guide to intensity of drug treatment for individuals with heart failure. We hypothesised that pharmacotherapy guided by plasma concentrations of the cardiac peptide aminoterminal brain natriuretic peptide (N-BNP) would produce a superior outcome to empirical trial-based therapy dictated by clinical acumen. 69 patients with impaired systolic function (left-ventricular ejection fraction <40%) and symptomatic heart failure (New York Heart Association class II-IV) were randomised to receive treatment guided by either plasma N-BNP concentration (BNP group) or standardised clinical assessment (clinical group). During follow-up (minimum 6-months, median 9.5 months), there were fewer total cardiovascular events (death, hospital admission, or heart failure decompensation) in the BNP group than in the clinical group (19 vs 54, p=0.02). At 6 months, 27% of patients in the BNP group and 53% in the clinical group had experienced a first cardiovascular event (p=0.034). Changes in left-ventricular function, quality of life, renal function, and adverse events were similar in both groups. N-BNP-guided treatment of heart failure reduced total cardiovascular events, and delayed time to first event compared with intensive clinically guided treatment.",2000.0,0,0
344,10798066,Evaluation and treatment of chronic renal failure.,A Moudgil; A Bagga,"Chronic renal failure (CRF) is the irreversible deterioration of renal function that gradually progresses to end stage renal disease (ESRD). The chief causes of CRF include obstructive uropathy, primary glomerular diseases, reflux nephropathy and hypoplastic or dysplastic kidneys. Progressive hyperperfusion and hyperfiltration causes increasing glomerular injury and further renal damage. Symptoms of CRF are usually seen when GFR is between 10-25% of normal. Children with severe CRF often suffer from failure to thrive, growth retardation, acidosis, anemia and renal osteodystrophy. Management of CRF aims at retarding progression of renal damage and treatment of complications related to renal dysfunction. Measures suggested to retard progression include protein restriction, strict control of hypertension, use of angiotensin converting enzyme inhibitors and control of hyperlipidemia. Appropriate amounts of protein and calories are recommended to prevent growth failure. Nutritional supplements are often required. The availability of recombinant erythropoietin, calcitriol and human growth hormone has significantly improved the management of these patients. Once ESRD supervenes, renal replacement therapy in the form of chronic peritoneal or hemodialysis and transplantation is necessary.",2000.0,0,0
345,10800878,"The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease.",K A Reardon; F A Mendelsohn; S Y Chai; M K Horne,"Animal studies have demonstrated an interaction within the striatum between the angiotensin and dopaminergic systems. In rats, the angiotensin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brain barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in the substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopril on the clinical features of moderately severe Parkinson's disease. After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in 'on phase' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also reported more 'on' periods during their waking day in their movement diary, p=0.007. Perindopril was well tolerated without any significant postural hypotension or renal dysfunction. These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study.",2000.0,0,0
346,10803486,Effects of fosinopril treatment on blood pressure during physical and mental stress test in essential hypertension.,D Yesilbursa; A Serdar; B Ilcol; B Türel; J Cordan,"In this study the effects of once daily administration of 10 mg fosinopril on blood pressure response to mental and physical stress were evaluated in mild to moderate essential hypertension. A total of 25 patients (14 women, 9 men) with mild to moderate essential hypertension were enrolled in this study. Before the treatment and after 10 mg/day fosinopril treatment for 2 months, systolic and diastolic blood pressure and heart rate were recorded at rest and while performing a mental arithmetic test. In addition, exercise stress testing with Bruce protocol were performed before and after the treatment and systolic and diastolic blood pressure and heart rate were recorded at rest and during peak exercise. Statistical analysis were done by using the paired t-test. During the mental arithmetic test, systolic and diastolic blood pressure were significantly reduced (p < 0.005 and p < 0.001, respectively) after 2 months fosinopril treatment. Systolic and diastolic blood pressure were also significantly reduced during the exercise stress test (p < 0.005 and p < 0.05) after the treatment. Heart rate did not change during either the mental arithmetic or the exercise test. As a result, once daily 10 mg fosinopril may be effective in reducing blood pressure, not only at rest, but also during stressful situations.",2000.0,0,0
347,10803488,,,,,0,0
348,10803861,"Losartan: a review of its use, with special focus on elderly patients.",K L Simpson; K J McClellan,"Losartan is an orally active, nonpeptide, selective angiotensin subtype 1 (AT1) receptor antagonist. It provides a more specific and complete blockade of the actions of angiotensin II than renin or ACE inhibitors. Short term (up to 12 weeks' duration) clinical trials have shown losartan to be as effective at lowering blood pressure (BP) [causes a decrease in BP < or = 26/20 mm Hg] in elderly patients with hypertension as recommended dosages of captopril, atenolol, enalapril, felodipine and nifedipine. In patients with isolated systolic hypertension (ISH) the efficacy of losartan was similar to that of atenolol. The addition of hydrochlorothiazide to losartan therapy provides greater antihypertensive efficacy, equivalent to that seen with captopril plus hydrochlorothiazide. Preliminary evidence also indicates that losartan therapy contributes to the regression of left ventricular hypertrophy associated with chronic hypertension. Exercise capacity is increased by losartan in patients with either asymptomatic or symptomatic heart failure. Results from the Losartan Heart Failure Survival or ELITE II (Evaluation of Losartan in the Elderly II) study indicate that there was no statistically significant difference between losartan and captopril in reducing overall deaths or in reducing sudden cardiac death and/or resuscitated cardiac arrest in patients with heart failure. Other than ELITE II, little conclusive long term mortality and morbidity data exist for losartan. Additional long term trials to evaluate the survival benefits of losartan in elderly patients with hypertension, renal disease or after an acute myocardial infarction are currently in progress. In elderly patients with hypertension, the incidence of treatment-related adverse events associated with once daily losartan (alone or in combination with hydrochlorothiazide) [19 to 27%] was similar to felodipine (23%) and nifedipine (21%), however, losartan tended to be better tolerated than captopril (11 vs 16%). Losartan was also better tolerated than atenolol in patients with ISH (10.4 vs 23%). In patients with heart failure the renal tolerability of losartan was similar to that of captopril, but losartan was associated with a lower withdrawal rate because of adverse events. No dosage adjustment is required in elderly or in patients with mild to moderate renal dysfunction, and the risk of first-dose hypotension is low. comparative data have shown losartan to be as effective as other antihypertensive agents in the treatment of elderly patients with hypertension. Treatment with losartan is therefore an option for first-line therapy in all patients with hypertension, particularly those who are not well managed with or who are intolerant of their current therapy. Morbidity and mortality data from the Losartan Heart Failure Survival (ELITE II) study show that losartan has potential in the treatment of heart failure.",2000.0,0,0
349,10805052,"Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients.",G T McInnes; K P O'Kane; H Istad; S Keinänen-Kiukaanniemi; H F Van Mierlo,"To compare candesartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability. This was a double-blind (double-dummy), randomised, parallel group comparison in patients with a mean sitting diastolic blood pressure 95-115 mm Hg on prior antihypertensive monotherapy. Treatments were candesartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily (n = 237) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily (n = 116) for 26 weeks. The primary efficacy variable was change in trough sitting diastolic blood pressure. Changes in mean sitting diastolic blood pressure did not differ significantly between the groups (mean difference 0.5 mm Hg; 95% confidence interval -1.6, 2.7, P = 0.20). No significant differences between the groups was found for other haemodynamic variables (sitting systolic blood pressure, standing blood pressure, sitting/erect heart rate, and proportion of responders and controlled patients). Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group (80% vs 69%, P = 0.020). The proportion of patients spontaneously reporting cough (23.1% vs 4.6%) and discontinuing therapy due to adverse events (12.0% vs 5.9%) was also higher in the lisinopril group compared with the candesartan cilexetil group. The fixed combinations of candesartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents. The fixed combination containing candesartan cilexetil is better tolerated than that containing lisinopril.",2000.0,0,0
350,10816399,Assessment of renal artery stenosis: comparison of captopril renography and gadolinium-enhanced breath-hold MR angiography.,V Bongers; J Bakker; J J Beutler; F J Beek; J M De Klerk,"To determine the accuracy of captopril renography (CR) and gadolinium-enhanced breath-hold magnetic resonance (MR) angiography in the diagnosis of 50-99% renal artery stenosis (RAS). Forty-three patients with possible RAS, of whom 53% had renal function impairment (creatinine >130 micromol/l), were included.(99m)Tc-mercaptoacetyl triglycine (MAG(3)) renography was performed after an oral dose of 25 mg captopril. Gadolinium-enhanced MR angiography was performed on a standard 1.5 Tesla system: TR 13.5, TE 3.5, flip angle 60 degrees, matrix 195 x 512. Intra-arterial digital subtraction angiography (DSA) was the standard of reference. Captropril renography accurately categorized 22 of 26 patients who had either uni- or bilateral RAS of 50-99%. The sensitivity and specificity of CR for the detection of 50-99% stenosis were 85 and 71%, respectively. With MR angiography one occluded artery was incorrectly diagnosed as a stenosis. Sensitivity and specificity were 100 and 94%, respectively. The difference between the accuracies of MR angiography and CR was statistically significant (P = 0.02). The accuracy of CR was lower in patients with renal impairment (70%) than in those with normal renal function (90%). MR angiography showed a high accuracy in diagnosing RAS of between 50 and 99%. CR was less accurate than MR angiography, especially in patients with renal function impairment. In patients with normal renal function, however, CR remains a useful diagnostic test.",2000.0,0,0
351,10818061,Influence of diabetes and type of hypertension on response to antihypertensive treatment.,M J Brown; A Castaigne; P W de Leeuw; G Mancia; C R Palmer; T Rosenthal; L M Ruilope,"The aim of our investigation was to determine whether the presence of additional risk factors or type of hypertension (diastolic or isolated systolic) influences blood pressure (BP) response to treatment. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study is a double-blinded outcome comparison of calcium channel blockade with diuretics in high-risk patients aged 55 to 80 years. Dynamic randomization between nifedipine once daily and hydrochlorothiazide/amiloride was performed to ensure that approximately equal numbers of patients in the 2 groups had each of the major cardiovascular risk factors. Patients with isolated systolic hypertension were also separately randomized. Atenolol or enalapril was the mandatory second-line drug. In 5669 patients who completed the 18-week titration, BP fell from 172+/-15/99+/-9 mm Hg (mean+/-SD) while receiving placebo to 139+/-12/82+/-7 mm Hg. Twenty-six percent of patients required 2 drugs, and 4% required 3 drugs. Patients with diabetes were the most resistant to treatment, requiring second and third drugs 40% and 100% more frequently than patients without diabetes and achieving marginally the highest final BP, for any risk group, of 141+/-13/82+/-8 mm Hg. Age, smoking, gender, hypercholesterolemia, left ventricular hypertrophy, and existing atherosclerosis had little (<1 mm Hg) or no influence on BP at the end of titration, but all except smoking slightly reduced the initial response of either systolic or diastolic BP. Patients with isolated systolic hypertension were slightly more responsive than average to treatment. Our findings suggest that in patients at high absolute risk of cardiovascular complications from hypertension, the risk factors themselves do not prevent the recommended BP targets from being achieved.",2000.0,0,0
352,10819408,Frequency-domain heart rate variability in 24-hour Holter recordings: role of spectral method to assess circadian patterns and pharmacological autonomic modulation.,F Badilini; P Maison-Blanche; P Champomier; J C Provost; P Coumel; H Milon,"Different spectral methodologies for heart rate variability were recently shown to provide the same qualitative results in the context of passive tilt test. However, the impact of the method and the use of normalized power units in long-term ECG monitoring is still debated. Autoregressive and Fast Fourier transform (FFT) spectral approaches were applied to assess circadian modulation and the effect of beta-blocker administration in mild hypertensive patients who underwent continuous ambulatory ECG recording (n = 44, 51 +/- 12 years, 30 men). Spectral analysis was applied to 5-minute sequences and spectral parameters representative of each circadian period (24 hour, day, night) were calculated. In baseline recordings, FFT spectral method provided a smaller estimate of total and very low frequency powers. On the contrary, low- and high-frequency components were systematically larger with FFT. Circadian variations were in favor of an increased overall nocturnal variability but of a reduced low frequency normalized power with both spectral methods. Chronic oral administration of beta-blocker induced an increase of all spectral components except for an unchanged low-frequency normalized power, independently from the spectral approach. In spite of quantitative differences, the qualitative assessment of circadian patterns and beta-blockade effect by autoregressive- and FFT-based spectral analyses is equivalent. The low-frequency component of heart rate variability cannot be considered a reliable direct marker of sympathetic activity in long-term ambulatory ECG recording.",2000.0,0,0
353,10820543,Scorpion sting.,S Mahadevan,,2001.0,0,0
354,10821360,Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.,M D Flather; S Yusuf; L Køber; M Pfeffer; A Hall; G Murray; C Torp-Pedersen; S Ball; J Pogue; L Moyé; E Braunwald,"We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p<O.001). For all five trials the ACE inhibitor group had lower rates of death than the placebo group (1,467/6,391 [23.0%] vs 1,710/6,372 [26.8%]; 0.80 [0.74-0.87]) and lower rates of reinfarction (571 [8.9%] vs 703 [11.0%]; 0.79 [0.70-0.89]), readmission for heart failure (876 [13.7%] vs 1202 [18.9%]; 0.67 [0.61-0.74]), and the composite of these events (2161 [33.8%] vs 2610 [41.0%]; 0.72 [0.67-0.78]; all p<0.0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and beta-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.",2000.0,0,0
355,10821361,Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.,B Pitt; P A Poole-Wilson; R Segal; F A Martinez; K Dickstein; A J Camm; M A Konstam; G Riegger; G H Klinger; J Neaton; D Sharma; B Thiyagarajan,"The ELITE study showed an association between the angiotensin II antagonist losartan and an unexpected survival benefit in elderly heart-failure patients, compared with captopril, an angiotensin-converting-enzyme (ACE) inhibitor. We did the ELITE II Losartan Heart Failure Survival Study to confirm whether losartan is superior to captopril in improving survival and is better tolerated. We undertook a double-blind, randomised, controlled trial of 3,152 patients aged 60 years or older with New York Heart Association class II-IV heart failure and ejection fraction of 40% or less. Patients, stratified for beta-blocker use, were randomly assigned losartan (n=1,578) titrated to 50 mg once daily or captopril (n=1,574) titrated to 50 mg three times daily. The primary and secondary endpoints were all-cause mortality, and sudden death or resuscitated arrest. We assessed safety and tolerability. Analysis was by intention to treat. Median follow-up was 555 days. There were no significant differences in all-cause mortality (11.7 vs 10.4% average annual mortality rate) or sudden death or resuscitated arrests (9.0 vs 7.3%) between the two treatment groups (hazard ratios 1.13 [95.7% CI 0.95-1.35], p=0.16 and 1.25 [95% CI 0.98-1.60], p=0.08). Significantly fewer patients in the losartan group (excluding those who died) discontinued study treatment because of adverse effects (9.7 vs 14.7%, p<0.001), including cough (0.3 vs 2.7%).",2000.0,0,1
356,10822316,Haemorheological effects of losartan and enalapril in patients with renal parenchymal disease and hypertension.,B I Shand,"The objective of this study was to compare the effects of the angiotensin II (ang II) antagonist, losartan and the angiotensin-converting enzyme inhibitor (ACEI), enalapril on haemorheology. Twenty-nine patients with renal parenchymal disease and hypertension were enrolled in the prospective, open, parallel study that involved a 14-day washout period followed by a 120-day treatment period. Patients were allocated randomly to receive either losartan 50-100 mg/day (n = 15) or enalapril 2.5-10 mg/day (n = 14) to achieve blood pressure control <140/90 mm Hg. Blood pressure, haemorheology profile and plasma fibrinogen concentration were measured after the washout phase and after 2, 10, 60, and 120 days of treatment. The data were analysed using ANOVA with repeated measures. Twenty-seven patients completed the study. Treatment with both losartan and enalapril was associated with a significant decrease (P < 0.05) in relative high shear rate whole blood viscosity, indicating an increase in blood cell deformability. In patients taking losartan, the increase in blood cell deformability did not result in a decrease in mean whole blood viscosity due to a concomitant, significant increase in mean plasma viscosity (P < 0. 01). In contrast, the improved cell deformability in patients treated with enalapril resulted in a small and statistically insignificant decrease in mean whole blood viscosity (P = 0.06; mean change = -0.15 mPa sec). The mechanism of the increase in blood cell deformability and the rise in plasma viscosity associated with losartan remain unclear. It is possible but unproven that the improvement in intrinsic blood cell rheology with losartan and enalapril may be the result of changes in cation transport systems and/or the consequence of the protective antioxidant properties of drug metabolites.",2000.0,0,0
357,10822319,Antihypertensive efficacy of the ACE-inhibitor perindopril in the elderly.,F H Leenen; J Tanner; C F McNally,"To assess the antihypertensive efficacy of the angiotensin-converting enzyme (ACE)-inhibitor, perindopril, in the elderly, patients >65 years of age with supine diastolic blood pressure (BP) > or =90 and < or =110 mm Hg at the end of a 4-week placebo washout period were treated with perindopril 4-8 mg/daily vs placebo using a multicentre, randomised, double-blind, parallel group design. Of the 191 patients entered, 183 completed 8 weeks of double-blind therapy. Average age was 72-73 years. Supine and standing BP at the end of the placebo run-in period were 173/96 vs 168/96 mm Hg. BPs were measured in the morning, 20-25 h after the previous day's dose (ie, at the end of the dosing interval). In the placebo group, supine and standing diastolic BP decreased by 3-4 mm Hg, and systolic BP by 6-7 mm Hg. In the perindopril-group, diastolic BP decreased by 6-7 mm Hg and systolic BP by 10-13 mm Hg (both P < 0.01 vs placebo). These data indicate a substantial placebo response of particularly systolic BP in older hypertensives and indicate the importance of a parallel placebo-group to assess the extent of the actual drug's effect. Perindopril caused additional decreases in diastolic BP by about 2 mm Hg, and in systolic BP by 4-5 mm Hg. The extent of this drug-effect may be less in older vs middle-aged hypertensives.",2000.0,0,0
358,10823314,Photoscratch testing in systemic drug-induced photosensitivity.,V Conilleau; A Dompmartin; M Michel; L Verneuil; D Leroy,"Because of numerous false-negative results, photopatch testing is seldom relevant in systemic drug-induced photosensitivity. These false-negative photopatch test results can be attributed to the inability of the drug to penetrate into the epidermis. In order to enhance the penetration of the tested drug into the epidermis, some authors proposed to breach the cutaneous barrier. We performed a prospective study comparing photopatch and photoscratch testing. Fifteen patients presenting with a systemic drug-induced photosensitivity, proved by a favourable outcome after discontinuing the drug, were tested. For each drug, photopatch and photoscratch tests were performed. Two-thirds of the patients had negative photopatch and photoscratch tests with the suspected drugs. Photopatch and photoscratch tests were positive and relevant, respectively, in 3 and 4 patients. Photoscratch tests induced more false-positive results due to irritation confirmed on control subjects. Our study proves that photoscratch tests do not change the sensitivity of phototesting.",2000.0,0,0
359,10824049,"Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension.",M U Naidu; P R Usha; T R Rao; J C Shobha,"Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering effect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose.",2000.0,0,0
360,10824365,Does combination therapy with a calcium channel blocker and an ACE inhibitor have additive effects on blood pressure reduction?,D A Edelman; R A Paul,"Reports in the medical literature have suggested that the effects on blood pressure (BP) of calcium channel blockers (CCBs) and angiotensin-converting enzyme (ACE) inhibitors are additive. Most reports have provided neither a definition of 'additive' nor the necessary information to determine whether the effects are additive. In this review of the medical literature, the effects of combination therapy were defined as additive if the sum of the mean reductions in BP following monotherapy with a CCB and an ACE inhibitor was not significantly different from the mean reduction in BP of combination therapy. The review generally showed that combination therapy is more effective than treatment with either monotherapy alone, based on mean decreases in either diastolic or systolic BP. The studies provided no clear evidence that the effects of combination therapy were either additive or less than additive.",2000.0,0,0
361,10826395,Practitioner's Trial on the Efficacy of Antihypertensive Treatment in the Elderly Hypertension (The PATE-Hypertension Study) in Japan.,T Ogihara,"Patients aged 60 years and older with essential hypertension were treated with an angiotensin-converting enzyme inhibitor (ACE-I), delapril (Adecut) or a long-acting calcium (Ca)-antagonist, manidipine (Calslot) for 3 years. The incidences of cardiovascular events as well as drug-related side effects were compared between the two groups to investigate whether both classes of antihypertensive drugs are beneficial in elderly hypertensive patients. There were no significant differences in characteristics of patients between the two intervention groups, except for slightly lower blood pressure (P = .08) in the Ca-antagonist group at the initiation of the study. There were no significant differences in total death between the two groups. Cardiovascular events (both fatal and nonfatal) were noted in 34 of 699 patients (22.5/1000 patient-years) in the ACE-I group and 50 of 1049 patients (19.7/1000 patient-years) in the Ca-antagonist group, with no significant difference found between the two groups. The correlation between cardiovascular incidence and the blood pressure attained during treatment showed a J-shaped phenomenon and suggests that an excessive reduction less than 120 mm Hg in systolic blood pressure (SBP) is unnecessary and may be harmful in certain cases. Side effects were more frequent in the ACE-I group than in the Ca-antagonist group (P = .01). Cough was the major adverse event, occurring in 5.0% of patients in the ACE-I group. In conclusion, the study indicates that both ACE-I (delapril) and Ca-antagonist (manidipine) were equally beneficial for reducing cardiovascular morbidity and mortality in elderly hypertensive patients. However, tolerability of ACE-I was lower due to the adverse event of coughing.",2000.0,0,1
362,10826401,Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide.,K Malmqvist; T Kahan; M Dahl,"The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT1) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.",2000.0,0,0
363,10826457,,,,,0,0
364,10827391,Effects of losartan and captopril on left ventricular volumes in elderly patients with heart failure: results of the ELITE ventricular function substudy.,M A Konstam; R D Patten; I Thomas; T Ramahi; K La Bresh; S Goldman; W Lewis; A Gradman; K S Self; V Bittner; W Rand; D Kinan; J J Smith; T Ford; R Segal; J E Udelson,"The mechanism by which angiotensin-converting enzyme inhibitors reduce mortality rates and disease progression in patients with heart failure is likely mediated in part through prevention of adverse ventricular remodeling. This study examined the effects of the angiotensin-converting enzyme inhibitor captopril and the angiotensin II type 1 receptor antagonist losartan on ventricular volumes and function in elderly patients with heart failure and reduced left ventricular ejection fraction (< or =40%). Patients underwent radionuclide ventriculograms (RVG) at baseline and were randomized to either captopril (n = 16) or losartan (n = 13). After 48 weeks, another RVG was obtained. Therapy was then withdrawn for at least 5 days, and the RVG was repeated while the patient was not receiving the drug. At 48 weeks both captopril and losartan significantly reduced left ventricular (LV) end-diastolic volume index (135 +/- 26 to 128 +/- 23 mL/m(2) for losartan, P <.05 vs baseline; 142 +/- 25 to 131 +/- 20 mL/m(2) for captopril, P <.01; mean (SD). Captopril also reduced LV end-systolic volume index (98 +/- 24 to 89 +/- 21 mL/m(2), P <.01 vs. baseline), whereas a nonsignificant trend was observed for the losartan group (97 +/- 23 to 90 +/- 16 mL/m(2), P = not significant). The between-group differences in the changes in LV volumes were not statistically significant. After drug withdrawal, LV end-diastolic volume index remained significantly lower than baseline in the captopril group (P <.01). Both captopril and losartan prevent LV dilation, representing adverse ventricular remodeling, previously seen with placebo treatment. Reverse remodeling was observed in the captopril group. On the basis of these results, the relative effects on LV remodeling do not provide a rationale for a survival benefit of losartan over captopril.",2000.0,0,1
365,10829361,Doxazosin in elderly patients with hypertension.,M H Weinberger; A Fawzy,"Hypertension constitutes a major cardiovascular risk factor of high prevalence in the elderly, and reducing elevated blood pressure has been shown to be of significant benefit in decreasing the incidence of cardiovascular and cerebrovascular disease in this patient population. Elderly patients are more likely to have comorbid disorders, such as dyslipidaemia, diabetes, renal disease, atherosclerosis and, for males, benign prostatic hyperplasia (BPH). Therefore, when choosing an antihypertensive agent for elderly patients, it is particularly important to ensure that treatment does not exacerbate comorbid conditions and does not interact deleteriously with any concurrent medication that the patient is taking. The alpha 1-adrenoceptor antagonist, doxazosin, has been shown to be an effective, well-tolerated antihypertensive therapy in elderly male patients and does not exacerbate--and in some cases improves--some other common disorders. Doxazosin has been shown to be effective in reducing the symptoms of BPH in elderly patients whose blood pressure is well controlled by concomitant antihypertensive medication. In addition, improvements in the symptoms of BPH as well as reductions in blood pressure have been observed in elderly men with mild-to-moderate hypertension. Doxazosin has been shown to have positive effects on lipid profiles and glycaemic control, which make it an attractive choice of therapy for elderly patients with hypertension and diabetes or dyslipidaemia. In addition, doxazosin is administered once daily, either in the morning or the evening, which may aid compliance, an important consideration in the elderly.",2000.0,0,0
366,10830252,Risk-benefit ratio of angiotensin antagonists versus ACE inhibitors in end-stage renal disease.,D A Sica; T W Gehr; A Fernandez,"The effective treatment of hypertension is an extremely important consideration in patients with end-stage renal disease (ESRD). Virtually any drug class--with the possible exception of diuretics--can be used to treat hypertension in the patient with ESRD. Despite there being such a wide range of treatment options, drugs which interrupt the renin-angiotensin axis are generally suggested as agents of choice in this population, even though the evidence in support of their preferential use is quite scanty. ACE inhibitors, and more recently angiotensin antagonists, are the 2 drug classes most commonly employed to alter renin-angiotensin axis activity and therefore produce blood pressure control. ACE inhibitor use in patients with ESRD can sometimes prove an exacting proposition. ACE inhibitors are variably dialysed, with compounds such as catopril, enalapril, lisinopril and perindopril undergoing substantial cross-dialyser clearance during a standard dialysis session. This phenomenon makes the selection of a dose and the timing of administration for an ACE inhibitor a complex issue in patients with ESRD. Furthermore, ACE inhibitors are recognised as having a range of nonpressor effects that are pertinent to patients with ESRD. Such effects include their ability to decrease thirst drive and to decrease erythropoiesis. In addition, ACE inhibitors have a unique adverse effect profile. As is the case with their use in patients without renal failure, use of ACE inhibitors in patients with ESRD can be accompanied by cough and less frequently by angioneurotic oedema. In the ESRD population, ACE inhibitor use is also accompanied by so-called anaphylactoid dialyser reactions. Angiotensin antagonists are similar to ACE inhibitors in their mechanism of blood pressure lowering. Angiotensin antagonists are not dialysable and therefore can be distinguished from a number of the ACE inhibitors. In addition, the adverse effect profile for angiotensin antagonists is remarkably bland, with cough and angioneurotic oedema rarely, if ever, occurring. In patients with ESRD, angiotensin antagonists are also not associated with the anaphylactoid dialyser reactions which occur with ACE inhibitors. The nonpressor effects of angiotensin antagonists--such as an influence on thirst drive and erythropoiesis--have not been explored in nearly the depth, as they have been with ACE inhibitors. Although ACE inhibitors have not been compared directly to angiotensin antagonists in patients with ESRD, angiotensin antagonists possess a number of pharmacokinetic and adverse effect characteristics, which would favour their use in this population.",2000.0,0,0
367,10836728,Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients.,G Mancia; S Omboni; E Agabiti-Rosei; R Casati; R Fogari; G Leonetti; G Montemurro; R Nami; A C Pessina; A Pirrelli; A Zanchetti,"Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.",2000.0,0,0
368,10836730,Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension.,G S Stergiou; I I Skeva; N M Baibas; L G Roussias; C B Kalkana; A D Achimastos; T D Mountokalakis,"The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.",2000.0,0,0
369,10839554,Combination antihypertensive drugs: recommendations for use.,N S Skolnik; J D Beck; M Clark,"The recommendation for first-line therapy for hypertension remains a beta blocker or diuretic given in a low dosage. A target blood pressure of less than 140/90 mm Hg is achieved in about 50 percent of patients treated with monotherapy; two or more agents from different pharmacologic classes are often needed to achieve adequate blood pressure control. Single-dose combination antihypertension therapy is an important option that combines efficacy of blood pressure reduction and a low side effect profile with convenient once-daily dosing to enhance compliance. Combination antihypertensives include combined agents from the following pharmacologic classes: diuretics and potassium-sparing diuretics, beta blockers and diuretics, angiotensin-converting enzyme (ACE) inhibitors and diuretics, angiotensin-II antagonists and diuretics, and calcium channel blockers and ACE inhibitors.",2000.0,0,0
370,10840011,Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment.,P Boutouyrie; C Bussy; D Hayoz; J Hengstler; N Dartois; B Laloux; H Brunner; S Laurent,"Local pulse pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean blood pressure (BP). The present study was designed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. Ninety-eight essential hypertensive patients were randomized to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high-resolution echo-tracking systems. PP was measured locally with applanation tonometry and independently of mean BP. After 9 months of treatment, mean BP, carotid PP, and intimal-medial thickness (IMT) decreased significantly, with no difference between the 2 groups. The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.",2000.0,0,0
371,10841227,"Clinical effects of early angiotensin-converting enzyme inhibitor treatment for acute myocardial infarction are similar in the presence and absence of aspirin: systematic overview of individual data from 96,712 randomized patients. Angiotensin-converting Enzyme Inhibitor Myocardial Infarction Collaborative Group.",R Latini; G Tognoni; A P Maggioni; C Baigent; E Braunwald; Z M Chen; R Collins; M Flather; M G Franzosi; J Kjekshus; L Køber; L S Liu; R Peto; M Pfeffer; F Pizzetti; E Santoro; P Sleight; K Swedberg; L Tavazzi; W Wang; S Yusuf,"We sought to determine whether the clinical effects of early angiotensin-converting enzyme (ACE) inhibitor (ACEi) treatment for acute myocardial infarction (MI) are influenced by the concomitant use of aspirin (ASA). Aspirin and ACEi both reduce mortality when given early after MI. Aspirin inhibits the synthesis of vasodilating prostaglandins, and, in principle, this inhibition might antagonize some of the effects of ACEi. But it is uncertain whether, in practice, this influences the effects of ACEi on mortality and major morbidity after MI. This overview sought individual patient data from all trials involving more than 1,000 patients randomly allocated to receive ACEi or control starting in the acute phase of MI (0-36 h from onset) and continuing for four to six weeks. Data on concomitant ASA use were available for 96,712 of 98,496 patients in four eligible trials (and for none of 1,556 patients in the one other eligible trial). Overall 30-day mortality was 7.1% among patients allocated to ACEi and 7.6% among those allocated to control, corresponding to a 7% (standard deviation [SD], 2%) proportional reduction (95% confidence interval 2% to 11%, p = 0.004). Angiotensin-converting enzyme inhibitor was associated with similar proportional reductions in 30-day mortality among the 86,484 patients who were taking ASA (6% [SD, 3%] reduction) and among the 10,228 patients who were not (10% [SD, 5%] reduction: chi-squared test of heterogeneity between these reductions = 0.4; p = 0.5). Angiotensin-converting enzyme inhibitor produced definite increases in the incidence of persistent hypotension (17.9% ACEi vs. 9.4% control) and of renal dysfunction (1.3% ACEi vs. 0.6% control), but there was no good evidence that these effects were different in the presence or absence of ASA (chi-squared for heterogeneity = 0.4 and 0.0, respectively; both not significant). Nor was there good evidence that the effects of ACEi on other clinical outcomes were changed by concomitant ASA use. Both ASA and ACEi are beneficial in acute MI. The present results support the early use of ACEi in acute MI, irrespective of whether or not ASA is being given.",2000.0,1,1
372,10842896,The role of angiotensin II receptors and their antagonists in hypertension.,P A van Zwieten,"The octapeptide angiotensin II is the major effector of the renin-angiotensin-aldosterone system. Angiotensin II causes a variety of potentially noxious biological effects, such as vasoconstriction, a rise in blood pressure, release of aldosterone, enhancement of the effect of catecholamines, and vascular and myocardial hypertrophy, including remodeling of the heart after myocardial infarction. All of these noxious effects of angiotensin II are mediated by angiotensin II receptors (AT receptors) of the AT1 subtype. The functional effects of AT2 receptors, which have been characterized by means of biochemical techniques, are so far not clearly identified. Stimulation of the AT2 receptor by means of angiotensin II is assumed to counteract vascular/myocardial remodeling and possibly to induce vasodilation. Accordingly, AT1 and AT2 receptors are believed to provoke opposite effects. It has drawn attention that fetal tissues contain a high density of AT2 receptors, which is lowered significantly after birth. The identification and analysis of AT receptors has been greatly stimulated by the development of non-peptidergic AT1 receptor antagonists, of which losartan is the prototype. It is so far unclear whether AT receptors are activated in hypertensive disease. A survey will be made of the hemodynamic effects of AT1 receptor antagonists, their interaction with AT receptors, and the probably important role of the sympathetic nervous system involved in the antihypertensive action of AT receptor antagonists.",2000.0,0,0
373,10843169,"Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial.",J R Petrie; A D Morris; S Ueda; M Small; R Donnelly; J M Connell; H L Elliott,"Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.",2000.0,0,0
374,10845831,Chronic proteinuric nephropathies: outcomes and response to treatment in a prospective cohort of 352 patients with different patterns of renal injury.,P Ruggenenti; A Perna; G Gherardi; R Benini; G Remuzzi,"The Ramipril Efficacy in Nephropathy (REIN) study found that angiotensin-converting enzyme (ACE) inhibitors effectively decreased proteinuria, glomerular filtration rate (GFR) decline (DeltaGFR), and incidence of end-stage renal disease (ESRD) in patients with proteinuric chronic nephropathies. In this study, we prospectively investigated the main clinical determinants of progression and response to treatment in the 352 patients enrolled into the REIN study. Mean DeltaGFR (0.56 +/- 0.05 [SEM] versus 0.21 +/- 0.05 mL/min/1.73 m(2)/mo; P = 0.0001) and incidence of ESRD (30% and 10%; P = 0.0001) were more than twice that in patients with proteinuria of 2 g/24 h or greater of protein compared with those with protein less than 2 g/24 h (relative risk [RR], 4.07; 95% confidence interval [CI], 2.20 to 7.52), as well as in patients with hypertension compared with normotension (mean DeltaGFR, 0.48 +/- 0. 05 versus 0.22 +/- 0.05 mL/min/1.73 m(2)/mon; P = 0.0006; ESRD, 25% versus 10%; P = 0.004; RR, 3.18; 95% CI, 1.38 to 7.32). Hypertension at study entry (P = 0.038), greater mean blood pressure on follow-up (P = 0.002), and urinary protein excretion rate (P = 0.0001) were independent predictors of faster DeltaGFR. DeltaGFR was approximately twofold faster in patients with type 2 diabetes than in those with primary glomerular disease (P = 0.002; including immunoglobulin A [IgA] nephropathy, P = 0.009); nephrosclerosis (P = 0.03), adult polycystic kidney disease (APKD), or chronic interstitial nephritis (P = 0.006). Diabetes at study entry (P = 0. 02) and greater mean blood pressure (P = 0.0001) and urinary protein excretion rate (P = 0.0001) on follow-up were independent predictors of faster DeltaGFR. After correction for baseline covariates, diabetes was also associated with an increased risk for progression to ESRD (RR, 2.39; 95% CI, 1.01 to 5.68; P < 0.05). At multivariate analyses, ramipril significantly decreased DeltaGFR (regression coefficient,-0.23 +/- 0.11 [SEM]; P = 0.036) and ESRD (RR, 2.08; 95% CI, 1.21 to 3.57; P = 0.008) in patients with baseline proteinuria of 2 g/24 h or greater of protein, and the renoprotective effect increased for increasing levels of proteinuria. Ramipril decreased DeltaGFR to a similar extent in normotensive and hypertensive patients (-0.14 +/- 0.11 versus -0.14 +/- 0.09) and significantly limited ESRD in hypertensive patients (RR, 2.03; 95% CI, 1.26 to 3. 26; P = 0.004). DeltaGFR was decreased by 42% in primary glomerular disease (P = 0.017), by 35% in IgA nephropathy, and by 37% in nephrosclerosis, but was not improved in type 2 diabetes, APKD, or interstitial nephritis. At multivariate analyses, ramipril significantly slowed DeltaGFR (-0.24 +/-0.08; P = 0.004) and progression to ESRD (RR, 2.32; 95% CI, 1.36 to 3.96; P = 0.002) in patients without diabetes, but not in patients with diabetes, who tended to have a faster DeltaGFR (+0.62 +/- 0.44) on ramipril therapy. In summary, patients with proteinuria of 2 g/24 h or greater of protein, preexisting hypertension, or type 2 diabetes were faster progressors. Greater blood pressure and degree of proteinuria were the strongest determinants of faster GFR decline. The renoprotective effect of ramipril was similar in patients with normotension and hypertension. Hypertensive patients and those with proteinuria of 2 g/24 h or greater of protein, primary glomerular disease, or nephrosclerosis gained the most from ACE inhibitor treatment. During the study period, those with proteinuria less than 2 g/24 h of protein, type 2 diabetes, or polycystic kidney disease did not benefit by treatment to an appreciable extent.",2000.0,0,0
375,10845947,Diabetes care needs evidence based interventions to reduce risk of vascular disease.,C D Byrne; S H Wild,,2000.0,0,0
376,10847330,Hypertension in end-stage renal disease patients.,P Zager; J Nikolic; D S Raj; A Tzamaloukas; M Campbell,"The prevalence of hypertension is extremely high in end-stage renal disease, and is a probable contributor to the epidemic of cardiovascular disease in end-stage renal disease. However, the paucity of prospective, randomized clinical trials makes it difficult to precisely define treatment strategies. Therefore, at present time the guidelines developed by the National Kidney Foundation's Cardiovascular Disease Task Force should be followed.",2000.0,0,0
377,10847331,Large multicentre hypertension trials.,I B Puddey,"The earlier large multicentre trials in hypertensive patients addressed questions of whether mild to moderate hypertension should be treated and whether similar approaches would be effective in elderly hypertensive patients or those with isolated systolic hypertension. The research focus of recent trials has now shifted to how rather than whether such patients should be treated. Trials such as the Hypertension Optimal Treatment study attempted to discern optimal targets for long-term blood pressure control. Although unsuccessful in this primary aim, they have established the safety of aggressive blood pressure lowering to diastolic targets of less than 80 mmHg as well as the safety and efficacy of a calcium entry blocker as a first line antihypertensive approach. The Captopril Prevention Project study and Swedish Trial in Old Patients with Hypertension-2 trial focussed on whether there might be specific antiatherosclerotic advantages of the newer agents (angiotensin converting enzyme inhibitors and calcium entry blockers) over conventional therapy in comparison studies with beta blockers and diuretics. Similar efficacy for cardiovascular outcomes appears to be emerging for each of the major classes of drugs with the degree of blood pressure lowering of prime importance in cardiovascular disease prevention.",2000.0,0,0
378,10852646,Lisinopril: a review of its use in congestive heart failure.,K Simpson; B Jarvis,"The ACE inhibitor lisinopril is a lysine derivative of enalaprilat, the active metabolite of enalapril. In patients with heart failure, maximum pharmacodynamic effects are produced 6 to 8 hours after administration of the drug and persist for 12 to 24 hours. High doses (32.5 to 35mg, administered once daily) of lisinopril in the Assessment of Treatment with Lisinopril and Survival (ATLAS) study demonstrated clinically important advantages over low doses (2.5 to 5mg, administered once daily) of the drug in the treatment of congestive heart failure. High doses of lisinopril were more effective than low doses in reducing the risk of major clinical events in patients with heart failure treated for 39 to 58 months. Compared with recipients of low doses, those receiving high doses of lisinopril had an 8% lower risk of all-cause mortality (p = 0.128), a 12% lower risk of death or hospitalisation for any reason (p = 0.002) and 24% fewer hospitalisations for heart failure (p = 0.002). These benefits were associated with significant cost savings. In short term (generally 12 weeks' duration) randomised, double-blind, parallel-group, multicentre clinical trials, lisinopril was significantly more effective than placebo and was at least as effective as captopril, enalapril, digoxin and irbesartan at improving symptomatic end-points and clinical status in patients with heart failure. Lisinopril is generally well tolerated by patients with heart failure. In controlled clinical trials, the most common adverse events occurring in recipients of the drug were dizziness, headache, hypotension and diarrhoea. Overall adverse event profiles for patients treated with high or low doses of lisinopril in the ATLAS study were similar. However, high doses of lisinopril used in the ATLAS study were associated with a higher incidence of adverse events, importantly hypotension and worsening renal function; nevertheless, these events were generally well managed by altering the dose of lisinopril or concomitant medications. Furthermore, despite the higher incidence of some adverse events with high doses of lisinopril, the frequency of treatment discontinuations because of adverse events was the same in the high and low dose groups. Lisinopril (when added to diuretics and/or digoxin) provides symptomatic benefits in patients with congestive heart failure. The ATLAS study demonstrated that high doses of lisinopril significantly reduced the risk of the combined end-point of morbidity and mortality compared with low doses of the drug. Importantly, there was no clinically significant decrease in the tolerability of the drug with use of a high dose. Lisinopril is at least as effective and as well tolerated as other members of the ACE inhibitor class for the treatment of congestive heart failure.",2000.0,0,0
379,10854673,Omapatrilat--the ups and downs of an exciting but complicated new drug.,A J Coats,,2001.0,0,0
380,10854683,"Effects of enalapril and isradipine alone and in combination on blood pressure, renal function and echocardiographic parameters in mild hypertension.",M L De Rosa; G Maddaluno; F Lionetti; U Di Palma; L Albanese; P Cardace; A Baiano; C Vigorito,"A study was carried out to evaluate the influence of antihypertensive treatment with combined low doses of enalapril plus isradipine (5+5 mg daily) compared with those of either drug at a higher dose level (10 mg daily) by double-blind, three-way crossover study (balanced Latin square design) in 102 subjects (mean age 51.9 +/- 7.42 years) with essential hypertension. Left ventricular mass and function were evaluated by M-B mode echocardiography, renal function by glomerular filtration rate (GFR) and by serum and 24-h urinary Na+ and K+ during wash-out period and after 24 weeks of treatment. The supine blood pressure for subjects given placebo was 171/103 mmHg. After 24 weeks of treatment, systolic and diastolic supine blood pressure were significantly lower with 5 mg isradipine plus 5 mg enalapril (134/84 mmHg) than with 10 mg enalapril (137/84 mmHg) or with 10 mg isradipine (144/85 mmHg). Left ventricular posterior wall and septal thickness were significantly and similarly reduced in all groups. Left ventricular systolic and diastolic end diameters were not significantly changed. Left ventricular mass (LVM) was significantly reduced in E plus I group and enalapril group. GFR was not significantly altered. The 24-h urinary Na+ significantly increased with enalapril, more so than isradipine. The combination was tolerated better than either monotherapy. We observed no clinically significant changes in laboratory variables including blood lipoproteins. The combination of isradipine plus enalapril reduced blood pressure more effectively and was better tolerated than other drug alone. All three groups showed similar changes in echocardiographic indices and no change in renal function.",2001.0,0,0
381,10855738,"Efficacy and safety of a new long-acting drug combination, trandolapril/verapamil as compared to monotherapy in primary hypertension. Swedish TARKA trialists.",B E Karlberg; M Andrup; A Odén,"To evaluate the clinical efficacy and safety of a new antihypertensive drug combination of trandolapril/verapamil compared to monotherapy with verapamil or trandolapril, in patients with mild to moderate primary hypertension. A multicentre, prospective, randomized, double-blind, controlled cross-over study with specific statistical considerations. Eighteen primary health care centres and out-patient hospital clinics in Sweden. Two hundred and twenty-six outpatients with uncomplicated primary hypertension with a baseline sitting diastolic blood pressure (BP) between 95 and 115 mmHg. After a 4-week placebo period, patients were randomized to treatment for 8 weeks with trandolapril/verapamil (2 mg/180 mg) or each drug alone (verapamil 240 mg, trandolapril 2 mg) for 8 weeks. Treatment responses (blood pressure (BP) fall and rate pressure product) to the three regimens with statistical comparison and also in relation to plasma concentrations of active renin (AR). Adverse events and safety were also evaluated. The mean BP fall was significantly greater with the combination (20/15 mmHg), p < 0.00054, as compared to both trandolapril (14/11 mmHg) or verapamil (13/11) mmHg. The difference between verapamil and trandolapril was not significant. Rate pressure product decreased significantly more on the combination, p < 0.001, than on trandolapril or verapamil alone. Treatment response to trandolapril was positively correlated to initial AR (r = 0.30-0.43). All treatments were well tolerated and safe. The new fixed drug combination trandolapril/verapamil was superior to monotherapy with either of these drugs alone regarding reduction of both BP and rate pressure product. This combination can be safely and effectively used for the treatment of mild to moderate primary hypertension.",2000.0,0,0
382,10855739,Study on COgnition and Prognosis in the Elderly (SCOPE): baseline characteristics.,L Hansson; H Lithell; I Skoog; F Baro; C M Bánki; M Breteler; A Castaigne; M Correia; J P Degaute; D Elmfeldt; K Engedal; C Farsang; J Ferro; V Hachinski; A Hofman; O F James; E Krisin; M Leeman; P W de Leeuw; D Leys; A Lobo; G Nordby; B Olofsson; G Opolski; M Prince; F M Reischies,"The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multi-centre, prospective, randomized, double-blind, parallel-group study. The primary objective of SCOPE is to assess the effect of the angiotensin II type 1 (AT1) receptor blocker, candesartan cilexetil 8-16 mg once daily, on major cardiovascular events in elderly patients (70-89 years of age) with mild hypertension (DBP 90-99 and/or SBP 160-179 mmHg). The secondary objectives of the study are to test the hypothesis that antihypertensive therapy can prevent cognitive decline (as measured by the Mini Mental State Examination, MMSE) and dementia, and to assess the effect of therapy on total mortality, myocardial infarction (MI), stroke, renal function, and hospitalization. A total of 4964 patients from 15 participating countries were recruited during the randomization phase of SCOPE, exceeding the target population of 4000. The mean age of the patients at enrolment was 76 years, the ratio of male to female patients was approximately 1:2, and 52% of patients were already being treated with an antihypertensive agent at enrolment. The majority of patients (88%) were educated to at least primary school level. At randomization, mean sitting blood pressure values were SBP 166 mmHg and DBP 90 mmHg, and the mean MMSE score was 28. Previous cardiovascular disease in the study population included myocardial infarction (4%), stroke (4%) and atrial fibrillation (4%). Men, more often than women, had a history of previous MI, stroke and atrial fibrillation. A greater percentage of men were smokers (13% vs 6% in women) and had attended university (11% vs 3% of women). Of the randomized patients, 21% were 80 years of age. In this age group smoking was less common (4% vs 10% for 70-79-year-olds) and fewer had attended university (4% vs 7% for 70-79-year-olds). The incidence of MI was similar in both age groups. However, stroke and atrial fibrillation had occurred approximately twice as frequently in the older patients. The patients' mean age at baseline was similar in the participating countries, and most countries showed the approximate 1:2 ratio for male to female patients. There was also little inter-country variation in terms of mean SBP, DBP or MMSE score. However, there was considerable regional variation in the percentage of patients on therapy prior to enrolment.",2000.0,0,0
383,10856732,Improvement of cardiac output in patients with severe heart failure by use of ACE-inhibitors combined with the AT1-antagonist eprosartan.,B Gremmler; M Kunert; H Schleiting; L J Ulbricht,"The efficacy of ACE-inhibitor therapy is well documented in the treatment of chronic heart failure. As pharmacological mechanisms of ACE-inhibition and angiotensin II AT1-receptor-antagonists differ, an additional positive effect concerning left ventricular function can be expected in combining both classes of drugs. Twenty patients (64.9+/-8.5 years) with advanced chronic heart failure (NYHA class III) receiving long-term medication with digitalis, diuretics and ACE-inhibitors were randomized to either eprosartan (540+/-96 mg/day) or placebo, according to a blinded protocol. Hemodynamic measurements by impedance cardiography were performed at baseline and after 8.85+/-1. 5 days of study medication treatment. Additional treatment with eprosartan resulted in a higher cardiac output than in the control group (P<0.05). While in the active treatment group cardiac output increased significantly from baseline (2.27-3.24 l/min, P=0. 039), there was no change in the control group. The additional treatment with the AT1-receptor antagonist eprosartan, given to severe heart failure patients, who received digitalis, diuretics and ACE-inhibitors, resulted in a beneficial effect by increasing cardiac output. This effect may be due to eprosartan's additional property of blocking the autocrine interaction of locally and not ACE-generated angiotensin II with their respective vascular and myocardial AT1-receptors as well as the influence on prejunctional AT1-receptors located on sympathetic nerve terminals.",2000.0,0,0
384,10856735,Angiotensin converting enzyme (ACE) inhibitors in the treatment of heart failure in general practice in north Cumbria.,M Toal; R Walker,"A great deal of research has demonstrated the benefits of treating patients with chronic heart failure with Angiotensin Converting Enzyme (ACE) inhibitors. There is rather less research on the actual uptake of treatment in general practice, and in particular methods that might improve that uptake. To study the attitudes and practice of medical practitioners in North Cumbria in the treatment of heart failure. Semi-structured interviews with 16 general practitioners and nine hospital physicians in the Carlisle area and an audit of general practice case notes. Two hundred and fifty-eight patients were identified with heart failure. Prevalence was 1.1%. Fifty percent were on an ACE inhibitor, the mean dose of which was less than half the typical research dose. Patients who had an echocardiogram were much more likely to be on an ACE inhibitor. General practitioners were enthusiastic to use ACE inhibitors, but felt that greater access to echocardiography was required. Hospital physicians were happy to improve access within an agreed protocol. Improved uptake of ACE inhibitors could be assisted by the development of a protocol for investigation and treatment. This protocol should be evidence-based and agreed between local GPs, hospital physicians and the Health Authority.",2000.0,0,0
385,10856736,"Clinical trials update: OPTIME-CHF, PRAISE-2, ALL-HAT.",S Thackray; K Witte; A L Clark; J G Cleland,"This is a summary of reports of presentation made at the American College of Cardiology 49th Scientific Sessions, Anaheim, 12-15 March 2000. Studies with a particular interest for heart failure physicians have been reviewed. OPTIME-CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. OPTIME-CHF was a randomised-controlled trial comparing a 48-h infusion of Milrinone or standard therapy in 951 patients recruited over a 2-year period. Patients were excluded if the investigator believed their clinical condition mandated inotropic therapy. Patients were randomised within 48 h of admission for an acute exacerbation of chronic heart failure to receive Milrinone or placebo infision for 48 h. Of the patients 43% were diabetics, 70% were receiving an angiotensin converting enzyme inhibitor, 25% were already on a beta-Blocker, and 34% had atrial fibrillation. There was no significant difference between the two groups in length of hospital stay during the index admission, subsequent readmissions and days in hospital over the following 60 days. Subjective clinical assessment scores were also no different. There was an average admission rate over the next year of one per patient in both groups. However, there was a significant increase in the incidence of sustained hypotension in the Milrinone group, which accounted for all of the increased adverse event rates for the active therapy. The 60-day mortality was 10% in both groups. This and previous trials of the oral formulation of Milrinone have now clearly demonstrated a lack of benefit with Milrinone in either during acute exacerbations of or in stable severe chronic heart failure [Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral Milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468-1475.]. Medium sized studies of Milrinone in patients with milder severities of heart failure also suggested an adverse impact on prognosis in the presence or absence of digoxin [DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral Milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677-683.]. Whether Milrinone even has a role for the management of a haemodyamic crisis requiring inotropic therapy must also be questioned.",2000.0,0,0
386,10857949,Prevalence of renal artery stenosis in subjects with type 2 diabetes and coexistent hypertension.,J Valabhji; S Robinson; C Poulter; A C Robinson; C Kong; C Henzen; W M Gedroyc; M D Feher; R S Elkeles,"To assess the prevalence of renal artery stenosis (RAS) in subjects with type 2 diabetes and coexistent hypertension by using magnetic resonance angiography (MRA) of the renal arteries, to assess clinical and biochemical predictors of RAS, and to assess the hemodynamic significance of RAS, by using the captopril test (a measure of the response of plasma renin activity to a single oral dose of captopril). A total of 117 subjects with type 2 diabetes and coexistent hypertension between 40 and 70 years of age and with creatinine concentrations < 150 micromol/l were recruited from two inner-city general diabetes clinics. All subjects underwent MRA of the renal arteries. In a subgroup of 85 subjects, data concerning possible clinical and biochemical predictors of RAS were collected, and the captopril test was performed. For comparison of a continuous variable between subjects with a positive MRA and those with a negative MRA, the Mann-Whitney test was used. For comparison of a discrete variable between subjects with a positive MRA and those with a negative MRA, Fisher's exact test was used. The prevalence of RAS detected by using MRA in 117 hypertensive type 2 diabetic subjects was 17%; 19 subjects had unilateral RAS, and only 1 subject had bilateral RAS. A femoral bruit was significantly more common in subjects with a positive MRA versus subjects with a negative MRA (21 vs. 0%; Fisher's exact test P < 0.005); however, other clinical features of atherosclerotic disease were not statistically associated. Greater duration of hypertension and treatment with statins were features of subjects with RAS (P < 0.05). The captopril test was negative in all subjects, although the antihypertensive response to oral captopril was significantly greater in subjects with RAS detected by MRA. RAS is common in hypertensive type 2 diabetic subjects. The presence of a femoral bruit is a useful predictive clinical marker. The captopril test is not useful in predicting the hemodynamic significance of RAS in this patient group.",2000.0,0,0
387,10857950,Influence of insertion/deletion polymorphism in the ACE-I gene on the progression of diabetic glomerulopathy in type 1 diabetic patients with microalbuminuria.,S Rudberg; L M Rasmussen; H J Bangstad; R Osterby,"To investigate the influence of the insertion/deletion polymorphism of the ACE gene on the progression of early diabetic glomerulopathy in patients with and without antihypertensive treatment (AHT). There were 30 microalbuminuric patients with >5 years of type 1 diabetes who had renal biopsies taken at baseline and after 26-48 months of follow-up. Of the 30 patients, 13 (4 with II genotype and 9 with ID and DD genotypes) were randomized to AHT (enalapril or metoprolol) during the study. The ACE genotype was determined by a polymerase chain reaction. Glomerular structural changes were measured by stereological methods. Of the patients, 8 had the II genotype, 19 had ID genotype, and 3 had DD genotype. During the study, basement membrane thickness, matrix star volume, and the overall diabetic glomerulopathy index were increased in patients with ID and DD genotypes only (P < 0.001, P = 0.01, P < 0.001, respectively). Among those with ID and DD genotypes, progression of basement membrane thickening and diabetic glomerulopathy index were increased in those without AHT, as compared with the antihypertensive treated patients (P < 0.001, P = 0.02, respectively). In multivariate analysis, the ACE genotype had an independent influence on the progression of basement membrane thickening (P = 0.01), when AHT (P < 0.001) and the mean HbAlc during the study (P < 0.001) were also taken into account. ACE genotype tended to be independently associated with the diabetic glomerulopathy index (P = 0.05). Microalbuminuric type 1 diabetic patients carrying the D-allele have an increased progression of diabetic glomerulopathy. Presence of this allele and no AHT seems to enhance this process. Larger studies are needed to confirm the clinical significance of our findings.",2000.0,0,0
388,10860225,Alpha-blockers and congestive heart failure: early termination of an arm of the ALLHAT trial.,D G Vidt,"The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a large, randomized double-blind study comparing four antihypertensive agents (chlorthalidone, doxazosin, amlodipine, and lisinopril) in hypertensive patients older than 55 years. The doxazosin arm was terminated early, when the trial's safety and monitoring board noted a twofold higher incidence of congestive heart failure in patients receiving doxazosin than in those receiving chlorthalidone (8.13% vs 4.45% at 4 years, P < .001).",2000.0,0,0
389,10867848,Enalapril in paediatric patients with Alport syndrome: 2 years' experience.,W Proesmans; H Knockaert; D Trouet,"Enalapril, a long-acting inhibitor of angiotensin-converting enzyme, was given for 2 years to seven children with Alport syndrome. Five patients had a classical X-linked form of the disease; two siblings had the autosomal recessive variant. Their age was between 5.15 and 13.75 years when enalapril was started. All patients had haematuria and proteinuria, creatinine clearance was > 80 ml/min per 1.73 m2 in all, and only one patient was hypertensive. The starting dose of enalapril (0.1 mg/kg body weight per day) was increased progressively according to individual clinical tolerance. The median doses were 0.13, 0.12, 0.21 and 0.29 mg/kg at 6, 12, 18 and 24 months, respectively. Median values of mean blood pressure were 95 mmHg at the start and 84 mmHg after 24 months. Median daily proteinuria decreased from 52 mg/kg to 18 mg/kg at 6 months, 21 mg/kg at 12 months, 12 mg/kg at 18 months and 30 mg/kg at 24 months. Serum creatinine increased over time from a median of 0.64 mg/dl at baseline to 0.77 mg/dl at 24 months. Concomitantly, there was a decrease in GFR from 104 to 83 ml/min per 1.73 m2 at 18 months and an increase again to 95 ml/min per 1.73 m2 at 24 months. Analysis of the individual data showed three patterns: no response (n = 2), temporary response (n = 2) and sustained response (n = 3). When given enalapril at the dosages mentioned, Alport patients as a group display a marked reduction in urinary protein excretion with a nadir of 23% of the baseline figure at 18 months, a decrease that cannot be accounted for by the slight decrease in glomerular filtration rate. Although these are preliminary data, it is recommended to try an angiotensin-converting enzyme inhibitor in every paediatric Alport patient with proteinuria.",2001.0,0,0
390,10868506,Delayed diagnosis of recurrent visceral angio-oedema secondary to ACE inhibitor therapy.,D L Jardine; J C Anderson; A D McClintock,,2000.0,0,0
391,10868869,Enalapril prevents clinical proteinuria in diabetic patients with low ejection fraction.,S E Capes; H C Gerstein; A Negassa; S Yusuf,"Clinical proteinuria is a risk factor for both end-stage renal disease and cardiovascular disease. The prevalence of clinical proteinuria, its correlates and predictive value, and the effect of ACE inhibitors in preventing clinical proteinuria in diabetic and nondiabetic patients with left ventricular (LV) dysfunction are unknown. The Studies of Left Ventricular Dysfunction (SOLVD) trials were analyzed to determine the baseline distribution of clinical proteinuria and related cardiovascular risk factors, the effect of baseline proteinuria on the risk of hospitalization for congestive heart failure (CHF) and mortality, and the effect of enalapril in preventing new clinical proteinuria. A total of 5,487 out of 6,797 SOLVD participants (81%) were assessed for proteinuria at baseline. A total of 177 patients (3.2%) had baseline proteinuria. These patients had significantly higher systolic (137 vs. 125 mmHg, P < or = 0.001) and diastolic (83 vs. 77 mmHg, P < or = 0.001) blood pressure levels, a higher prevalence of diabetes (41 vs. 18%, P < or = 0.001), a lower ejection fraction (26.2 vs. 27.3%, P < or = 0.05), and greater degree of CHF (New York Heart Association [NYHA] class III/IV in 22 vs. 10%, P < or = 0.001) than patients without baseline proteinuria. Patients with baseline proteinuria also had higher rates of hospitalization for CHF (relative risk 1.81 [95% CI 1.37-2.41], P = 0.0001) and mortality (1.73 [1.34-2.24], P = 0.0001). Enalapril prevented clinical proteinuria in diabetic patients (0.38 [0.17-0.81], P = 0.0123) but not in nondiabetic patients (1.43 [0.77-2.63], P = 0.2622) without baseline proteinuria. Clinical proteinuria is an independent predictor of hospitalization for CHF and mortality in diabetic and nondiabetic patients with LV dysfunction. Enalapril significantly reduces the risk of clinical proteinuria in diabetic patients with LV dysfunction.",2000.0,0,1
392,10868884,Severe nonproductive cough and cough-induced stress urinary incontinence in diabetic postmenopausal women treated with ACE inhibitor.,Y J Lee; Y F Chiang; J C Tsai,,2000.0,0,1
393,10871979,The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group.,J M Flack; C Yunis; J Preisser; C B Holmes; G Mensah; B McLean; E Saunders,"Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects. We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached. Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fast group at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were ""serious"" vs only 12% in the slow group. Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.",2000.0,0,0
394,10877041,Fluoroquinolone-induced renal failure.,B M Lomaestro,"Fluoroquinolones are generally well tolerated, clinically useful antimicrobials. This paper highlights rare, but potentially serious, adverse effects involving the kidney. Other antimicrobials have long been known to cause various forms of nephrotoxicity occurring as allergic interstitial nephritis, granulomatous interstitial nephritis, necrotising vasculitis, allergic tubular nephritis or a tubular necrosis. A Medline search (1985 to May 1999) of ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, trovafloxacin, enoxacin, sparfloxacin, grepafloxacin, gatifloxacin, clinafloxacin and moxifloxacin was conducted to ascertain the incidence and features of fluoroquinolone nephrotoxicity. Unfortunately, the data primarily consist of case reports and temporally related events. The incidence of these adverse effects is hard to estimate, and the cause may be multifactorial. While the use of ciprofloxacin appears to increase the risk, this may be due to its longer and more widespread use when compared with the newer agents.",2000.0,0,0
395,10878692,Evaluation of the effects of fixed combinations of sustained-release verapamil/trandolapril versus captopril/hydrochlorothiazide on metabolic and electrolyte parameters in patients with essential hypertension.,R Cifková; R Nakov; E Novozámská; Z Hejl; Z Petrzílková; R Poledne; P Stávek; D Compagnone,"The objective of this randomised open, active controlled, cross-over study was to evaluate the effect of a fixed combination of verapamil SR/trandolapril compared to captopril/hydrochlorothiazide on serum lipids, lipoproteins, and other metabolic and electrolyte parameters in patients with essential hypertension. Another objective was to assess the efficacy and safety of both combinations. One hundred hypertensives with systolic blood pressure 140-209 mm Hg and diastolic blood pressure 90-119 mm Hg were evaluated after 16 weeks receiving a fixed combination of verapamil SR 180 mg/ trandolapril 2 mg (VT) or captopril 50 mg/hydro- chlorothiazide 25 mg (CH) both given once daily. Lipids and lipoproteins were assessed in duplicate on 2 consecutive days. The study was completed by 80 patients. There was no statistically significant difference between the two combined regimens with respect to low-density lipoprotein (LDL)-cholesterol for the 'intention-to-treat' population measured at the end of each treatment period (3.44 +/- 0.87 mmol/L with VT, and 3.46 +/- 0.86 mmol/L with CH). No differences were found for other lipid parameters like total cholesterol, triglycerides, apolipoproteins A1 and B, Lp(a). High-density lipoprotein (HDL)-cholesterol was significantly higher with VT (1.39 +/- 0.01 vs 1.35 +/- 0.01, P < 0. 03). Serum potassium declined while uric acid and glucose increased on CH. In conclusion, no significant differences were found in LDL-cholesterol and in other lipid parameters with the exception of HDL-cholesterol which was significantly higher on VT. Serum potassium declined while uric acid and glucose increased on CH (all significantly). Both fixed combinations were well tolerated. The incidence of adverse events was higher on CH. Both fixed combinations significantly lowered BP. Journal of Human Hypertension (2000) 14, 347-354",2000.0,0,0
396,10878693,"Difference in blood pressure, but not in heart rate, between measurements performed at a health centre and at a hospital by one and the same physician.",I Enström; K Pennert; L H Lindholm,"Blood pressure (BP) has been found to vary between examiners, for example it is often higher when measured by a physician than by a nurse. Whether the location for the physician-measured BP is also a source of variation has, however, not been studied. Hence, we found it of interest to find out if the location used for examination was of any significance. To explore if BP and/or heart rate measured in the same subjects by the same general practitioner in the health centre and at the hospital, differed. Twenty-five hypertensive and 25 age-matched normotensive middle-aged men had their office BP and heart rate recorded by one and the same female general practitioner (IE) who was well known to them, at both the health centre before ambulatory BP equipment was attached to the subject and at the clinical physiological department before an exercise test. The hypertensive patients performed an exercise test and ambulatory BP was measured before and after being treated. The hypertensive patients' office BP was lower at the health centre than at the hospital, both when they were untreated and after they were treated. The difference (systolic/diastolic (s.d.)) was 9.4/6.0 (7.4/2.7) mm Hg (P < 0.001 for systolic and diastolic BP), when they were untreated. Corresponding figures when they were treated were 5.4/4.0 (9.4/4.7) mm Hg, a significant difference in diastolic BP (P < 0.001). The normotensive subjects also had a lower office BP at the health centre than at the hospital. The difference (systolic/diastolic (s.d. ) was 1.8/5.3 (7.0/5.0) mm Hg (P < 0.001 for diastolic BP). Heart rate did not differ between recordings in the health centre and in the hospital, either in the hypertensives or in the normotensives. Office BP differed significantly between measurements performed in the health centre and at the hospital. Hence, being examined at a hospital seemed to be a stronger stimuli in most patients than to be examined in a health centre. When diagnosing or evaluating treatment in hypertension, this may have implications. Journal of Human Hypertension (2000) 14, 355-358",2000.0,0,0
397,10879671,Extracorporal therapy with AN69 membranes in combination with ACE inhibition causing severe anaphylactoid reactions: still a current problem?,M C Kammerl; R M Schaefer; F Schweda; M Schreiber; G A Riegger; B K Krämer,"The negatively charged membrane AN69 is known to evoke anaphylactoid reactions both without and with concomitant ACE inhibition. Underlying reasons are mainly the induction of bradykinin release due to the negatively charged membrane and the reduced degradation of bradykinin due to ACE inhibition. This complication has been reported repeatedly, but anaphylactoid reactions still occur in clinical practice. We recently had to treat two patients who suffered anaphylactoid reactions during extracorporal therapy with an AN69 membrane and simultaneous ACE inhibition. The first incident occurred in a patient on hemodialysis, the second was in a patient on continuous venovenous hemofiltration. An anaphylactoid reaction induced by an AN69 membrane during continuous, extracorporal treatment in combination with ACE inhibition has not been reported so far. Our report intends to serve as a reminder that the potentially lethal combination of AN69 membranes with ACE inhibitor treatment should be avoided.",2001.0,0,0
398,10883412,Antihypertensive effect of low-dose hydrochlorothiazide alone or in combination with quinapril in black patients with mild to moderate hypertension.,I V Radevski; Z P Valtchanova; G P Candy; M N Hlatswayo; P Sareli,"In this study, using 24-hour ambulatory blood pressure (BP) monitoring, the authors assessed the potential for BP control using hydrochlorothiazide (HCTZ, 12.5 mg daily), given as a monotherapy over 12 months to 49 black South African patients with mild to moderate hypertension (mean day diastolic blood pressure [DBP] > or = 90 and < 115 mmHg). Uncontrolled patients received fixed combination of quinapril/HCTZ 10/12.5, 20/12.5, and 20/25 mg, with dose titration at 3 monthly intervals if BP control was not achieved (day DBP < 90 mmHg). Overall, profound and sustained BP reduction was observed at the end of the study. The 24-hour BP decreased from 151 +/- 14/98 +/- 7 to 136 +/- 15/87 +/- 9 mmHg (p < 0.0001 at end of study vs. baseline); the mean day BP decreased from 155 +/- 14/104 +/- 7 to 140 +/- 15/91 +/- 10 mmHg (p < 0.0001 at end of study vs. baseline). The overall control (mean day DBP < 90 mmHg) and response (decrease in day DBP > or = 10 mmHg) rates were 49% and 61%, respectively. At the end of the study, only 2 patients (4%) remained on treatment with HCTZ. Out of the initial 12 patients controlled on HCTZ at 3 months (12/49, 24%), 5 patients remained controlled at 6 months and only 1 patient at 12 months. In contrast, quinapril/HCTZ combinations maintained their antihypertensive effect up to 9 months, with a significant number of patients (22/49, 45%) requiring the highest dose of the combination (20/25 mg daily). In conclusion, low-dose HCTZ should not be recommended as monotherapy in black patients with mild to moderate hypertension due to the fact that the BP-lowering effect is attenuated already at 6 months of treatment, with most patients requiring the addition of the ACE inhibitor.",2000.0,0,0
399,10886125,Angioedema and cough in Nigerian patients receiving ACE inhibitors.,A A Ajayi; A Q Adigun,,2000.0,0,0
400,10894321,Effect of enalapril and nifedipine on orthostatic hypotension in older hypertensive patients.,I Slavachevsky; R Rachmani; Z Levi; D Brosh; M Lidar; M Ravid,"To compare the effect of enalapril with long-acting nifedipine on orthostatic hypotension in older patients. A prospective, double blinded, cross-over study. The outpatient clinic of a university hospital. Thirty-nine patients aged 65 years or older with systolic blood pressure (SBP) of 140-190 mm Hg and diastolic blood pressure (DBP) of 90-110 mm Hg. Enalapril 5-20 mg od or nifedipine 30-90 mg od for 8 weeks, followed by 4 weeks washout and cross-over for a second 8-week period. Supine and standing 0-, 1-, and 5-minutes blood pressure was recorded before and at the end of each treatment period. At baseline, SBP was 158.8 +/- 8.7 mm Hg, and DBP was 97.1 +/- 5.9 mm Hg. There was a decline in SBP of 6.1 +/- 2.7 mm Hg and 8.4 +/- 4.1 mm Hg after 1 and 5 minutes of standing, respectively. Both agents caused a significant decline in supine blood pressure. Enalapril: supine SBP 158.8 +/- 8.7 to 143 +/- 7.3 mm Hg; supine DBP 97.1 +/- 5.9 to 85.1 +/- 5.1 mm Hg (P = .0001). The drop in SBP after standing for 5 minutes was only 2.4 +/- 1.6 mm Hg with no change in diastolic values. A > or = 10 mm Hg drop in SBP was observed in only three patients, and no patient experienced a decline of 20 mm Hg or more. Nifedipine: supine SBP: 160.3 +/- 9 to 145.3 +/- 8.1 mm Hg; supine DBP: 96.3 +/- 5.7 to 86.3 +/- 5.8 (P = .0001). Nifedipine induced an orthostatic decline in SBP values; there was an 8.7 +/- 4.8 mm Hg difference between supine and 5 minutes standing values (P = .0005) without change in diastolic values. An orthostatic decline in SBP of > or = 10 mm Hg occurred in 13 patients, and there was a drop of > or = 20 mm Hg in six patients. The cross-over of enalapril and nifedipine reproduced the hypotensive effect and reversed the postural effect. (P = .0002 nifedipine vs enalapril) Enalapril and nifedipine were equipotent in reducing supine blood pressure levels. Enalapril also reduced the number of orthostatic episodes significantly, whereas nifedipine aggravated this phenomenon.",2000.0,0,0
401,10895836,Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes.,M Pahor; B M Psaty; M H Alderman; W B Applegate; J D Williamson; C D Furberg,"To assess whether ACE inhibitors are superior to alternative agents for the prevention of cardiovascular events in patients with hypertension and type 2 diabetes. This study is a review and meta-analysis of randomized controlled trials that included patients with type 2 diabetes and hypertension who were randomized to an ACE inhibitor or an alternative drug, were followed for > or =2 years, and had adjudicated cardiovascular events. A total of 4 trials were eligible. The Appropriate Blood Pressure Control in Diabetes (ABCD) trial (n = 470) compared enalapril with nisoldipine, the Captopril Prevention Project (CAPPP) (n = 572) compared captopril with diuretics or beta-blockers, the Fosinopril Versus Amlodipine Cardiovascular Events Trial (FACET) (n = 380) compared fosinopril with amlodipine, and the U.K. Prospective Diabetes Study (UKPDS) (n = 758) compared captopril with atenolol. The cumulative results of the first 3 trials showed a significant benefit of ACE inhibitors compared with alternative treatments on the outcomes of acute myocardial infarction (63% reduction, P < 0.001), cardiovascular events (51% reduction, P < 0.001), and all-cause mortality (62% reduction, P = 0.010). These findings were not observed in the UKPDS. The ACE inhibitors did not appear to be superior to other agents for the outcome of stroke in any of the trials. None of the findings were explained by differences in blood pressure control. Compared with the alternative agents tested, ACE inhibitors may provide a special advantage in addition to blood pressure control. The question of whether atenolol is equivalent to captopril remains open. Conclusive evidence on the comparative effects of antihypertensive treatments will come from large prospective randomized trials.",2001.0,0,0
402,10895868,Angiotensin II blockade is associated with decreased plasma leukocyte adhesion molecule levels in diabetic nephropathy.,S Andersen; C G Schalkwijk; C D Stehouwer; H H Parving,,2001.0,0,0
403,10898445,Long-term effect of angiotensin-converting enzyme inhibitor in volume overloaded heart during growth: a controlled pilot study.,Y Mori; M Nakazawa; H Tomimatsu; K Momma,"This study examined whether long-term therapy with an angiotensin-converting enzyme (ACE) inhibitor reduces excessive increases in left ventricular (LV) mass as well as volume in growing children with aortic regurgitation or mitral regurgitation. The ACE inhibitor reduces volume overload and LV hypertrophy in adults with aortic or mitral regurgitation. This study included 24 patients whose ages ranged from 0.3 to 16 years at entry to the study. On echocardiography, we measured LV size, systolic function and mass. After obtaining baseline data, patients were allocated into two groups. Twelve patients were given an ACE inhibitor (ACE inhibitor group), and 12 patients were not (control group). Echo parameters were again assessed after an average 3.4 years of follow-up. Left ventricular parameters at baseline in the two groups were similar. The Z value of LV end-diastolic dimensions decreased from +0.82 +/- 0.55 to +0.57 +/- 0.58 in the ACE inhibitor group, whereas it increased from +0.73 +/- 0.85 to +1.14 +/- 1.04 in the control group (mean change -0.25 +/- 0.33 for the ACE inhibitor group vs. +0.42 +/- 0.48 for the control group, p = 0.0007). The mass normalized to growth also reduced from 221 +/- 93% to 149 +/- 44% of normal in the ACE inhibitor group and increased from 167 +/- 46% to 204 +/-59% of normal in the control group (mean change -72 +/- 89% of normal for the ACE inhibitor group vs. +37 +/- 35% of normal for the control group, p = 0.0007). Long-term treatment with ACE inhibitors is effective in reducing not only LV volume overload but also LV hypertrophy in the hearts of growing children with LV volume overload.",2000.0,0,0
404,10901769,Reducing premature death and renal failure in Australian aboriginals. A community-based cardiovascular and renal protective program.,W E Hoy; P R Baker; A M Kelly; Z Wang,"To describe results of a systematic treatment program to modify renal and cardiovascular disease in an Aboriginal community whose rates of renal failure and cardiovascular deaths are among the highest in Australia. Longitudinal survey of people during treatment, and comparison of rates of natural death and renal failure with those in a historical control group. Tiwi Islands (population, about 1800), November 1995 to December 1998. All adults with blood pressure > or = 140/90, with diabetes and urinary albumin/creatinine ratio (ACR) > or = 3.4 g/mol (microalbuminuria threshold), or with progressive overt albuminuria (ACR > or = 34 g/mol) were eligible for treatment. The historical control group comprised 229 people who satisfied these criteria in the pretreatment period 1992-1995. Perindopril, combined with calcium-channel blockers and diuretics if needed to achieve blood pressure goals; attempts to improve control of blood glucose and lipid levels; health education. Blood pressure, ACR, serum creatinine level and glomerular filtration rate (GFR) over two years of treatment; rates of renal failure and natural death compared with control group (analysed on intention-to-treat basis). 258 people enrolled in the program, and 118 had complete data for two years of treatment. In these 118, blood pressures fell significantly, while ACR and GFR stabilised. Rates of the combined endpoints of renal failure and natural death per 100 person-years were 2.9 for the treatment group (95% CI, 1.7-4.6) and 4.8 for the control group (95% CI, 3.3-7.0). After adjustment for baseline ACR category, the relative risk of the treatment group versus the control group for these combined endpoints was 0.47 (95% CI, 0.25-0.86; P = 0.013). Treatment benefit was especially marked in people with overt albuminuria or hypertension and in non-diabetic people. The estimates of benefit were supported by a fall in community rates of death and renal failure. Aboriginal people can participate enthusiastically in chronic disease management, with rapid, dramatic improvement in clinical profiles and mortality. Similar programs should be introduced urgently into other Aboriginal communities nationwide.",2000.0,0,0
405,10901822,AT1 receptor blockers--cost-effectiveness within the South African context.,A N Anderson; F Wessels; I Moodley; K Kropman,"Hypertension is a leading chronic disease in South Africa, Significant mortality results from this condition and from stroke and ischaemic heart disease in which hypertension plays a major role. The objective of this study was to evaluate the evidence for the clinically effective and cost-effective treatment of hypertension, given that the clinician has decided to administer an AT1 receptor blocker. A cost-effectiveness analysis was undertaken from the perspective of the funder of health care in the private sector. A predetermined protocol defined the study scope, the comparators (candesartan, losartan, valsartan and irbesartan) and the inclusion criteria for peer-reviewed data. Data for the clinical efficacy of the comparators, measured as the reduction (mmHg) in sitting diastolic blood pressure (SDBP) achieved, were extracted, statistically assessed and reported. The combinability of the data from different clinical trials was confirmed using analyses of variance. A pharmacoeconomic model was developed by combining these clinical results with South African retail prices and testing the results at a 95% confidence level. Significant difference in clinical effectiveness was found among the comparators, with the following mean reductions in SDBP observed: candesartan 10.57, irbesartan 9.07, losartan 8.89 and valsartan 7.11 mmHg. Candesartan was found to be significantly more effective than losartan. Valsartan was found to be less effective than the other 3 comparators. No significant difference was found between irbesartan and either candesartan or losartan. The reduction in SDBP per R100 spent indicated that candesartan was more cost-effective than the other comparators, among which there were no significant differences. Incremental savings of R5.0 million annually could be achieved by the funders of private health care for every 100,000 successfully treated patients using candesartan. Significant differences exist in both the clinical and cost-effectiveness measures used in this study for the comparators. The findings from the analysis will be valuable in decision-making processes for both the funders and providers of health care. This analysis can be enhanced further by the inclusion of additional clinical benefits and long-term health outcomes when the relevant data become available.",2000.0,0,0
406,10902066,Angiotensin II-receptor antagonists: an overview.,R Dina; M Jafari,"Angiotensin II (AT-II)-receptor antagonists are reviewed. Research focused on blocking the renin-angiotensin system (RAS) led to the discovery of angiotensin-converting-enzyme (ACE) inhibitors, which are effective in the treatment of hypertension but are associated with a high frequency of cough and other adverse effects. AT-II-receptor antagonists were developed as agents that would more completely block the RAS and thus decrease the adverse effects seen with ACE inhibitors. AT-II-receptor antagonists include losartan, valsartan, irbesartan, candesartan, eprosartan, telmisartan, and tasosartan. Several clinical trials have demonstrated that AT-II-receptor antagonists are as effective as calcium-channel blockers, beta-blockers, and ACE inhibitors in the treatment of hypertension and induce fewer adverse effects. The adverse effects of AT-II-receptor antagonists--dizziness, headache, upper-respiratory-tract infection, cough, and gastrointestinal disturbances--occur at about the same rate as with placebo. [corrected]. All available AT-II-receptor antagonists seem to be equally effective in reducing both systolic and diastolic blood pressure, and they are comparable in cost. Currently, AT-II-receptor antagonists are used either as monotherapy in patients who cannot tolerate ACE inhibitors or in combination with other antihypertensive agents. Angiotensin II-receptor antagonists are well tolerated and are as effective as ACE inhibitors in decreasing blood pressure.",2001.0,0,0
407,10904023,Effect of angiotensin II antagonist eprosartan on hyperglycemia-induced activation of intrarenal renin-angiotensin system in healthy humans.,S Y Osei; D A Price; L M Laffel; M C Lansang; N K Hollenberg,"We have previously reported that hyperglycemia in healthy human subjects increased the renal vasodilator response to the angiotensin-converting enzyme inhibitor captopril. This observation raised intriguing possibilities relevant to the pathogenesis of nephropathy in patients with diabetes mellitus. To ascertain whether the effect of captopril was indeed mediated by a reduction in angiotensin II (Ang II) formation, we performed another study in which an Ang II antagonist, eprosartan, was used in place of captopril. Nine healthy subjects were studied in high sodium balance (ie, sodium intake 200 mmol/d). On the first day, the subjects received 600 mg eprosartan orally, and renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured. Glucose was infused intravenously on the second and third study days to increase plasma glucose to a level below the threshold for glycosuria ( approximately 8.8 mmol/L). Eprosartan at a dose of 600 mg or placebo was administered randomly on the second or third study day 1 hour after initiation of glucose infusion. RPF increased (by 76+/-7 mL. min(-1). 1.73 m(-2), P<0.01) in response to sustained moderate hyperglycemia and then increased further (by 147+/-15 mL. min(-1). 1. 73 m(-2), P<0.01) when eprosartan was administered during hyperglycemia. Eprosartan, conversely, did not affect RPF and GFR in normoglycemic subjects. GFR was not affected by either hyperglycemia or eprosartan. Neither plasma renin activity nor plasma Ang II concentration changed during hyperglycemia, suggesting that the hormonal responses responsible for the enhanced renal vasodilator response to eprosartan occurred within the kidney. The enhancement of the renal vasodilator effect of eprosartan during hyperglycemia is consistent with activation of the intrarenal renin-angiotensin system.",2000.0,0,0
408,10904284,"Reduction in left ventricular hypertrophy in hypertensive patients treated with enalapril, losartan or the combination of enalapril and losartan.",A C Avanza; L M El Aouar; J G Mill,"To compare the regression of left ventricular hypertrophy in patients with moderate hypertension treated with enalapril, losartan or a combination of the two drugs at lower doses. Patients of both sexes with moderate hypertension confirmed by ambulatory monitoring of arterial blood pressure and with left ventricular hypertrophy on echocardiogram were assigned to three groups: enalapril (35 mg/day, n=15), losartan (175 mg/day, n=15) and enalapril losartan (15 mg+100 mg/day, n=16). The patients received the drugs for 10 months. The three therapeutic regimens were equally effective in reducing blood pressure and left ventricular mass index (LVMI, g/m2): 141+/-3.9 to 123+/-3.6 in the enalapril group (p<0.05), from 147+/-3.8 to 133+/-2.8 in the losartan group (p<0.05), and from 146+/-3.0 to 116+/-4.0 in the enalapril+losartan group (p<0.05). However, the percent reduction of LVMI was significantly greater (p<0.01) in the enalapril+losartan group (20.5+/-5.0%) than in enalapril (12.4+/-3.2%) and the losartan (9.1+/-2.1%) groups. Normalization of LVMI was obtained in 10 out of the 16 patients who received enalapril+ losartan, in 6 out of the 15 patients who received only enalapril and in 4 out of the 15 patients treated with losartan. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist (AT1 receptor antagonist) in patients produced an additional effect on the reduction of left ventricular hypertrophy. This finding may depend on a more complete inhibition of the cardiac renin-angiotensin.",2000.0,0,0
409,10907969,Advances in the treatment of congestive heart failure: new approaches for an old disease.,M Z Skrabal; J A Stading; K A Behmer-Miller; D E Hilleman,"Heart failure is a symptom complex of varied etiology associated with substantial mortality. Approximately 5 million Americans have the disease, with 400,000 new cases diagnosed each year. Despite better understanding of its pathophysiology, therapeutic options remain suboptimal and the syndrome remains associated with high rates of hospitalization and loss of economic productivity. Management traditionally included vasodilators, diuretics, and digoxin, with a focus on controlling symptoms and improving ejection fraction and exercise capacity. Drug therapy now is focused on improving survival, with a reduction in health care costs related to hospitalizations. Drugs with a proven benefit in reducing morbidity and mortality are angiotensin-converting enzyme inhibitors, beta-blockers, and the combination of hydralazine plus a nitrate. Diuretics, digoxin, dihydropyridine calcium channel blockers, phosphodiesterase inhibitors, catecholamine infusions, amiodarone, left ventricular assist devices, and transplantation are also options.",2001.0,0,0
410,10908079,Electrophysiological changes of angiotensin-converting enzyme inhibition after myocardial infarction.,Y S Tuininga; A C Wiesfeld; D J van Veldhuisen; I C van Gelder; H J Crijns,"To investigate whether prevention of remodeling would translate into a more stable electrophysiological profile, the investigators randomized 56 patients to treatment with angiotensin-converting enzyme (ACE) inhibition or placebo for 3 months after myocardial infarction. Programmed electrical stimulation revealed no significant differences in inducibility of monomorphic sustained ventricular tachycardia (VT), whereas ventricular fibrillation (VF) tended to be lower in the ACE-inhibitor group. Effective refractory periods were consistently longer, and dispersion of refractoriness was significantly shorter in the ACE-inhibitor group. The investigators conclude that in this small patient group ACE inhibition may mildly add to a more stable electrophysiological profile.",2001.0,0,0
411,10912746,"Comparison of three blood pressure measurement methods for the evaluation of two antihypertensive drugs: feasibility, agreement, and reproducibility of blood pressure response.",S Ragot; N Genès; L Vaur; D Herpin,"Our objective was to compare three different methods of blood pressure measurement through the results of a controlled study aimed at comparing the antihypertensive effects of trandolapril and losartan. Two hundred and twenty-nine hypertensive patients were randomized in a double-blind parallel group study. After a 3-week placebo period, they received either 2 mg trandolapril or 50 mg losartan once daily for 6 weeks. At the end of both placebo and active treatment periods, three methods of blood pressure measurement were used: a) office blood pressure (three consecutive measurements); b) home self blood pressure measurements (SBPM), consisting of three consecutive measurements performed at home in the morning and in the evening for 7 consecutive days; and c) ambulatory blood pressure measurements (ABPM), 24-h BP recordings with three measurements per hour. Of the 229 patients, 199 (87%) performed at least 12 valid SBPM measurements during both placebo and treatment periods, whereas only 160 (70%) performed good quality 24-h ABPM recordings during both periods (P < .0001). One hundred-forty patients performed the three methods of measurement well. At baseline and with treatment, agreement between office measurements and ABPM or SBPM was weak. Conversely, there was a good agreement between ABPM and SBPM. The mean difference (SBP/DBP) between ABPM and SBPM was 4.6 +/- 10.4/3.5 +/- 7.1 at baseline and 3.5 +/- 10.0/4.0 +/- 7.0 at the end of the treatment period. The correlation between SBPM and ABPM expressed by the r coefficient and the P values were the following: at baseline 0.79/0.70 (< 0.001/< .0001), with active treatment 0.74/0.69 (0.0001/.0001). Hourly and 24-h reproducibility of blood pressure response was quantified by the standard deviation of BP response. Compared with office blood pressure, both global and hourly SBPM responses exhibited a lower standard deviation. Hourly reproducibility of SBPM response (10.8 mm Hg/6.9 mm Hg) was lower than hourly reproducibility of ABPM response (15.6 mm Hg/11.9 mm Hg). In conclusion, SBPM was easier to perform than ABPM. There was a good agreement between these two methods whereas concordance between SBPM or ABPM and office measurements was weak. As hourly reproducibility of SBPM response is better than reproducibility of both hourly ABPM and office BP response, SBPM seems to be the most appropriate method for evaluating residual antihypertensive effect.",2001.0,0,0
412,10913472,Effect of quinapril initiated during progressive remodeling in asymptomatic patients with healed myocardial infarction.,P Gaudron; L Kugler; K Hu; D Fraccarollo; W Bauer; C Eilles; G Ertl,"Approximately 20% of patients with healed myocardial infarction develop asymptomatic progressive left ventricular (LV) dilation and remodeling and are at increased risk for progression to symptomatic congestive heart failure and premature death. It was the goal of this study to test whether quinapril may interrupt this process and to analyze potential mechanisms. Of 138 patients with an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation and were randomized in a prospective, double-blind study to placebo or quinapril. At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/- 3%) and end-diastolic volume (gated single-photon emission computed tomography) increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril (n = 12), respectively. Progressive dilation continued in patients taking placebo (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6 months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs placebo). Wedge pressure during bicycle exercise was similar at baseline, but at 12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of asymptomatic LV dilation and remodeling after remote myocardial infarction, possibly due to attenuation of an exercise-induced increase in LV filling pressure.",2000.0,0,0
413,10913814,"The non-insulin-dependent diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design, organization, and patient recruitment. DIABHYCAR Study Group.",M Lièvre; M Marre; G Chatellier; P Plouin; J Réglier; L Richardson; F Bugnard; D Vasmant,"The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a randomized, prospective, double-blind, placebo-controlled, multicenter international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with type II diabetes and micro- or macroalbuminuria. The main outcome of the study is the time to first occurrence of either death from a cardiovascular origin, including sudden death, nonfatal myocardial infarction, stroke, or congestive heart failure, or requirement of hemodialysis or renal transplantation. The study was launched in France in early 1995 with the participation of general practitioners only, but had to be extended to 15 other countries in 1997 due to difficulties in recruitment. Since 2.5 years after the beginning of the trial the observed event rate was much less than anticipated, it was decided to increase recruitment and follow-up duration and to include congestive heart failure in the definition of the main outcome to keep the study power at a satisfactory level. Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the early discontinuation for efficacy of another study of ramipril in high cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406 instead of 500 patients presented a main outcome) and the Data Safety and Monitoring Board recommended that the study continue. Follow-up is planned to end on March 31, 2001.",2000.0,0,0
414,10915233,"Long-term effects of losartan and enalapril, alone or with a diuretic, on ambulatory blood pressure and cardiac performance in hypertension: a case-control study.",P Verdecchia; G Schillaci; G P Reboldi; N Sacchi; B Bruni; G Benemio; C Porcellati,"The long-term effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on ambulatory blood pressure and cardiac performance have never been examined comparatively. We compared losartan and enalapril in their long-term effects on office and ambulatory blood pressure, cardiac structure and function, and routine biochemical tests. In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood pressure monitoring and echocardiography before and after an average of 3.3 years of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio with a group of 66 subjects treated with enalapril 20mg daily. Case-control sampling was based on age (+/-5years), sex, pre-treatment office blood pressure (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment (+/-6months). An additional group of subjects who interrupted their treatment with enalapril (n=18) or losartan (n =2) because of unwanted effects before execution of the follow-up study was not included in the analysis. Hydrochlorothiazide was added during follow-up in order to optimize blood pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic) in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril group. Office and ambulatory blood pressures were lowered to a similar extent by losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change in left ventricular mass over time was more closely associated with the change in ambulatory blood pressure than with office blood pressure in both groups. Left ventricular internal diameter did not change with either drug. The endocardial shortening fraction, mid-wall shortening fraction and Doppler indexes of active diastolic relaxation did not change with either drug. None of the biochemical parameters showed a significant change. Serum uric acid showed a slight and non-significant reduction only in the losartan group. In this case-control study in uncomplicated subjects with essential hypertension, losartan and enalapril, alone or combined with a diuretic, effectively and equally lowered office and ambulatory blood pressure and induced a significant reduction in left ventricular mass during long-term treatment. Left ventricular systolic and diastolic function remained unchanged with either regimen.",2000.0,0,0
415,10915394,,,,,0,0
416,10916100,Long-term comparison of losartan and enalapril on kidney function in hypertensive type 2 diabetics with early nephropathy.,Y Lacourcière; A Bélanger; C Godin; J P Hallé; S Ross; N Wright; J Marion,"The objectives of this study were to compare the effects of the angiotensin II receptor blocker, losartan, to those of the angiotensin-converting enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic subjects with early nephropathy. The tolerability of these agents and their effect on the metabolic profile were also evaluated. The study was a one-year prospective, double-blind trial with losartan and enalapril administered alone or in combination with hydrochlorothiazide and other antihypertensive agents. ABP and renal and biochemical parameters were measured at baseline and after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2 diabetics with early nephropathy completed the study. Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a statistical difference between groups. Geometric means for urinary albumin excretion (UAE) decreased significantly (P < 0.001) in patients treated with losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from 73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at 52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR) was stabilized at the end of therapy and was identical in both treatment groups. Treatment with enalapril was associated with a significantly higher incidence of cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with losartan. Our results indicate that a one-year course of antihypertensive therapy with either losartan or enalapril significantly reduces UAE in hypertensive type 2 diabetic patients with early nephropathy. The reduction in UAE with each treatment is similarly related to decrements in ABP. In addition, the rate of decline in GFR is similar in both treatment groups.",2000.0,0,0
417,10916115,Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism.,D Hernández; J Lacalzada; E Salido; J Linares; A Barragán; V Lorenzo; L Higueras; B Martín; A Rodríguez; I Laynez; J M González-Posada; A Torres,"Cardiac complications are the main cause of death in renal transplantation (RT), and left ventricular hypertrophy (LVH) may play an important role in these patients. The unfavorable genotype of the angiotensin-converting enzyme (ACE) gene has been associated with cardiovascular disease, including LVH. ACE inhibitors (ACEIs) reduce LVH, but little is known about the effects of ACEIs on LVH in RT patients with different insertion/deletion (I/D) genotypes of the ACE gene. We prospectively studied 57 stable nondiabetic RT patients with hypertension and echocardiographic LVH as well as a functional graft for 69.5 +/- 5.6 months. Patients randomly received either lisinopril 10 mg/day (group A, N = 29; 5 were excluded due to reversible acute renal failure) or placebo (group B, N = 28) for 12 months. Echocardiography (M-mode, 2-B, and color flow Doppler) was performed at baseline and 6 and 12 months later by the same examiner without previous knowledge of the genetic typing. The ACE genotype (I or D alleles) was ascertained by polymerase chain reaction (PCR; group A, DD = 10 and ID/II = 14; group B, DD = 15 and ID/II = 13). All patients maintained a good renal function (serum creatinine <2.5 mg/dL) during the follow-up and both groups received a similar proportion of antihypertensive drugs (beta-blockers 83 vs. 79%; Ca antagonists 66 vs. 68%; alpha1-adrenoreceptor antagonists 50 vs. 67%) during the study. As expected, mean arterial blood pressure and hemoglobin levels showed a higher percentage reduction in group A versus group B (-4 +/- 2.8 vs. 2.1 +/- 2.6%, P = 0.07, and -11.5 +/- 1.5 vs. -0.5 +/- 2.3%, P < 0.01, respectively). Group A patients showed a significantly higher decrement in LV mass index (LVMI) than group B at the end of follow-up, after adjusting for age, baseline LVMI, time after grafting and changes in systolic blood pressure, renal function, and hemoglobin levels (group A, -9.5 +/- 3.5% vs. group B, 3 +/- 3.2%, P < 0.05). As a result, 46% of group A and only 7% of group B patients showed a reduction of LVMI >/=15% (P < 0.01). The beneficial effect of lisinopril on LVMI reduction was more evident in DD patients (placebo DD, 8.4 +/- 4.1% vs. lisinopril DD, -7.2 +/- 5.3, P < 0.05), and a trend was observed in patients with other genotypes (placebo ID/II, 2.8 +/- 5.4% vs. lisinopril ID/II, -11.4 +/- 5%, P = 0.33). Lisinopril decreases LVM in renal transplant patients with hypertension and LVH, and the ACE gene polymorphism may predict the beneficial effect of this therapy. This finding may be important in targeting prophylactic interventions in this population.",2000.0,0,0
418,10918548,"Practice vs ambulatory blood pressure measurement under treatment with ramipril (PLUR Study): a randomised, prospective long-term study to evaluate the benefits of ABPM in patients on antihypertensive treatment.",J Schrader; S Lüders; C Züchner; M Herbold; G Schrandt,"The usefulness of ambulatory blood pressure monitoring (ABPM) vs casual blood pressure measurement in the physicians practice (PM) for the routine management of patients with hypertension concerning total mortality and morbidity has been compared in a prospective, randomised, open multicentre study with a 5-year follow-up. The study was performed in general practitioners offices in Germany from 1991 to 1997. A total of 1298 patients with essential hypertension were included. Cardio- and cerebrovascular events, total mortality/morbidity and drug-saving effects in hypertensives treated according to two different methods of blood pressure measurement were the primary and secondary endpoints of the study. A total of 239 patients from group 1 (ABPM, n = 651), and 208 from group 2 (PM, n = 647) prematurely discontinued the study. The reason for discontinuation in 55 of these patients (20 from group 1 and 35 from group 2) was that they reached the main endpoint (total mortality/morbidity and cardio- and cerebrovascular events) of the study. The difference was statistically significant (P = 0.037) in favour of group 1. Cardio- and cerebrovascular events also occurred in a lower number of patients (n = 14) in group 1, as compared to group 2 (n = 24). The difference however was not significant (P = 0. 097). A difference in a direct drug-saving effect could not be observed between the two groups but 22% of the initially screened patients were detected with the ABPM to have white coat hypertension and thus these patients did not receive antihypertensive treatment.",2000.0,0,0
419,10919035,Effects of angiotensin-converting enzyme inhibitors and sclerotherapy on portal hemodynamics in patients with portal hypertension.,A A Nasr; N G el-Hak; M E Settein; M A Khafagy; M T Tadros,"Since pharmacotherapy of portal hypertension has always been a subject of wide interest, we decided to study the effects of different angiotensin-converting enzyme inhibitors and endoscopic sclerotherapy on portal hemodynamics in patients with portal hypertension and bleeding esophageal varices. The study included 72 patients with portal hypertension divided into 6 equal groups. Endoscopic sclerotherapy was done to all patients every 2 weeks for 3 months. In addition, the first 5 groups of patients were maintained on angiotensin-converting enzyme inhibitors for 3 months as follows: group I on perindopril, II on ramipril, III on fosinopril, IV on lisinopril and V on captopril. Portal hemodynamics were determined before and after therapy (using an ultrasonic duplex system). New Doppler portal indices were derived and portal vein kinetic pressure was estimated for the first time by using data derived from the ultrasonic duplex system. 1) Short-term endoscopic sclerotherapy alone resulted in significant elevation of portal vein kinetic pressure, wall stress index and flow volume (P < 0.01) and non-significant increase in the total portal circulation resistance index (P > 0.05) and significantly decreased portal vein compliance and distensibility indices (P < 0.05); 2) Angiotensin-converting enzyme inhibitors reduced the maximum and average portal velocities, the portal flow volume, total portal circulation resistance index and increased portal vein compliance and distensibility indices, hence they reduced the portal vein kinetic pressure significantly in group IV (P < 0.05 for the flow volume and P < 0.01 for other indices); 3) The only side effect encountered was allergic cough (in 8.33% of patients). No effects were noticed on the pulse, systolic, diastolic or mean blood pressures or Child-Pugh Score of liver disease. 1) Angiotensin-converting enzyme inhibitors when added to endoscopic sclerotherapy can ameliorate the effects of the latter on portal hemodynamics in patients with portal hypertension; 2) Portal vein kinetic pressure, total portal circulation resistance index, portal vein wall stress index, compliance and distensibility indices are new Doppler portal indices that proved to be of value in the follow-up of patients with portal hypertension under sclerotherapy alone or in conjunction with pharmacotherapy; 3) Angiotensin-converting enzyme inhibitors are safe drugs that can be used for portal decompression with endoscopic sclerotherapy. Their use as sole portal anti-hypertensive agents still awaits further studies.",2001.0,0,0
420,10923574,Durability of improvement achieved in a clinical trial. Is compliance an issue?,I Enström; K Pennert; L H Lindholm,"The effects seen in clinical trials may not translate to actual practice situations. We examined the persistence of blood pressure effects 31 months after a clinical trial of treatment with hypotensive agents. Nineteen previously untreated middle-aged men with hypertension had their office and ambulatory blood pressure recorded after 4 weeks of placebo treatment, 4 weeks of active treatment in a clinical trial, and 31 months of treatment in clinical practice. All recording was done by the same physician (IE). Mean 24-hour blood pressure was 138/92 mm Hg after 4 weeks of placebo treatment, 128/85 mm Hg after 4 weeks of active treatment in the clinical trial, and 136/87 mm Hg after a mean of 31 months of treatment in clinical practice. The corresponding blood pressure values > or =140/90 mm Hg during the daytime were 47%, 24%, and 39%, and office blood pressures were 155/101, 145/93, and 150/91 mm Hg. Individual comparison revealed that 6 of the 19 patients had higher mean 24-hour blood pressure after several months of treatment in clinical practice than after 4 weeks of active treatment in the clinical trial. In our study, the significantly reduced blood pressure in the clinical trial did not persist when followed up in clinical practice. At follow-up, one third of the patients had blood pressure values similar to those before active treatment. The reason for this is unclear, but inconsistent compliance may play a part in the lack of durability of the improvements. Our results indicate that effects seen in short-term clinical trials may not translate to long-term benefits in clinical practice.",2000.0,0,0
421,10924944,Diuretic therapy in Afrocaribbeans with uncomplicated essential hypertension.,A Ester; E Teuben; J C Nossent,,2000.0,0,0
422,10929934,Eprosartan: a review of its use in the management of hypertension.,G L Plosker; R H Foster,"Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Results of large (n > 100) randomised double-blind studies in patients with mild, moderate or severe hypertension demonstrated that the antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single daily dose or in 2 divided doses) is significantly greater than that of placebo and at least as good as that of enalapril. In placebo-controlled trials, eprosartan achieved mean reductions from baseline in trough sitting systolic blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7 mm Hg. Response rates associated with once daily administration of eprosartan 400 to 800 mg were approximately double those with placebo. Overall, eprosartan was well tolerated with a similar tolerability profile to that of placebo. In comparative trials, in which the incidence of persistent dry cough was evaluated as the primary end-point, enalapril was several-fold more likely to induce this adverse event than eprosartan (the difference being statistically significant regardless of study population and definition of cough). In conclusion, the angiotensin II receptor antagonist eprosartan is a well tolerated and effective antihypertensive agent that is administered once or twice daily without regard to meals. Eprosartan has a low potential for serious adverse events, and the drug has not been associated with clinically significant drug interactions. Unlike ACE inhibitors such as enalapril, eprosartan does not have a high propensity to cause persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic option in the management of patients with hypertension.",2001.0,0,0
423,10931799,Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial.,B F Uretsky; K Thygesen; P W Armstrong; J G Cleland; J D Horowitz; B M Massie; M Packer; P A Poole-Wilson; L Ryden,"Sudden unexpected death frequently occurs in chronic heart failure. The importance of acute coronary events in triggering sudden death (SD) is unclear. We evaluated at autopsy the prevalence of acute coronary findings (coronary thrombus, ruptured plaque, or myocardial infarction [MI]) and their relation to SD. Autopsy results in 171 patients in the randomized ATLAS trial were reviewed. The prevalence of acute coronary findings was 33%: in 54% of patients with significant coronary artery disease (CAD) who died suddenly, 32% who died of myocardial failure, but in non-CAD patients, they were present in only 5% and 10% respectively. The percentage of patients classified as dying of MI was 28% in the autopsy group versus 4% in the nonautopsied group (P<0.0001). Of the autopsied group with acute MI, 97% (31 of 32 patients) with SD and 40% (6 of 15 patients) with myocardial failure did not have the MI diagnosed during life. When undiagnosed MI was classified as ""sudden unexpected"" or ""myocardial failure"" from clinical information only, the distribution of death causes was similar in the autopsy and nonautopsied groups. Acute coronary findings are frequent and usually not clinically diagnosed in heart failure patients with CAD, particularly in those dying suddenly, suggesting the importance of acute coronary events as a trigger for SD in this setting.",2000.0,0,0
424,10933355,"Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.",S MacMahon; N Sharpe; G Gamble; A Clague; C N Mhurchu; T Clark; H Hart; J Scott; H White,"The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.",2000.0,0,0
425,10933569,Intermediate but not low doses of aspirin can suppress angiotensin-converting enzyme inhibitor-induced cough.,A Tenenbaum; E Grossman; J Shemesh; E Z Fisman; I Nosrati; M Motro,"This self-matched control study aimed to compare the efficiency of two different regimens of active treatment: aspirin in low (100 mg daily) versus intermediate (500 mg daily) doses in abolishing angiotensin-converting enzyme inhibitor (ACEI)-induced cough. A dry bothersome cough is the most common adverse class effect of all angiotensin-converting enzyme inhibitors. Prostaglandins (PG) have been pinpointed as playing a leading role in the genesis of ACEI-associated cough. The role of different doses of the most commonly used PG inhibitor-aspirin-in ACEI cough modification was not yet elucidated. Of 350 consecutive ACEI-treated patients, we identified 34 (9.7%) nonsmoking ACEI-related coughers. Patients with lung disease, nonsteroidal anti-inflammatory drug (NSAID) treatment, and those who did not agree to participate in the study were excluded. In the remaining 14 ACEI coughers (eight men, six women; mean age, 63 +/- 11 years), the treatment was discontinued; the dry cough completely disappeared, but returned in all patients within 1 week after ACEI reintroduction. At the end of the rechallenge period, patients started a low dose of aspirin for 1 week, switching thereafter to the intermediate dose of aspirin for an additional week. On each visit the cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low doses of aspirin were ineffective in suppressing ACEI-induced cough, whereas intermediate doses completely abolished cough in five patients and reduced coughing in all but one patient; CS and CF decreased, respectively, from 2.5 +/- 1.0 to 0.9 +/- 1.1, P < .002 and from 6.6 +/- 2.4 to 2.4 +/- 1.1, P < .0002. Overall, intermediate doses of aspirin beneficially modified cough scores in 13 (93%) patients, enabling nine (64%) to continue ACEI treatment. Aspirin did not influence blood pressure control either in hypertensives or in postinfarction patients. We conclude that intermediate but not low doses of aspirin probably can suppress ACEI-induced cough. These findings propose a new alternative therapeutic approach for patients with ACEI-related cough, especially those in whom ACEI treatment seems to be essential.",2001.0,0,0
426,10935667,Perindopril for elderly people with chronic heart failure: the PEP-CHF study. The PEP investigators.,J G Cleland; M Tendera; J Adamus; N Freemantle; C S Gray; M Lye; D O'Mahony; L Polonski; J Taylor,"The prevalence of chronic heart failure (CHF) rises with increasing age, from < 1% in those below 65 years of age to > 5% in those over 65 years of age and is a major cause of morbidity and mortality in older people. Recent European guidelines point to a major deficiency in our knowledge of how to treat diastolic chronic heart failure, and a lack of information on treatment for heart failure in the elderly in general. The aims of this trial are to assess the potential benefits of the ACE inhibitor perindopril to treat chronic heart failure in elderly people, in the absence of any major left ventricular systolic dysfunction. One thousand people over the age of 70 years will be recruited into this study. Evidence of chronic heart failure will be confirmed by clinical criteria and echocardiography. Once a diagnosis of chronic heart failure has been confirmed, the patient will receive either perindopril or placebo in addition to their usual treatment. Death, and unplanned heart failure related hospitalisations, are the primary outcomes. Quality of life, as measured by the Guyatt questionnaire will be assessed at the beginning of the study and at 1 year. Sub-studies of this trial include a 6-min walking test and more detailed evaluation of ventricular function (as assessed by echocardiography). Both parameters will be measured at 8 weeks and 1 year, and analysed against baseline data. Cognitive function in this group of patients will also be evaluated at baseline and 1 year. This trial is due to report in the year 2001.",2000.0,0,1
427,10935777,The value of repeated echocardiographic evaluation in patients with idiopathic dilated cardiomyopathy during treatment with metoprolol or captopril.,K Jansson; U Dahlström; K E Karlberg; E Karlsson; O Nyquist; E Nylander,"Serial echocardiographic investigations were carried out on patients with idiopathic dilated cardiomyopathy, to evaluate treatment effects on left ventricular (LV) performance during therapy with either metoprolol or captopril. Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of heart failure (NYHA II-III) and a mean age of 49 years were included in the investigation. The patients were investigated with Doppler echocardiography before treatment, after 3 and 6 months of treatment (either metoprolol or captopril) and 1 month after withdrawal of treatment. Intra- and inter-investigator reproducibility was acceptable, with a coefficient of variation of less than 5% for LV dimensions. A reduction in LV dimensions was seen in both treatment groups. In the metoprolol group there was also an increase in LV stroke volume and fractional shortening. The non-invasive data were in accordance with invasive measurements of stroke volume and LV filling pressure. In patients with idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure, echocardiography seemed to be sufficiently reproducible to be used for determination of treatment effects in a longitudinal heart failure study. Both metoprolol and captopril were well tolerated and had favourable effects on LV performance.",2001.0,0,0
428,10937952,"Haemodynamic, neurohumoral and exercise effects of losartan vs. captopril in chronic heart failure: results of an ELITE trial substudy. Evaluation of Losartan in the Elderly.",A R Houghton; M Harrison; A J Cowley,"The AT1 receptor antagonists differ from the angiotensin converting enzyme inhibitors by achieving a more complete blockade of angiotensin II's actions and by not affecting bradykinin metabolism. There is little information on whether this causes clinically significant differences in haemodynamics, neurohormones and exercise tolerance in heart failure. To compare the effects of losartan and captopril upon central and regional haemodynamics, neurohormones and exercise capacity in heart failure. In a double-blind, randomised trial 18 patients aged > or =65 years with symptomatic heart failure were allocated to treatment with losartan (10 patients) or captopril (eight patients). Patients underwent assessment at baseline, after the first dose, at 12 weeks and at 24 weeks. Systolic blood pressure fell by - 10.7% 1 h after captopril 6.25 mg (P = 0.007) and by - 4.8% 3 h after losartan 12.5 mg (P = 0.02). The blood pressure reduction was sustained with losartan at 12 and 24 weeks. Systemic vascular resistance fell acutely after captopril (-16.4%, P = 0.01). Captopril caused an acute and sustained rise in superior mesenteric artery blood flow (+ 22.9%, P = 0.04), and a slower rise in renal artery blood flow (+31.7%, P = 0.01). Losartan had no acute effects on regional haemodynamics but had increased superior mesenteric artery blood flow by 38.1% at 12 weeks (P = 0.02). There were no substantial differences between losartan and captopril, and no changes occurred in neurohormones or exercise capacity. No substantial differences were observed between losartan and captopril on central or regional haemodynamics, neurohormones or exercise capacity in elderly patients with stable symptomatic heart failure.",2000.0,0,1
429,10937982,"Placebo-controlled comparison of candoxatril, an orally active neutral endopeptidase inhibitor, and captopril in patients with chronic heart failure.",D B Northridge; P F Currie; D E Newby; J J McMurray; M Ford; N A Boon; H J Dargie,"To compare the effects on exercise capacity of the neutral endopeptidase inhibitor candoxatril, and the angiotensin converting enzyme inhibitor captopril, in patients with mild to moderate heart failure. In this multi-centre double-blind placebo controlled study, 60 patients with NYHA Class I-III heart failure were randomised to candoxatril 200 mg b.d. (n = 22), captopril 25-50 mg b.d. (n = 23) or placebo (n = 15). Treadmill exercise tests were carried out weekly during a 5-week single-blind placebo run-in phase until a stable baseline was achieved, and repeated at 4 weekly intervals during the 12-week double-blind treatment phase. Nine patients withdrew from the study--four candoxatril and five captopril. The placebo-adjusted increase in exercise duration after 12 weeks was 56 s (95% CI, -26 to +137 s; P = 0.12) with candoxatril and 37 s (-43 to + 117 s; P = 0.29) with captopril. Both candoxatril and captopril were well tolerated and treadmill exercise duration appeared to increase during 12 weeks of therapy but this did not achieve statistical significance. This study tentatively suggests that in patients with heart failure, neutral endopeptidase inhibition may provide similar symptomatic benefits to angiotensin converting enzyme inhibition.",2000.0,0,1
430,10937983,Baseline clinical characteristics of patients recruited into the assessment of treatment with lisinopril and survival study.,J G Cleland; P Armstrong; J D Horowitz; B Massie; M Packer; P A Poole-Wilson; L Rydén,"The beneficial effect of ACE inhibitors on mortality has been established in a series of trials. However, in clinical practice, ACE inhibitors are commonly administered in doses much lower than those shown to be effective in the landmark trials. This report describes the baseline characteristics of the patients recruited into the ATLAS study by age and gender sub-groups. The ATLAS study compared the effects of 'low' dose (2.5-5.0 mg/day) to 'high' dose (32.5-35.0 mg/day) lisinopril in a double-blind study of 3164 patients with moderate to severe heart failure and left ventricular ejection fraction < 30% during a mean follow-up period of 46 months. The primary end-point was all cause mortality and the principal secondary end-point a composite of all-cause hospitalisation or all-cause mortality. Among patients with heart failure selected for the presence of left ventricular systolic function there were few differences among age groups or between genders. Older patients were not so heavy, were more likely to have ischaemic heart disease, hypertension and atrial fibrillation contributing to their heart failure and had a higher blood urea. Women were not so heavy as men. Age and gender had no major influence on mean ejection fraction or baseline treatment in the ATLAS study. Weight and renal function may alter the plasma concentration of any given dose of an ACE inhibitor. Potential interactions between dose of lisinopril, weight and renal function will be explored after the study is completed.",2000.0,0,0
431,10938481,Angiotensin II antagonists are superior to ACE inhibitors; David vs. Goliath.,K Dickstein,,2000.0,0,0
432,10938492,First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Slovak Investigator Group.,J Vítovec; J Spinar,"First-dose hypotension refers to an observed reduction in blood pressure after the administration of the first dose of ACE inhibitors in patients with congestive heart failure. To compare the first-dose responses of low-dose enalapril and perindopril in patients with stable symptomatic chronic heart failure. Single blind, randomised, multicenter, parallel, prospective study. Patients (N=298) with chronic heart failure due to ischemic heart disease or dilated cardiomyopathy, NYHA II-IV, ejection fraction<40%, age>18 years, naive to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single dose of 2. 5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical examinations were performed before entry into the study. Ambulatory blood pressure monitoring started 2 h before the study medication was given, and continued for at least 10 h after the medication. The maximum drop in blood pressure appeared approximately 4 h after dose administration in both groups, and was more pronounced in the enalapril group. Patients in the enalapril group had a significantly higher incidence of asymptomatic hypotension. No symptomatic hypotension requiring a change in medication or a prolongation of hospitalisation was observed. A low dose of perindopril is well-tolerated at initiation of ACE inhibitor therapy in patients with chronic heart failure and causes less first-dose hypotension than a low dose of enalapril.",2000.0,0,1
433,10940667,Acute treatment of ischemic stroke. European Stroke Initiative (EUSI).,W Hacke; M Kaste; T Skyhoj Olsen; J Bogousslavsky; J M Orgogozo,,2000.0,0,0
434,10947144,Is losartan superior to captopril in reducing all-cause mortality in elderly patients with symptomatic heart failure?,T H Trojian; E A Jackson,,2000.0,0,1
435,10947200,Short-term effect of captopril on microalbuminuria in children with glycogen storage disease type Ia.,H Ozen; G Ciliv; N Koçak; I N Saltik; A Yüce; F Gürakan,"Early signs of renal dysfunction in glycogen storage disease type Ia (GSD Ia) are glomerular hyperfiltration and proteinuria. In a non-randomized study, the effect of captopril on the improvement of proteinuria in GSD Ia patients with microalbuminuria was investigated. A positive effect has been shown for the insulin-dependent diabetes mellitus patients. Microalbuminuria was defined as albumin/creatinine ratio (mg/mmol) more than 2.5 in spot urine. Nineteen (52.7%) out of 36 patients had microalbuminuria, and 8 patients received captopril at a dose of 1 mg/kg per day. Microalbuminuria was evaluated periodically during the follow-up period. Of the captopril-treated patients, one was lost to follow-up. In the remaining 7 patients, urinary albumin excretion normalized in 3 patients (42.9%) and decreased at least by 50% in another 3 patients (42.8%) after 6 months of treatment. One patient, who was the oldest, did not have any benefit. In untreated patients, only two patients had a decrease in microalbuminuria of more than 50%. Patients with microalbuminuria had significantly higher blood lactate (p < 0.05) and plasma triglyceride (p < 0.01) concentrations and significantly lower blood bicarbonate concentration (p < 0.05) than those patients without it. Additionally, the patients with microalbuminuria had been diagnosed earlier than those without microalbuminuria (p < 0.05). Patients with microalbuminuria have more severe clinical and laboratory findings than those without microalbuminuria. Captopril at a dose of 1 mg/kg per day seems to be effective in at least 50% of GSD Ia patients with microalbuminuria.",2001.0,0,0
436,10948081,Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease.,B Schwartzkopff; M Brehm; M Mundhenke; B E Strauer,"In hypertensive heart disease, no data are available on the repair of coronary resistance vessels in patients after long-term ACE inhibitor treatment. Fourteen patients with essential hypertension were studied with coronary flow reserve and with transvenous endomyocardial biopsy before and after 12 months of antihypertensive treatment with perindopril (4 to 8 mg/d, mean 5.9+/-2.3 mg/d). Left ventricular muscle mass index decreased by 11% (from 145+/-41 to 128+/-36 g/m(2), P=0.04). Maximal coronary blood flow was increased by 54% (from 170+/-46 to 263+/-142 mL. min(-1). 100 g(-1), P=0.001), and minimal coronary vascular resistance was diminished by 33% (from 0.67+/-0.21 to 0.45+/-0.19 mm Hg. min. 100 g. mL(-1), P=0.001); consequently, coronary reserve increased by 67% from 2.1+/-0.6 to 3. 5+/-1.9 (P=0.001). Structural analysis revealed regression of periarteriolar collagen area by 54% (from 558+/-270 to 260+/-173 microm(2), P=0.04) and of total interstitial collagen volume density by 22% (from 5.5+/-3.8 Vv% to 4.3+/-3.2 Vv%, P=0.04), whereas arteriolar wall area was slightly but not significantly reduced. Long-term therapy with the ACE inhibitor perindopril induces structural repair of coronary arterioles that is mainly characterized by the regression of periarteriolar fibrosis and associated with a marked improvement in coronary reserve. These findings indicate the beneficial reparative effects of ACE inhibition on coronary microcirculation in hypertensive heart disease.",2000.0,0,0
437,10954007,Pilot study of combined blockade of the renin-angiotensin system in essential hypertensive patients.,M Azizi; A Linhart; J Alexander; A Goldberg; J Menten; C Sweet; J Ménard,"Additive hemodynamic effects of combined blockade of the renin-angiotensin system by an angiotensin I converting enzyme inhibitor and an angiotensin II antagonist have been observed in sodium-depleted normotensive volunteers and in patients with congestive heart failure. To investigate whether the same additive hemodynamic effects occur in patients with hypertension and to verify the safety of such an approach. Multicenter, randomized, double-blind, parallel-group, pilot study. 177 patients with mild-to-moderate hypertension [diastolic blood pressure (DBP): 95-115 mmHg after a 4-week placebo run-in period] were included in the study. Combination therapy consisting of 50 mg losartan daily and 10 mg enalapril daily was administered for 6 weeks. The effects of this therapeutic regimen was compared with similar groups of patients who received either 50 mg losartan daily or 10 mg enalapril daily. 24-hour ambulatory mean DBP and clinic DBP measured at trough after 6 weeks of treatment. 24-hour ambulatory mean DBP did not significantly differ between treatment groups although the combination tended to lower BP more. The combination therapy was more effective on clinic DBP measured at trough than was losartan by 3.2 mmHg [confidence interval (95%, CI) 0.7-5.7 mmHg, P = 0.012], and more effective than enalapril by 4.0 mmHg (95% CI, 1.5-6.4 mmHg, P = 0.002). In a subgroup of 28 patients, higher plasma active renin and angiotensin I levels during blockade by the combination therapy were observed. This finding confirmed that the combination of the two agents inhibited the renin-angiotensin system to a greater extent than did either agent alone. A combination of 10 mg enalapril daily and 50 mg losartan daily safely induces a supplementary, although modest, fall in clinic DBP in patients with mild-to-moderate essential hypertension.",2001.0,0,0
438,10967698,[The quality of life of hypertensive patients treated with prazosin (sustained-release) or enalapril: a randomized controlled trial over 24 weeks].,S M Consoli; S Troy; C Bernaud,"The importance of the criterion of Quality of Life (QOL) for compliance with antihypertensive drugs led us to study the QOL of 51 hypertensives receiving 2.5 mg of the new formulation of prazosin (sustained release), compared with 49 subjects treated by a converting enzyme inhibitor (enalapril 10 mg), in a double-blind randomized trial. QOL, assessed by means of a 22 item self-administered questionnaire, improved significantly with prazosin, during the 24 weeks of the trial. In the intention to treat analysis, the global score of QOL increased from 46.3 +/- 8.4 to 51.6 +/- 8.9 (p < 0.0001); the covariance analysis showed that the improvement was obtained as early as the 8th week. A similar favourable evolution was observed for anxiety, retardation and anhedonia components, computed from the same questionnaire. No significant difference in QOL evolution was found between prazosin and enalapril. Both treatments proved equivalent in respect of efficacy on blood-pressure values, and tolerance, estimated through the number of dropouts or side-effects. These results confirm the benefit to QOL of hypertensive patients of the new formulation of prazosin.",2000.0,0,0
439,10968237,Preliminary experience with the angiotensin II receptor antagonist irbesartan in chronic kidney disease.,R O von Vigier; P M Zberg; O Teuffel; M G Bianchetti,"Blocking the formation of angiotensin II with converting enzyme inhibitors is an established intervention for kidney disease. The advent of antagonists of the angiotensin II receptor has increased the options for inhibiting the renin-angiotensin-aldosterone system. In adults, angiotensin II antagonists have antihypertensive and antiproteinuric effects similar to those of converting enzyme inhibitors and an adverse effect profile similar to that of placebo. In children, no information is available on angiotensin II antagonists. A total of 20 children (aged 4 to 17 years) with chronic kidney disease received the angiotensin II antagonist irbesartan given once daily. They had hypertension (n = 11), overt proteinuria (n = 3), or both (n = 6). At last follow-up, 2 to 17 months after starting irbesartan (median dosage: 3.3 mg/kg body weight daily), arterial pressure was significantly reduced: the systolic value by 16 [6-22] and the diastolic value by 11 [4-22] mmHg (median and interquartile range). In nine patients with proteinuria, the urinary albumin/creatinine ratio significantly decreased by 145 [105-209] mg/mmol. The frequency of reported adverse events was similar before and with irbesartan. In children with chronic kidney disease the effects of the angiotensin II antagonist irbesartan on arterial pressure and proteinuria mimic those observed with the converting enzyme inhibitors. The effectiveness of a single daily dose and the paucity of side-effects suggest that angiotensin II antagonists expand therapeutic options for inhibiting the renin-angiotensin-aldosterone system in children.",2001.0,0,0
440,10968427,Vasopeptidase inhibition and angio-oedema.,F H Messerli; J Nussberger,,2000.0,0,0
441,10968433,"Comparison of vasopeptidase inhibitor, omapatrilat, and lisinopril on exercise tolerance and morbidity in patients with heart failure: IMPRESS randomised trial.",J L Rouleau; M A Pfeffer; D J Stewart; D Isaac; F Sestier; E K Kerut; C B Porter; G Proulx; C Qian; A J Block,"We aimed to assess in patients with congestive heart failure whether dual inhibition of neutral endopeptidase and angiotensin-converting enzyme (ACE) with the vasopeptidase inhibitor omapatrilat is better than ACE inhibition alone with lisinopril on functional capacity and clinical outcome. We did a prospective, randomised, double-blind, parallel trial of 573 patients with New York Heart Association (NYHA) class II-IV congestive heart failure, left-ventricular ejection fraction of 40% or less, and receiving an ACE inhibitor. Patients were randomly assigned omapatrilat at a daily target dose of 40 mg (n=289) or lisinopril at a daily target dose of 20 mg (n=284) for 24 weeks. The primary endpoint was improvement in maximum exercise treadmill test (ETT) at week 12. Secondary endpoints included death and comorbid events indicative of worsening heart failure. Week 12 ETT increased similarly in the omapatrilat and lisinopril groups (24 vs 31 s, p=0.45). The two drugs were fairly well tolerated, but there were fewer cardiovascular-system serious adverse events in the omapatrilat group than in the lisinopril group (20 [7%] vs 34 [12%], p=0.04). There was a suggestive trend in favour of omapatrilat on the combined endpoint of death or admission for worsening heart failure (p=0.052; hazard ratio 0.53 [95% CI 0.27-1.02]) and a significant benefit of omapatrilat in the composite of death, admission, or discontinuation of study treatment for worsening heart failure (p=0.035; 0.52 [0.28-0.96]). Omapatrilat improved NYHA class more than lisinopril in patients who had NYHA class III and IV (p=0.035), but not if patients with NYHA class II were included. Our findings suggest that omapatrilat could have some advantages over lisinopril in the treatment of patients with congestive heart failure. Thus use of vasopeptidase inhibitors could constitute a potentially important treatment for further improving the prognosis and well being of patients with this disorder.",2000.0,0,1
442,10972368,Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT).,M J Brown; C R Palmer; A Castaigne; P W de Leeuw; G Mancia; T Rosenthal; L M Ruilope,"The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established. We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension. We did a prospective, randomised, double-blind trial in Europe and Israel in 6321 patients aged 55-80 years with hypertension (blood pressure > or = 150/95 mm Hg, or > or = 160 mm Hg systolic). Patients had at least one additional cardiovascular risk factor. We randomly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system (GITS) formulation (n=3157), or co-amilozide (hydrochlorothiazide 25 mg [corrected] plus amiloride 2.5 mg; n=3164). Dose titration was by dose doubling, and addition of atenolol 25-50 mg or enalapril 5-10 mg. The primary outcome was cardiovascular death, myocardial infarction, heart failure, or stroke. Analysis was done by intention to treat. Primary outcomes occurred in 200 (6.3%) patients in the nifedipine group and in 182 (5.8%) in the co-amilozide group (18.2 vs 16.5 events per 1000 patient-years; relative risk 1.10 [95% CI 0.91-1.34], p=0.35). Overall mean blood pressure fell from 173/99 mm Hg (SD 14/8) to 138/82 mm Hg (12/7). There was an 8% excess of withdrawals from the nifedipine group because of peripheral oedema (725 vs 518, p<0.0001), but serious adverse events were more frequent in the co-amilozide group (880 vs 796, p=0.02). Deaths were mainly non-vascular (nifedipine 176 vs co-amilozide 172; p=0.81). 80% of the primary events occurred in patients receiving randomised treatment (157 nifedipine, 147 co-amilozide, difference 0.33% [-0.7 to 1.4]). Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications. The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy.",2000.0,0,0
443,10973843,Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.,R H Fagard; J A Staessen; L Thijs; J Gasowski; C J Bulpitt; D Clement; P W de Leeuw; J Dobovisek; M Jääskivi; G Leonetti; E O'Brien; P Palatini; G Parati; J L Rodicio; H Vanhanen; J Webster,"The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. Patients who were >/=60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (>/=160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.",2000.0,0,0
444,10980214,"Rationale, design, and baseline characteristics of a trial of prevention of cardiovascular and renal disease with fosinopril and pravastatin in nonhypertensive, nonhypercholesterolemic subjects with microalbuminuria (the Prevention of REnal and Vascular ENdstage Disease Intervention Trial [PREVEND IT]).",G F Diercks; W M Janssen; A J van Boven; A A Bak; P E de Jong; H J Crijns; W H van Gilst,"This study describes the rationale, design, and baseline characteristics of a trial to determine whether treatment with fosinopril 20 mg/day and/or pravastatin 40 mg/ day will prevent cardiovascular and renal disease in nonhypertensive (RR <160/100 mm Hg and not using antihypertensive medication) and nonhypercholesterolemic (total cholesterol <8.0 or <5.0 mmol/L in case of previous myocardial infarction and not using lipid lowering medication) men and women with persistent microalbuminuria (urinary albumin excretion >10 mg/L once in an early morning spot urine and 15 to 300 mg/24-hour at least once in two 24-hour urine collections). The Prevention of REnal and Vascular ENdstage Disease Intervention Trial is a single-center, double-blind, randomized, placebo-controlled trial with a 2 x 2 factorial design. The 864 randomized subjects will be monitored for a minimum of 4 years and a maximum of 5 years. The primary efficacy parameter is defined as the combined incidence of all-cause mortality or hospital admission for documented (1) nonfatal myocardial infarction, (2) myocardial ischemia, (3) heart failure, (4) peripheral vascular disease, (5) cerebrovascular accident and/or (6) end-stage renal disease.",2001.0,0,1
445,10980583,Vasopeptidase inhibition: cardiovascular therapy for the new millennium?,M Walters; J Reid,,2000.0,0,0
446,10981547,"Amlodipine is comparable to angiotensin-converting enzyme inhibitor for long-term renoprotection in hypertensive patients with renal dysfunction: a one-year, prospective, randomized study.",H Kumagai; K Hayashi; H Kumamaru; T Saruta,"Unlike angiotensin converting enzyme inhibitors (ACEI), few long-term studies have shown calcium antagonists to retard the progression of renal dysfunction. Our aim was to prospectively compare the effects of amlodipine and ACEI (enalapril) on renal function in hypertensive patients with renal impairment due to chronic glomerulonephritis and essential hypertension. A total of 72 hypertensive patients with serum creatinine (Cr) > 1.5 mg/dL were randomly allocated to treatment with either drug. During a 1-year period, 33% of the patients treated with ACEI dropped out due to adverse events, whereas 9% of patients with amlodipine dropped out. Data of 28 patients were available for analysis of more than 1-year follow-up. Reductions in blood pressure were comparable between the amlodipine (from 165/101 to 138/81 mm Hg) and ACEI groups. Serum Cr increased from 2.1+/-0.8 (SD) to 2.6+/-1.0 mg/dL with amlodipine (n = 16), but the difference was equivalent to that with ACEI (n = 12). Creatinine clearance (Ccr) in the moderate dysfunction group (basal Cr, 1.5 to 2.0 mg/dL) changed from 36+/-10 to 33+/-11 mL/min (not significant) with amlodipine, and the change was similar to that noted with ACEI. Annual declines in Ccr with amlodipine (-3.7 mL/min/year) and ACEI (-2.6 mL/min/year) were comparable, and both tended to be smaller than the annual decline in glomerular filtration rate reported in the Modification of Diet in Renal Disease study (-6 mL/min/year). Serum potassium was increased significantly (P < .01), from 4.5+/-0.4 to 5.3+/-0.8 mEq/L, only in the ACEI group. This 1-year prospective study demonstrated the effect of amlodipine on renal function to be likely the same as that of ACEI. Furthermore, amlodipine was better tolerated than ACEI for hypertensive patients with renal dysfunction.",2001.0,0,0
447,10988281,Efficacy of candesartan cilexetil alone or in combination with amlodipine and hydrochlorothiazide in moderate-to-severe hypertension. UK and Israel Candesartan Investigators.,G A MacGregor; J R Viskoper; T F Antonios; F J He,"This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P:<0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.",2000.0,0,0
448,10988282,Effect of indomethacin on blood pressure lowering by captopril and losartan in hypertensive patients.,P R Conlin; T J Moore; S L Swartz; E Barr; L Gazdick; C Fletcher; P DeLucca; L Demopoulos,"NSAIDs are known to attenuate the effects of some antihypertensive medications. It is not known whether the new class of angiotensin II receptor antagonists is similarly affected. We conducted a multicenter study assessing the effect of indomethacin on the antihypertensive effects of losartan and captopril. After 4 weeks of placebo washout, hypertensive patients received 6 weeks of active antihypertensive therapy with either 50 mg losartan once daily (n=111) or 25 mg captopril twice daily for 1 week, which was increased to 50 mg twice daily for 5 weeks (n=105). This was followed by 1 week of concomitant therapy with indomethacin (75 mg daily). The primary outcome measure was the change in mean 24-hour ambulatory diastolic blood pressure after the addition of indomethacin. Both captopril and losartan significantly lowered ambulatory diastolic blood pressure (losartan -5.3 mm Hg, P:<0.001; captopril -5.6 mm Hg, P:<0.001) after 6 weeks of therapy. Indomethacin significantly attenuated the 24-hour ambulatory diastolic blood pressure for both losartan (2.2 mm Hg, P:<0.05) and captopril (2.7 mm Hg, P:<0.001) and also attenuated the effect of captopril on trough sitting diastolic blood pressure. Changes in daytime diastolic blood pressure (7:00 AM to 11:00 PM) were similar to the 24-hour response in both groups. Nighttime diastolic blood pressure (11:01 PM to 6:59 AM) was significantly attenuated in captopril-treated patients (2.0 mm Hg, P:<0.05), but losartan was unaffected (0.4 mm Hg). Thus, concurrent treatment with indomethacin similarly attenuates the 24-hour antihypertensive response to losartan and captopril.",2000.0,0,0
449,10989729,[Local pulse pressure and regression of arterial wall hypertrophy during antihypertensive treatment. CELIMENE study. The Celiprolol Intima-Media Enalapril Efficacy study].,P Boutouyrie; C Bussy; A I Tropeano; D Hayoz; J Hengstler; N Dartois; B Laloux; H Brunner; S Laurent,"Local Pulse Pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean BP. The present study was designed to assess whether a beta-adrenoceptor antagonist or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through the reduction in carotid PP rather than by lowering mean BP, and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. Ninety-eight essential hypertensive patients were randomised to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high resolution echotracking systems. PP was measured locally with PP applanation tonometry, and independently of mean BP. After 9 month's treatment, mean BP, carotid PP and intima-media thickness (IMT) decreased significantly, with no difference between the tow groups. The reduction in carotid pression pulsée, but not in mean BP, was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.",2000.0,0,0
450,10989734,[The estimation of cardiovascular risk in hypertensive patients is not modified by management of the hypertension].,O Hanon; G Franconi; J J Mourad; A Baleydier; I Croce; X Girerd,"To compare antihypertensive therapeutic strategies and efficacy whether the physicians were aware or not of the calculated cardiovascular risk at 10 years obtained from the Framingham equation. It was also possible to evaluate the concordance of the general physicians estimation of the cardiovascular risk with the calculated percentage. The participation of 953 general physicians to the study allowed to achieve an estimation of the absolute cardiovascular risk for 1,243 hypertensives. Patients were randomised in 2 groups according to the knowledge or not by the physicians of the calculated risk. The therapeutic strategy included a monotherapy (Fosinopril 20 mg/days) for a follow up of 8 weeks, with the possibility to increase the treatment after 4 weeks (Fosinopril + hydrochlorotiazide). To be included, patients had to be more than 18 and less than 75 years, and a blood pressure above 140/90 mmHg. Estimated and calculated cardiovascular risk at 10 years, were classified according to the 1999 WHO-ISH guidelines: low risk < 15%, medium risk 15-20%, high risk 20-30%, very high risk > 30%. In this population, aged 60 +/- 10 years, with 54% of men, the concordance between estimated risk and calculated risk was of 35%. This concordance was better for the ""low risk"" and ""very high risk"", but remains inferior to 50%. The determinants of concordance were: gender (male), smoking and a low HDL cholesterol. After 8 weeks of treatment, no difference was observed between the 2 groups concerning final blood pressure level, percentage of normalised patients and number of patients with bi-therapy. General physicians estimation of cardiovascular risk at 10 years of hypertensive subjects has a bad concordance with the calculated risk according to Framingham equation. The results of this study indicate that the estimation of cardiovascular risk of hypertensive subjects does not modify the management of hypertension.",2000.0,0,0
451,10993857,Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease.,C G Brilla; R C Funck; H Rupp,"In arterial hypertension, left ventricular hypertrophy (LVH) includes myocyte hypertrophy and fibrosis, which leads to LV diastolic dysfunction and, finally, heart failure. In spontaneously hypertensive rats, myocardial fibrosis was regressed and LV diastolic function was improved by treatment with the angiotensin-converting enzyme inhibitor lisinopril. Whether this holds true for patients with hypertensive heart disease was addressed in this prospective, randomized, double-blind trial. A total of 35 patients with primary hypertension, LVH, and LV diastolic dysfunction were treated with either lisinopril (n=18) or hydrochlorothiazide (HCTZ; n=17). At baseline and after 6 months, LV catheterization with endomyocardial biopsy, Doppler echocardiography with measurements of LV peak flow velocities during early filling and atrial contraction and isovolumic relaxation time, and 24-hour blood pressure monitoring were performed. Myocardial fibrosis was measured by LV collagen volume fraction and myocardial hydroxyproline concentration. With lisinopril, collagen volume fraction decreased from 6.9+/-0.6% to 6. 3+/-0.6% (P:<0.05 versus HCTZ) and myocardial hydroxyproline concentration from 9.9+/-0.3 to 8.3+/-0.4 microg/mg of LV dry weight (P:<0.00001 versus HCTZ); this was associated with an increase in the early filling and atrial contraction LV peak flow velocity ratio from 0.72+/-0.04 to 0.91+/-0.06 (P:<0.05 versus HCTZ) and a decrease in isovolumic relaxation time from 123+/-9 to 81+/-5 ms (P:<0.00002 versus HCTZ). Normalized blood pressure did not significantly change in either group. No LVH regression occurred in lisinopril-treated patients, whereas with HCTZ, myocyte diameter was reduced from 22. 1+/-0.6 to 20.7+/-0.7 microm (P:<0.01 versus lisinopril). In patients with hypertensive heart disease, angiotensin-converting enzyme inhibition with lisinopril can regress myocardial fibrosis, irrespective of LVH regression, and it is accompanied by improved LV diastolic function.",2000.0,0,0
452,10995971,Influence of angiotensin-converting enzyme inhibitor treatment of the carotid artery intima-media complex in renal allograft recipients.,T Cieciura; G Senatorski; K Rell; T Baczkowska; L Paczek; L Gradowska; B Foroncewicz; K Mucha; Z Gaciong,,2000.0,0,0
453,10996582,Drug-induced hyperkalemia: old culprits and new offenders.,M A Perazella,"Prescribed medications, over-the-counter drugs, and nutritional supplements are used by many patients. Although most of these products are well tolerated, drug-induced hyperkalemia may develop in patients with underlying renal impairment or other abnormalities in potassium handling. Drug-induced hyperkalemia most often occurs from impaired renal potassium excretion. However, disturbed cellular uptake of a potassium load as well as excessive ingestion or infusion of potassium-containing substances may also occur. Physicians must be aware of medications that can precipitate hyperkalemia, how these drugs induce alterations in potassium homeostasis, and the patient characteristics that increase the risk of hyperkalemia.",2001.0,0,0
454,10999062,Effect of captopril on serum angiotensin converting enzyme and blood pressure in hypertensive patients.,R Singh; O P Kalra; P U Sarma; K M Prabhu,"The effect of chronic captopril therapy on serum angiotensin converting enzyme (ACE) was studied in 30 patients with essential hypertension. Patients were assessed for serum ACE levels serially every week for 4 weeks. Thirty healthy individuals served as controls. The basal serum ACE level among hypertensives (57.4 +/- 37.2 u/l) was found to be significantly higher (p < 0.001) than the controls (33.3 +/- 8.8 u/l). One week after starting captopril therapy, serum ACE levels fell to almost half the basal values (p < 0.001). However, thereafter, it rose to levels higher than the basal level even though the blood pressure remained well controlled. Our study suggests that besides its action on ACE, captopril may lower the blood pressure by other mechanisms as well.",2000.0,0,0
455,10999084,Efficacy of enalapril in the treatment of steroid resistant idiopathic nephrotic syndrome.,P K Prasher; P P Varma; K V Baliga,"Fifteen patients of idiopathic nephrotic syndrome who failed to respond to 8 weeks of corticosteroid therapy formed the material for this study. There were 10 males and 5 females, age ranging from 4 to 56 years. Three patients had hypertension. Histological lesions were focal and segmental glomerulosclerosis (FSGS) in 8; membranous glomerulonephritis in 3; mesangial proliferative glomerulonephritis in 2 and membranoproliferative glomerulonephritis in 2 patients. Proteinuria ranged from 3.64 to 8.66 g/1.73 m2/day. Serum albumin ranged between 2.2 to 3.3 g/dl. Serum creatinine was elevated > 1.5 mg/dl in 3 cases. After discontinuing steroids, enalapril was started in a dose of 2.5 mg/day and increased by 2.5 mg/day every 3-4 days till the maximum tolerated dose but not exceeding 20 mg/day. Proteinuria, serum albumin and serum creatinine estimations were done every 4 weeks for six months and every three months thereafter. Patients were followed up for 6 to 30 months. Proteinuria decreased to < 1.5 g/1.73 m2/day in 12 patients (80%) and to < 0.5 g/1.73 m2/day in 10 patients (66.7%) by 8 weeks. There was no significant decrease in proteinuria in 3 (20%) patients; two of these were cases of FSGS and one of membranoproliferative glomerulonephritis. Oedema, hypoalbuminaemia and hypercholesterolaemia returned to normal in all patients who had a decrease in the proteinuria. There was no correlation between the histological lesion and response to enalapril. There was no rise in the serum creatinine level above the baseline in any of the patients. Except for cough in one patient, no other significant side effects were observed. We conclude that enalapril is effective in reducing proteinuria and thereby the morbidity in steroid resistant nephrotic syndrome irrespective of the underlying pathology.",2000.0,0,0
456,11004045,A comparative study between a calcium channel blocker (Nicardipine) and a combined alpha-beta-blocker (Labetalol) for the control of emergence hypertension during craniotomy for tumor surgery.,R A Kross; E Ferri; D Leung; M Pratila; C Broad; M Veronesi; J A Melendez,"We compared the efficacy of the combination of enalaprilat/labetalol with that of enalaprilat/nicardipine to prevent emergence postcraniotomy hypertension. A prospective, randomized open labeled clinical trial was designed to compare the incidence of breakthrough hypertension (systolic blood pressure [SBP] > 140 mm Hg) and adverse effects (hypotension, tachycardia, and bradycardia) between the two drug combinations. Secondarily, the effects of the drugs on SBP, mean blood pressure, and diastolic blood pressure were evaluated over the course of the study. Forty-two patients received enalaprilat 1.25 mg IV at dural closure followed by either multidose nicardipine 2 mg IV or labetalol 5 mg IV to maintain the SBP below 140 mm Hg. SBP was similarly controlled in both groups. There was a marginally smaller incidence of failures and adverse effects with labetalol. Blood pressure profiles were similar for both groups.",2000.0,0,0
457,11008329,[Effect of ACE-inhibitors on left ventricular remodeling after acute anterior or posterior myocardial infarct. Cine- magnetic resonance tomography study].,M Konermann; H J Odenthal; C Altmann; F Laschewski; B Rawert; H J Trappe; B M Sanner,"The question whether patients with posterior infarctions (PMI) have a comparable benefit of an ACE-inhibitor therapy to those with anterior infarction (AMI) is still open. The study was undertaken to investigate the different influence of ACE inhibitors on the remodeling of the left ventricle after AMI or PMI. 52 patients (Pt.) (17 female, 38-73 years) were randomized to receive either 25-75 mg/day captopril (C) or 5-20 mg/day fosinopril (F) beginning on day 7 after acute myocardial infarction. 28 Pt. had AMI, 24 Pt. PMI. Infarct size was determined by the creatine kinase integral method. 50 Pt. were examined by cine magnetic resonance imaging 1 and 26 weeks after infarction. We determined: left ventricular end-diastolic (LVEDVI) and end-systolic (LVESVI) volume index, ejection fraction (EF), infarction weight (IW), left ventricular muscle mass (MM), systolic wall thickening (SWT) and motility (MOT) of the vital myocardium, and clinical behavior according to the guidelines of the New York Heart Association (NYHA). The results were compared with those of a sample (V) without ACE inhibitor therapy (10 females, 21 males, 36-75 years, 19 AMI, 12 PMI). There were no significant differences between C and F. Without ACE-inhibition therapy LVEDVI increased by 28.2% in AMI, by 18.4% in PMI (p < 0.001), with ACE-inhibition by 13.7% in AMI and by 9.9% in PMI (p < 0.001). LVESVI increased in V by 40.1% in AMI, by 28.5% in PMI (p < 0.001). With ACE-inhibitor we found an increase of 11.2% in AMI and 5.3% in PMI (p < 0.001). EF decreased without ACE-inhibitor by 18.7% in AMI and by 10.2% in PMI (p < 0.001), with ACE-inhibition increased by 4.3% in AMI and PMI, respectively (n. s.). NYHA got better in all groups, by 17.4% in AMI and 20.8% in PMI without ACE-inhibitor (n.s.), by 45.5% in AMI and 31.6% in PMI with ACE-inhibitor (p < 0.001). IG increased by 15.5% in AMI and 8.8% in PMI in V (p < 0.001), by 11.2% in AMI and 5.3% in PMI with C or F (p < 0.001). MM got bigger in V by 16.6% in AMI and 12.7% in PMI (p < 0.05), with ACE-inhibitor by 11.7% in AMI and 8.0% in PMI (p < 0.05). sWD increased by 12.9% in AMI and by 6.7% in PMI in V (p < 0.01), by 37.1% in AMI and 88.0% in PMI with C or F (p < 0.001). MOT decreased by 39.6% in AMI and 14.9% in PMI without ACE-inhibition (p < 0.001) and increased by 4.3% in AMI and by 5.0% in PMI with ACE-inhibitor (n. s.). All differences between V and the ACE-inhibitor groups were significant. Even patients with PMI clearly benefit from ACE-inhibitor therapy, but less than those with AMI. Captopril and fosinopril show no different effects after myocardial infarction.",2001.0,0,0
458,11009288,Comparison of quinapril versus atenolol: effects on blood pressure and cardiac mass after renal transplantation.,B Suwelack; U Gerhardt; M Hausberg; K H Rahn; H Hohage,"Based on epidemiologic facts on elevated cardiovascular mortality in renal allograft recipients, an echocardiographic 2-year follow-up in hypertensive renal allograft recipients was conducted. This study provides evidence that, in contrast to atenolol, quinapril, independent of blood pressure reduction, reduces left ventricular hypertrophy and improves left ventricular diastolic function in this population.",2000.0,0,0
459,11011346,"Endothelium-dependent responses in patients with hypercholesterolemic coronary artery disease under the effects of simvastatin and enalapril, either separately or combined.",R J Esper; R Machado; J Vilariño; J L Cacharrón; C A Ingino; C A García Guiñazú; E Bereziuk; A L Bolaño; D H Suarez,"Endothelial dysfunction is an early event in atherosclerotic disease that precedes clinical manifestations and complications. The noninvasive assessment of endothelial function in patients with risk factors undergoing clinical treatment is an important medical advance. In this setting, altered endothelial function in patients with coronary hypercholesterolemia and its modifications by treatment with enalapril and simvastatin, either separately or in combination, was assessed in the brachial artery in a randomized, double-blind, 2-period crossover study. Thirty-eight patients were separated in 2 groups. Group 1 (18 patients, 3 female, mean age 63 +/- 6.0 years) received simvastatin 10 mg/d for 8 weeks and simvastatin plus enalapril 5 mg/d for another 8 weeks. Group 2 (20 patients, 3 female, mean age 64 +/- 5.8 years) received enalapril 5 mg/d for 8 weeks and enalapril plus simvastatin 10 mg/d for another 8 weeks. All subjects underwent measurements of brachial artery diameter before and after postischemic hyperemia with high-resolution ultrasound at basal conditions (control) and under the effects of the drugs at the end of 8 and 16 weeks. Cholesterol and LDL cholesterol levels significantly decreased with simvastatin treatment alone or with enalapril. Mean baseline arterial diameter was 5.24 +/- 1.25 mm in group 1 and 4.83 +/- 0.99 mm in group 2 (not significant). In group 1 after the first 8 weeks, endothelium-dependent vasodilation significantly increased with simvastatin treatment (control, 4.4%; 8 weeks, 7.6%; P <.001). After 16 weeks with the addition of enalapril, a further increase in vasodilation was seen (8.6%, P <.05 vs 8 weeks). In group 2, with enalapril treatment an increase in vasodilation versus control was seen (control, 4.3%; 8 weeks, 5.8%; P <.01). After 16 weeks, with the addition of simvastatin an additional increase in vasodilation was observed (9.1%, P <.001 vs 8 weeks). After nitroglycerin, vasodilation in group 1 at control, 8, and 16 weeks was 17%, 17.5%, and 18%, respectively. In group 2, nitroglycerin vasodilation at control, 8, and 16 weeks was 21%, 21%, and 22%, respectively. Simvastatin significantly increased the postischemic vasodilator response in patients with coronary hypercholesterolemia, either as single treatment or added to enalapril. Similarly, the response was increased by enalapril, either alone or while simvastatin was being administered. Both drugs improve vasodilation and additive effects appear to be present.",2001.0,0,0
460,11011944,Occupational UVA-induced allergic photodermatitis in a welder due to hydrochlorothiazide and ramipril.,S N Wagner; F Welke; M Goos,,2001.0,0,0
461,11012557,"A double-blind, placebo-controlled study to assess tolerability, pharmacokinetics and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.",M Bani; A Colantoni; M Guillaume; F Macchi; G Moroni; S Persiani,"The objective of this study was to evaluate the tolerability of a novel dual ACE-NEP inhibitor, Z13752A, after the oral administration of rising single doses in healthy volunteers. This study was also a preliminarily investigation of Z13752A pharmacodynamics (PD) and pharmacokinetics (PK). In this randomized, placebo-controlled, sequential study, two alternating panels of eight healthy male volunteers each (six subjects receiving the active treatment + two subjects receiving placebo) were treated with increasing oral doses of Z13752A: 10, 50, 200, and 600 mg were given to panel I and 20, 100, 400 and 800 mg were given to panel II. The study was double-blind relative to placebo or active treatment, and was open with respect to the dose levels. The same volunteer received placebo only once. Single oral doses of Z13752A, as high as 800 mg, were well tolerated. Only six mild-to-moderate adverse events mainly headache, were reported and appeared to be of little clinical relevance. After administration of 200, 400, 600 and 800 mg of Z13752A, a nonsignificant fall in diastolic blood pressure was detected, in both the standing and supine position. After single oral doses of Z13752A, ACE inhibition appeared to be significant at all the doses tested, linearly correlated with the dose and was almost complete at doses > or = 100-200 mg. NEP inhibition was indicated by elevation of ANP and cGMP plasma concentrations in almost all subjects. In the 200-800 mg dose range, Z13752A produced a 50-100% increase of plasma cGMP levels and a 50-80% elevation in urinary cGMP concentrations. Detectable plasma levels of Z13752A were found in all the treated subjects. Z13752A was well and rapidly absorbed, with peak concentrations reached approximately 2.5 h after administration. The mean apparent elimination half-life from plasma was approximately 12 h. The pharmacokinetics of Z13752A after single oral doses were characterized by low intersubject variability and appeared to be dose-independent. Z13752A showed a good single dose tolerability profile at doses up to 800 mg. The pharmacokinetic data indicate that Z13752A administered orally is rapidly absorbed and available to the systemic circulation in humans. The relatively slow clearance indicates that a once-a-day dose regimen could be considered for Z13752A.",2001.0,0,0
462,11014323,Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients.,J Stangier; C A Su; W Roth,"A series of studies was conducted in healthy young males and healthy elderly males or females to evaluate the pharmacokinetic profile of telmisartan. In addition, two phase-II clinical trials assessed the pharmacokinetics and the safety of telmisartan in mild-to-moderate hypertensive patients. Telmisartan was given as a single oral (1-160 mg) or intravenous (10-160 mg) dose to young males. In another multiple-dose study, telmisartan 320 mg was administered orally once daily for 7 days to healthy young male subjects. Elderly subjects received oral telmisartan (20 and 120 mg) once daily for 7 days. Telmisartan doses of 10, 20, 40, 80, 120 and 160 mg were taken once daily by mild-to-moderate hypertensive patients for 7 days. Additionally, oral telmisartan (40, 80 or 120 mg) was administered once daily for 28 days to hypertensive subjects. Following oral dosing, median time to maximum plasma telmisartan concentration was 0.5 - 2 h, with maximum plasma concentrations increasing disproportionately with dose. By contrast, plasma concentrations were directly related to the intravenous dose. Steady state was observed after 5-7 days of once-daily administration, and there was no clinically relevant accumulation at 28 days. The plasma concentration-time profiles were similar in all study groups and were characterized by fast absorption and a rapid biexponential decline after the peak plasma concentration, with a prolonged terminal elimination phase (> 20 h in healthy and hypertensive subjects). Telmisartan was well tolerated, with a low incidence of drug-related adverse events. The most frequent event was headache, which also occurred in placebo-treated control subjects. No changes in heart rate, electrocardiograms or clinical chemistry were detected following receipt of telmisartan. The study thus shows that high systemic levels of telmisartan, which are well tolerated, can be attained in healthy adults of any age and in hypertensive subjects. The long terminal elimination half-life makes telmisartan suitable for once-daily dosing and contributes to the sustained efficacy over the full 24-h dosing interval.",2001.0,0,0
463,11015012,Increased urinary NAG excretion in hypertensives can decline with antihypertensive treatment.,S Turkmen; H Uzun; S Aydin; R Ozaras; V Tahan; G E Oztekin; S Dondurmaci,,2001.0,0,0
464,11015024,Comparison between the angiotensin II receptor antagonist candesartan cilexetil and the angiotensin-converting enzyme inhibitor trandolapril in microalbuminuria of patients with early diabetic nephropathy.,T Nakamura; C Ushiyama; S Suzuki; N Shimada; K Sekizuka; I Ebihara; Y Takahashi; A Tanaka; H Koide,,2001.0,0,1
465,11021956,"A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring.",T Littlejohn; W Mroczek; T Marbury; C P VanderMaelen; R F Dubiel,"To compare the antihypertensive efficacy and tolerability of telmisartan 80 mg with valsartan 80 mg throughout a 24 h dosing interval. A prospective, randomized, open-label, blinded end point, parallel group study. Treatment efficacy was compared using ambulatory blood pressure monitoring (ABPM), cuff sphygmomanometry and calculated responder rates. Tolerability was assessed by physical examination, laboratory parameters, 12-lead electrocardiogram, blood pressure and heart rate monitoring, and evaluation of adverse events. Thirty-five centres in the United States. Four hundred and twenty-six patients with mild to moderate essential hypertension entered the study. Ninety-two per cent (n=393) completed the study. Patients underwent a four-week, single-blind, placebo run-in period before being randomly assigned to once-daily oral telmisartan 80 mg (n=214) or valsartan 80 mg (n=212) for an eight-week, open-label treatment period. Treatment with telmisartan was associated with a significantly greater mean reduction from baseline in the last 6 h ABPM mean for diastolic blood pressure compared with the valsartan-treated group (-7.5+/-0.6 mmHg versus -5.2+/-0.6 mmHg, respectively, P<0.01). Secondary analyses showed significantly greater efficacy with telmisartan 80 mg than with valsartan 80 mg, including greater mean reductions from baseline of ABPM (systolic blood pressure and diastolic blood pressure) during the daytime (06:00 to 21:59) and morning (06:00 to11:59) hours, and larger decreases in trough cuff blood pressure (P<0.01). Both treatments showed placebo-like tolerability profiles. Telmisartan 80 mg once daily was superior to valsartan 80 mg once daily in reducing diastolic blood pressure during the last 6 h of the 24 h dosing interval. These results may be due to telmisartan's longer plasma half-life or to a higher potency compared with valsartan, such that a higher dose of valsartan may produce effects similar to those of 80 mg telmisartan. These data confirm the long duration of action of telmisartan with consistent and sustained control of blood pressure over 24 h and during the last 6 h of the dosing interval. Both treatments were well tolerated; the adverse event data confirmed the excellent tolerability profiles of telmisartan and valsartan that have been reported previously.",2001.0,0,0
466,11022900,Prospective studies of diagnosis and intervention: the Dutch experience.,B C van Jaarsveld; P Krijnen,"This prospective multicenter study included 1,205 patients, who were referred for difficult-to-treat hypertension or analysis of possible secondary hypertension. After a standardized selection protocol based on sharply defined drug-resistant hypertension or renal function impairment during angiotensin-converting enzyme inhibition, patients underwent renal scintigraphy and a captopril-renin challenge test. A set of clinical characteristics was also recorded. Sensitivity and specificity of renal scintigraphy for diagnosing renal artery stenosis were 0.72 and 0.90 and of the captopril-renin test 0.77 to 0.91 and 0.69 to 0.75 depending on the criterion used. The clinical characteristics were used to construct a clinical prediction rule for renal artery stenosis, which had a sensitivity of 0.68 and a specificity of 0.87 at a cut-off level of 30% predicted probability. However, with the prediction rule a sensitivity of 0.90 could be reached by performing arteriography only in patients with a predicted probability of stenosis of > or =10%, resulting in a considerable reduction of the number of arteriograms to be made. A diagnostic strategy is advocated starting with drug-resistant hypertension and continuing to renal arteriography only in patients with increased probability of stenosis. Patients with atherosclerotic renal artery stenosis were then randomized to balloon angioplasty (n = 56) versus antihypertensive medication (n = 50). Three months after randomization 22 patients from the medication group underwent balloon angioplasty in second instance. In an intention-to-treat analysis, no difference in blood pressure was found between the groups after 3 months, nor after 12 months of follow-up, although there was a small medication-sparing effect of balloon angioplasty. The lack of a beneficial effect of balloon angioplasty compared with medication could not be attributed to the high stenosis recurrence rate after angioplasty, nor to the fact that the inclusion criterion was set at a stenosis level of > or =50% so that patients with relatively mild stenosis were also included. Renal function after angioplasty was slightly better in the angioplasty group than in the medication group, and improvement of the renal scintigram occurred more often after angioplasty. Apart from the treatment of patients with specific characteristics, the presented therapeutic approach starts with extending the antihypertensive drug therapy to control blood pressure. Only if blood pressure cannot be controlled or if renal function deteriorates, balloon angioplasty (with stent placement) is indicated.",2001.0,0,0
467,11023927,Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).,K K Teo; J R Burton; C E Buller; S Plante; D Catellier; W Tymchak; V Dzavik; D Taylor; S Yokoyama; T J Montague,"This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.",2001.0,0,0
468,11023935,"Effects of antihypertensive therapy on glucose and insulin metabolism and on left ventricular mass: A randomized, double-blind, controlled study of 21 obese hypertensives.",R Kuperstein; Z Sasson,"Glucose and insulin levels are associated with left ventricular mass (LVM) in insulin-resistant individuals. Antihypertensive drugs have different effects on glucose and insulin metabolism (GIM) and on LVM. To evaluate whether the effects of antihypertensive therapy on LVM are associated with its effects on GIM, we compared the effects of atenolol and perindopril on these parameters in a group of insulin-resistant, obese hypertensives. A total of 21 obese, nondiabetic hypertensives who were aged 55+/-12 years, had a body mass index of 32.8+/-5.0 kg/m(2), were free of coronary or valvular heart disease, and had normal LV function were randomized to treatment with atenolol (n=11) or perindopril (n=10). Echocardiographic LVM corrected for height (LVM/height) and GIM (3-hour intravenous glucose tolerance test) were measured after 4 to 6 weeks of washout and 6 months of treatment. Baseline characteristics were similar in both groups. Atenolol and perindopril effectively reduced blood pressure (from 149+/-13/98+/-4 to 127+/-8/82+/-6 mm Hg and from 148+/-9/98+/-4 to 129+/-9/82+/-6 mm Hg, respectively, for the atenolol and perindopril groups; P:=0.002). Atenolol significantly worsened GIM parameters, fasting glucose levels (5.3+/-0.9 to 6.0+/-1.5 mmol/L; P:=0.003), fasting insulin levels (121+/-121 to 189+/-228 pmol/L; P:=0.03), and most other relevant metabolic measures (P:<0.05 for all). Perindopril did not affect GIM. Atenolol did not affect LVM/height (119+/-12 to 120+/-17 g/m; P:=0.8), whereas perindopril significantly reduced LVM/height (120+/-13 to 111+/-19 g/m; P:=0.04). In obese, hypertensive individuals, adequate and similar blood pressure control was achieved with perindopril and atenolol. However, perindopril but not atenolol was associated with a more favorable GIM profile and led to a significant regression of LVM.",2001.0,0,0
469,11029598,ACE-inhibition modulates some endothelial functions in healthy subjects and in normotensive type 1 diabetic patients.,C G Schalkwijk; R A Smulders; J Lambert; A J Donker; C D Stehouwer,"The usefulness of treatment with an angiotensin-converting enzyme-inhibitor (ACE-inhibitor) in normotensive patients with type 1 diabetes is controversial. We investigated whether ACE-inhibition improves endothelial function in such patients and compared the responses to those in healthy subjects. We studied 23 healthy volunteers (controls, aged 29.8 [SD 7.0] years) and 24 type 1 diabetic patients (aged 28.7 [9. 6] years; HbA1c 8.1 [1.2]%; diabetes duration 13.8 [2-30] years; blood pressure < 140/90 mm Hg; 7 with microalbuminuria) after 5 weeks of ACE-inhibition (quinapril, 10 mg day-1) and placebo in a randomized, double-blind cross-over design. Estimates of endothelial function obtained were by flow-mediated vasodilation and plasma levels of endothelium-derived proteins. As estimated from the measurements on placebo, type 1 diabetic patients, as compared to the controls, had some impairment of endothelial function: plasma tissue-type plasminogen activator levels were lower (3.5 vs. 5.4 ng mL(-1), P<0.05), but there were no significant differences in brachial artery flow-mediated vasodilation or plasma levels of von Willebrand Factor, endothelin-1, plasminogen activator inhibitor-1, soluble E-selectin or vascular cell adhesion molecule-1. As compared to placebo, ACE-inhibition increased flow-mediated vasodilation in controls (by 3.84% points [95% CI, 0.66 - 7.02], P<0.05), but not in type 1 diabetic patients (0.82% points [95% CI, -2.72 - 4.36], P = 0.64; P = 0.08 vs. controls). On ACE-inhibition soluble E-selectin levels decreased both in controls (from 43.0 to 37.0 ng mL(-1), P<0.01) and in type 1 diabetic patients (from 41.0 to 39.0 ng mL(-1), P = 0.09). Other endothelial markers did not change during ACE-inhibition. Normotensive type 1 diabetic patients with normoalbuminara or microalbuminuria have mild endothelial dysfunction. Short-term ACE-inhibition improves endothelial function as reflected by a decreased sE-selectin in healthy subjects and in normotensive type 1 diabetic patients. In healthy subjects, ACE-inhibition increases flow-mediated vasodilation. In contrast, in type 1 diabetic patients, ACE-inhibition does not affect flow-mediated vasodilation.",2001.0,0,0
470,11034011,Angioedema of the small bowel due to an angiotensin-converting enzyme inhibitor.,M P Chase; G S Fiarman; F J Scholz; R P MacDermott,"We describe a case of a 72-year-old woman who presented with two episodes of abdominal pain, vomiting, and diarrhea. Abdominal computed tomographic scans done during each episode demonstrated edema of the small bowel. Review of the patient's history revealed that she had been started on a treatment of lisinopril for hypertension 1 month before the first episode and had her prescribed dose increased 24 hours before each presentation. Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema was suspected and the medication was discontinued. The patient has remained symptom-free while not taking the ACE inhibitor for 1 year. Review of the literature reveals only nine similar cases. All cases, including ours, occurred in women. Angioedema of the small bowel associated with ACE inhibitors is rare and often is not recognized before surgical exploration. Angioedema of the gastrointestinal tract should be considered in symptomatic patients taking ACE inhibitors.",2001.0,0,0
471,11041675,Effect of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPP) randomized trial. The Captopril Prevention Project (CAPP) Study Group.,,,2000.0,0,0
472,11044229,ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group.,G L Bakris; M Siomos; D Richardson; I Janssen; W K Bolton; L Hebert; R Agarwal; D Catanzaro,"Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency. The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.",2001.0,0,0
473,11045392,Enalapril and prednisone in children with nephrotic-range proteinuria.,A Delucchi; F Cano; E Rodriguez; E Wolff; X Gonzalez; M A Cumsille,"The effect of enalapril and low prednisone doses on the urinary protein electrophoretic pattern was studied in 13 pediatric patients with glomerular diseases and steroid-resistant nephrotic syndrome. Enalapril was administered at doses of 0.2-0.6 mg/kg per day for 24-84 months, and prednisone was introduced 2 months later in 11 patients at doses of 30 mg/m2 on alternate days. The urine protein electrophoretic pattern showed a reduction of 80% and 70% in the total protein and albumin, respectively, after enalapril. Total urinary protein decreased from 5.46 to 1.1 g/m2 per day (P<0.001). A marked change from a pattern of non-selective urinary protein loss to an albumin-selective proteinuria was observed. Mean total plasma proteins increased from 4.7 to 5.43 g/dl (P<0.001). Four patients became free of proteinuria 24 months after enalapril was started, but only 2 remained free of proteinuria at 48 months of follow-up. The other 11 patients had persistent albuminuria of between 0.5 and 2.6 g/m2 per day with a selective urinary electrophoretic pattern. No additional decrease was observed after steroids were introduced. A clinical improvement in edema was observed in all children. Three patients developed transient acute renal failure, during the course of an infectious disease; 2 developed peritonitis and 1 pneumopathy. In these patients withdrawal of enalapril was necessary until a complete recovery of renal function was observed. Four patients were hypertensive on admission, achieving normal blood pressure 1 month after enalapril was started. No episodes of systemic arterial hypotension were seen. Creatinine clearance and serum potassium showed no statistically significant change.",2001.0,0,0
474,11048472,Treatment of arterial hypertension in the elderly with diltiazem vs ramipril.,R Terranova; S Luca,"Around 40% of the elderly population suffer from arterial hypertension. An effective antihypertensive treatment is therefore required. Calcium antagonists are used to treat hypertension because, owing to their mechanism of action, they can provoke systemic, as well as coronary vasodilatation. In this study the authors aimed to evaluate the activity and tolerability of diltiazem compared to ramipril in a group of elderly patients suffering from essential arterial hypertension. A controlled single-blind study was performed in which patients were randomly assigned to one of two groups, A and B, consisting of 25 patients each, treated respectively with 300 mg sustained-release diltiazem or 5 mg ramipril in a single daily dose. The study lasted 6 months and evaluated systolic and diastolic pressure and heart rate. The evolution was positive in all patients in Group A and most patients in Group B, with the normalisation of both systolic and diastolic values. Heart rate showed a more persistent fall in Group A, but this was expected owing to the mechanism of action of diltiazem. No patient in Group A had to suspend treatment, whereas one patient in Group B had to interrupt therapy following the onset of a persistent cough. Both treatments resulted in similar changes in systolic and diastolic arterial blood pressure. In the light of these results, it can be affirmed that, at an oral dose of 300 mg/day, sustained-release diltiazem was found to be effective and well tolerated in the treatment of mild to moderate essential arterial hypertension in the aged.",2001.0,0,0
475,11048826,HOPE for all people with diabetes? Heart Outcomes Prevention Evaluation.,S M Marshall,,2001.0,0,0
476,11050792,Management of heart failure: evidence versus practice. Does current prescribing provide optimal treatment for heart failure patients?,F D Hobbs,"Heart failure is an increasingly common and costly chronic disorder, with a rising prevalence of at least 2% in populations over the age of 45 years, mortality rates that are as poor as common solid cancers, and very high health care utilisation costs. Despite increased evidence supporting a range of effective interventions, predominantly therapeutic, there remain significant degrees of physician underperformance in terms of heart failure diagnosis and management. Until the early 1990s, the management of heart failure was largely confined to the symptomatic relief of patients with well established heart failure in fluid overload. The introduction of angiotensin-converting enzyme (ACE) inhibitors provided the first treatments that beneficially altered the prognosis of patients with the most common expression of heart failure, namely established systolic dysfunction, whether symptomatic or asymptomatic. Evidence has now extended these benefits to delaying progression of heart failure and reducing hospitalisation. Much of our understanding of the pathophysiology of heart failure stems from these studies. More recent data has clarified the limited role of digoxin, the important benefits of beta-blockade and aldosterone blockers as adjuvants to ACE inhibition, and the emerging evidence on angiotensin II antagonists. There are, in contrast to these positive findings, reliable data from Europe and North America revealing significant underperformance of primary care and hospital physicians in heart failure diagnosis and management, with evidence of underuse and underdosing of evidence-based therapies. Limited qualitative data suggest the reasons for this underperformance are complex and relate to lack of access to objective testing of ventricular function and exaggerated concerns over treatment risks and side-effects. Heart failure represents a complex cluster of aetiologies and risks that are not easy to correctly identify, even in specialist settings. Since there is now powerful evidence on how heart failure can be modified and improved, explicit guidance is needed for which suspected patients should be referred, for confirmation of diagnosis and advice on appropriate treatment regimes, and for which patients can be handled mainly within primary care but with enhanced access to objective non-invasive tests to improve diagnostic reliability and to stratify patients to evidence-based therapies. Current evidence suggests that in North America and Europe today primary care physicians do underperform in their management of patients with heart failure, often owing to factors outside of their immediate control.",2001.0,0,0
477,11054617,Valsartan in acute myocardial infarction trial (VALIANT): rationale and design.,M A Pfeffer; J McMurray; A Leizorovicz; A P Maggioni; J L Rouleau; F Van De Werf; M Henis; E Neuhart; P Gallo; S Edwards; M A Sellers; E Velazquez; R Califf,"Survivors of acute myocardial infarction (MI) complicated by heart failure and/or resulting in left ventricular dysfunction are at heightened risk for subsequent death and major nonfatal cardiovascular events. Inhibition of the renin-angiotensin system with an angiotensin-converting enzyme inhibitor has consistently been demonstrated to result in reductions in these risks by approximately 20%. The development of angiotensin II receptor blockers offers a new, more specific, and theoretically more complete pharmacologic mode to inhibit the adverse influence of angiotensin II. Valsartan in Acute Myocardial Infarction (VALIANT) is a multicenter, double-blind, randomized, active controlled parallel group study comparing the efficacy and safety of long-term treatment with valsartan, captopril, and their combination in high-risk patients after MI. The trial is designed with 3 arms, giving equal statistical consideration to survival comparisons of captopril versus the angiotensin II receptor blocker valsartan, as well as the combination of captopril plus valsartan, compared with a proven effective dose of captopril. This 14,500-patient trial is designed with an 86% power to detect a 15% reduction in mortality rate with either use of valsartan compared with captopril. The trial encourages optimal individualization of other proven therapies in acute and chronic infarction, and the international patient body ensures good representation of multiple practice patterns. VALIANT is a large international investigative effort that will evaluate the role of valsartan in the management of patients with MI associated with heart failure and/or left ventricular dysfunction. The use of a proven dose of captopril and the comparator arms with valsartan alone or in combination with captopril provides a unique test of whether the angiotensin II receptor blocker can make an additional improvement in clinical outcomes beyond angiotensin-converting enzyme inhibitors.",2001.0,0,0
478,11055467,Results of the STOP-Hypertension-2 trial.,L Hansson,"The second Swedish Trial in Old patients with Hypertension (STOP-Hypertension-2) was conducted to compare the effects of ""newer"" antihypertensive therapies (angiotensin converting enzyme [ACE] inhibitors and calcium antagonists) and established therapies (beta-blockers and diuretics) on cardiovascular mortality and morbidity in elderly hypertensive patients. A total of 6614 patients were randomized to receive conventional treatment, ACE inhibitors or calcium antagonists, and followed for a mean of 5 years. The primary endpoint was a combination of fatal stroke, fatal myocardial infarction and other fatal cardiovascular disease; secondary endpoints were a combination of fatal or non-fatal stroke or myocardial infarction, and other cardiovascular mortality. The three treatments produced similar reductions in supine systolic blood pressure. There were no significant differences in the risk of cardiovascular events between patients receiving conventional therapy and those receiving newer therapies. All three treatments were well tolerated. The STOP-Hypertension-2 results thus add to the extensive literature showing the benefits of blood pressure reduction in elderly hypertensive patients. Moreover, they are consistent with current management guidelines which emphasise the importance of the achieved blood pressure reduction in the prevention of cardiovascular events.",2001.0,0,0
479,11055468,The outcome of STOP-Hypertension-2 in relation to the 1999 WHO/ISH hypertension guidelines.,L H Lindholm,"The 1999 hypertension management guidelines issued by the World Health Organization and the International Society of Hypertension emphasize the importance of blood pressure reduction in the prevention of cardiovascular events. Furthermore, they conclude that the benefits of treatment are due to blood pressure lowering per se, rather than to any specific antihypertensive therapy. The results of the second Swedish Trial in Old Patients with Hypertension (STOP-Hypertension-2) are consistent with these recommendations, since in this trial angiotensin converting enzyme (ACE) inhibitors and calcium antagonists reduced blood pressure to the same extent as conventional therapy with beta-blockers and diuretics in elderly hypertensive patients, and the three treatments produced similar reductions in the risk of cardiovascular events. Furthermore, a first subgroup analysis of cardiovascular mortality showed that the three treatments seemed equally effective in diabetic patients. The STOP-Hypertension-2 data, therefore, are fully consistent with the 1999 hypertension management guidelines, and underline the advantages offered by both older and newer antihypertensive therapies.",2001.0,0,0
480,11055475,Underestimation of 24-hour hypotensive efficacy of nifedipine GITS versus enalapril: ambulatory recording as an adjunct to clinical blood pressure measurement.,K L Schulte; T Lenz; M Fischer; W Meyer-Sabellek; R Gotzen,"Short-acting calcium entry blockers should be used primarily in slow-release form. Furthermore, studies of the antihypertensive efficacy of drugs can be negatively influenced by between 15% and 30% of the enrolled patients not being hypertensive according to ambulatory blood pressure (BP) measurement. Thus, a randomized double-blind multicenter parallel-group study was conducted to compare the effect of nifedipine GITS (gastrointestinal therapeutic system) with enalapril. After a 2-week placebo run-in period, 186 patients with a sitting diastolic BP > or = 95 mmHg were enrolled for an 8-week treatment period. They received 30-60 mg nifedipine GITS or 5-10 mg enalapril. Diastolic BP fell comparably from 99 to 87 mmHg (p < 0.01) in the nifedipine GITS group, and from 100 to 88 mmHg (p < 0.01) in the enalapril group. The increase in BP 2 h before waking, however, was suppressed significantly more by nifedipine. Furthermore, this study highlighted the existence of ""whitecoat"" hypertension in a number of patients, especially when clinical BP was used to identify hypertension. Of the patients who had been identified as hypertensive before randomization by standardized BP measurement, 53 (28.5%) were identified as non-hypertensives by 24-h BP monitoring. This led to an underestimation of the efficacy of the antihypertensive therapy. Nifedipine GITS as well as enalapril are comparably effective antihypertensive drugs.",2001.0,0,0
481,11056094,Angiotensin II receptor subtypes in the skeletal muscle vasculature of patients with severe congestive heart failure.,S L Malendowicz; P V Ennezat; M Testa; L Murray; E H Sonnenblick; T Evans; T H LeJemtel,"Vascular remodeling occurs in the skeletal muscle of patients with severe congestive heart failure (CHF); this remodeling is mediated in part by increased activity of the renin-angiotensin system. Animal models suggest that in the vasculature, angiotensin II receptor type 2 (AT2-R) expression may be upregulated in pathological states associated with vascular remodeling. The therapeutic effects of an AT1-R antagonist may, therefore, be in part due to increased plasma angiotensin II levels, which stimulate AT2-R. However, whether AT2-R is expressed in the skeletal muscle vasculature of patients with severe CHF is unknown. The steady-state transcript levels of the AT1-R and AT2-R genes were analyzed by reverse transcription-polymerase chain reaction in RNA samples prepared from the skeletal muscle of 12 patients with severe CHF (f1.gif"" BORDER=""0"">O(2)<10 mL. kg(-1). min(-1)) and 5 age-matched healthy subjects who underwent vastus lateralis biopsies. Human fetal skeletal muscle RNA served as a positive control for the expression of AT1-R and AT2-R gene transcripts. Transcripts from the AT1-R gene were detected readily in all samples. In contrast, transcripts from the AT2-R gene were only detected in fetal skeletal muscle samples and could not be detected in the skeletal muscle vasculature of healthy subjects or that of CHF patients, who were treated with either angiotensin-converting enzyme inhibitors or AT1-R antagonists. The AT2-R gene is not expressed in the skeletal muscle of patients with CHF. In the absence of detectable AT2-R gene transcripts, the AT2-R pathway is unlikely to contribute to the effects of AT1-R antagonists on the skeletal muscle vasculature in patients with severe CHF.",2001.0,0,0
482,11057435,Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.,P Gosse; D J Sheridan; F Zannad; O Dubourg; P Guéret; Y Karpov; P W de Leeuw; J L Palma-Gamiz; A Pessina; W Motz; J P Degaute; C Chastang,"To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. European hospitals, general practitioners and cardiologists. Hypertensive patients aged > or = 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. LVMI variation in the perprotocol population. Indapamide SR 1.5 mg significantly reduced LVMI (-8.4 +/- 30.5 g/m2 from baseline; P< 0.001), but enalapril 20 mg did not (-1.9 +/- 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: -6.5 g/m2, P = 0.013 (-4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P< 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.",2001.0,0,0
483,11061732,Safety and costs of initiating angiotensin converting enzyme inhibitors for heart failure in primary care: analysis of individual patient data from studies of left ventricular dysfunction.,J Mason; P Young; N Freemantle; R Hobbs,"To estimate the costs and consequences of diagnosing symptomatic heart failure with left ventricular systolic dysfunction and initiating angiotensin converting enzyme inhibitors in primary care. Analysis of individual patient data from studies of left ventricular dysfunction (SOLVD) to identify complications during test dose and titration phases. Two randomised controlled trials in secondary care. 7487 patients taking a test dose of enalapril at enrolment to the treatment and prevention trials; 2569 patients with clinical signs of heart failure and established left ventricular dysfunction entered the treatment trial. Discontinuation during the test dose period. Discontinuation or reduction of dose during the first year of treatment for heart failure. Costs of diagnosis and titration of treatment. During the test dose phase, 585 patients (7.8%) reported side effects; 136 (1.8%) of these discontinued because of severe side effects. During the titration phase, compared with placebo, enalapril was associated with an increased risk of dose reduction due to hypotension (odds ratio 2.09, 95% confidence interval 1.15 to 3.82). However, overall, there was no difference in the rates of side effects leading to dose reduction or withdrawal between the enalapril and placebo groups. The costs of diagnosing heart failure with left ventricular systolic dysfunction and initiating and titrating an angiotensin converting enzyme inhibitor in primary care are pound300 to pound400. Treatment with angiotensin converting enzyme inhibitors can be safely started for patients with heart failure and left ventricular systolic dysfunction in primary care.",2001.0,0,1
484,11069435,Drugs used in secondary prevention after myocardial infarction: case presentation.,S Maxwell; W S Waring,,2001.0,0,0
485,11071799,Long-term prognosis of diabetic patients with myocardial infarction: relation to antidiabetic treatment regimen. The TRACE Study Group.,I Gustafsson; P Hildebrandt; M Seibaek; T Melchior; C Torp-Pedersen; L Køber; P Kaiser-Nielsen,"The present study was performed to evaluate pre-admission history, presentation, initial treatment and long-term mortality in patients with myocardial infarction and diabetes. Between 1990 and 1992, 6676 patients with acute myocardial infarction were screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study. In this cohort 719 (11%) of the patients had a history of diabetes. Among the diabetic patients 19% were treated with insulin, 52% with oral hypoglycaemic agents and 29% with diet only. The diabetic patients were slightly older, more likely to be female and had a higher prevalence of known cardiovascular disease. Even though the diabetic patients had the same frequency of ST-segment elevation on the electrocardiogram and the same admission delay, treatment with thrombolysis and aspirin was less frequently prescribed to the diabetic patients than to patients without diabetes. The mortality rate was significantly increased in the diabetic patients, 7-year mortality being 79% in insulin-treated, 73% in tablet-treated and 62% in diet-treated diabetic patients compared with 46% in patients without diabetes. In a multivariate analysis only diabetic patients treated with oral hypoglycaemic agents or with insulin had an increased mortality compared with non-diabetic patients. Patients with diabetes mellitus and myocardial infarction are treated with thrombolysis to a lesser extent than non-diabetic patients. Diabetic patients treated with oral hypoglycaemic agents or insulin, but not those treated with diet alone, have a significantly increased mortality following acute myocardial infarction compared with non-diabetic patients.",2001.0,0,0
486,11071803,"Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial.",L Rydén; P W Armstrong; J G Cleland; J D Horowitz; B M Massie; M Packer; P A Poole-Wilson,"An analysis was designed to determine whether chronic heart failure patients at high cardiovascular risk benefited to the same extent from high-dose lisinopril as the whole ATLAS population. A retrospective analysis was performed on high-risk heart failure patients in the Assessment of Treatment with Lisinopril And Survival (ATLAS) trial (total number of patients 3164) comparing highdose (32.5-35 mg. day(-1)) vs low-dose (2.5-5 mg. day(-1)) lisinopril for a median of 46 months. These high-risk patients included those with hypotension, hyponatraemia, compromised renal function, the elderly and patients with diabetes mellitus at baseline. In the whole study population, high-dose lisinopril led to a trend in risk reduction of all-cause mortality (primary end-point P=0.128) and a significant risk reduction in all-cause mortality plus hospitalization (principal secondary end-point P=0.002). Subgroup analyses were performed for these end-points. There were no consistent interactions between age, baseline sodium, creatinine or potassium values, and treatment effect. Diabetics showed a beneficial response to high-dose therapy that was at least as good as that in non-diabetics. The underlying higher morbidity/mortality rates in diabetics mean that high-dose lisinopril has potential for a larger absolute clinical impact in these patients. Long-term high-dose lisinopril was as effective and well-tolerated in high-risk patients, including those with diabetes mellitus, as for the ATLAS study population as a whole.",2001.0,0,1
487,11075752,Isolated visceral angioedema: an underdiagnosed complication of ACE inhibitors?,T J Byrne; D D Douglas; M E Landis; J P Heppell,"Angiotensin-converting enzyme (ACE) inhibitors are known to cause potentially fatal peripheral angioedema in some patients. ACE inhibitors may also cause isolated visceral angioedema, a rarely reported complication. This article describes 2 patients who experienced this complication. Both patients came to medical attention with episodes of recurrent abdominal symptoms that had occurred while taking ACE inhibitors for hypertension. Each patient had undergone surgical procedures for symptoms that persisted after surgery and were ultimately relieved with cessation of their ACE inhibitors. These cases call attention to what may be an underappreciated cause of abdominal pain in patients presenting to emergency departments.",2001.0,0,0
488,11077134,First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction.,J Spinar; J Vitovec; L Pluhacek; L Spinarova; B Fischerova; J Toman,"First dose hypotension after the administration of an angiotensin-converting enzyme inhibitor in patients with acute myocardial infarction is one of the most important adverse events of this type of treatment. There is no information about first dose hypotension after angiotensin type 1-receptor blocker in this type of patient. To compare the first dose responses to low dose captopril and losartan in patients with acute myocardial infarction. Single blind, randomised, multicentric, prospective study. Patients (n=320) with confirmed acute myocardial infarction, age >18 years, treated by direct percutaneous transluminal coronary angioplasty, thrombolysis and/or heparin, were randomised to receive a single dose of 6.25-12.5 mg captopril or 12.5-25 mg losartan within 24 h of hospital admission. Baseline laboratory and clinical examinations were performed before entering the study. Blood pressure monitoring started at hospital admission and continued for at least 8 h after the medication (second dose of captopril was given after 8 h). The maximal blood pressure fall appeared about 1 h after the first dose of captopril and 3.5 h after the first dose of losartan. Patients in the captopril group had significantly higher incidence of asymptomatic hypotension (38%) than patients treated with losartan (24%) (P<0.001). No difference in hypotension requiring a change in medication was observed. Low dose of losartan is safe for initiating therapy in patients with acute myocardial infarction within 24 h of hospital admission.",2001.0,0,0
489,11078175,Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril.,T O Morgan; A Anderson; D Bertram,"Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.",2001.0,0,0
490,11078178,Effects of isradipine or enalapril on blood pressure in salt-sensitive hypertensives during low and high dietary salt intake. MIST II Trial Investigators.,S G Chrysant; A B Weder; D A McCarron; M Canossa-Terris; J D Cohen; P A Gunter; B P Hamilton; A J Lewin; R F Mennella; L W Kirkegaard; M R Weir; M H Weinberger,"This large multicenter study, tested the antihypertensive effects of isradipine, a dihydropyridine calcium channel blocker and enalapril, an angiotensin-converting enzyme inhibitor, in salt-sensitive hypertensive patients under low and high salt intake diets. After a 3-week (weeks -9 to -6) of ad lib salt diet, those patients who had a sitting diastolic blood pressure (SDBP) of > or =95 but < or =115 mm Hg qualified to enter a 3-week (weeks -6 to -3) placebo run-in low salt diet (50 to 80 mmol Na+/day). Then high salt (200 to 250 mmol Na+/day) was added to the placebo treatment for 3 weeks (weeks -3 to 0). Those patients who demonstrated an increase in SDBP > or =5 mm Hg from the low to high salt diet were considered salt sensitive and were randomized into a 4-week (weeks 0 to 4) double-blind treatment period of either isradipine 2.5 to 10 mg twice a day, enalapril 2.5 to 20 mg twice a day, or placebo. Then they entered a 3-week (weeks 4 to 7) placebo washout phase of low salt diet (50 to 80 mmol Na+/day). After week 7 and while the low salt diet was continued the patients were restarted on their double-blind treatment for 4 more weeks (weeks 7 to 11) and the study was completed. Of 1,916 patients screened, 464 were randomized into the double-blind treatment phase and 397 completed the study. Both isradipine and enalapril decreased the sitting systolic blood pressure (SSBP) and SDBP during the high salt diet, to a similar degree, whereas enalapril caused a greater reduction in SSBP and SDBP than isradipine during the low salt diet (11.3 +/- 1.2/7.7 +/- 0.7 mm Hg v 7.7 +/- 0.9/4.8 +/- 0.6 mm Hg, mean +/- SEM, respectively, P < .02). Within drugs, the effect of isradipine on blood pressure (BP) was higher during the high than the low salt diet (14.9 +/- 1.5 v 7.6 +/- 1.3 mm Hg for SSBP and 10.1 +/- 0.6 v 4.8 +/- 0.9 mm Hg for SDBP, P < .001), but enalapril exerted a similar effect during both diets. Because salt restriction lowered both SSBP and SDBP, the lowest BP achieved with both drugs were during the salt restriction phase.",2001.0,0,0
491,11079643,"Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes.",C Cheetham; J Collis; G O'Driscoll; K Stanton; R Taylor; D Green,"The present study examined the effect on forearm endothelial function of an angiotensin II type 1 receptor antagonist, losartan, in subjects with non-insulin-dependent diabetes mellitus (NIDDM). Angiotensin-converting enzyme (ACE) inhibition with enalapril improves acetylcholine (ACh)-dependent endothelial function in patients with NIDDM. This could be mediated through angiotensin II and the type 1 receptor or could be due to inhibition of kininase II and a bradykinin preserving effect. It is therefore relevant to determine whether a type 1 receptor antagonist improves endothelial function. The influence of losartan (50 mg daily for four weeks) on endothelium-dependent and independent vasodilator function was determined in 9 NIDDM subjects using a double-blinded placebo-controlled crossover protocol. Forearm blood flow was measured using strain-gauge plethysmography. Losartan significantly decreased infused arm vascular resistance in response to three incremental doses of intrabrachial acetylcholine (p < 0.05, ANOVA). The forearm blood flow ratio (flow in infused to noninfused arm) was also increased (p < 0.01). Responses to sodium nitroprusside and monomethyl arginine were not significantly changed. Losartan administration at 50 mg per day improved endothelium-dependent dilation of resistance vessels in patients with NIDDM. That is, blockade of the angiotensin II type 1 receptors improves endothelial function in NIDDM. At least some of the similarly beneficial effect of ACE inhibition is probably mediated also through the angiotensin II-type 1 receptor pathway. The use of a type 1 receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain endothelial function in NIDDM subjects.",2001.0,0,0
492,11081319,[The effect of one-year treatment with captopril on exercise tolerance and myocardial ischemia in patients with myocardial infarction ].,M Wierzchowiecki; J Filipiak; K Poprawski; S Ozegowski; K Szymanowska; A Sieńko,"The aim of the study was to assess the effect of 1-year captopril therapy initiated 1-4 days (mean: 21-24 h) after beginning of AMI on exercise performance and myocardial ischemia during cycle ergometer test. 93 pts with first documented Q-wave AMI, aged L 70 years were qualified for the study. 50 of the pts were randomly included to the captopril group, 43 to the control group. In both groups pts with inferior AMI (accordingly 66% and 72%) and normal LV function (EF > or = 40% in ECHO) were prevailed in the study. Captopril therapy was initiated with the dose of 3.125 mg, then every 8 hours the dose of 6.25 mg was administered in Ist and IInd day, 12.5 mg--in III day and 25 mg from IV day on. Exercise cycle ergometer tests (ExT) were performed in every pt at 14 day, and 1, 3, 6 and 12 months after AMI. The ExT began at 25 W of power and was increased at 2-minute intervals by 25 W until fatigue or other typical cause of termination of the test. In the captopril group duration of ExT lengthened significantly in comparison with initial test (on 14 day) after 3 (6.4 +/- 1.47 vs 5.3 +/- 1.54 min; p < 0.01), 6 (6.7 +/- 1.59 vs 5.3 +/- 1.54 min; p < 0.001) and 12 months (7.0 +/- 1.22 vs 5.3 +/- 1.54 min; p < 0.001). In the control group exercise time was longer after 6 and 12 months compared to initial examination (accordingly 6.4 +/- 1.43 and 6.5 +/- 1.26 vs 4.8 +/- 1.47 min; p < 0.001). However, the differences regarding this time between the captopril and control group were not significant on consecutive control stages. The final result of the test (positive, negative, doubtful) did not differ significantly in both groups on consecutive examination stages. Captopril administered during 1-year period after AMI slightly improved physical working capacity (accelerated the improvement) and had no effect on ischemia during estimated cycle ergometer test. These results may depend on inclusion to the study predominantly pts with normal LV function and interior MI.",2001.0,0,0
493,11081765,Renal implications of the renin-angiotensin-aldosterone system blockade in heart failure.,L M Ruilope; V Barrios; M Volpe,"The renin-angiotensin-aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin-angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.",2001.0,0,0
494,11090788,Comparison of efficacy and side effects of combination therapy of angiotensin-converting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension.,F H Messerli; S Oparil; Z Feng,"The present 2 multicenter studies were designed to evaluate whether patients with essential hypertension derived equal benefits from use of combination therapy with a calcium antagonist and angiotensin-converting enzyme (ACE) inhibitor as from doubling the dose of the calcium antagonist. After a 2-week washout and a 2-week single-blind placebo run-in period, a total of 1,390 patients were treated with either nifedipine 30 mg (study 1) or amlodipine 5 mg (study 2) once daily for 4 weeks. The 1,079 patients whose diastolic blood pressure remained between 95 and 115 mm Hg were randomized to 8 weeks of double-blind therapy with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/ benazepril 20 mg, nifedipine 30 mg or nifedipine 60 mg (study 1), and amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg or amlodipine 10 mg (study 2). Both doses of the calcium antagonist/ACE inhibitor combination therapy lowered diastolic pressure as much as the high dose and significantly better than the lower dose of calcium antagonist monotherapy (with either nifedipine or amlodipine). However, 15% of patients in the nifedipine high-dose monotherapy group and 24% in the amlodipine high-dose monotherapy group presented with some form of edema. In contrast, the incidence of edema was similar for patients treated with both combination therapy and low-dose calcium antagonists. Thus, combination therapy with a calcium antagonist and an ACE inhibitor provides blood pressure control equal to that of high-dose calcium antagonist monotherapy but with significantly fewer dose-dependent adverse experiences such as vasodilatory edema. Inc.",2001.0,0,0
495,11090798,Effect of angiotensin-converting enzyme inhibitor on cardiopulmonary baroreflex sensitivity in patients with acute myocardial infarction.,M Hikosaka; F Yuasa; R Yuyama; M Motohiro; J Mimura; A Kawamura; T Sumimoto; T Sugiura; T Iwasaka,"We evaluated the effect of angiotensin-converting enzyme inhibition (quinapril) on cardiopulmonary baroreflex sensitivity in 30 patients with uncomplicated myocardial infarction (quinapril group, 15 patients; placebo group, 15 patients) at 5 and 10 days after the onset of myocardial infarction. This study indicates that quinapril improved cardiopulmonary baroreflex and thus reduced sympathetic outflow in patients with acute myocardial infarction.",2001.0,0,0
496,11092994,"Effects of angiotensin-converting enzyme inhibitor, angiotensin II receptor antagonist and calcium antagonist on urinary podocytes in patients with IgA nephropathy.",T Nakamura; C Ushiyama; S Suzuki; M Hara; N Shimada; K Sekizuka; I Ebihara; H Koide,"The urinary podocyte is postulated to be a marker for estimation of the severity of active glomerular injury and a predictor of disease progression in children with glomerulonephritis. Non-dihydropyridine calcium antagonist, including verapamil, reduce proteinuria to an extent similar to that of the angiotensin-converting enzyme inhibitor (ACEI), including trandolapril, but to a greater extent than other antihypertensives. Angiotensin (Ang) II receptor antagonists, including candesartan cilexetil, show potent and long-term preventive effects against the progression of renal injury. The aim of the present study is to assess whether verapamil, trandolapril and candesartan cilexetil affect proteinuria and urinary podocytes in patients with IgA nephropathy. Thirty-two normotensive patients aged 18-54 years with biopsy-proven IgA nephropathy, nonnephrotic proteinuria (1-3 g/day), and normal renal function (creatinine clearance >80 ml/min) were studied. Twenty patients with diffuse mesangial proliferative glomerulonephritis (non-IgA PGN) and 20 healthy controls were also included in this study. The number of urinary podocytes in patients with advanced IgA nephropathy (n = 16) was significantly higher than that in patients with the disease in the mild stage (n = 16) (p < 0.01) or in patients with non-IgA PGN (p < 0.01). Urinary podocytes were not detected in healthy controls. The 32 patients with IgA nephropathy were randomly divided into four treatment groups: those treated with verapamil (120 mg/day, n = 8); those treated with trandolapril (2 mg/day, n = 8); those treated with candesartan cilexetil (8 mg/day, n = 8), and those given a placebo (n = 8). Treatment continued for 3 months. Antiproteinuric response in the trandolapril group was similar to that in the candesartan cilexetil group (-38 vs. -40%). The action of trandolapril or candesartan cilexetil was greater than that of verapamil (p < 0.01). Reduction in the number of urinary podocytes from baseline was significantly greater in patients treated with trandolapril or candesartan cilexetil than in patients treated with verapamil (p < 0.01). However, there was no difference between patients treated with trandolapril and those treated with candesartan cilexetil. Proteinuria and urinary podocytes were unaffected in the placebo group. These data suggest that urinary podocytes may be a marker of disease activity in adult patients with IgA nephropathy and that trandolapril and candesartan cilexetil are more effective than verapamil in reducing the number of podocytes.",2001.0,0,0
497,11095026,Effect of ramipril on ambulatory blood pressure and albuminuria in renal hypertension.,M Soergel; M Verho; E Wühl; J Gellermann; L Teichert; K Schärer,"Inhibition of the angiotensin-converting enzyme (ACE) exerts a renoprotective effect in adult patients with chronic kidney disease. We evaluated prospectively changes in blood pressure (BP), protein excretion and renal function after administration of the long-acting ACE inhibitor ramipril as monotherapy during 6 months in 14 moderately hypertensive children aged 5-18 years with various nephropathies. Four patients initially had a decreased glomerular filtration rate (GFR below 60 ml/min/1.73 m2). BP was evaluated by ambulatory 24-h monitoring. After 2 weeks of treatment by oral ramipril (1.5 mg/m2 once daily), mean values of systolic and diastolic 24-h ambulatory BP fell by more than 5 mmHg in nine patients. In eight patients the dose was doubled. At the end of the study systolic BP was below the 95th percentile in 9 and diastolic BP in 13 patients. The initially reduced nocturnal dip increased significantly. Of 11 patients with an increased albumin excretion (median 1.3 g/g creatinine), 6 responded to ramipril by a median reduction of 78% (range 24-83%), whilst in 5 albuminuria increased (median +19%). GFR was well preserved and no other adverse effects from the drug were noted. The study demonstrates that ramipril is an efficacious antihypertensive agent in children with renal hypertension. It is well tolerated, even in mild renal insufficiency. In addition, the drug has a persistent antiproteinuric action in about half of the patients contributing to conserve renal function.",2001.0,0,0
498,11095154,Cerebral complications of hypertension.,A S Rigaud; M L Seux; J A Staessen; W H Birkenhäger; F Forette,"Ischaemic and degenerative brain diseases are a major health problem leading to a devastating loss of autonomy. Hypertension has been shown to carry an increased risk not only for cerebrovascular morbidity and mortality but also for cognitive impairment and dementia. Although diastolic blood pressure is considered an important risk factor, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of brain complications. Therefore the treatment of these conditions must urgently become a widespread tool of prevention. All the randomised placebo-controlled trials completed for the last 30 years have shown a reduction in fatal and/or non-fatal strokes. In the most recent trials in isolated systolic hypertension in older patients, the benefit was even greater because of the higher risk in these populations. The new classes of drugs, in particular, calcium-channels blockers and angiotensin-converting enzyme inhibitors, have been shown to be as effective as the originally used diuretics and beta-blockers. Active treatment in the Syst-Eur trial based on nitrendipine as first step, possibly associated with enalapril and/or hydrochlorthiazide reduced not only stroke and cardiovascular complications but also the incidence of dementia including Alzheimer's disease. This important finding must be confirmed by further trials specifically focusing on the prevention of dementia. In addition, the importance of pulse pressure as a risk factor, underlines the need for new drugs which could increase aortic distensibility and decrease systolic blood pressure without greatly reducing diastolic pressure. Improving the management of hypertension offers new opportunities to reduce age-related disease in older people and to promote healthy aging.",2001.0,0,0
499,11095157,The renin-angiotensin system in the year 2000.,M G Nicholls; J I Robertson,,2001.0,0,0
500,11095163,"Hypertension drug trials: past, present, and future.",P S Sever; N R Poulter,,2001.0,0,0
501,11096321,Comparison of enalapril and losartan in the treatment of posttransplant erythrocytosis.,A Celik; E Ok; A Unsal; H Töz; G Atabay,,2001.0,0,0
502,11097307,Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions.,M Blanca; S Posadas; M J Torres; L Leyva; C Mayorga; L Gonzalez; C Juarez; J Fernández; L F Santamaria,"In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor. We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms. These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.",2001.0,0,0
503,11103060,Update in geriatrics.,W J Hall; R M Leipzig,,2001.0,0,0
504,11105370,Drug-related pemphigus and angiotensin converting enzyme inhibitors.,C S Ong; N Cook; S Lee,"A 105-year-old woman developed pemphigus foliaceus. She had been on fosinopril, an angiotensin-converting enzyme inhibitor (ACE inhibitor) for 4 years. Anti-intercellular cement substance antibodies were positive with titre > 160. She died during admission of an unrelated illness. A 57-year-old man developed pemphigus vulgaris after 11 months treatment with quinapril. At 14 months after developing pemphigus, this man continues on prednisone and azathioprine. We speculate that these are cases of ACE-inhibitor-related pemphigus and we review ACE-inhibitor-related pemphigus.",2001.0,0,0
505,11105808,A comparative study of losartan and enalapril on erythropoiesis and renal function in hypertensive patients with renal parenchymal disease.,B I Shand; K L Lynn,,2001.0,0,0
506,11107510,Systolic hypertension in older patients: are calcium channel antagonists safe?,J D Rutherford,The Editor and Associate Editors are pleased that our readership will have the opportunity to benefit from a series of contributions by Dr John Rutherford addressing current issues in pharmacology and therapeutics pertinent to coronary artery disease. We are pleased also that Dr Rutherford will provide authoritative perspectives on topics of immediate interest on a regular basis.,2001.0,0,0
507,11110232,"A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension.",Y Lacourcière,"Blockade of the renin-angiotensin-aldosterone system (RAAS) is the preferred mechanism of action for controlling hypertension in select groups of patients, including those with diabetic nephropathy and heart failure. Currently, 2 classes of drugs work by blocking the RAAS, albeit by differing mechanisms: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II angiotensin type 1 receptor blockers (ARBs). The goal of this study was to assess the comparative efficacy and tolerability of the ARB irbesartan and the ACE inhibitor enalapril in patients > or = 65 years of age with mild to moderate hypertension (sitting diastolic blood pressure [DBP], 95 to 110 mm Hg). Elderly (> or = 65 years of age) patients were recruited from 26 Canadian study centers for a randomized, double-blind, 8-week clinical trial. Exclusion criteria included sitting DBP >110 mm Hg or sitting systolic blood pressure (SBP) >200 mm Hg, angina pectoris, myocardial infarction, cardiac procedure, stroke, or transient ischemic attack within 6 months of randomization, as well as other preexisting or present severe medical or psychologic conditions. Patients were randomly assigned to receive a single daily dose of irbesartan 150 mg (n = 70) or enalapril 10 mg (n = 71) with treatment doses of study drugs doubled at week 4 for sitting DBP > or = 90 mm Hg. Reductions from baseline blood pressure measurements at trough (24 +/- 3 hours after the last dose of medication) were assessed for sitting DBP and sitting SBP. Comparative tolerability to study drugs was also assessed. The intent-to-treat analysis demonstrated similar reductions at week 8 in both DBP and SBP for both groups. For the primary efficacy analysis of sitting DBP, there was a mean reduction from baseline of 9.6 mm Hg and 9.8 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.93). The mean reduction from baseline in sitting SBP was 10.1 mm Hg and 11.6 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.54). Normalization rates (sitting DBP <90 mm Hg) at week 8 did not differ between groups (52.9% in the irbesartan group and 54.9% in the enalapril group; P = 0.81). No statistical difference existed between the 2 groups with respect to serious adverse events or discontinuations due to adverse events. Irbesartan was associated with a significantly lower incidence of cough than was enalapril (4.3% vs 15.5%, respectively; P = 0.046). Irbesartan is an effective and well-tolerated antihypertensive for elderly patients with mild to moderate hypertension. This study establishes that irbesartan has better tolerability than enalapril with respect to cough and suggests that irbesartan is as effective at lowering blood pressure but better tolerated than an ACE inhibitor in hypertensive patients > or = 65 years of age.",2001.0,0,0
508,11110735,"Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study.",C E Mogensen; S Neldam; I Tikkanen; S Oren; R Viskoper; R W Watts; M E Cooper,"To assess and compare the effects of candesartan or lisinopril, or both, on blood pressure and urinary albumin excretion in patients with microalbuminuria, hypertension, and type 2 diabetes. Prospective, randomised, parallel group, double blind study with four week placebo run in period and 12 weeks' monotherapy with candesartan or lisinopril followed by 12 weeks' monotherapy or combination treatment. Tertiary hospitals and primary care centres in four countries (37 centres). 199 patients aged 30-75 years. Candesartan 16 mg once daily, lisinopril 20 mg once daily. Blood pressure and urinary albumin:creatinine ratio. At 12 weeks mean (95% confidence interval) reductions in diastolic blood pressure were 9.5 mm Hg (7.7 mm Hg to 11.2 mm Hg, P<0.001) and 9.7 mm Hg (7.9 mm Hg to 11.5 mm Hg, P<0.001), respectively, and in urinary albumin:creatinine ratio were 30% (15% to 42%, P<0.001) and 46% (35% to 56%, P<0.001) for candesartan and lisinopril, respectively. At 24 weeks the mean reduction in diastolic blood pressure with combination treatment (16.3 mm Hg, 13.6 mm Hg to 18.9 mm Hg, P<0. 001) was significantly greater than that with candesartan (10.4 mm Hg, 7.7 mm Hg to 13.1 mm Hg, P<0.001) or lisinopril (mean 10.7 mm Hg, 8.0 mm Hg to 13.5 mm Hg, P<0.001). Furthermore, the reduction in urinary albumin:creatinine ratio with combination treatment (50%, 36% to 61%, P<0.001) was greater than with candesartan (24%, 0% to 43%, P=0.05) and lisinopril (39%, 20% to 54%, P<0.001). All treatments were generally well tolerated. Candesartan 16 mg once daily is as effective as lisinopril 20 mg once daily in reducing blood pressure and microalbuminuria in hypertensive patients with type 2 diabetes. Combination treatment is well tolerated and more effective in reducing blood pressure.",2001.0,0,0
509,11113718,Effect of beta 1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril.,B Sturm; R Pacher; J Strametz-Juranek; R Berger; B Frey; B Stanek,"The survival benefit of beta-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of beta-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported. To investigate the effect of atenolol, a hydrophilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial. One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction < or = 25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12. 5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89+/-11 mg/day, range 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events. After 395+/-266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01) The data suggest that in patients with advanced left ventricular dysfunction, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.",2001.0,0,0
510,11113722,Baseline demographics of the Valsartan Heart Failure Trial. Val-HeFT Investigators.,J N Cohn; G Tognoni; R Glazer; D Spormann,"The Valsartan Heart Failure Trial (Val-HeFT) is the first large-scale randomized, multinational clinical study to assess the efficacy and safety of valsartan, an angiotensin II receptor blocker, added to conventional therapy, including angiotensin-converting enzyme inhibitors, in heart failure patients. A total of 5010 patients with an ejection fraction <40% have been randomized to either valsartan titrated to 160 mg b.i.d. or to placebo. Baseline characteristics of patients in Val-HeFT are presented and compared with other major clinical trials in heart failure. Baseline data were collected and summary statistics calculated. The study population has a mean age of 62.7 years and is 80% male, 90.3% white, 6.9% black, and 2.8% Asian. Antecedent coronary heart disease is reported in 57.2% of patients. Angiotensin-converting enzyme inhibitors are prescribed for 92.7% of patients, diuretics for 85.8%, digoxin for 67.3%, and beta-blockers for 35.6%. Subgroup comparisons by age, sex, race and ejection fraction quartile show small differences in baseline characteristics. Overall the Val-HeFT population is generally representative of the population of patients with mild to moderate heart failure in industrialized countries.",2001.0,0,0
511,11113723,Low doses vs. high doses of the angiotensin converting-enzyme inhibitor lisinopril in chronic heart failure: a cost-effectiveness analysis based on the Assessment of Treatment with Lisinopril and Survival (ATLAS) study. The ATLAS Study Group.,M J Sculpher; L Poole; J Cleland; M Drummond; P W Armstrong; J D Horowitz; B M Massie; P A Poole-Wilson; L Ryden,"A cost-effectiveness analysis of high and low doses of the angiotensin-converting enzyme (ACE) inhibitor lisinopril in the treatment of chronic heart failure. A cost-effectiveness analysis using data from a randomized controlled trial, ATLAS, where 3164 patients with chronic heart failure were allocated to a high-dose (daily target dose 32.5-35 mg) or low-dose strategy (daily target dose 2.5-5.0 mg) of lisinopril. Differential costs were based on resource use data collected in the trial costed using UK unit costs. Cost-effectiveness analysis related differential costs to differential life-years during a 4-year trial follow-up. The mean total number of hospital in-patient days per patient was 18. 5 in the high dose group and 22.5 in the low dose group. Over the whole duration of the trial, the mean (S.D.) daily dose of lisinopril in the high-dose group was 22.5 mg (15.7 mg) compared to 3.2 mg (2.5 mg) in the low-dose group. The mean difference in cost per patient was pound sterling 397 lower in the high-dose group [95% CI (high-dose-low-dose) - pound sterling 1263 to pound sterling 436]. Mean life-years per patient were 0.085 years higher in the high-dose group [95% CI (high-dose-low-dose) -0.0074 to 0.1706). Based on mean costs and life-years, high-dose therapy dominates low-dose (less costly and more effective). Allowing for uncertainty in mean costs and life-years, the probability of high-dose therapy being less costly than low dose was 82%. If a decision maker is willing to pay at least pound sterling 3600 per life-year gained, the probability of high-dose being more cost-effective was 92%. The ATLAS Study showed that the treatment of heart failure with high-doses of lisinopril has a high probability of being more cost-effective than low-dose therapy.",2001.0,0,1
512,11115082,ACEI/ATRA therapy decreases proteinuria by improving glomerular permselectivity in IgA nephritis.,K T Woo; Y K Lau; K S Wong; G S Chiang,"It has been postulated that angiotensin-converting enzyme inhibitor/angiotensin receptor antagonist (ACEI/ATRA) may decrease proteinuria in patients with glomerulonephritis by its action on the glomerular basement membrane. We therefore studied the relationship between the response of patients with IgA nephritis (IgAN) to ACEI/ATRA therapy by decreasing proteinuria and its effect on the selectivity index (SI) in these patients. Forty-one patients with biopsy-proven IgAN entered a control trial, with 21 in the treatment group and 20 in the control group. The entry criteria included proteinuria of 1 g or more and/or renal impairment. Patients in the treatment group received ACEI/ATRA or both with three monthly increases in dosage. In the control group, hypertension was treated with atenolol, hydrallazine, or methyldopa. The following tests were performed at three monthly intervals: serum creatinine, total urinary protein, SI, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and low molecular weight (LMW) proteinuria. After a mean duration of therapy of 13 +/- 5 months, in the treatment group, there was no significant change in serum creatinine, proteinuria, or SI, but in the control group, serum creatinine deteriorated from 1.8 +/- 0.8 to 2.3 +/- 1.1 mg/dL (P < 0.05). Among the 21 patients in the treatment group, 10 responded to ACEI/ATRA therapy determined as a decrease in proteinuria by 30% (responders), and the other 11 did not respond (nonresponders). Among the responders, SI improved from a mean of 0.26 +/- 0.07 to 0.18 +/- 0. 07 (P < 0.001), indicating a tendency toward selective proteinuria. This was associated with an improvement in serum creatinine from mean 1.7 +/- 0.6 to 1.5 +/- 0.6 mg/dL (P < 0.02) and a decrease in proteinuria from a mean of 2.3 +/- 1.1 to 0.7 +/- 0.5 g/day (P < 0. 001). After treatment, proteinuria in the treatment group (1.8 +/- 1. 6 g/day) was significantly less than in the control group (2.9 +/- 1. 8 g/day, P < 0.05). The post-treatment SI in the responder group (0. 18 +/- 0.07) was better than that of the nonresponder group (0.33 +/- 0.11, P < 0.002). Eight out of 21 patients in the treatment group who had documented renal impairment had improved renal function compared with two in the control group (chi2 = 4.4, P < 0. 05). Of the eight patients in the treatment group who improved their renal function, three normalized their renal function compared with one from the control group. Our data suggest that ACEI/ATRA therapy may be beneficial in patients with IgAN with renal impairment and nonselective proteinuria, as such patients may respond to therapy with improvement in protein selectivity, decrease in proteinuria, and improvement in renal function. ACEI/ATRA therapy probably modifies pore size distribution by reducing the radius of large unselective pores, causing the shunt pathway to become less pronounced, resulting in less leakage of protein into the urine.",2001.0,0,0
513,11115412,"Losartan, an angiotensin type I receptor antagonist, improves conduit vessel endothelial function in Type II diabetes.",C Cheetham; G O'Driscoll; K Stanton; R Taylor; D Green,"We have demonstrated previously that inhibition of angiotensin-converting enzyme (ACE) with enalapril and angiotensin II blockade with losartan improve acetylcholine-dependent endothelial function in resistance vessels of patients with Type II diabetes. It was therefore of interest to examine the effect of losartan on conduit vessel function in this group. The influence of losartan (50 mg daily for 4 weeks) on endothelium-dependent and -independent vasodilator function was determined in 12 subjects with Type II diabetes using a randomized, double-blind, placebo-controlled crossover protocol. Conduit vessel endothelial function was assessed using high-resolution ultrasound and the brachial artery response to reactive hyperaemia (flow-mediated dilation; FMD); glyceryl trinitrate (GTN) was used as a non-endothelium-dependent dilator. Losartan administration significantly increased the FMD response from 5.2+/-0.7% (mean+/-S.E.M.) to 7.4+/-0.6% of vessel diameter (P<0.05; paired t-test). There was no effect of losartan on the endothelium-independent responses to GTN (17.8+/-1.8% to 17.6+/-1.2%). Consistent with our previous findings in resistance vessels, administration of 50 mg of losartan daily improves NO-mediated dilation in the conduit vessels of subjects with Type II diabetes. Together with the findings that both ACE inhibition and angiotensin II blockade improve resistance vessel function in this group, it is likely that at least some of the beneficial effect is mediated through the angiotensin II/type I receptor pathway. A type I receptor antagonist seems a reasonable alternative to an ACE inhibitor to maintain conduit vessel endothelial function in Type II diabetic subjects.",2001.0,0,0
514,11116103,Effect of enalapril on exhaled nitric oxide in normotensive and hypertensive subjects.,H Sumino; T Nakamura; T Kanda; K Sato; T Sakamaki; T Takahashi; Y Saito; J Hoshino; T Kurashina; R Nagai,"We investigated whether an angiotensin-converting enzyme (ACE) inhibitor increases the production of nitric oxide (NO) in exhaled air in normotensive and hypertensive subjects. In study 1, 8 normotensive male subjects received a single oral dose of enalapril (5 mg) or nitrendipine (10 mg) in a crossover manner. Exhaled air was collected at baseline, and at 2, 4, and 8 hours after administration of the drug. In study 2, 10 normotensive subjects (6 men and 4 women) and 10 hypertensive subjects (6 men and 4 women) received a single oral dose of enalapril (5 mg). Exhaled air was collected at baseline and at 2 and 4 hours after administration of the drug. In study 1, enalapril significantly increased the NO release rate from the lung in normotensive subjects (36.9+/-5.1 pmol/s at baseline versus 58.3+/-7.3 pmol/s at 4 hours, P<0.01). Nitrendipine did not change the NO release rate. In study 2, enalapril significantly increased the release of NO from the lung in normotensive subjects (40.4+/-6.0 pmol/s at baseline versus 70. 3+/-11.4 pmol/s at 4 hours, P<0.01) but not in hypertensive subjects. ACE inhibition increased NO production from the lung in normotensive subjects but not in hypertensive patients. The reduction of angiotensin II production and/or the accumulation of bradykinin in the pulmonary tissue may be responsible for increased NO production in components of the lung, such as the pulmonary vascular endothelium, bronchial epithelial cells, macrophages, nasopharyngeal cells, and neurons. However, the effects of ACE inhibition on NO production from the lung differ between hypertensive subjects and normotensive subjects.",2001.0,0,0
515,11117374,Effects of long-term treatment with verapamil on left ventricular function and myocardial blood flow in patients with dilated cardiomyopathy without overt heart failure.,D Neglia; G Sambuceti; A Giorgetti; M Bartoli; P Salvadori; O Sorace; G Puccini; A L'Abbate; O Parodi,"Myocardial blood flow (MBF) abnormalities are present in early stage dilated cardiomyopathy (DCM) and have been attributed to coronary microvascular abnormalities. The favorable effects of verapamil on coronary microcirculation might indicate its use in early stage DCM. We assessed the safety of long-term combination therapy of verapamil and enalapril and its effects on both left ventricular function and myocardial perfusion compared with enalapril alone in 18 patients with DCM (15 men, 3 women; mean age, 50+/-9 years) without overt heart failure (NYHA class I-II). At baseline and after 6 months of randomized treatment with either enalapril (10-20 mg) (nine patients, group 1) or enalapril (10-20 mg) and verapamil (120-240 mg) (nine patients, group 2), left ventricular function was assessed at rest, during handgrip, and during bicycle exercise by equilibrium radionuclide angiography. Mean MBF was measured at rest and after dipyridamole by positron emission tomography (PET) and 13N-ammonia as a flow tracer. At baseline, the two groups had reduced left ventricular ejection fraction at rest, which was further impaired during isometric exercise, but increased at peak bicycle exercise. MBF was similarly reduced in the two groups at rest and during dipyridamole. During treatment, no adverse events occurred in either group. After 6 months there was no significant difference in the main study variables either between the two groups or within each group before and after treatment. Long-term combination therapy with verapamil and enalapril is safe in patients with DCM without overt heart failure. Despite no favorable effect on myocardial perfusion, combined treatment prevented deterioration of left ventricular function, similarly to enalapril alone.",2001.0,0,0
516,11124620,No effect of losartan on response to erythropoietin therapy in patients undergoing hemodialysis.,A Kato; T Takita; M Furuhashi; T Takahashi; Y Maruyama; A Hishida,,2001.0,0,0
517,11124828,Comparison of two clinical scales for causality assessment in hepatotoxicity.,M I Lucena; R Camargo; R J Andrade; C J Perez-Sanchez; F Sanchez De La Cuesta,"This study was performed to compare the assessments of drug-induced liver injury obtained with 2 methods, the Council for International Organizations of Medical Sciences (CIOMS) scale and the recently validated Maria & Victorino (M&V) clinical scale, in cases submitted to a registry of hepatotoxicity. A total of 215 cases of hepatotoxicity reported with a structured reporting form were evaluated by 3 independent experts. Because of the use of multiple drugs, 228 ratings were generated. The probability of the diagnosis was classified as definitive, probable, possible, unlikely, or excluded, and evaluated for consistency with a weighted kappa statistical test. Absolute agreement between the 2 scales was observed in 42 cases (18%, weighted kappa 0.28) with disagreement of 1 level in 108 cases (47%), and of 2 levels in 70 cases (31%). The best correlation between the 2 scales was obtained for drug-induced liver injury involving a suggested immunoallergic mechanism: the disagreement was 1 level or less in 72% of the cases (34 of 48), compared with 60% of the cases (85 of 141) that involved a presumed idiosyncratic metabolic mechanism. The lowest agreement (6%) was observed in cases with evidence of cholestasis. No agreement was found in cases of fulminant hepatitis or death. The CIOMS scale showed better discriminative power and produced assessments closer to those of specialists. The performance of the M&V scale was poor in reactions with long latency periods (i.e., amoxycillin/clavulanic acid), evolution to chronicity after withdrawal (cholestatic pattern), or death.",2001.0,0,0
518,11127439,"Effect of very early angiotensin-converting enzyme inhibition on left ventricular dilation after myocardial infarction in patients receiving thrombolysis: results of a meta-analysis of 845 patients. FAMIS, CAPTIN and CATS Investigators.",P J de Kam; A A Voors; M P van den Berg; D J van Veldhuisen; J Brouwer; H J Crijns; C Borghi; E Ambrosioni; J S Hochman; T H LeJemtel; J H Kingma; M S Sutton; W H van Gilst,"We sought to investigate the effect of angiotensin-converting enzyme (ACE) inhibition <9 h after myocardial infarction (MI) on left ventricular (LV) dilation in patients receiving thrombolysis. The ACE inhibitors reduce mortality after MI. Attenuation of LV dilation has been suggested as an important mechanism. The data of 845 patients with three-month echocardiographic follow-up after MI were combined from three randomized, double-blind, placebo-controlled studies. The criteria for these studies included: 1) thrombolytic therapy; 2) ACE inhibition within 6 to 9 h; and 3) evaluation of LV dilation as the primary objective. The ACE inhibitor was started 3.2+/-1.7 h after the patients' first (mainly, 85%) anterior MI. After three months, LV dilation was not significantly attenuated by very early treatment with an ACE inhibitor. The diastolic volume index was attenuated by 0.5 ml/m2 (95% confidence interval [CI] -1.5 to 2.5, p = 0.61), and the systolic volume index by 0.5 ml/m2 (95% CI -1.0 to 1.9, p = 0.50). Subgroup analysis demonstrated that LV dilation was significantly attenuated by ACE inhibitor treatment for patients in whom reperfusion failed. In contrast, LV dilation was almost unaffected by ACE inhibitor treatment in successfully reperfused patients. We could not demonstrate attenuation of LV dilation in patients receiving thrombolysis by ACE inhibitor treatment within 6 to 9 h after MI. We speculate that very early treatment with an ACE inhibitor has a beneficial effect on LV remodeling only in patients in whom reperfusion failed. Other mechanisms may be responsible for the beneficial effects of ACE inhibitors in successfully reperfused patients after MI.",2001.0,0,0
519,11127445,Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group.,J N Nanas; G Alexopoulos; M I Anastasiou-Nana; K Karidis; A Tirologos; S Zobolos; V Pirgakis; L Anthopoulos; D Sideris; S F Stamatelopoulos; S D Moulopoulos,"We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril. Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting. Two hundred and forty-eight patients with advanced CHF (age 56.3+/-12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9+/-4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42+/-19.3 mg/day, n = 126). At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6+/-0.7 and had a mean systolic blood pressure (SBP) of 117+/-18 mm Hg, a mean heart rate (HR) of 85+/-16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0+/-9.8%. In group 2, patients were in NYHA class 2.6+/-0.7; their SBP was 118+/-17 mm Hg, HR 83+/-15 beats/min and LVEF 18.8+/-8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9+/-0.7) in both groups; SBP was 111+/-16 and 111+/-17 mm Hg, HR 77+/-12 and 79+/-13 beats/min and LVEF 31+/-19% and 30+/-12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF. No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.",2001.0,0,1
520,11128340,Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy: response to Tarnow et al.,M E Cooper,,2001.0,0,0
521,11128341,Long-term renoprotective effect of nisoldipine and lisinopril in type 1 diabetic patients with diabetic nephropathy.,L Tarnow; P Rossing; C Jensen; B V Hansen; H H Parving,"To compare the long-term effect on kidney function of a long-acting calcium antagonist (nisoldipine) versus a long-acting ACE inhibitor (lisinopril) in hypertensive type 1 diabetic patients with diabetic nephropathy. We performed a 4-year prospective, randomized, double-dummy controlled study comparing nisoldipine (20-40 mg once a day) with lisinopril (10-20 mg once a day). The study was double-blinded for the first year and single-blinded thereafter. The study included 51 hypertensive type 1 diabetic patients with diabetic nephropathy. Three patients dropped out during the first month; results for the remaining 48 patients are presented. At baseline, the two groups were comparable: glomerular filtration rate (GFR) was 85 +/- 5 and 85 +/- 6 ml x min(-1) x [1.73 m](-2); mean 24-h ambulatory blood pressure was 108 +/- 3 and 105 +/- 2 mmHg, and albuminuria was 1,554 mg/24 h (95% CI 980-2,465) and 1,033 mg/24 h (760-1,406) in the lisinopril and nisoldipine groups, respectively. Mean 24-h arterial blood pressure during the study did not differ between the lisinopril and nisoldipine groups (100 +/- 2 and 103 +/- 1 mmHg, respectively). The time-course of albuminuria differed between groups (P < 0.001). Whereas initiation of treatment with lisinopril resulted in a reduction from baseline albuminuria by 52% (95% CI 14-73), albuminuria in the nisoldipine group did not change throughout the study GFR declined in a biphasic manner with an initial (0-6 months) reduction of 1.3 +/- 0.3 ml x min(-1) x month(-1) in the lisinopril group compared with 0.2 +/- 0.4 ml x min(-1) x month(-1) in the nisoldipine group (P < 0.01). The subsequent sustained decline (6 to 48 months or the end of treatment) was identical in the two groups: 0.5 +/- 0.1 ml min(-1) x month(-1) (NS). Two patients in the lisinopril group and three patients in the nisoldipine group entered therapy for end-stage renal failure. Long-term treatment with lisinopril or nisoldipine has similar beneficial effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients.",2001.0,0,0
522,11128360,Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension: results of a randomized controlled trial.,P O'Hare; R Bilbous; T Mitchell; C J O' Callaghan; G C Viberti; Ace-Inhibitor Trial to Lower Albuminuria in Normotensive Insulin-Dependent Subjects Study Group,"To assess if low (1.25 mg) and/or standard (5 mg) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria (incipient diabetic nephropathy) in normotensive type 1 diabetic patients. This study, using a multicenter randomized placebo-controlled double-blind parallel group, was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Ireland. We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure; of these, 140 patients 18-65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria, defined as urinary albumin excretion rate (AER) of 20-200 microg/min, were enrolled in the study. The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years. AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo (P = 0.013). More patients on ramipril regressed to normoalbuminuria (<20 microg/min), with 11% for 1.25 mg ramipril, 20% for 5 mg ramipril, and 4% for placebo (P = 0.053). Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril. Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group (from 132 to 129 mmHg) and in the 5 mg ramipril group (from 134 to 130 mmHg) (P = 0.003, compared with placebo). No statistically significant changes were observed in glomerular filtration rate (GFR) between the placebo- and ramipril-treated groups during the 2-year period. Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.",2001.0,0,0
523,11129038,Angioedema for the epiglottis associated with enalapril.,K Tsunoda; F Hozaki; J Aikawa,,2001.0,0,0
524,11129125,Lercanidipine: a review of its use in hypertension.,K J McClellan; B Jarvis,"Lercanidipine is a vasoselective dihydropyridine calcium antagonist which causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug and as such has a slower onset and longer duration of action than a number of other calcium antagonists. Preclinical evidence suggests that lercanidipine has antiatherogenic potential and it may also protect against end-organ damage. In well controlled clinical studies, once daily administration of lercanidipine 10 or 20mg effectively reduced blood pressure (BP) compared with placebo in patients with mild to moderate hypertension without affecting heart rate. Response rate (percentage of patients with diastolic BP < or =90mm Hg or reduced by > or =10mm Hg from baseline) ranged from 50 to 66% with lercanidipine 10 mg/day and up to 86% with lercanidipine 20 mg/day. The drug had a long duration of action: clinical measurements for diastolic BP yielded a trough/peak ratio of >0.8 for both lercanidipine dosages in 1 study. Comparative trials, either published in full or as abstracts, found lercanidipine 10mg once daily for > or =4 weeks to be at least as effective as atenolol 50mg once daily, candesartan cilexetil 16 mg/day, captopril 25mg twice daily, enalapril 20 mg/day, hydrochlorothiazide 12.5mg once daily, irbesartan 150 mg/day and slow release nifedipine 20mg twice daily in patients with mild to moderate hypertension. In addition, lercanidipine 20 mg/day was as effective as amlodipine 10 mg/day. Lercanidipine is effective in the treatment of elderly patients (aged 60 to 85 years) with mild to moderate essential hypertension and in those with isolated systolic hypertension. In addition, monotherapy with lercanidipine 20 or 40 mg/day has shown efficacy in patients with severe hypertension, and add-on therapy helped control BP in a large proportion of patients with severe hypertension not responding sufficiently to beta-blockers, diuretics or ACE inhibitors. Unpublished data indicate that the drug reduces blood pressure in patients with type 2 (non-insulin-dependent) diabetes mellitus, without adversely affecting glucose homeostasis. Lercanidipine was well tolerated in clinical trials, with most treatment-related adverse events typical of dihydropyridine calcium antagonists, namely headache, flushing, dizziness and ankle oedema. Lercanidipine is an effective and well tolerated once daily antihypertensive agent in patients with mild to moderate hypertension. In addition, the drug may reduce BP when used as monotherapy in patients with severe hypertension or when used adjunctively in patients with resistant hypertension. Importantly, lercanidipine appears to be at least as effective and well tolerated as other commonly used antihypertensive agents. The drug therefore represents a useful therapeutic option in the management of patients with hypertension and will be particularly useful in patients not responding to, or intolerant of, antihypertensive agents from other drug classes.",2001.0,0,0
525,11130522,Health outcomes associated with calcium antagonists compared with other first-line antihypertensive therapies: a meta-analysis of randomised controlled trials.,M Pahor; B M Psaty; M H Alderman; W B Applegate; J D Williamson; C Cavazzini; C D Furberg,"Several observational studies and individual randomised trials in hypertension have suggested that, compared with other drugs, calcium antagonists may be associated with a higher risk of coronary events, despite similar blood-pressure control. The aim of this meta-analysis was to compare the effects of calcium antagonists and other antihypertensive drugs on major cardiovascular events. We undertook a meta-analysis of trials in hypertension that assessed cardiovascular events and included at least 100 patients, who were randomly assigned intermediate-acting or long-acting calcium antagonists or other antihypertensive drugs and who were followed up for at least 2 years. The nine eligible trials included 27,743 participants. Calcium antagonists and other drugs achieved similar control of both systolic and diastolic blood pressure. Compared with patients assigned diuretics, beta-blockers, angiotensin-converting-enzyme inhibitors, or clonidine (n=15,044), those assigned calcium antagonists (n=12,699) had a significantly higher risk of acute myocardial infarction (odds ratio 1.26 [95% CI 1.11-1.43], p=0.0003), congestive heart failure (1.25 [1.07-1.46], p=0.005), and major cardiovascular events (1.10 [1.02-1.18], p=0.018). The treatment differences were within the play of chance for the outcomes of stroke (0.90 [0.80-1.02], p=0.10) and all-cause mortality (1.03 [0.94-1.13], p=0.54). In randomised controlled trials, the large available database suggests that calcium antagonists are inferior to other types of antihypertensive drugs as first-line agents in reducing the risks of several major complications of hypertension. On the basis of these data, the longer-acting calcium antagonists cannot be recommended as first-line therapy for hypertension.",2001.0,0,0
526,11130523,"Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration.",B Neal; S MacMahon; N Chapman; Blood Pressure Lowering Treatment Trialists' Collaboration,"This programme of overviews of randomised trials was established to investigate the effects of angiotensin-converting-enzyme (ACE) inhibitors, calcium antagonists, and other blood-pressure-lowering drugs on mortality and major cardiovascular morbidity in several populations of patients. We did separate overviews of trials comparing active treatment regimens with placebo, trials comparing more intensive and less intensive blood-pressure-lowering strategies, and trials comparing treatment regimens based on different drug classes. The hypotheses to be investigated, the trials to be included, and the outcomes to be studied were all selected before the results of any participating trial were known. Individual participant data or group tabular data were provided by each trial and combined by standard statistical techniques. The overview of placebo-controlled trials of ACE inhibitors (four trials, 12,124 patients mostly with coronary heart disease) revealed reductions in stroke (30% [95% CI 15-43]), coronary heart disease (20% [11-28]), and major cardiovascular events (21% [14-27]). The overview of placebo-controlled trials of calcium antagonists (two trials, 5520 patients mostly with hypertension) showed reductions in stroke (39% [15-56]) and major cardiovascular events (28% [13-41]). In the overview of trials comparing blood-pressure-lowering strategies of different intensity (three trials, 20,408 patients with hypertension), there were reduced risks of stroke (20% [2-35]), coronary heart disease (19% [2-33]), and major cardiovascular events (15% [4-24]) with more intensive therapy. In the overviews comparing different antihypertensive regimens (eight trials, 37,872 patients with hypertension), several differences in cause-specific effects were seen between calcium-antagonist-based therapy and other regimens, but each was of borderline significance. Strong evidence of benefits of ACE inhibitors and calcium antagonists is provided by the overviews of placebo-controlled trials. There is weaker evidence of differences between treatment regimens of differing intensities and of differences between treatment regimens based on different drug classes. Data from continuing trials of blood-pressure-lowering drugs will substantially increase the evidence available about any real differences that might exist between regimens.",2001.0,0,1
527,11130772,Association between blood pressure reduction with antihypertensive treatment and sleep apnea activity.,L Grote; K Wutkewicz; L Knaack; T Ploch; J Hedner; J H Peter,"This study investigated whether a drug therapy-induced reduction in nocturnal blood pressure (BP) was associated with decreased sleep apnea activity. Two polysomnographies from 54 hospitalized male hypertensive, obstructive sleep apnea patients were analyzed in a double-blind, randomized, parallel-group trial of the angiotensin-converting enzyme inhibitor cilazapril (C), 2.5 mg once daily, or placebo (P). Blood pressure was measured by means of an intra-arterial catheter. Compared with P, C lowered mean arterial BP during non-rapid eye movement (NREM) (-8.3 +/- 10.7 mm Hg, P = .05) and REM sleep (-8.6 +/- 10.1 mm Hg, P = .02). Respiratory disturbance index (-8.6 +/- 3.2 events/h of sleep (n/h), P = .01) and apnea index (AI) (-6.6 +/- 3.0 n/h, P = .04) during NREM sleep were lowered by C and, to a lesser extent, by P (-5.9 +/- 3.2 n/h, P = .07 and -5.0 +/- 3.6 n/h, P = .18, respectively). The effect on AI and hypopnea index (HI) during REM sleep was not significant for C (-5.9 +/- 3.4 and 0.1 +/- 2.0, NS, respectively) and P (-2.6 +/- 3.9 and 1.6 +/- 2.0, NS, respectively). There was a significant linear correlation between the change in REM systolic BP and the change in REM AI (r = 0.28, P = .04); the mean BP change correlated negatively with the change in HI (-0.28, P = .04). During NREM sleep there was no significant correlation between changes in BP and the treatment effects on sleep apnea activity. Blood pressure reduction after short-term antihypertensive treatment did not affect sleep disordered breathing during NREM sleep. Reduced BP was associated with a weak reduction of AI and a slight increase of HI during REM sleep. It appears that elevated BP contributes only marginally to sleep apnea severity in hypertensive patients with obstructive sleep apnea.",2001.0,0,0
528,11131271,"Comparison of long-term therapeutic effect of an ACE inhibitor, temocapril, with that of a diuretic on microalbuminuria in non-diabetic essential hypertension.",H Shionoiri; T Kosaka; E Kita; T Takizawa; I Takasaki,"Many investigators have reported that angiotensin-converting enzyme (ACE) inhibitors have antiproteinuric effects and retard the progression of renal impairment in diabetic patients. On the other hand, those effects of ACE inhibitors have not been well established in patients with essential hypertension. This study was conducted to prospectively evaluate whether an ACE inhibitor, temocapril, could modify the urinary microalbumin excretion rate (UAE) in hypertensive outpatients who had no signs of renal impairment. To compare the long-term effect of temocapril with that of a diuretic on UAE, hypertensive patients treated with a diuretic (trichlormethiazide) were enrolled in a prospective study if they had normal serum creatinine levels and no overt proteinuria during a 3-month screening period. A urinary microalbumin-to-urinary-creatinine ratio (mg albumin/mmol Cr) was used as an estimate of UAE. Patients visited the hospital monthly to determine blood pressure (BP) and UAE. After baseline observation during the treatment with the diuretic, the subjects were randomly divided into two groups. In group A, the diuretic was switched to temocapril, 2 to 4 mg once daily for 12 months. In group B, the subjects continued to receive the diuretic for an additional 12 months. Seventy-six outpatients (41 men and 35 women; mean age, 59.0+/-1.4 years) with essential hypertension entered the study. The effects of temocapril on BP appeared to be clinically similar to those of the trichlormethiazide, but the use of temocapril significantly decreased UAE. In group A (n=37), UAE decreased significantly (p<0.01) from the baseline value of 4.19+/-0.37 mg albumin/mmol Cr to 2.47+/-0.29 and 2.68+/-0.28 mg albumin/mmol Cr at the 6th and 12th month of temocapril therapy, respectively. In contrast, in group B (n=39) UAE was unchanged (baseline, 4.16+/-0.63 mg albumin/mmol Cr; 6 months, 4.92+/-0.72; 12 months, 4.71+/-0.74). These results indicate that long-term therapy with temocapril may be superior in reducing UAE than is diuretic therapy in patients with essential hypertension who had no signs of renal impairment.",2001.0,0,0
529,11131272,Blood pressure control in Japanese hypertensives with or without type 2 diabetes mellitus.,S Katayama; M Inaba; T Morita; T Awata; K Shimamoto; R Kikkawa,"Patients with type 2 diabetes mellitus and hypertension are thought to be at high risk for cardiovascular diseases. Recent guidelines for treatment of hypertension such as the JNC VI and WHO/ISH guidelines, recommend that antihypertensive agents be strated at as low as at 130/85 mmHg and that blood pressure be lowered to less than 130/85 mmHg. Our study was designed to clarify how well and to what extent blood pressure (BP) was controlled in Japanese hypertensive patients with or without type 2 diabetes mellitus. We interviewed two hundred physicians, randomly sellected from among the members of the Japanese Society of Hypertension (JSH) (n=98) and the Japanese Diabetes Society (JDS) (n=102) and obtained information regarding five most recent cases of hypertension with (n=954 in total) and their 2 most recent cases of hypertension without diabetes (n=371 in total). The achieved BP was below 140/90 mmHg in 40.5% of non-diabetic and 38.3% of diabetic hypertensives. The percentage of patients whose BP was less than 130/85 mmHg was 10.8% in nondiabetics and 11.4% in diabetics. The average number of hypotensive agents used was 1.46 in nondiabetics and 1.52 in diabetics. Physicians prescribed more ACE inhibitors and alpha-blockers in diabetics than in nondiabetics, although Ca-antagonists were administered in more than 70% of patients irrespective of whether or not they had diabetes. In contrast, fewer beta-blockers and diuretics were administered to diabetics. These results suggest that although Japanese physicians are considering the effects of hypotensive agents on metabolism and renal function when they treat diabetic hypertensives, the achieved blood pressure in both hypertensives with and those without diabetes is insufficient, with only one of ten patients having a blood pressure less than 130/85 mmHg even among diabetics. Improved blood pressure control will therefore be needed to treat high risk groups such as patients with diabetes mellitus.",2001.0,0,0
530,11131273,Effects of lisinopril and nitrendipine on urinary albumin excretion and renal function in patients with mild to moderate essential hypertension.,Y Ogawa; T Haneda; T Hirayama; H Ide; A Obara; J Maruyama; H Morimoto; H Tanaka; J Kato; T Hayakawa; N Hasebe; K Kikuchi,"The present study was designed to evaluate the effects of an ACE inhibitor, lisinopril, and a calcium antagonist, nitrendipine, on urinary albumin excretion (UAE) and renal function in mild to moderate essential hypertensive patients with microalbuminuria. After the 4-week drug-free period, 17 patients were randomly divided into two groups. The first group (group 1: n=8) received lisinopril 10-20 mg daily for 8 weeks followed by nitrendipine 5-10 mg daily for another 8 weeks. The second group (group 2: n=9) received nitrendipine 5-10 mg daily for 8 weeks followed by lisinopril 10-20 mg daily for another 8 weeks. The mean blood pressure (MBP) significantly decreased in a similar manner in both groups. UAE significantly decreased after 8 weeks of treatment with lisinopril in group 1 and after 8 weeks of subsequent treatment with lisinopril in group 2. On the other hand, UAE was not altered by treatment with nitrendipine. The changes in UAE were significantly correlated with changes in MBP after 8 weeks of treatment with nitrendipine, but not after 8 weeks of treatment with lisinopril. No significant changes in creatinine clearance, urinary excretion of sodium or urinary N-acetyl-beta-D-glucosaminide were observed by any treatment in either group. These results suggest that lisinopril, not nitrendipine, reduces UAE in essential hypertensive patients with microalbuminuria independently of its effective antihypertensive properties.",2001.0,0,0
531,11131930,Randomised comparison of losartan vs. captopril on quality of life in elderly patients with symptomatic heart failure: the losartan heart failure ELITE quality of life substudy.,A J Cowley; B L Wiens; R Segal; M W Rich; N C Santanello; E J Dasbach; B Pitt; ELITE Investigators. Evaluation of Losartan in the Elderly,"To measure health-related quality-of-life (HRQoL) in elderly symptomatic heart failure patients following treatment with an angiotensin II receptor antagonist (losartan) vs. an angiotensin-converting-enzyme (ACE) inhibitor (captopril). Patients (age > or = 65 years) were randomised to losartan, titrated to 50 mg once daily, or captopril, titrated to 50 mg three times daily, as tolerated. Sickness Impact Profile (SIP) and Minnesota Living with Heart Failure (LIhFE) questionnaires were administered at baseline, weeks 12 and 48. Composite hypothesis testing of change in HRQoL from baseline for completers, and withdrawal for unfavourable events (death, clinical/laboratory adverse experience) was used to account for differential dropout rates. In 203 patients completing the substudy (week 48), significant and comparable improvements in HRQoL from baseline were observed for both treatment groups (p < or = 0.001). Although there was a trend favouring losartan vs. captopril for the composite HRQoL endpoint (unadjusted p = 0.018, one-sided), this was not considered significant after adjusting for multiple testing. Significantly more captopril patients in the substudy subset withdrew for unfavourable reasons (19.6 vs. 10.9%, p = 0.038). Significant improvements in HRQoL were observed in elderly patients with symptomatic heart failure treated with losartan and captopril long-term. A trend favouring losartan in the composite measure of drug tolerability/quality of life was not significant, but losartan was generally better tolerated than captopril in that significantly fewer losartan patients discontinued therapy.",2001.0,0,1
532,11134846,Oral blistering diseases.,K E Bowers,,2001.0,0,0
533,11134847,Adverse drug reactions in the mouth.,S R Porter; C Scully,,2001.0,0,0
534,11135082,Ramipril prolongs life and is cost effective in chronic proteinuric nephropathies.,P Ruggenenti; E Pagano; L Tammuzzo; R Benini; L Garattini; G Remuzzi,"Our objectives were to predict the long-term cost and efficacy of the angiotensin-converting enzyme, ramipril, in patients with nondiabetic chronic nephropathies. The time to end-stage renal disease (ESRD) was predicted by two different models based on the rate of glomerular filtration rate decline (DeltaGFR) and incidence of ESRD (events) measured during the Ramipril Efficacy in Nephropathy Trial in 117 and 166 patients, respectively, randomized to comparable blood pressure control with ramipril or conventional therapy. Direct medical costs of conservative and renal replacement therapy were estimated by a payer perspective, and cases more and less favorable to ramipril were computed by a sensitivity analysis. The study took place at the Clinical Research Center for Rare Diseases, ""Aldo & Cele Daccò,"" Bergamo, Italy. Patients included those with chronic, nondiabetic nephropathies and persistent urinary protein excretion rate >/=3 g/24 h. Time to ESRD, survival, and direct costs of conservative and renal replacement therapy are discussed. Both in the DeltaGFR-based or events-based models, ramipril delayed progression to ESRD and prolonged patient survival by 1.5 to 2.2 and 1.2 to 1.4 years, respectively, and saved $16,605 to $23,894 lifetime and $2, 422 to $4203 yearly direct costs per patient. Even in the less favorable hypotheses, ramipril allowed lifetime and yearly cost savings that exceeded 10 to 11 and 20 to 40 times, respectively, the additional costs related to prolonged survival. In our study population, ramipril prolongs life while saving money because of its beneficial effect on the course of nondiabetic chronic nephropathies.",2001.0,0,0
535,11139094,Update on recent clinical trials in congestive heart failure.,A S Betkowski; P J Hauptman,"Understanding of the pathophysiology of heart failure has advanced over the last decade, resulting in new therapeutic advances. Convincing data exist that angiotensin-converting enzyme (ACE) inhibition and adrenergic blockade are the most important therapies and have the capacity to improve survival and lower morbidity. Higher doses of both ACE inhibitors and beta-blockers appear to provide additional benefits. The aldosterone antagonist spironolactone, when used in severe heart failure, provides additional survival advantage when added to standard triple therapy. Angiotensin receptor blockers have not been shown to be superior to ACE inhibitors, and their role in heart failure treatment requires further investigation. No trial's data support the use of inotropic agents or calcium channel blockers in heart failure. A number of new therapeutic agents, including vasopressin antagonists and tumor necrosis factor-alpha receptor antibody are in phase II and III clinical trials. If proved beneficial, they may provide new treatment options for patients with heart failure. Nevertheless, the current challenge is to increase the use of proven therapies, namely ACE inhibitors and beta-blockers, to improve outcomes in the rapidly growing population of patients with congestive heart failure.",2001.0,0,0
536,11141144,"Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor (lisinopril): randomised, placebo controlled, crossover study.",H Schrader; L J Stovner; G Helde; T Sand; G Bovim,"To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine. Double blind, placebo controlled, crossover study. Neurological outpatient clinic. Sixty patients aged 19-59 years with migraine with two to six episodes a month. Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for one week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a two week wash out period. Second treatment period of one placebo tablet once daily for one week and then two placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril. Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment. In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment versus placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment versus placebo. Intention to treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points. The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine.",2001.0,0,0
537,11141678,Acute liver failure due to enalapril.,M Jeserich; C Ihling; H P Allgaier; P A Berg; C Heilmann,"This report presents a 46-year-old man who was treated for hypertension with the angiotensin-converting-enzyme (ACE) inhibitor enalapril. After 3 years of continuous treatment he presented with jaundice and progressive liver failure that continued despite withdrawal of the medication. The patient was taking no other medication. All known causes of acute liver failure could be excluded indicating a drug-induced liver damage after long-term treatment with enalapril. Analysis of liver biopsies revealed a pathomorphological pattern comparable to than observed in severe halothane hepatitis. Serological studies including T-cell stimulation with enalapril and a broad spectrum of tests for autoimmunity including autoantibodies against calreticulin, the major Ca2+ and Zn2+ binding protein of the endoplasmic reticulum and suggested to be involved in the pathogenesis of halothane hepatitis were negative. Thus, the mechanism of enalapril-induced liver injury remains obscure. Liver failure progressed and finally led to orthotopic liver transplantation. To our knowledge, this is the longest duration of chronic treatment with an ACE inhibitor before liver failure occurred. In addition, liver failure progressed despite withdrawal of the medication. It is concluded that even after long-term treatment with an ACE inhibitor liver failure may be induced. Therefore, regular monitoring of liver enzymes should be considered.",2001.0,0,0
538,11144658,Immunological principles of adverse drug reactions: the initiation and propagation of immune responses elicited by drug treatment.,D J Naisbitt; S F Gordon; M Pirmohamed; B K Park,"Adverse drug reactions account for between 2 to 5% of all hospital admissions and can prevent the administration of an otherwise effective therapeutic agent. Hypersensitivity or immune-mediated reactions, although less common, tend to be proportionately more serious. There is convincing evidence to implicate the immune system in the pathogenesis of hypersensitivity reactions. Our understanding of the way in which the immune system recognises drugs is based on the hapten hypothesis; the onset of hypersensitivity involves drug bioactivation, covalent binding to proteins, followed by uptake, antigen processing and T cell proliferation. Central to this hypothesis is the critical role of drug metabolism, with the balance between metabolic bioactivation and detoxification being one important component of individual susceptibility. The purpose of this review is to classify drug hypersensitivity reactions in terms of their clinical presentation, and also to consider recent advances in our understanding of the chemical, biochemical and, in particular, cellular immunological mechanisms of hypersensitivity. The following topics are reviewed: (i) drug disposition and cellular metabolism; (ii) mechanisms of antigen processing and presentation; (iii) the role of cytokines and co-stimulatory molecules in the induction and maintenance of a polarised immune response; and (iv) the application of the hapten hypothesis, danger hypothesis and serial triggering model to drug hypersensitivity. A greater understanding of the mechanism(s) of hypersensitivity may identify novel therapeutic strategies and help to combat one of the more severe forms of adverse reactions to drugs.",2001.0,0,0
539,11157185,Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease.,M R Walters; A Bolster; A G Dyker; K R Lees,"The purpose of this study was to investigate the effect of the angiotensin-converting enzyme inhibitor perindopril on mean arterial blood pressure (MABP), cerebral blood flow (CBF), and glomerular filtration rate in hypertensive stroke patients with moderate to severe internal carotid artery (ICA) disease or ICA occlusion. Twenty-four nonacute ischemic stroke patients who had MABP readings >100 mm Hg and moderate to severe ICA stenosis or occlusion were randomized to receive perindopril 4 mg daily or placebo for 14 days. MABP, ICA flow, and both middle cerebral artery (MCA) velocity and resistance index were measured before dose, at 5 time points over the subsequent 24 hours, and finally at 2 weeks. Brain hexamethyl propylene amine oxide single photon emission computed tomography scans were performed before drug administration and at time of peak drug effect (6 to 8 hours) after the first dose. Glomerular filtration rate was measured with (51)Cr EDTA before medication and at 14 days. A placebo-corrected BP fall of 17/10 mm Hg was seen (P:=0.017), which was maximal at 5.5 hours. No significant change in ICA flow or MCA velocity was seen between groups. No significant change in hemispheric CBF was seen. The mean change from baseline in the treated group was -0.79 mL. 100 g(-1). min(-1) (95% confidence interval [CI], 1.65 to -3.23); mean change in the placebo group was -1.9 mL. 100 g(-1). min(-1) (95%CI, 3.02 to -6.92). Peri-infarct CBF was similarly unaffected. One of the treated patients developed transient acute renal impairment and was withdrawn from the study on day 4. Perindopril lowers BP without lowering CBF in hypertensive stroke patients with moderate to severe ICA stenosis or occlusion; monitoring of this patient population for the complications of renal artery stenosis should be considered.",2001.0,0,0
540,11161080,Angiotensin converting enzyme inhibitor induced hyperkalaemic paralysis.,D Dutta; M Fischler; A McClung,"Secondary hyperkalaemic paralysis is a rare condition often mimicking the Guillain-Barré syndrome. There have been a few case reports of hyperkalaemia caused by renal failure, trauma, and drugs where the presentation has been with muscle weakness. A case of hyperkalaemic paralysis caused by an angiotensin converting enzyme inhibitor is reported.",2001.0,0,0
541,11161931,Sex and the heart: what is the role of the cardiologist?,P Rerkpattanapipat; M S Stanek; M N Kotler,,2001.0,0,0
542,11163738,"Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study.",A Sigurdsson; S V Eriksson; C Hall; T Kahan; K Swedberg,"Angiotensin-converting enzyme inhibitors improve long-term survival in patients with left ventricular dysfunction after a myocardial infarction, but their mechanism of action is not entirely clear. The neurohormonal effects may be important in this respect, as well as an early hemodynamic unloading induced by these drugs. The primary objective was to assess the effect of trandolapril on plasma levels of atrial natriuretic peptide. A secondary objective was to assess the effects of trandolapril on selected neurohormones, vasoactive peptides and enzymes, which may be important in the development of left ventricular remodeling and heart failure following an acute myocardial infarction. A total of 119 patients with an acute myocardial infarction and a wall motion index < or =1.2 (16-segment echocardiographic model) were randomized to double blind treatment with trandolapril or placebo within 3-7 days after the onset of infarction. Blind treatment was discontinued 21 days after the index infarction. Venous blood samples were collected at rest, before randomization and on the day after treatment was discontinued. At the end of the study, there were no differences in plasma levels of atrial natriuretic peptide between the two treatment groups. Angiotensin-converting enzyme activity was suppressed and plasma renin activity was higher in the trandolapril group. No differences in plasma levels of N-terminal pro-atrial natriuretic peptide, brain natriuretic peptide, aldosterone, noradrenaline, adrenaline, vasopressin, big endothelin-1 and neuropeptide Y were found between the two treatment groups. There were positive correlations between several markers of neurohormonal activation at baseline and variables expressing left ventricular dysfunction and clinical heart failure. Neurohormonal activation is related to left ventricular dysfunction. The effects of 2-3 weeks of angiotensin-converting enzyme inhibition on neurohormonal activation does not predict the already established beneficial long-term effects after myocardial infarction. Thus, early modulation of circulatory neurohormone levels may not be a major mechanism for the efficacy of angiotensin-converting enzyme inhibitors in these patients. Selected plasma hormone markers may still be used to identify patients who might get the greatest benefit from treatment.",2001.0,0,0
543,11165421,Operational aspects of terminating the doxazosin arm of The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,S L Pressel; B R Davis; J T Wright; T S Geraci; C Kingry; C E Ford; L B Piller; J Bettencourt; B Kimmel; C Lusk; H Parks; L M Simpson; C Nwachuku; C D Furberg; ALLHAT Collaborative Research Group,"The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, practice-based trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI). The double-blind, active-controlled component of ALLHAT was designed to determine whether the rate of the primary outcome-a composite of fatal coronary heart disease and nonfatal myocardial infarction-differs between diuretic (chlorthalidone) treatment and each of three other classes of antihypertensive drugs: a calcium antagonist (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin) in high-risk hypertensive persons ages 55 years and older. In addition, 10,377 ALLHAT participants with mild to moderate hypercholesterolemia were also enrolled in a randomized, open-label trial designed to determine whether lowering serum LDL cholesterol with an HMG CoA reductase inhibitor (pravastatin) will reduce all-cause mortality as compared to a control group receiving ""usual care."" In January 2000, an independent data review committee recommended discontinuing the doxazosin treatment arm. The NHLBI director promptly accepted the recommendation. This article discusses the steps involved in the orderly closeout of one arm of ALLHAT and the dissemination of trial results. These steps included provisional preparations; the actual decision process; establishing a timetable; forming a transition committee; preparing materials and instructions; informing 65 trial officers and coordinators, 628 active clinics and satellite locations, 313 institutional review boards, over 42,000 patients, and the general public; reporting detailed trial results; and monitoring the closeout process. Control Clin Trials 2001;22:29-41",2001.0,0,0
544,11171786,Comparative effect of ace inhibition and angiotensin II type 1 receptor antagonism on bioavailability of nitric oxide in patients with coronary artery disease: role of superoxide dismutase.,B Hornig; U Landmesser; C Kohler; D Ahlersmann; S Spiekermann; A Christoph; H Tatge; H Drexler,"Flow-dependent, endothelium-mediated vasodilation (FDD) and activity of extracellular superoxide dismutase (EC-SOD), the major antioxidative enzyme of the arterial wall, are severely impaired in patients with coronary artery disease (CAD). We hypothesized that both ACE inhibitor (ACEI) and angiotensin II type 1 receptor antagonist (AT(1)-A) increase bioavailability of nitric oxide (NO) by reducing oxidative stress in the vessel wall, possibly by increasing EC-SOD activity. Thirty-five patients with CAD were randomized to 4 weeks of ACEI (ramipril 10 mg/d) or AT(1)-A (losartan 100 mg/d). FDD of the radial artery was determined by high-resolution ultrasound before and after intra-arterial N-monomethyl-L-arginine (L-NMMA) to inhibit NO synthase and before and after intra-arterial vitamin C to determine the portion of FDD inhibited by oxygen free radicals. EC-SOD activity was determined after release from endothelium by heparin bolus injection. FDD was improved after ramipril and losartan (each group P<0.01), and in particular, the portion of FDD mediated by NO, ie, inhibited by L-NMMA, was increased by >75% (each group P<0.01). Vitamin C improved FDD initially, an effect that was lost after ramipril or losartan. After therapy, EC-SOD activity was increased by >200% in both groups (ACEI, 14.4+/-1.1 versus 3.8+/-0.9 and AT(1)-A, 13.5+/-1.0 versus 3.9+/-0.9 U. mL(-1). min(-1); each P<0.01). CONCLUSIONS-Four weeks of therapy with ramipril or losartan improves endothelial function to similar extents in patients with CAD by increasing the bioavailability of NO. Our results suggest that beneficial long-term effects of interference with the renin-angiotensin system may be related to reduction of oxidative stress within the arterial wall, mediated in part by increased EC-SOD activity.",2001.0,0,0
545,11171788,Effects of early use of atenolol or captopril on infarct size and ventricular volume: A double-blind comparison in patients with anterior acute myocardial infarction.,J Galcerá-Tomás; F J Castillo-Soria; M M Villegas-García; R Florenciano-Sánchez; J G Sánchez-Villanueva; J A de La Rosa; A Martínez-Caballero; J A Valentí-Aldeguer; P Jara-Pérez; M Párraga-Ramírez; I López-Martínez; L Iñigo-García; F Picó-Aracil,"beta-Blockers and ACE inhibitors reduce early mortality when either one is started in the first hours after myocardial infarction (MI). Considering the close correlation between morphological changes and prognosis, we aimed to investigate whether the benefit of both beta-blockers and ACE inhibitors might reside in a similar protective effect on infarct size or ventricular volume. In a randomized, double-blind comparison between early treatment with captopril or atenolol in 121 patients with acute anterior MI, both drugs showed a similar reduction in mean blood pressure. However, only the atenolol-treated patients showed a significant early reduction in heart rate. Infarct size, obtained from the perfusion defect in resting single photon emission imaging, was higher in captopril-treated patients than in atenolol-treated patients: 29.8+/-12% versus 20.8+/-12% (P:<0.01) by polar map and 28.3+/-13% versus 20.0+/-13% (P:<0.01) by tomography. Changes from baseline to 1 week and to 3 months in ventricular end-diastolic volume, assessed by echocardiography, were as follows: 58+/-14 versus 64+/-19 (P<0.05) and 65+/-21 mL/m(2) (P<0.05), respectively, with captopril, and 58+/-18 versus 64+/-18 (P<0.05) and 69+/-30 mL/m(2) (P<0.05), respectively, with atenolol. Neither group showed significant changes in end-systolic volume. Among patients with perfusion defect >18% (n=51), those treated with atenolol showed a significant increase of end-systolic and end-diastolic ventricular volumes, whereas captopril-treated patients did not. Although early treatment with atenolol or captopril results in similar overall short- and medium-term preservation of ventricular function and volumes, in patients with larger infarctions, a beta-blocker alone does not adequately protect myocardium from ventricular dilatation.",2001.0,0,1
546,11174337,Regional wall stress predicts ventricular remodeling after anteroseptal myocardial infarction in the Healing and Early Afterload Reducing Trial (HEART): an echocardiography-based structural analysis.,Y Aikawa; L Rohde; J Plehn; S C Greaves; F Menapace; M O Arnold; J L Rouleau; M A Pfeffer; R T Lee; S D Solomon,"Increased left ventricular (LV) wall stress after myocardial infarction (MI) has been implicated in LV remodeling. However, the relationship between LV wall stress and LV remodeling is incompletely defined. We prospectively studied the relationship between regional wall stress and LV remodeling by application of the finite element method to end-systolic LV models from patients enrolled in the Healing and Early Afterload Reducing Therapy (HEART) Trial. Individual LV models were constructed from orthogonal apical echocardiographic views obtained at day 14 after anteroseptal MI in 64 patients. Of these, 31 patients received low-dose (0.625 mg) ramipril and 33 patients received full-dose (10 mg) ramipril. LV wall stress was calculated by the finite element method and correlated with change in LV volume from day 14 to day 90 after MI. Among all patients, increases in apical regional wall stress were associated with LV volume changes (P -trend =.015). The relationship between apical regional wall stress and change in LV volume was strongest in the low-dose ramipril group (r = 0.53, P =.002) and remained significant after adjustment for end-diastolic volume, infarct size, ejection fraction, and systolic blood pressure yet was attenuated in the full-dose ramipril group. Apical regional wall stress is an independent predictor of subsequent LV remodeling after MI. The relationship between increased apical wall stress and LV dilatation appears to be attenuated by full-dose angiotensin-converting enzyme inhibition.",2001.0,0,0
547,11174888,Treatment of advanced heart failure.,M Jessup; S Brozena,"The incidence of chronic heart failure has increased, with a corresponding increase in morbidity and mortality, and has made a substantial financial impact on our society. Improved therapy for heart failure has resulted in a significant prolongation of survival, a decreased number of hospitalizations, and an enhanced quality of life for many patients. It can reasonably be expected, therefore, that adherence to a rational medical regimen for these patients might decrease costs as well. Management of patients with severe heart failure begins with identifying the etiology and educating the patients and their families. Angiotensin-converting enzyme inhibitors are the cornerstone of therapy but only after diagnostic tests are performed to establish the etiology and extent of myocardial dysfunction. Because cardiac transplantation is a therapeutic option for only a limited number of patients, other surgical and medical therapies have to be viewed as the mainstay of a treatment strategy.",2001.0,0,0
548,11174914,Treatment of hypertension in patients with diabetes: lessons from recent trials.,R Agarwal,"Hypertension plays a critical role in causing a high rate of cardiovascular events in patients with diabetes mellitus. Large trials show that lowering blood pressure in the patient with diabetes who has hypertension has profoundly favorable effects. This review discusses recent trials to answer the question of how low patients' blood pressure should go and which agents should be used to achieve this goal. The National Institutes of Health's guidelines, published in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, call for a blood pressure goal of <130/85 mmHg in patients with diabetes. Based on data from the recent trials, an even lower blood pressure of <130/80 mmHg in patients with diabetes and hypertension appears to be appropriate. Observational studies show that the lowest cardiovascular event rate is observed in patients with diabetes whose systolic blood pressure is <120 mmHg. Thus, goal blood pressure in patients with diabetes who have hypertension may need to be revised lower, to <120/80 mmHg. In patients with overt proteinuria of 1 g/d or more, mean arterial pressure of <92 mmHg is recommended. Available evidence justifies the use of angiotensin-converting enzyme (ACE) inhibitors as first-line agents and angiotensin receptor blockers in those patients who are intolerant to ACE inhibitors. Because the blood pressure goal is lower in patients with diabetes who are hypertensive, these patients require the use of multiple agents. Diuretics or long-acting calcium channel blockers are logical second choices because of their synergistic blood pressure reduction effect observed with ACE inhibitors. Alpha-blockers should be used with caution, however. In patients with renal disease, loop diuretics may be required to reduce sodium and volume overload and to improve blood pressure control.",2001.0,0,0
549,11176729,Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.,B M Massie; P W Armstrong; J G Cleland; J D Horowitz; M Packer; P A Poole-Wilson; L Rydén,"Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.",2001.0,0,0
550,11177312,Physical activity and risk for cardiovascular events in diabetic women.,F B Hu; M J Stampfer; C Solomon; S Liu; G A Colditz; F E Speizer; W C Willett; J E Manson,"Increased physical activity has been associated with reduced risk for cardiovascular disease in the general population, but data are limited on its role among persons with type 2 diabetes mellitus. To determine whether physical activity decreases risk for cardiovascular disease among diabetic women. Prospective cohort study. The Nurses' Health Study. 5125 female nurses with diabetes. Physical activity was first assessed in 1980 and was updated in 1982, 1986, 1988, and 1992 through validated questionnaires. Average hours of moderate or vigorous exercise and a metabolic equivalent of task (MET) score were computed. During 14 years of follow-up (31 432 person-years), 323 new cases of cardiovascular disease were documented (225 cases of coronary heart disease and 98 cases of stroke). The age-adjusted relative risks according to average hours of moderate or vigorous activity per week (<1, 1 to 1.9, 2 to 3.9, 4 to 6.9, >/=7) were 1.0, 0.93 (95% CI, 0.69 to 1.26), 0.82 (CI, 0.61 to 1.10), 0.54 (CI, 0.39 to 0.76), and 0.52 (CI, 0.25 to 1.09) (P < 0.001 for trend). These figures did not change materially after adjustment for smoking, body mass index, and other cardiovascular risk factors (1.0, 1.02, 0.87, 0.61, and 0.55, respectively; P = 0.001 for trend). In separate analyses, levels of physical activity were inversely associated with coronary heart disease and ischemic stroke. Among women who did not exercise vigorously, the multivariate relative risks for cardiovascular disease across quartiles of MET score for walking were 1.0, 0.85, 0.63, and 0.56 (P = 0.03 for trend). Faster usual walking pace was independently associated with lower risk. Among diabetic women, increased physical activity, including regular walking, is associated with substantially reduced risk for cardiovascular events.",2001.0,0,0
551,11179530,Effect of quinapril on intimal hyperplasia after coronary stenting as assessed by intravascular ultrasound.,J Kondo; T Sone; H Tsuboi; H Mukawa; T Kosokabe; M Tsuzuki; T Tomida; T Suzuki; H Kamiya; K Hayashi; H Matsui; K Okumura,"We studied whether angiotensin-converting enzyme inhibition with quinapril treatment can prevent in-stent restenosis after successful implantation of Palmaz-Schatz stents. Intravascular ultrasound study, but not quantitative coronary angiography analysis, revealed that quinapril treatment significantly prevented the loss of both minimal lumen cross-sectional area and lumen volume in stents, in addition to reducing the increase in intimal hyperplasia volume.",2001.0,0,0
552,11181464,Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE).,E Lonn; S Yusuf; V Dzavik; C Doris; Q Yi; S Smith; A Moore-Cox; J Bosch; W Riley; K Teo; SECURE Investigators,"Activation of the renin-angiotensin-aldosterone system and oxidative modification of LDL cholesterol play important roles in atherosclerosis. The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE), a substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, was a prospective, double-blind, 3x2 factorial design trial that evaluated the effects of long-term treatment with the angiotensin-converting enzyme inhibitor ramipril and vitamin E on atherosclerosis progression in high-risk patients. A total of 732 patients >/=55 years of age who had vascular disease or diabetes and at least one other risk factor and who did not have heart failure or a low left ventricular ejection fraction were randomly assigned to receive ramipril 2.5 mg/d or 10 mg/d and vitamin E (RRR-alpha-tocopheryl acetate) 400 IU/d or their matching placebos. Average follow-up was 4.5 years. Atherosclerosis progression was evaluated by B-mode carotid ultrasound. The progression slope of the mean maximum carotid intimal medial thickness was 0.0217 mm/year in the placebo group, 0.0180 mm/year in the ramipril 2.5 mg/d group, and 0.0137 mm/year in the ramipril 10 mg/d group (P=0.033). There were no differences in atherosclerosis progression rates between patients on vitamin E and those on placebo. Long-term treatment with ramipril had a beneficial effect on atherosclerosis progression. Vitamin E had a neutral effect on atherosclerosis progression.",2001.0,0,0
553,11181983,"Membranous nephropathy, hydrocarbon exposure and genetic variants of hydrocarbon detoxification.",C W Gradden; P Pai; P Hindell; D J O'Donoghue; H Mason; G M Bell,"Modulation of biotransformation by genetic traits may be important in determining environmentally-induced nephrotoxicity. We conducted a case-control study to investigate the role of occupational hydrocarbon exposure, along with polymorphisms of the genes coding for N-acetyltransferase 2 (NAT2) and glutathione S-transferase mu (GSTmu), in the development of idiopathic membranous glomerulonephritis (IMGN). Patients (n=36) with biopsy-proven IMGN were matched with healthy controls for age, gender, and geographical area. Lifetime hydrocarbon exposure was assessed by a validated questionnaire. The polymorphisms of the NAT2 and GSTmu genes (GSTM1) were defined by use of a polymerase chain reaction on white-cell DNA from peripheral blood. Exposure to hydrocarbons was significantly greater in patients with IMGN than in controls (mean+/-SEM hydrocarbon exposure score 11 003+/-2955.7 vs. 4352+/-1418, p<0.02). NAT2 acetylator status was identical in patients and controls with 23 (63.9%) fast and 13 (36.1%) slow acetylators in each group. GSTmu was present in 15 (41.7%) patients and 16 (44.4%) controls. While occupational exposure to hydrocarbons remains a likely factor in its pathogenesis, further work is required to identify the genetic polymorphisms that modulate the risk of IMGN.",2001.0,0,0
554,11181984,"Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus.",J Kvetny; G Gregersen; R S Pedersen,"Diabetic nephropathy is one of the leading causes of end-stage renal disease. We examined whether ACE inhibitor treatment may have a nephroprotective effect in normotensive insulin-dependent diabetic patients without microalbuminuria and with normal glomerular filtration rate (GFR), and whether any effect was associated with the ACE genotype. In a prospective double-blind randomized study, normotensive patients with type 1 diabetes mellitus with normal serum creatinine and no microalbuminuria were treated with either placebo or perindopril, an ACE inhibitor. Urine albumine/creatinine ratio (ACR), mean blood pressure (MBP) and index of glomerular filtration rate (GFR) based on S-creatinine were determined. ACE genotype was determined by electrophoresis. ACR was higher in the placebo group than in the perindopril group after 4 months, and continued to increase during the study period. After 36 months of observation, ACR in the placebo group was 1.7+/-1.1 mg/mmol, and 0.6+/-0.2 mg/mmol in the ACE-inhibitor-treated group (p<0.001, Mann-Whitney test). During treatment, a significant increase in ACR in the placebo group (p=0.007), Wilcoxon matched paired test) was observed. There were no differences between the groups regarding MBP or GFR. The nephroprotective effects of ACE inhibitor treatment was not associated with the ACE genotype (II, ID, DD).",2001.0,0,1
555,11182173,The combination ace-inhibitors plus canreonate in patients with anterior myocardial infarction: safety and tolerability study.,P Di Pasquale; V Alessi; O Barberi; A Scandurra; V Bucca; G Maringhini; S Scalzo; S Paterna,"There is recent evidence that aldosterone (ALDO) exerts pro-fibrotic effects, acting via the mineral-corticoid receptors in cardiovascular tissues and partial aldosterone escape during ACE-inhibition treatment occurs. A double blind randomised study was performed to evaluate the feasibility, and tolerability of the administration of the 25 mg/day of canreonate plus captopril versus captopril alone in patients with anterior AMI unsuitable for thrombolysis and/or not receiving thrombolytic treatment, and unreperfused after thrombolysis. Fifty five patients hospitalised for anterior AMI,with a serum creatinine concentration <2.0 mg/dl and a serum K concentration <5.0 mmol per liter were randomised in 2 groups: Group A included 27 patients who received captopril and 25 mg i.v. of canreonate (1 mg/h for the 1st 72 h and then orally 25 mg/day. Group B (28 patients) received captopril and placebo. Ten days after admission they underwent echocardiography to determine end systolic volume (ESV), ejection fraction (EF), End diastolic diameter EDD, E/A ratio, E deceleration time (dec. time) and isovolumetric relaxation time (IVRT), E and A peak velocities. All patients did not show patency of the infarct related artery (7-10 days after AMI) and the 2 groups were similar in regard to age, sex, diabetes, smoking habits, hypertension, CK enzymatic peak, adjuvant therapy, EF, ESV, and incidence of CABG/PTCA. One patient only showed increase of serum K>5.5 mmol/dl and creatinine >2.0 mg per liter after 10 days of treatment (group A). The mitral E/A ratio was higher in group A than group B (0.85+/-0.18 and 0.75+/-0.14) respectively, P=0.024. Creatinine, blood urea and serum K did not show significant differences between groups. No side effects were observed during the study period. The incidence of vessel diseases was similar in both groups. Our data suggest that the combination of captopril plus canreonate in feasible in early treatment of AMI patients.",2001.0,0,0
556,11182175,Effects of the replacement of the angiotensin converting enzyme inhibitor enalapril by the angiotensin II receptor blocker telmisartan in patients with congestive heart failure. The replacement of angiotensin converting enzyme inhibition (REPLACE) investigators.,P H Dunselman; Replacement of Angiotensin Converting Enzyme Inhibition (REPLACE) Investigators,"To compare the effects on maximal exercise tolerance of 12 weeks of four dosages of telmisartan (10/20/40/80 mg once daily), an AT(1) specific angiotensin II receptor antagonist, or continuation on the angiotensin converting enzyme inhibitor enalapril, in patients with stable, mild-to-moderate congestive heart failure (NYHA Class II and III and left ventricular ejection fraction < or =40%). Multicenter, double-blind, parallel-group trial in 378 patients, randomized to once-daily treatment with telmisartan 10, 20, 40 mg, 80 mg, or continuation of enalapril 10 mg twice daily for 12 weeks. Primary efficacy parameter: change from baseline to final visit in bicycle exercise duration. Secondary efficacy parameters included left ventricular ejection fraction, quality-of-life parameters, arterial blood pressures, neurohormonal changes and NYHA classification. The mean age of the patients was 64+/-9 years, 89% male, history of myocardial infarction in 68%, NYHA-II: 63%, NYHA-III: 37%, ejection fraction 26.4(7)%, and a reproducible impaired exercise capacity. All patients were on diuretics and enalapril 10 mg twice daily, and 39% were taking digitalis at study entry. No clinically relevant or statistically significant (P<0.05) differences were observed in the primary efficacy parameter: mean changes (s) in exercise tolerance were +8.6, +8.2, +2.2, and +7.1 for the telmisartan 10-, 20-, 40-, and 80-mg groups, respectively, and +1.4 for enalapril. There was a small but significant increase in blood pressure in all but the 80 mg telmisartan groups, compared to enalapril. Telmisartan and enalapril had comparable adverse event profiles. Cough occurred in 5.6% of the enalapril patients and in 3% of the telmisartan patients (NS). (1) In patients with stable, mild-to-moderate congestive heart failure, enalapril could be replaced by telmisartan for a period of 12 weeks without deterioration in exercise capacity or clinical status. (2) No differences were observed in exercise capacity between the four dosages of telmisartan.",2001.0,0,0
557,11185629,"Absorption, metabolism, and excretion of intravenously and orally administered [14C]telmisartan in healthy volunteers.",J Stangier; J Schmid; D Türck; H Switek; A Verhagen; P A Peeters; S P van Marle; W J Tamminga; F A Sollie; J H Jonkman,"The study was conducted in healthy male volunteers to evaluate the absorption, metabolic pattern, and mode of elimination of telmisartan, a nonpeptide angiotensin II receptor antagonist. [14C]telmisartan was administered orally in solution as a single 40 mg dose to 5 subjects. A further 5 subjects received short-term intravenous infusion of [14C]telmisartan 40 mg. Measurement of total 14C radioactivity in plasma showed that about 50% was absorbed following oral administration, with maximum plasma concentration observed after 0.5 to 1 hour. Absolute bioavailability was 43%. On average, 84% of total radioactivity in plasma reflected the parent compound. The remainder of total radioactivity could be ascribed to the glucuronide conjugate of telmisartan, which represented the only metabolite in man. About 99.5% of telmisartan was bound to plasma protein, mainly to albumin and alpha-1-acid glycoprotein. Telmisartan was reversibly distributed into erythrocytes. More than 90% of administered dose was excreted within 120 hours, and the excretion balance was complete 144 hours after dosing. Radioactivity was almost exclusively (> 98%) excreted via the feces; urinary excretion accounted for < 1% of the dose, irrespective of the route of administration. In the small fraction excreted into urine, the glucuronide conjugate of telmisartan was predominant. Although some telmisartan glucuronide was detected in plasma, only unchanged drug was identified in the feces. No changes in vital signs, electrocardiogram, or clinical laboratory tests were detected following telmisartan administration, and adverse events, predominantly unrelated to treatment and of mild intensity, were infrequent. One subject fainted and, on another occasion, reported faintness; these events were probably due to the antihypertensive action of the intravenous study medication.",2001.0,0,0
558,11185630,Multiple-dose pharmacokinetics of telmisartan and of hydrochlorothiazide following concurrent administration in healthy subjects.,C L Young; V C Dias; J Stangier,"This open-label, crossover study had two objectives: to compare the steady-state pharmacokinetics of high-dose telmisartan with and without coadministered high-dose hydrochlorothiazide and to compare the steady-state pharmacokinetics of hydrochlorothiazide with and without coadministered telmisartan. A total of 13 healthy males and females of nonchildbearing potential received the following oral, once-daily medications, each for 7 days: telmisartan 160 mg, hydrochlorothiazide 25 mg, and telmisartan 160 mg plus hydrochlorothiazide 25 mg. Between medication periods, there was a 14-day washout. Blood was collected at intervals over 48 and 84 hours, respectively, at the end of the 7-day dosing period for the determination of plasma telmisartan and hydrochlorothiazide concentrations by high-performance liquid chromatography. Predose blood samples were also collected on days 1, 6, and 7. Tolerability of single-agent and combination medication was monitored. For hydrochlorothiazide and telmisartan, given alone or in combination, there were no appreciable differences in trough plasma concentrations between days 6, 7, and 8; thus, at day 7, both agents had achieved steady state. Mean values of the primary end points (Cmax and AUC0-24) and secondary end points (Cmin and t1/2) for both telmisartan and hyrochlorothiazide were unaffected when administered simultaneously. Moreover, concurrent telmisartan had no effect on urinary excretion of hydrochlorothiazide. Transient lightheadedness, associated with postural hypotension, was the most common adverse event. The absence of any significant effects on the pharmacokinetics of either hydrochlorothiazide or telmisartan shows that no dose adjustment is required if the two agents are given concurrently for the management of hypertension.",2001.0,0,0
559,11185631,Steady-state pharmacodynamics and pharmacokinetics of warfarin in the presence and absence of telmisartan in healthy male volunteers.,J Stangier; C A Su; M G Hendriks; J J van Lier; F A Sollie; B Oosterhuis; J H Jonkman,"The effects of multiple-dose telmisartan on the steady-state pharmacodynamics and pharmacokinetics of warfarin were assessed in 12 healthy young males in an open-label, single-period study conducted over 30 days. Subjects received loading doses of oral once-daily warfarin on days 1 to 5, which were individually adjusted at days 6 and/or 9 to attain stable predose prothrombin time values (INRpre) of between 1.2 and 1.8 by the end of medication phase 1 (day 14). From days 15 to 24 (medication phase 2), subjects received oral once-daily telmisartan 120 mg in addition to individualized oral doses of once-daily warfarin. On days 25 to 31 (medication phase 3), oral once-daily warfarin was again administered alone at individualized doses. Under steady-state conditions, INRpre remained unchanged during medication phases 1, 2, and 3. The difference between phases 1 and 3 was -0.04 (95% confidence interval [CI]: -0.7 to 0.10) and between phases 2 and 1 was 0.03 (95% CI: -0.11 to 0.10). Mean trough plasma warfarin concentrations (Cpre) were stable during medication with warfarin alone but showed a small, although statistically significant, decrease during the combined-medication phase. The point estimate of the ratio of phase 2/phase 1 was 0.89 (95% CI: 0.84 to 0.95). The decrease in Cpre did not result in decreased anticoagulation. This suggests that the extent of pharmacokinetic interaction between telmisartan and warfarin is limited, and since telmisartan had no effect on INRpre and the concomitant medication was well tolerated, there is no evidence for a clinically relevant interaction between telmisartan and warfarin.",2001.0,0,0
560,11185632,Pharmacokinetics of acetaminophen and ibuprofen when coadministered with telmisartan in healthy volunteers.,J Stangier; C A Su; A Fraunhofer; W Tetzloff,"Two open-label, two-way, crossover studies were performed to assess any pharmacokinetic interaction of telmisartan with either acetaminophen or ibuprofen. Healthy male adult volunteers (n = 12) received a single oral dose of acetaminophen 1 g alone and with oral telmisartan 120 mg in one study. Oral ibuprofen 400 mg three times daily with and without oral once-daily telmisartan 120 mg was given for 7 days in the other study conducted in 6 males and 6 females. In both studies, there was a washout period of > or = 13 days between single and combination medication administration. The primary end points Cmax and AUC were compared between combination (acetaminophen or ibuprofen + telmisartan) and single-agent medication (acetaminophen or ibuprofen). Pharmacokinetic drug interaction was assessed by analysis of variance (ANOVA) and calculation of 90% confidence intervals (CI) for treatment ratios using log-transformed parameters. Bioequivalence (i.e., lack of interaction) was concluded if the 90% CI of the ratios for both Cmax and AUC were within the acceptance limit of 0.80 to 1.25. Geometric mean Cmax values for acetaminophen and R-(-)- and S-(+)-ibuprofen enantiomers were similar with and without telmisartan coadministration (12.6 micrograms/mL vs. 14.1 micrograms/mL; 17.3 micrograms/mL vs. 16.7 micrograms/mL; 19.4 micrograms/mL vs. 19.5 micrograms/mL, respectively), and values for R-(-)- as well as S-(+)-ibuprofen were bioequivalent. Geometric mean AUC values for acetaminophen and R-(-)- and S-(+)-ibuprofen were also bioequivalent with and without telmisartan. The distribution and elimination parameters of both acetaminophen and ibuprofen were comparable in the presence or absence of telmisartan. The concomitant and single-agent medications were all well tolerated. In conclusion, the long half-life and excellent safety profile of telmisartan were unaffected by concurrent acetaminophen or ibuprofen medication; thus, once-daily dosing of telmisartan can be maintained, which may help to optimize patient compliance, and patients may self-administer concomitant acetaminophen or ibuprofen.",2001.0,0,0
561,11185633,Pharmacokinetics of repeated oral doses of amlodipine and amlodipine plus telmisartan in healthy volunteers.,J Stangier; C A Su,"This open-label, crossover study was performed to establish if there is evidence for interaction between telmisartan, an angiotensin II antagonist, and amlodipine, a class II (dihydropyridine) calcium channel antagonist, on the basis of pharmacokinetics and safety. In a two-way crossover trial, 12 healthy Caucasian males were randomized to receive once daily for 9 days oral amlodipine 10 mg with or without oral telmisartan 120 mg. After a washout period of > or = 13 days, the subjects were switched to the other medication regimen. The geometric means of the primary pharmacokinetic parameters at steady state (day 9) for amlodipine when given alone were the following: maximum plasma concentration (Cmax) 17.7 ng/mL, area under the plasma concentration-time curve (AUC) 331 ng.h/mL, and renal clearance 39.5 mL/min, with 8% of the total amlodipine dose being excreted. When concomitant telmisartan was given, the respective values were 18.7 ng/mL, 352 ng.h/mL, and 43.0 mL/min, with 9.4% of the total amlodipine dose being excreted renally. The limits of the 90% confidence intervals (CIs) for the ratios of these steady-state parameters were 0.97 to 1.14 for Cmax and 0.98 to 1.16 for AUC; both were within the predefined reference range (0.8 to 1.25) for bioequivalence. The high intersubject variability in urinary amlodipine excretion resulted in bioequivalence not being demonstrated for renal clearance. Adverse effects were few, mild to moderate in intensity, and transient whether amlodipine was given alone or with telmisartan. Vital signs, except for blood pressure, and clinical laboratory values were unaffected by either medication. The findings of this study show that concomitant telmisartan and amlodipine may be administered as there is no clinically significant variation in primary pharmacokinetic parameters of amlodipine in the presence of telmisartan, and the safety of the combination is comparable to that of amlodipine alone.",2001.0,0,0
562,11185634,Pharmacokinetics and safety of intravenous and oral telmisartan 20 mg and 120 mg in subjects with hepatic impairment compared with healthy volunteers.,J Stangier; C A Su; G Schöndorfer; W Roth,"The pharmacokinetics and safety of telmisartan were assessed in subjects with hepatic impairment in a single-center, open-label study. Single oral doses of telmisartan 20 mg and 120 mg, separated by a washout period of 14 days, were given to 12 hepatically impaired subjects and 12 healthy subjects. In 5 hepatically impaired subjects who received both oral doses, a single i.v. infusion of telmisartan 120 mg was later administered. After oral dosing, the pharmacokinetic profile of telmisartan was characterized by rapid absorption and disposition kinetics and a slow terminal elimination phase with mean half-lives of 27 to 42 hours. The maximum plasma concentration and area under the telmisartan plasma concentration-time curve (AUC0-infinity) increased in hepatically impaired subjects compared with healthy volunteers 6.4-fold and 2.7-fold, respectively, for telmisartan 20 mg and 3.2-fold and 3.1-fold, respectively, for telmisartan 120 mg. Maximum plasma concentrations and AUC0-infinity after i.v. infusion were markedly elevated compared with values obtained from other studies conducted in healthy volunteers. Hepatic impairment resulted in an apparent increase in the absolute bioavailability of telmisartan, and total clearance following oral and i.v. administration was significantly reduced compared with healthy volunteers. Plasma protein binding of telmisartan was > or = 99.5% in hepatically impaired and healthy subjects and was not changed when compared to healthy subjects. Oral and i.v. telmisartan were well tolerated in both the hepatically impaired and the healthy; headache was the most common potentially telmisartan-related adverse event. Changes in vital signs and clinical laboratory parameters were transient and of no clinical relevance. The good tolerability of telmisartan in hepatically impaired patients demonstrated in this study, the proven sustained blood pressure control in hypertensive patients, and the increased exposure in patients with hepatic dysfunction suggest that effective treatment of hypertensive patients with impaired hepatic function would be achieved even with the lowest dose of telmisartan available. The increased bioavailability of telmisartan suggests that lower doses of telmisartan should be considered when the drug is administered to patients with hepatic impairment.",2001.0,0,0
563,11185635,Pharmacokinetics of single-dose telmisartan 120 mg given during and between hemodialysis in subjects with severe renal insufficiency: comparison with healthy volunteers.,J Stangier; C A Su; R Brickl; H Franke,"The pharmacokinetics of oral telmisartan 120 mg evaluated in subjects with severe renal insufficiency between dialyses and during hemodialysis were compared with those observed in healthy male subjects. Between dialyses and during dialysis, the plasma concentration-time curves of subjects with renal insufficiency were lower than those of healthy subjects. The mean plasma protein binding of telmisartan was 99.5% in healthy subjects, compared with mean values of 99.1% between dialyses and 98.8% during dialysis. Only very small amounts of telmisartan were removed by dialysis. Single doses of telmisartan 120 mg were well tolerated in subjects with severe renal insufficiency when administered either between dialyses or during dialysis, and no clinically relevant changes in vital signs were detected. In conclusion, the maximum plasma concentrations of telmisartan and areas under the plasma concentration-time curves in subjects with severe renal insufficiency were markedly reduced compared with healthy subjects. The fraction of telmisartan not bound to plasma proteins was increased approximately twofold. Changes in the pharmacokinetic profile in subjects with renal insufficiency did not affect the safety profile of telmisartan, which was well tolerated in these subjects.",2001.0,0,0
564,11185637,Dose response and safety of telmisartan in patients with mild to moderate hypertension.,D H Smith; K M Matzek; J Kempthorne-Rawson,"This randomized, double-blind, double-dummy, placebo-controlled, parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension (diastolic blood pressure [DBP] 100 to 114 mmHg). After a 28-day placebo run-in period, patients were randomized to 28 days of once-daily, double-blind, double-dummy treatment with telmisartan 40, 80, or 120 mg; enalapril 20 mg; or placebo. Blood pressure (BP) was manually recorded for 12 hours after the first dose and after 24 hours at baseline (Day 0), Day 1, and Day 28 of double-blind treatment. Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations. All doses of telmisartan and enalapril significantly reduced BP compared with placebo (p < or = 0.01). Mean +/- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 +/- 1.3 mmHg and 9.8 +/- 1.3 mmHg in the telmisartan groups, 9.6 +/- 1.3 mmHg with enalapril, and 1.5 +/- 1.3 mmHg with placebo. Mean +/- SE reductions in supine systolic blood pressure (SBP) were between 10.0 +/- 2.2 mmHg and 15.5 +/- 2.2 mmHg with telmisartan versus 10.2 +/- 2.1 mmHg with enalapril; placebo increased supine SBP by 3.5 +/- 2.1 mmHg. The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril. No significant linear trend in BP reduction was evident among telmisartan doses. Reductions in SBP and DBP were maintained over the 24-hour period at Day 28. Treatment did not affect supine heart rate. Trough/peak DBP ratios were > or = 85% for all telmisartan doses versus 65% for enalapril. High interpatient variability in telmisartan plasma concentrations was observed. For example, mean +/- SD values for Cmax were 159 +/- 104 ng/mL for telmisartan 40 mg, 693 +/- 606 ng/mL for telmisartan 80 mg, and 1635 +/- 1406 ng/mL for telmisartan 120 mg. Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40, 80, and 120 mg are at the plateau region of the concentration-response curve. All active treatments were well tolerated, with tolerability profiles similar to placebo, and telmisartan did not produce any clinically relevant first-dose effects. These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan.",2001.0,0,0
565,11195609,Combination treatment with telmisartan and hydrochlorothiazide in black patients with mild to moderate hypertension.,J B McGill; P A Reilly,"Hydrochlorothiazide (HCTZ) is commonly used to treat black patients with hypertension. To avoid the metabolic disturbances associated with high-dose HCTZ, blood pressure control may be achieved by combining low doses with another antihypertensive. The study was undertaken to assess the tolerability and antihypertensive dose-response efficacy of telmisartan and HCTZ and their combination in black patients with mild to moderate hypertension (mean supine blood pressure 140/95-200/114 mmHg). Following a 4-week, single-blind, placebo run-in period, 222 black patients were randomized to once-daily treatment with one of 20 different double-blind combinations of telmisartan (0, 20, 40, 80, 160 mg) and HCTZ (0, 6.25, 12.5, 25 mg) for 8 weeks. Blood pressure was measured at baseline and after 2, 4, and 8 weeks. Telmisartan 80 mg/HCTZ 12.5 mg reduced supine trough diastolic blood pressure (DBP)--primary efficacy parameter--by 13.3 mmHg, and supine trough systolic blood pressure (SBP) by 21.5 mmHg. These reductions represented benefits of 13.7/8.7 mmHg over telmisartan 80 mg and 12.3/8.1 mmHg over HCTZ 12.5 mg (p < 0.01). Telmisartan 40 mg/HCTZ 12.5 mg reduced supine trough SBP/DBP by 14.3/10.0 mmHg, amounting to 12.3/3.3 mmHg more than telmisartan 40 mg and 5.1/4.8 mmHg more than HCTZ 12.5 mg. This reached significance for the comparisons with telmisartan 40 mg for SBP and HCTZ 12.5 mg for DBP (p<0.05). A response surface analysis and therapeutic response rates confirmed the additive antihypertensive effects of telmisartan and HCTZ. All treatments were well tolerated, with side-effect profiles comparable with placebo. Adverse events were mainly transient and of mild to moderate severity. Telmisartan 80 mg combined with HCTZ 12.5 mg is effective and well tolerated in black patients with mild to moderate hypertension, providing greater antihypertensive activity than the corresponding monotherapies.",2001.0,0,0
566,11195610,Heart rate-lowering and -regulating effects of once-daily sustained-release diltiazem.,W E Boden; M Vray; E Eschwege; D Lauret; R Scheldewaert,"Epidemiologic evidence suggests that an elevated heart rate (HR) is an adverse and independent prognostic factor in arterial hypertension and other cardiovascular diseases. Although diltiazem is characterized as an HR-lowering calcium antagonist, no studies have quantified the magnitude of HR changes in patients with angina or hypertension. The study was undertaken to explore the magnitude of proportional HR reduction at varying levels of resting HR with the sustained-release formulation of diltiazem (SR diltiazem) at the usual clinical doses of 200 or 300 mg once daily. This meta-analysis was conducted on six comparative double-blind studies including 771 patients with angina or hypertension in which SR diltiazem 200-300 mg once daily was compared either with placebo or with other agents known not to influence HR (angiotensin-converting enzyme inhibitors, diuretics). Sustained-release diltiazem decreases elevated baseline HR, with an increasing effect at higher initial rates. Multiple comparisons by baseline HR category showed a significant difference between both groups for baseline HR of 74-84 beats/min and > or = 85 beats/min (p = 0.001). Sustained-release diltiazem had no significant HR-decreasing effect on baseline HR < or =74 beats/min but appears to have a genuine regulating effect on HR: it reduces tachycardia without inducing excessive bradycardia. These findings are in contrast to those with dihydropyridine calcium antagonists, which tend to increase HR and have been associated with an adverse outcome in acute cardiovascular conditions. At the same time, there is evidence to suggest that HR-lowering calcium-channel blockers decrease cardiovascular event rates following myocardial infarction. When calcium antagonists are indicated for use in patients with angina or hypertension, an HR-lowering agent, that is, diltiazem rather than dihydropyridine, should be recommended.",2001.0,0,0
567,11195960,[Use captopril and estradiol-medroxyprogesterone in premenopausal hypertensive patients].,F J Zayas Jaime; H Ortega Clavero; A Baños Baños; F Lazo Javalera,"The premenopause period is that which precedes the actual menopause, when a decrease of the ovarian hormones is present, leading to cardiovascular diseases as arterial hypertension, acute myocardial infarction and cerebrovascular diseases. We evaluated the antihypertensive response of the estradiol-medroxyprogesterone, to reduce arterial pressure in the premenopausal patient. In a clinical trial from March 1997 to September 1998, 106 patients with systemic hypertension, symptoms hypoestrogenism and estradiol levels less than 30 pg/mL were evaluated. They were randomized at a trial in two groups with pursuit of 6 months. Group A: 53 with captopril, Group B: 53 with estradiol-medroxyprogesterone. The arterial pressure, cholesterol, triglycerides and symptoms hypoestrogenism were analyzed before and after the treatment. The statistical analysis was performed with Student T. A decrease of arterial pressure was observed with estradiol, the same as with captopril with a p < 0.05. Decrease of cholesterol and triglycerides were more significant in the estradiol group with a p < 0.05. A bigger attenuation of symptoms of the hypoestrogenism existed in the estradiol group. The antihypertensive response with estradiol was the same as with captopril in the premenopausal patient with systemic hypertension.",2001.0,0,0
568,11197588,New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure.,P Martineau; J Goulet,"To critically review the studies comparing angiotensin II (AgII) receptor antagonists with placebo or angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure (CHF). A MEDLINE search (1988 to January 2000) was used to identify pertinent literature. Additional references were also retrieved from selected articles. As most published CHF studies were performed with candesartan and losartan, these agents are the main focus of this article. However, all identified comparative clinical studies were reviewed and included, regardless of the agent used. AgII receptor antagonists inhibit the effects of AgII at its sub-type 1 receptor, independently of AgII's synthesis pathway. They present a hemodynamic profile similar to that of ACE inhibitors, without reflex neurohormonal activation. They have been shown to be at least as effective as ACE inhibitors in improving symptoms, exercise capacity, and New York Heart Association functional class in CHF patients. Although the ELITE (Evaluation of Losartan in the Elderly) trial suggested that losartan improved survival compared with captopril, this study was not designed to look at mortality. ELITE-II, an adequately powered study, showed no difference in mortality rates between patients taking captopril and those taking losartan. The combination of AgII receptor antagonists and ACE inhibitors provides additional benefit on blood pressure lowering and prevention of ventricular remodeling. AgII receptor antagonists are well tolerated, with an incidence of adverse effects similar to or lower than that of ACE inhibitors. Their lack of effect on bradykinin degradation might explain their lower incidence of cough. The data cumulated thus far in patients with CHF highlight that ACE inhibitors must remain the treatment of choice and that AgII receptor antagonists may be considered as an acceptable alternative for patients who are intolerant to ACE inhibitors.",2001.0,0,0
569,11201013,The role of ACE inhibitors in the treatment of hypertensive elderly patients.,M Gosch,"Hypertension has a high prevalence among elderly patients. Randomised trials have already demonstrated that treating healthy older persons with hypertension is highly efficacious. Nevertheless some questions have arisen. On the one hand the generalizability of these trial results, particularly for older persons with serious medical comorbidities and poor functional status, is not clear. On the other hand different antihypertensive drugs have shown to be effective. Which drug for which patient? Even data from randomised intervention trials showing that the treatment affects cardiovascular morbidity and mortality, were missing, ACE inhibitors have been used for more than a decade to treat high blood pressure. For a younger population the captopril prevention project showed no differences between ACE inhibitors and conventional antihypertensive treatment (diuretics, beta-blocker) concerning the primary endpoints (myocardial infarction, stroke and other cardiovascular death). The STOP-2 study also confirmed these results for elderly patients. When treating elderly patients one must be aware of physiological changes with age and the comorbidities. Of significance among this patient group is declining renal function. Admissions for uraemia that are related to the use of ACE inhibitors are still commonplace, although many cases are preventable by monitoring renal function, but guidelines are still missing. Concerning the comorbidities ACE inhibitors have benefits compared to other antihypertensive drugs, especially in cases of heart failure, diabetes and coronary heart disease.",2001.0,0,0
570,11204290,Quinapril treatment enhances vascular sensitivity to insulin.,R D Feldman; N D Schmidt,"Insulin-mediated vasodilation has been shown to be impaired with hypertension and aggravated by dietary sodium restriction. Whether vascular insulin resistance in this setting could be improved by antihypertensive therapy was unknown. Therefore, we determined the effect of therapy with an angiotensin-converting enzyme inhibitor, on vascular sensitivity to insulin in hypertensive subjects fed a sodium-restricted diet. The effects of 3 months of therapy with quinapril on vascular sensitivity to insulin was assessed in 11 hypertensive subjects using a randomized, placebo-controlled, double-blind design. Vascular sensitivity to insulin was assessed by determination of the insulin ED50 from dorsal hand vein linear variable differential transformer in phenylephrine-preconstricted vessels. Subjects were maintained on a 75 mmol/day sodium diet for 3 days prior to each study. Quinapril therapy significantly improved vascular sensitivity to insulin, as assessed by a decrease in the ED50 for insulin (ED50 insulin: placebo = 501 +/- 189 [muU/ min; quinapril = 276 +/- 100 muU/min P < 0.05). Isoproterenol-mediated relaxation was also enhanced by quinapril treatment (maximal isoproterenol-mediated relaxation: Placebo = 92 +/- 15% of baseline distension; Quinapril = 151 +/- 31% P < 0.05). The current study suggests the hypothesis that the ACE-inhibitor quinapril has beneficial effects on vascular function in general, and on insulin-mediated vascular responses, in particular.",2001.0,0,0
571,11204308,Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group.,A Zanchetti; G Crepaldi; M G Bond; G V Gallus; F Veglia; A Ventura; G Mancia; G Baggio; L Sampieri; P Rubba; S Collatina; E Serrotti,"The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.",2001.0,0,0
572,11212064,"Long-term renal and cardiovascular effects of antihypertensive treatment regimens based upon isradipine, perindopril and thiazide.",I Sihm; K Thygesen; L R Krusell; O Lederballe,"The aim of this study was to describe the renal function (renal hemodynamics, water and sodium handling) and its relation to cardiovascular structural changes in a population of essential hypertensive patients before and after antihypertensive treatment. Glomerular filtration rate and renal plasma flow were measured by a constant infusion technique. The reference substances used were [131I]iodohippurate (Hippuran) and [125I]iothalamate. The lithium clearance method was used for measuring renal water and sodium handling. Microalbuminuria was measured. A subcutaneous gluteal biopsy was taken and the media thickness to lumen diameter ratio of small resistance vessels was determined. Left ventricular mass index was determined by echocardiography. Thirty-seven patients with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with regimens based upon either isradipine, perindopril or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. Investigations were performed before and after 9 months of normalization of blood pressure. Renal function in untreated hypertensive patients was characterized by increased renal vascular resistance, decreased renal blood flow, normal glomerular filtration fraction and normal serum creatinine. No association was found between peripheral resistance vessel structure in subcutaneous vessels and renal hemodynamic parameters. Patients with severe left ventricular hypertrophy (left ventricular mass >360 g) had lower glomerular filtration fraction, greater renal vascular resistance, lower renal blood flow and increased microalbuminuria in comparison with patients with less pronounced cardiac changes. After 1 year of treatment, which had a profound effect on heart and vessel structure, renal hemodynamics were unchanged in patients receiving antihypertensive treatment regimens based on the ACE inhibitor perindopril or the Ca-antagonist isradipine, whereas renal plasma flow was reduced, glomerular filtration rate preserved and filtration fraction significantly increased in those treated with a regimen based on diuretics. The serum creatinine concentration was decreased in the former group, whereas it was unchanged in the latter two. Significantly detrimental effect on uric acid homeostasis was only found in patients treated with a regimen based on diuretics.",2001.0,0,0
573,11212065,Comparative study of home and office blood pressure in hypertensive patients treated with enalapril/HCTZ 20/6 mg: the ESPADA study.,C Campo; G Fernández; J González-Esteban; J Segura; L M Ruilope; ESPADA Study Group,"The introduction and generalization of 24-h ambulatory blood pressure (BP) monitoring has shown the clinical relevance of home BP. The aim of this study was to assess the validity of home-measured BP for monitoring and controlling patients with arterial hypertension while on a homogeneous treatment. An additional objective was to establish the degree of office BP control obtained. This was a prospective, longitudinal, observational and multicenter study in a cohort of 156 patients of both sexes, aged over 18 years and with essential hypertension. All of them received the fixed combination enalapril/HCTZ 20/6 mg as the only hypertensive agent for at least 4 weeks previously. Office BP was the average of three measurements. For home BP, a semi-automated device (OMRON HEM 705 CP) was used. The patients measured their BP twice a day for 2 consecutive days. The average differences between the two measuring methods were low, but significant: 3.99 mmHg for systolic BP (SBP; p < 0.05), 2.02 mmHg for diastolic BP (DBP; p < 0.05). Pearson's regression coefficient between the office and home values was highly significant (p < 0.0001) for SBP, DBP and heart rate. Home BP measurement was highly reproducible as shown by the high within-class correlation coefficient for individual measurements on the first day compared with the second: 0.88 (95% confidence interval, CI 0.82-0.92; p < 0.00001) for SBP and 0.89 for DBP (95% CI 0.83-0.93; p < 0.00001). The percentage of patients with strict office DBP and SBP control (< 140/90 mmHg) was 61.3% and with DBP control (<90 mmHg) 92%. In conclusion, in the ESPADA study, the application of home BP measurement is valid, reproducible and shows a high correlation with office BP.",2001.0,0,0
574,11212974,"Long-term effects of amlodipine and lisinopril on left ventricular mass and diastolic function in elderly, previously untreated hypertensive patients: the ELVERA trial.",W F Terpstra; J F May; A J Smit; P A de Graeff; T K Havinga; E van den Veur; F H Schuurman; B Meyboom-de Jong; H J Crijns,"To compare the effects of a calcium antagonist (amlodipine) and an angiotensin converting enzyme inhibitor (lisinopril) on left ventricular mass and diastolic function in elderly, previously untreated hypertensives. A double-blind randomized parallel group trial. Effects of amlodipine and lisinopril on left ventricular mass and diastolic function (E/A Ratio) (The ELVERA trial). Rural northern Netherlands: population screening new diagnosed hypertensive subjects. The study population comprised 166 newly diagnosed hypertensive (aged 60-75) with diastolic blood pressure between 95-115 mmHg and/or systolic blood pressure between 160-220 mmHg. Patients were randomly allocated to receive 5-10 mg amlodipine or 10-20 mg lisinopril for 2 years. Prior and after 1 and 2 years of treatment left ventricular mass, indexed by body surface (LVMI) was estimated by 2-D mode echocardiography according to Devereux with use of Penn convention. Early to atrial filling ratio (E/A) was assessed by transmitral flow. Change from baseline of LVMI and E/A ratio was evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis. Both amlodipine and lisinopril led to equivalent reduction in systolic and diastolic blood pressure. At the end of the study the amlodipine group led to LVMI decrease by 21.8 g/m < or = [95% confidence interval (CI), 18.3-25.3] and E/A ratio increased by 0.08 (95% CI, 0.05-0.11). In the lisinopril group LVMI decreased by 22.4 g/m < or = (95%, CI, 19.0-25.8) and E/A ratio increased by 0.07 (95% CI, 0.04-0.10). No statistically significant differences were found in changes in LVMI and E/A ratio between amlodipine and lisinopril. A long-term study, the ELVERA trial proves that amlodipine and lisinopril reduce left ventricular mass and improve diastolic function to a similar extent in elderly newly diagnosed hypertensive patients.",2001.0,0,1
575,11213857,A review of budesonide inhalation suspension in the treatment of pediatric asthma.,S J Szefler,"Asthma is recognized as an inflammatory disease, and inhaled corticosteroids are the mainstay of treatment in patients with persistent disease. Until recently, no inhaled corticosteroid was approved in the United States for children aged 4 years and younger, and no practical dosage form was available for infants and young children unable to use metered-dose inhalers effectively. Budesonide inhalation suspension (BIS) is a glucocorticoid with high topical and low systemic activity. In children aged 12 months-8 years, BIS improves asthma symptoms and lung function and decreases the need for breakthrough bronchodilators. Long-term follow-up studies in children concluded that BIS is well tolerated, with little or no effect on growth and hypothalamic-pituitary-adrenal axis function. Thus it is a valuable therapeutic alternative to systemic corticosteroid therapy in infants and young children.",2001.0,0,0
576,11216965,Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade.,A F van den Heuvel; P H Dunselman; T Kingma; P Verhorst; F Boomsma; W H van Gilst; D J van Veldhuisen,"We sought to study the effect of angiotensin-converting enzyme inhibition on exercise-induced myocardial ischemia. Although angiotensin-converting enzyme inhibitors have been shown to reduce ischemic events after myocardial infarction, few data are available regarding their direct anti-ischemic effects in patients with coronary artery disease. We studied 43 patients (average age 63 +/- 8 years) with exercise-induced myocardial ischemia (> or =0.1 mV ST depression, despite optimal beta blockade) and normal left ventricular function (ejection fraction >0.50). In a double-blind, placebo-controlled parallel design, patients were treated with angiotensin-converting enzyme inhibitor (enalapril 10 mg twice daily) or placebo. Assessments were made after three weeks (short-term) and 12 weeks (long-term). At baseline, the groups were well matched for all clinical characteristics. After three weeks, there was a slight but not significant increase in time to 0.1 mV ST depression in both groups (p = NS); rate pressure product (RPP = heart rate x systolic blood pressure) was also unaffected. After 12 weeks, however, time to 0.1 mV ST depression further increased in the enalapril group (5.6 +/- 1.9 min) but was unchanged in the placebo group (4.4 +/- 1.3 min; p < 0.05 between groups). In contrast, RPP was not affected. Concentrations of both atrial and brain natriuretic peptides at peak exercise tended to be lower by enalapril, if compared to placebo (p = NS). Angiotensin-converting enzyme inhibition may reduce exercise-induced myocardial ischemia in patients with normal left ventricular function. Further studies are needed to elucidate the mechanisms involved.",2001.0,0,0
577,11217909,The ACE gene polymorphism and cough threshold for capsaicin after cilazapril usage.,T Takahashi; E Yamaguchi; K Furuya; Y Kawakami,"Persistent dry cough is an occasional but clinically important adverse reaction to angiotensin I-converting enzyme (ACE) inhibitors (ACEI). Its reported incidence is variable, and why cough occurs in only certain individuals has been unclear. An insertion/deletion (I/D) polymorphism of the ACE gene is associated with serum ACE activity. We have previously shown that susceptibility to cough induced by ACEI is associated with this polymorphism such that patients with genotype II are more susceptible to cough than patients with other genotypes. In order to confirm and extend our previous observation, we conducted a randomized, placebo-controlled, double-blind, cross-over study in 10 healthy volunteers with genotype II and 10 with genotype DD. The cough threshold was determined by the concentration of inhaled capsaicin causing two or more coughs. After the usage of an ACEI, cilazapril, for 4 weeks, changes in the cough threshold in subjects with genotype II [before: 6.6+/-3.7 nM (mean+/-SD); after: 5.0+/-4.6 nM] significantly differed from those in subjects with genotype DD (before: 9.0+/-9.4 nM; after: 9.3+/-9.1 nM). Skin responses to intradermal bradykinin, which is a substrate of ACE and tussigenic, were significantly increased in subjects with genotype II (before: 1.6+/-0.6 vs. after: 2.6+/-0.5 cm2, P<0.05) but not in subjects with genotype DD (before: 1.4+/-0.5 vs. after: 1.6+/-0.6 cm2, n.s.) after usage of cilazapril. By contrast, skin responses to intradermal substance P did not change in subjects with either genotype. These findings provide further evidence of a link between ACEI-induced cough and I/D polymorphism of the ACE gene and suggest that ACEIs induce cough by modulating the tissue level of bradykinin.",2001.0,0,0
578,11219319,Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders.,S Aksöyek; N Ozer; K Aytemir; S Kes; Turkish Multicentre Verapamil and Trandolapril Study Group,"Verapamil SR (180 mg) plus trandolapril (2 mg) is a potent antihypertensive combination but the efficacy and safety of this treatment has not been studied fully in hypertensive patients with metabolic disorders. We enrolled 298 patients with mild to moderate hypertension who had at least one of the following disorders: diabetes mellitus, hypercholesterolaemia or mild renal failure. The sitting systolic pressure and diastolic blood pressures were significantly decreased after 12 weeks of treatment. Blood pressure was inadequately controlled in only 24 patients (8.8%). Progressive decreases in blood glucose, total cholesterol, low-density lipoprotein and triglyceride levels were observed during the study. There was no significant change in blood urea nitrogen, creatinine and transaminase levels (p > 0.05). There was a significant decrease in microalbuminuria levels. There was no significant change in glycosylated haemoglobin levels in diabetic patients. Verapamil SR plus trandolapril is an effective drug combination in the treatment of hypertension. It may be used safely in patients with diabetes mellitus, hyperlipidaemia and mild renal failure.",2001.0,0,0
579,11220888,[Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension].,S A Shal'nova; S Iu Martsevich; A D Deev; N P Kutishenko; S K Kukushkin; E M Manoshkina; E V Alimova; Iu E Semenova; A V Lebedev; I P Koniakhina; A V Zagrebel'nyĭ,"To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.",2001.0,0,0
580,11222470,Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study.,D Skudicky; A Bergemann; K Sliwa; G Candy; P Sareli,"We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of beta-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and beta-blockers, the addition of pentoxifylline would have an additive beneficial effect. In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5 to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from 24+/-9% to 31+/-13%, P:=0.03, in the treatment group. In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.",2001.0,0,0
581,11230280,Hypothesis: Beta-adrenergic receptor blockers and weight gain: A systematic analysis.,A M Sharma; T Pischon; S Hardt; I Kunz; F C Luft,"One of the arguments put forward against the primary use of beta-blockers has been concern about adverse metabolic effects, such as unfavorable effects on lipids or insulin sensitivity. Another less-appreciated potential drawback is their propensity to cause weight gain in some patients. In 8 evaluable prospective randomized controlled trials that lasted >/=6 months, body weight was higher in the beta-blocker than in the control group at the end of the study. The median difference in body weight was 1.2 kg (range -0.4 to 3.5 kg). A regression analysis suggested that beta-blockers were associated with an initial weight gain during the first few months. Thereafter, no further weight gain compared with controls was apparent. There was no relationship between demographic characteristics and changes in body weight. Based on these observations, the first-line use of beta-blockers in obese hypertensive patients should be reviewed. Obesity management in overweight hypertensive patients may be more difficult in the face of beta-blocker treatment.",2001.0,0,0
582,11230836,Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.,M Oosterga; A A Voors; Y M Pinto; H Buikema; J G Grandjean; J H Kingma; H J Crijns; W H van Gilst,"The QUO VADIS study was designed to explore whether 1 year of angiotensin-converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia in patients who underwent coronary artery bypass grafting (CABG). Patients (n = 149) scheduled for CABG were randomized 4 weeks before surgery. Study medication was used from randomization up to 1 year after CABG. Exercise testing was performed at randomization; the exercise test was repeated 1 year after CABG and patients underwent 48-hour Holter monitoring. Clinical ischemic events were recorded and defined as death, revascularization, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack. Baseline characteristics were similar between groups. Total exercise time increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75 seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST-segment changes at randomization; 33% of patients had ischemic ST-segment changes 1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring, the number of patients experiencing > or = 1 episodes of ischemia was equal in both groups. Treatment with quinapril significantly reduced clinical ischemic events after CABG: 15% in patients on placebo versus 4% of patients on quinapril (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term quinapril treatment significantly reduced clinical ischemic events within 1 year after CABG, although ischemia at exercise testing and Holter monitoring was unchanged.",2001.0,0,0
583,11230840,Effects of omapatrilat on systemic arterial function in patients with chronic heart failure.,D R McClean; H Ikram; A H Garlick; I G Crozier,"The mechanisms of action of omapatrilat, an agent that inhibits both neutral endopeptidase 24.11 and angiotensin-converting enzyme, on arterial function in patients with heart failure have not been previously reported. Forty-eight patients in New York Heart Association functional class II to III, left ventricular ejection fraction < or = 40%, and in sinus rhythm were randomized to a dose-ranging (2.5, 5, 10, 20, or 40 mg) study of omapatrilat for 12 weeks. Measurements were obtained at baseline and 12 weeks. Decreases in systolic (25.0 +/- 4.5 vs 2.8 +/- 5.0 mm Hg, p < 0.05) and mean arterial (13.9 +/- 3.0 vs 0.3 +/- 3.3 mm Hg, p < 0.05) pressure were seen after 12 weeks of therapy with higher doses. Ventricular-arterial coupling was improved with a dose-related decrease in augmentation index (-13.8 +/- 1.7% vs +6.1 +/- 2.1%, p < 0.01). There was no change in resting forearm blood flow between groups; however, maximum forearm vasodilator response during reactive hyperemia increased in the high-dose groups compared with the control group (+266 +/- 43% vs - 14 +/- 92%, p < 0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic peptide levels (30 +/- 11 vs -2 +/- 7 pmol/L, p < 0.01) in high-dose groups consistent with endopeptidase 24.11 inhibition. Omapatrilat shows beneficial changes in ventricular-vascular coupling and arterial function in heart failure.",2001.0,0,0
584,11230847,Are angiotensin II receptor blockers more efficacious than placebo in heart failure? Implications of ELITE-2. Evaluation of Losartan In The Elderly.,C Berry; J Norrie; J J McMurray,"In the light of the recent randomized controlled trials in chronic heart failure, it is now commonly assumed that treatment with an angiotensin-receptor blocker (ARB) is equivalent to treatment with an angiotensin-converting enzyme (ACE) inhibitor. We performed an imputed placebo analysis using previous placebo-ACE inhibitor trials and the current ACE inhibitor-ARB comparison studies, which shows that ARBs may not even be superior to placebos, let alone an ACE inhibitor.",2001.0,0,1
585,11231440,Systemic and renal effects of atrial natriuretic peptide in patients with heart failure treated with angiotensin-converting enzyme inhibitor or in acute saline solution loading.,H Tomiyama; G Watanabe; M Abe; R Okazaki; H Yoshida; N Doba,"Our purpose was to study the effects of atrial natriuretic peptide (ANP) on cardiorenal functions when it is used to manage patients with heart failure who are receiving an angiotensin-converting enzyme inhibitor (ACEi) or in acute saline solution loading. Seventeen patients with mild to moderate heart failure were entered into protocol 1 or 2. Protocol 1 was ANP (30 ng/kg/min) infused before and after treatment with ACEi (n = 9). Protocol 2 was acute saline loading with or without coadministration of ANP (n = 8). In both protocols cardiorenal hemodynamics and urinary sodium excretion were assessed before and after each intervention. Protocol 1: Although ANP infusion significantly increased urinary sodium excretion to a similar extent before and after ACEi treatment, the infusion increased the glomerular filtration rate (75 +/- 16 --> 82 +/- 15 mL/min, P <.05) and renal blood flow (390 +/- 123 --> 438 +/- 140 mL/min, P <.05) only before ACEi treatment. Protocol 2: Acute saline solution loading decreased plasma renin activity (P <.05) but did not affect ANP level. Coadministration of ANP with saline solution load enhanced the increase of urinary sodium excretion (75% +/- 34% increase) compared with the acute saline solution load alone (49% +/- 33% increase) (P <.05) but had no affect on renal hemodynamics. When ANP is used in patients with mild to moderate heart failure who are on combined ACEi treatment or in acute saline solution loading, the vasodilatory effect of ANP is blunted while the natriuretic effect of ANP is preserved. The renin-angiotensin system seems to modulate the vasodilatory effect of ANP.",2001.0,0,0
586,11232737,Management of type 2 diabetes mellitus in the elderly: special considerations.,J Rosenstock,"The principles of managing type 2 diabetes mellitus in the elderly are no different from those in younger patients, but the priorities and therapeutic strategies need to be cautiously individualised. The objectives of treatment are to improve glycaemic control in a stepwise approach that involves nonpharmacological methods including diet and exercise, and pharmacological therapy including mixtures of oral antihyperglycaemic agents alone or in combination with insulin. Although the goals of treatment may be the same for elderly and younger patients, certain aspects of type 2 diabetes in the elderly require special consideration. Treatment decisions are influenced by age and life expectancy, comorbid conditions and severity of the vascular complications. Adherence to dietary therapy, physical activity, and medication regimens may be compromised by comorbid conditions and psychosocial limitations. Drug-induced hypoglycaemia has been the main consideration and the most serious potential complication. In addition, the long term macrovascular and microvascular complications of type 2 diabetes are a source of significant morbidity and mortality. Indeed, vascular and neuropathic complications are already present at the time of diagnosis in a significant number of patients, and the impact of improved diabetes control depends on the age and life expectancy of the patient. Age-related changes in pharmacokinetics and the potential for adverse effects and drug interactions should also be considered when choosing appropriate pharmacological therapy. In general, a conservative and stepwise approach to the treatment of the elderly patient with type 2 diabetes is suggested; treatment may be initiated with monotherapy, followed by early intervention with a combination of oral agents including a sulphonylurea as a foundation insulin secretagogue in addition to a supplemental insulin sensitiser. Insulin therapy is eventually required if significant hyperglycaemia [glycosylated haemoglobin (HbA1c) >8%] persists despite oral combination therapy. Combination therapy with evening insulin and a long-acting sulphonylurea such as glimepiride is an effective strategy to improve hyperglycaemia in the elderly patient with type 2 diabetes in whom polypharmacy with oral agents is unsuccessful. In addition, such a regimen is simple to follow for the patient who may not be able to adhere to a more complicated insulin regimen. Hyperglycaemia in the elderly can be managed well with practical intervention and a straightforward treatment plan to enhance compliance. Optimal glycaemic control should be possible for every patient if treatment is individualised; however, strict glycaemic control may not be achievable in all patients or even desirable in many elderly patients.",2001.0,0,0
587,11236238,[The effect of treatment with enalapril versus losartan on levels of insulin resistance in patients with essential hypertension].,A Akel; A Wiecek; M Nowicki; F Kokot,"Insulin resistance and hyperinsulinaemia are presumed to participate in the pathogenesis of essential hypertension (EH). Insulin resistance is characterised by an impaired insulin-mediated glucose uptake. Participation of the renin-angiotensin system in the development of hyperinsulinaemia in EH patients has not been unanimously proven. The present study aimed to asses the influence of antihypertensive therapy with angiotensin converting enzyme inhibitor (ACEI, enalapril = 10 mg/day) (9 male patients) or angiotensin II AT-1 receptor blocker (A II RB = losartan 50 mg/day) (9 male patients) respectively on insulin sensitivity in patients with EH. 3-hours euglycaemic clamp test with constant infusion of insulin (50 mU/m2/min) was performed twice: before and after 8 weeks of therapy with ACEI or A II RB respectively. The control group (CG) consisted of 12 healthy males (clamp test was performed once). Serum insulin concentration (I) was estimated by radioimmunoassay. Glucose disposal rate (M-value = mg/kg/min) and tissue insulin sensitivity (M/I value = mg/kg/min per mU/l) were calculated in subjects of the CG and in patients with EH before and after antihypertensive therapy with ACEI or A II RB, respectively. In CG the M-value (7.38 +/- 0.13) and tissue insulin sensitivity (M/I = = 6.76 +/- 0.19) were significantly higher than in EH before treatment with ACEI (M-value = 5.44 +/- 0.16; M/I = = 4.57 +/- 0.18) or A II RB (M-value = 5.75 +/- 0.21; M/I = 4.77 +/- 0.31), respectively. ACEI therapy was followed by a significant increase of both M (6.82 +/- 0.25) and M/I (5.68 +/- 0.25) values. In contrast to ACEI, treatment with A II RB did not influence neither M (5.75 +/- 0.21) nor M/I (4.79 +/- 0.21) values respectively. In contrast to A II RB, ACEI shows a beneficial effect on insulin sensitivity in EH patients. This effect does not seem to be mediated by an influence on the AT-1 receptor.",2001.0,0,0
588,11239563,Vasopeptidase inhibitors: an emerging class of cardiovascular drugs.,J Bralet; J C Schwartz,,2001.0,0,0
589,11240426,Sarcoidosis: the nephrologist's view.,A Meyrier,,2001.0,0,0
590,11243277,Pharmacogenomics: a clinician's primer on emerging technologies for improved patient care.,J M Rusnak; R M Kisabeth; D P Herbert; D M McNeil,"Pharmacogenomics is a term recently coined to embody the concept of individualized and rational drug selection based on the genotype of a particular patient. Customization of drug therapy offers the potential for optimal safety and efficacy in an individual patient. Such a process contrasts current prescribing practices, which use medications shown to be safe and effective in patient populations or based on anecdotal experiences. Within patient populations, medications vary in their efficacy among individual patients. More importantly, a medication that is safe and effective in one patient may be ineffective or even harmful in another. Underlying many of these phenotypic differences are genotypic variants (polymorphisms) of key enzymes and proteins that affect the safety and efficacy of a drug in an individual patient. An understanding of these polymorphisms has the potential to enhance patient care by allowing physicians to customize the selection of medication to meet individual patient needs. Pharmacogenomics may also lead to improved compliance and shorter time to optimal disease management, thereby reducing morbidity and mortality. Significant cost savings could result from reductions in polypharmacy as well as from fewer physician encounters and hospitalizations for exacerbations of underlying illness and because of adverse drug reactions.",2001.0,0,0
591,11243303,Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group.,A Zanchetti; S Omboni,"The objective of this study was to compare the antihypertensive efficacy and tolerability of candesartan cilexetil (CC) with that of enalapril (E) and placebo (P) in hypertensives by clinic and ambulatory blood pressure (BP). The study was an Italian multicenter, randomized, double-blind, parallel group trial including 227 mild to moderate essential hypertensives (age range, 18 to 70 years). After 4 weeks of P, patients were randomized to 8 weeks of treatment with P or CC (4 mg) or E (10 mg) once daily, which was eventually increased to 8 mg and 20 mg once daily in nonresponders. At the end of each study phase, trough BP was measured by conventional sphygmomanometry and ambulatory BP was monitored over 24 h by a Spacelabs device. Analysis of 24-h BP profile included calculation of 24-h, daytime, nighttime, and hourly average values. In the 178 patients evaluable per protocol, at the end of 8 weeks of treatment, trough systolic (S) and diastolic (D) BP were similarly reduced by both active treatments (13 +/- 12 and 10 +/- 7 mm Hg for CC and 14 +/- 12 and 10 +/- 7 mm Hg for E) and significantly more by both treatments than by P (6 +/- 11 and 7 +/- 8 mm Hg, P < .01 v CC and E). In the 85 patients with valid 24-h recordings reduction in 24-h BP was again similar for the two active groups. The antihypertensive effect was still evident during h 23 and 24 after the last dose for both active treatments (8 +/- 20 v 5 +/- 18 mm Hg for SBP and 4 +/- 12 v 6 +/- 13 mm Hg for DBP, CC v E, respectively) but not for P. Heart rate was not significantly modified by either active treatment. The incidence of adverse events was greater in the E than in the CC group. Our study provides evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to 20 mg over 24 h, but is better tolerated than E.",2001.0,0,0
592,11244019,Impaired sodium excretion during mental stress in mild essential hypertension.,M P Schneider; A U Klingbeil; M P Schlaich; M R Langenfeld; R Veelken; R E Schmieder,"In hypertensive rats, environmental stress causes sodium retention by an exaggerated increase in renal sympathetic nerve activity, which is modulated by angiotensin II. We tested whether similar effects can be observed in humans. In 66 normotensive subjects (half of them with a family history of hypertension) and 36 subjects with mild essential hypertension, urinary sodium excretion and renal hemodynamics were examined at rest and during mental stress treated either with placebo or ACE inhibition in a double-blind, randomized, cross-over design. Despite a marked increase in glomerular filtration rate in response to mental stress (Deltaglomerular filtration rate, 4.3+/-7.7 mL/min in normotensives without versus 5.6+/-8.4 mL/min in normotensives with a family history versus 10.1+/-5.7 mL/min in patients with mild essential hypertension; P:<0.002), the increase in urinary sodium excretion was blunted in patients with mild essential hypertension (Deltaurinary sodium excretion, 0.12+/-0.17 mmol/min versus 0.10+/-0.14 mmol/min versus 0.05+/-0.14 mmol/min; P:<0.05). ACE inhibition corrected the natriuretic response to mental stress in subjects with mild essential hypertension (Deltaurinary sodium excretion, 0.05+/-0.14 mmol/min with placebo versus 0.13+/-0.19 mmol/min with ACE inhibition; P:<0.01); thus, after ACE inhibition, urinary sodium excretion increased similarly in all 3 groups. In conclusion, impaired sodium excretion occurs during mental stress in human essential hypertension but not in subjects with positive family history of hypertension. This abnormality in sodium handling during activation of the sympathetic nervous system appears to be mediated by angiotensin II.",2001.0,0,0
593,11244322,Intolerance to ACE-inhibitor drugs.,R Rault,,2001.0,0,0
594,11246058,Aspirin does not influence the effect of angiotensin-converting enzyme inhibition on left ventricular ejection fraction 3 months after acute myocardial infarction.,M Hurlen; T Hole; I Seljeflot; H Arnesen,"The aim of the present study was to evaluate the possible interaction between chronic aspirin therapy and angiotensin-converting enzyme inhibitor (ACE-I) on left ventricular ejection fraction (LVEF) in patients surviving an acute myocardial infarction (AMI). Forty-two patients with reduced LVEF were recruited from the warfarin aspirin reinfarction study (WARIS-II), a randomized, open study comparing enteric coated aspirin (160 mg/d), warfarin (INR 2.8--4.2) and the combination of aspirin (75 mg/d) and warfarin (INR 2.0--2.5) on mortality, reinfarction and stroke after AMI. LVEF and relevant biochemical measurements were performed before discharge and after 3 months. The overall LVEF increased during the study period from median 35 to 39% (P<0.001). There was no difference between patients on aspirin and warfarin regarding the main end point, LVEF. Furthermore, neither endothelin-1 nor ANP showed significant differences between the treatment groups. A possible interaction between ACE-I and aspirin might theoretically lead to reduced levels of renin activity in patients on aspirin, but we did not find any such inter-group difference. In conclusion, we did not find evidence of interaction between ACE-I and low-dose aspirin.",2001.0,0,0
595,11246059,"Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.",K McDonald; M Ledwidge; J Cahill; J Kelly; P Quigley; B Maurer; F Begley; M Ryder; B Travers; L Timmons; T Burke,"Despite a growing body of data demonstrating the benefits of multidisciplinary care in heart failure, persistently high rates of readmission, especially within the first month of discharge, continue to be documented. As part of an ongoing randomized study on the value of multidisciplinary care in a high risk (NYHA Class IV), elderly (mean age 69 years) heart failure population, we examined the effects of this intervention on previously high (20%) 1-month readmission rates. Unlike previous studies of this approach, both multidisciplinary (MC) and routine care (RC) populations were cared for by the cardiology service, complied with adherence to clinical stability criteria prior to discharge (100% of patients) and received at least target dose angiotensin-converting enzyme (ACE) inhibition with perindopril prior to discharge (94% of indicated patients). We analysed death and unplanned readmission for heart failure at 1 month. This early report from the first 70 patients (67% male, 71% systolic dysfunction with a mean ejection fraction of 31.0+/-6.7%) enrolled in this study demonstrates elimination of 1-month hospital readmission in both RC and MC groups. This unexpected result represents a dramatic improvement both for this patient cohort (20% 30-day readmission rate prior to enrollment reduced to 0% following the index admission in both care groups) and in comparison with available data. Critical contributors to this improvement appear to be specialist cardiology care, adherence to clinical stability criteria prior to discharge and routine use of target or high-dose ACE inhibitor therapy prior to discharge. Widespread application of this approach may have a dramatic improvement in morbidity of CHF while limiting the escalating costs of this condition.",2001.0,0,0
596,11246064,"Poles apart, but are they the same? A comparative study of Australian and Scottish patients with chronic heart failure.",S Stewart; L Blue; S Capewell; J D Horowitz; J J McMurray,"This paper reports on an international comparison of the characteristics, treatment and health outcomes of chronic heart failure (CHF) patients discharged from acute hospital care in Australia and Scotland. The baseline characteristics and treatment of 200 CHF patients recruited to a randomised study of a non-pharmacological intervention in Australia and 157 CHF patients concurrently recruited to a similar study in Scotland were compared. Subsequent health outcomes (including survival and readmission) within 3 months of discharge in those patients who received usual post-discharge care in Australia (n=100) and Scotland (n=75) were also compared. Individuals in both countries were predominantly old and frail with significant comorbidity likely to complicate treatment. Similar proportions of Australian and Scottish patients were prescribed either a 'high' (20 vs. 18%) or medium (64 vs. 66%) dose of an angiotensin-converting enzyme inhibitor. Proportionately more Australian patients were prescribed a long-acting nitrate, digoxin and/or a beta-blocker. At 3 months post-discharge, 57 of the 100 (57%: 95% CI 47--67%) Australian and 37 of the 75 (49%: 95% CI 38--61%) Scottish patients assigned to 'usual care' remained event-free (NS). Similarly, 15 vs. 12% required > or =2 unplanned readmission (NS) and 16 vs. 19% of Australian and Scottish patients, respectively, died (NS). Australian and Scottish patients accumulated a median of 0.6 vs. 0.9 days, respectively, of hospitalisation/patient/month (NS). On multivariate analysis (including country of origin), unplanned readmission or death was independently correlated with severe renal impairment (adjusted odds ratio 4.4, P<0.05), a previous hospitalisation for CHF (2.3, P<0.05), longer index hospitalisation (2.7 for >10 days, P<0.05) and greater comorbidity (1.3 for each incremental unit of the Charlson Index, P=0.05). Health outcomes among predominantly old and frail CHF patients appear to be independent of the health-care system in which the patient is managed and more likely to be dependent on the syndrome itself.",2001.0,0,0
597,11248601,A computerized method for identifying incidents associated with adverse drug events in outpatients.,B Honigman; P Light; R M Pulling; D W Bates,"In inpatients, computer monitors have been used to improve the detection of adverse drug events (ADEs). However, similar programs have not been available in outpatients. To describe an approach for detecting incidents suggesting that an ADE may have occurred in outpatients by adapting methods from inpatient computer monitoring and developing terminology searches of electronic medical records. One year of information from the outpatient electronic medical record (EMR) at one hospital and its clinics was reviewed. Altogether, 23064 patients and 88514 visits were identified. Patient demographics, medical problem lists, ICD-9 claims, patient allergies, medication history and all clinic visit notes were extracted and merged. We then searched for incidents suggesting that an ADE might be present using four methods: ICD-9 claims, new allergies, computer rules linking laboratory data to known medication exposures, and a medical terminology lexicon (M2D2). In this report, we describe how these search methods were developed to allow for ADE identification. The ability to carry out such quality-related work is an example of the benefits of the outpatient EMR that may not be apparent to those institutions considering adopting it.",2001.0,0,0
598,11248763,Heart failure therapy at the turn of the century.,S Goldstein,"Major changes in the treatment of heart failure have occurred in the last fifty years that have had a dramatic effect on its morbidity and mortality. Over two hundred years have passed since the demonstration of the benefit of digitalis in heart failure to the development of potent loop diuretics. The observation that vasodilators could improve both cardiac function and mortality led to the investigation of the Angiotensin Converting Enzyme Inhibitors (ACEI). Although these agents had significant vasodilator properties, their major benefit appears to be related to their ability to effect remodeling of the failing left ventricle. The most recent randomized clinical trials demonstrate that Beta Adrenergic Blocking agents can provide an incremental effect on both mortality and morbidity when added to therapy with ACEI. Although these agents have improved the outlook for the heart failure patient, they have had very little effect on the improvement of left ventricular function. Future research must be directed at methods to deal with this issue by either changing the contractile properties of the cardiomyocyte by pharmacologic or electrical therapy or by transplanting functional cells that can increase the number of functioning contractile units.",2001.0,0,0
599,11249891,"Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators.","R A Kloner; M Weinberger; J L Pool; S G Chrysant; R Prasad; S M Harris; T M Zyczynski; N K Leidy; E L Michelson; Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators","The comparative antihypertensive efficacy and tolerability of the angiotensin II receptor blocker candesartan cilexetil and the calcium channel blocker amlodipine were evaluated in an 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study in 251 adult patients (45% women, 16% black) with mild hypertension (stage 1). Following a 4- to 5-week placebo run-in period, patients with sitting diastolic blood pressure (BP) of 90 to 99 mm Hg received candesartan cilexetil 16 mg (n = 123) or amlodipine 5 mg (n = 128) once daily. After 4 weeks of double-blind treatment, patients were uptitrated to candesartan cilexetil 32 mg or amlodipine 10 mg once daily. There were no significant differences between the candesartan cilexetil and amlodipine regimens for reducing BP; mean systolic BP/diastolic BP reductions were -15.2/-10.2 mm Hg versus -15.4/-11.3 mm Hg, respectively (p = 0.88/0.25). Overall, 79% of patients on candesartan cilexetil and 87% of those on amlodipine were controlled (diastolic BP <90 mm Hg). A total of 3.3% of patients on candesartan cilexetil discontinued treatment, compared with 9.4% of patients on amlodipine, including 2.4% versus 4.7% for adverse events and 0% versus 1.6% for peripheral edema, respectively. Peripheral edema, the prespecified primary tolerability end point, occurred with significantly greater frequency in patients on amlodipine (22.1%; mild 8.7%, moderate 11.8%, severe 1.6%) versus patients on candesartan cilexetil (8.9%; mild 8.1%, moderate 0.8%) (p = 0.005). Candesartan cilexetil and amlodipine are both highly effective in controlling BP in patients with mild hypertension. Candesartan cilexetil offers a significant tolerability advantage with respect to less risk of developing peripheral edema.",2001.0,0,0
600,11249900,"Comparison of baseline data, initial course, and management: losartan versus captopril following acute myocardial infarction (The OPTIMAAL Trial). OPTIMAAL Trial Steering Committee and Investigators. Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan.",K Dickstein; J Kjekshus; OPTIMAAL Trial Steering Committee and Investigators. Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan,"The OPTIMAAL study was a multicenter, double-blind, randomized, parallel, trial in high-risk patients who were treated early after acute myocardial infarction that compared treatment with an angiotensin-converting enzyme inhibitor (captopril) and a selective angiotensin II antagonist (losartan) on survival and morbidity. A total of 5,477 patients with heart failure during the acute phase or with a new Q-wave anterior infarction or reinfarction were recruited. This study describes the baseline data and initial course of the cohort and compares these data and patient management across countries.",2001.0,0,0
601,11255520,Recovery of ventricular function after myocardial infarction in the reperfusion era: the healing and early afterload reducing therapy study.,S D Solomon; R J Glynn; S Greaves; U Ajani; J L Rouleau; F Menapace; J M Arnold; C Hennekens; M A Pfeffer,"Patients with reduced left ventricular function and ventricular enlargement after myocardial infarction are at significantly greater risk for congestive heart failure and death. Nevertheless, recovery of ventricular function occurs in a significant proportion of patients after myocardial infarction, and modern reperfusion strategies have been associated with increased recovery of function. To determine the extent and predictors of recovery of ventricular function after anterior Q-wave myocardial infarction in the reperfusion era. Subgroup analysis of the Healing and Early Afterload Reducing Therapy study. 35 medical centers in the United States and Canada. 352 patients with Q-wave anterior myocardial infarction. Placebo for 14 days, followed by full-dose (10 mg) ramipril until day 90; low-dose (0.625 mg) ramipril for 90 days; or full-dose ramipril for 90 days. All patients underwent reperfusion therapy. Echocardiography was performed on day 1 (before randomization), day 14, and day 90 after myocardial infarction. Left ventricular volume and ejection fraction were measured and wall-motion analyses were performed at all three time points in 249 patients and at baseline in an additional 12 patients who died during follow-up. Echocardiographic and nonechocardiographic predictors of ventricular recovery were examined. By day 90, 55 of 252 (22%) patients who had abnormal ejection fraction and wall-motion abnormalities on day 1 demonstrated complete recovery of function (ejection fraction in the normal range and infarct segment length of 0%), and an additional 36% (91 of 252 patients) demonstrated partial recovery of function. At 90 days, 53% (132 of 249) of patients had greater than 5% improvement in ejection fraction, whereas only 16% (39 of 249) had a decrease in ejection fraction of more than 5%. The majority of functional improvement occurred by day 14 after infarction. Of various clinical and echocardiographic measures obtained on day 1, peak creatine kinase level was the strongest independent predictor of subsequent recovery of ventricular function in multivariate analysis. Each 100-unit increase in peak creatine kinase was associated with a 4.3% decreased odds of recovery (P < 0.001) after adjustment for ejection fraction on day 1, extent of akinesis or dyskinesis, treatment regimen, Killip class, age, and sex. Significant myocardial stunning with subsequent improvement of ventricular function occurred in the majority of patients after Q-wave anterior myocardial infarction. A lower peak level of creatine kinase, an estimate of the extent of necrosis, is independently predictive of recovery of function. Early functional assessment (day 1 after acute myocardial infarction) had limited ability to predict recovery of ventricular function.",2001.0,0,0
602,11256540,Additional beneficial effects of canrenoate in patients with anterior myocardial infarction on ACE-inhibitor treatment. A pilot study.,P Di Pasquale; S Cannizzaro; A Giubilato; M G Vitrano; A Scandurra; F Giambanco; G Saccone; F M Sarullo; S Paterna,"Recent evidence suggests that, via the mineralocorticoid receptors present in cardiovascular tissues, aldosterone exerts profibrotic effects, and that partial aldosterone escape occurs during ACE-inhibitor treatment. A double-blind, randomized study was performed in order to evaluate the feasibility, tolerability, and the effects of the administration of 25 mg/day of canrenoate plus captopril versus captopril alone to patients with anterior acute myocardial infarction (AMI) unsuitable for or not receiving thrombolytic treatment and to patients in whom such treatment resulted or did not result in reperfusion. One hundred eighty-seven patients with anterior AMI were included in the present study. In all cases serum creatinine concentrations and serum K concentrations were < 2.0 mg/dl and < 5.5 mmol/l respectively. The patients were randomized in two groups: the canrenoate group included 94 patients who received captopril and 25 mg i.v. of canrenoate (1 mg/hour for the first 72 hours and then orally 25 mg/day) whereas the placebo group (93 patients) received captopril and placebo. On admission and on days 10, 90 and 180 all patients underwent echocardiography in order to determine the end-systolic volume (ESV), the ejection fraction (EF), the end-diastolic diameter, the E/A ratio, the E deceleration time as well as the isovolumetric relaxation time (IVRT) and the E and A peak velocities. Unreperfused patients did not show patency of the infarct-related artery whereas in reperfused patients this vessel was patent (7-10 days after AMI). The two groups were similar in age, sex, incidence of diabetes, smoking habits, hypertension, creatine kinase enzymatic peak, adjuvant therapy, baseline EF, ESV, and incidence of coronary artery bypass grafting/coronary angioplasty. Following 10 days of treatment (canrenoate group), only 9 patients presented with serum K and creatinine concentrations respectively > 5.5 mmol/l and > 2.0 mg/dl. Among those patients receiving canrenoate, the mitral E/A ratio was higher compared to the placebo group (p = 0.001) whereas the ESV was significantly reduced (p < 0.05). The deceleration time for reperfused patients receiving canrenoate was higher than that observed for reperfused patients in the placebo group. The intragroup EF was significantly increased (p = 0.042). Compared to the placebo group, the IVRT was significantly higher for unreperfused patients receiving canrenoate than in the placebo group (p = 0.001). Serum creatinine, blood urea and K levels as well as the incidence and extent of vessel disease were similar for both groups. No side effects were observed during the study period. Our data suggest that the combination of captopril plus canrenoate is feasible for the initial treatment of patients presenting with AMI. Besides, compared to captopril alone it is more efficacious in improving the E/A ratio, the ESV, the EF, and the IVRT.",2001.0,0,0
603,11258142,Physician perceptions of a national formulary.,P A Glassman; C B Good; M E Kelley; M Bradley; M Valentino; J Ogden; K W Kizer,"To assess the perceptions of US Department of Veterans Affairs (VA) physicians regarding effects of a National Formulary (NF) on patient care, access to drugs, physician workload, and resident training approximately 1 year after it was implemented. Cross-sectional survey. A questionnaire was sent to attending physicians working within the VA healthcare system. Participants included general internists (n = 2824), neurologists (n = 238), psychiatrists (n = 997), general surgeons (n = 429), and urologists (n = 152). The response rate was 45%. Most physicians (63%) thought that they could prescribe needed drugs; 65% agreed that patients could obtain needed nonformulary drugs. One third disagreed that access to prescription pharmaceuticals had increased; 29% stated the NF impinged on providing quality care to their own patients, and 21% thought it did so to patients from other VA facilities. Thirty eight percent of physicians perceived the NF to be more restrictive than private sector formularies; 16% thought that the NF diminished the ability to train residents for managed care. Forty percent thought that the NF added to workload. Generalists more often perceived that the NF improved their ability to provide care compared with neurologists (27% vs 18%, P = .046), psychiatrists (27% vs 22%, P = .027), and internal medicine subspecialists (27% vs 18%, P = .001). Physicians with more clinic time were more likely to perceive that the NF increased workload. Although differences of opinions among physicians were noted, most responding VA physicians did not perceive that the NF adversely affected patient care, access to pharmaceuticals, physician workload, or resident training.",2001.0,0,0
604,11258145,Renal effects of angiotensin-converting enzyme inhibitors that result in cost savings and improved patient outcomes.,A L Swislocki; D Siegel,"In some patients with renal disease, use of angiotensin-converting enzyme (ACE) inhibitors is thought to improve renal function, whereas in others their use leads to worsening. Many questions remain about the categories of patients that benefit from ACE inhibitor use. To clarify the use of ACE inhibitors in patients with renal disease. A literature review focusing on various renal diseases, ACE inhibitors, and criteria of cost effectiveness was performed. Almost 100 clinical studies were reviewed. Treatment with ACE inhibitors seems to have beneficial effects in type 1 and type 2 diabetes mellitus with nephropathy, AIDS nephropathy, and other nondiabetic renal diseases. Use of these agents in these diseases decreases the progression of renal disease and the need for dialysis, resulting in potential cost savings and improved quality of life. Data supporting goal blood pressures indicate the need to aggressively decrease this risk factor. Use of ACE inhibitors is hazardous in bilateral renal artery stenosis, particularly with volume depletion, but may be valuable in patients with unilateral stenosis. In African Americans, ACE inhibitor treatment is likely to be of benefit, although required doses may be higher than for whites, and caution must be exercised in certain situations. The potential efficacy of angiotensin receptor blockers and other new drugs that affect the renin-angiotensin system is assessed. Use of ACE inhibitors has benefit in renal disease states characterized by increased glomerular perfusion pressure, their use in other renal disease states, particularly those characterized by reduced glomerular perfusion pressure, may be risky. The benefits conferred by ACE inhibitor therapy are so dramatic in terms of cost savings and improved quality of life that their use in certain clinical situations should be strongly encouraged in managed care and other practice settings.",2001.0,0,0
605,11259147,"Specialty-related differences in the epidemiology, clinical profile, management and outcome of patients hospitalized for heart failure; the OSCUR study. Oucome dello Scompenso Cardiaco in relazione all'Utilizzo delle Risore.",P Bellotti; L P Badano; N Acquarone; R Griffo; G Lo Pinto; A P Maggioni; C Mattiauda; G Menardo; P Mombelloni; OSCUR Investigators,"This study was designed to identify potential specialty-related differences in the epidemiology, clinical profile, management and outcome of patients hospitalized for congestive heart failure in departments of cardiology or internal medicine. From 1 July to 31 December 1998, we prospectively recorded epidemiological and clinical data from patients with congestive heart failure consecutively admitted to 11 departments of cardiology and 12 departments of internal medicine in Liguria, a northern area of Italy. The overall study population included 749 patients; 22% were treated by cardiologists and 78% by internists (P<0.0001). Patients managed by cardiologists were more likely to undergo echocardiography (92% vs 37%), Holter monitoring (25% vs 3%) and exercise stress testing (20% vs 0.5%) than those managed by internists (P=0.001). At discharge, patients treated by cardiologists were more likely to be prescribed beta-blockers (41% to 4%) and ACE inhibitors (100% to 74%) than those treated by internists (P<0.0001), and the latter medication at higher dosages by cardiologists than internists. In addition, patients followed by cardiologists were younger (70+/-9 to 79+/-1 years;P<0.0001), more likely to be male (61% to 50%;P=0.011) and to have coronary artery disease (57% to 45%;P<0.006) than those followed by internists. Conversely, patients followed by internists were more likely to have diabetes, chronic obstructive pulmonary disease, atrial fibrillation and renal failure (P<0.03). In the overall study population, 53 patients (7%) died during hospitalization. Patients treated by cardiologists had a mortality not significantly different from that of patients treated by internists (10% and 6%, respectively;P=0.067), although congestive heart failure was more severe on admission in patients treated by cardiologists. Cardiologists follow published guidelines for congestive heart failure more strictly than internists, but treat a smaller number of patients who are younger, have more severe congestive heart failure and fewer co-morbidities than those managed by internists.",2001.0,0,0
606,11259720,Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay.,S Cazeau; C Leclercq; T Lavergne; S Walker; C Varma; C Linde; S Garrigue; L Kappenberger; G A Haywood; M Santini; C Bailleul; J C Daubert; Multisite Stimulation in Cardiomyopathies (MUSTIC) Study Investigators,"One third of patients with chronic heart failure have electrocardiographic evidence of a major intraventricular conduction delay, which may worsen left ventricular systolic dysfunction through asynchronous ventricular contraction. Uncontrolled studies suggest that multisite biventricular pacing improves hemodynamics and well-being by reducing ventricular asynchrony. We assessed the clinical efficacy and safety of this new therapy. Sixty-seven patients with severe heart failure (New York Heart Association class III) due to chronic left ventricular systolic dysfunction, with normal sinus rhythm and a duration of the QRS interval of more than 150 msec, received transvenous atriobiventricular pacemakers (with leads in one atrium and each ventricle). This single-blind, randomized, controlled crossover study compared the responses of the patients during two periods: a three-month period of inactive pacing (ventricular inhibited pacing at a basic rate of 40 bpm) and a three-month period of active (atriobiventricular) pacing. The primary end point was the distance walked in six minutes; the secondary end points were the quality of life as measured by questionnaire, peak oxygen consumption, hospitalizations related to heart failure, the patients' treatment preference (active vs. inactive pacing), and the mortality rate. Nine patients were withdrawn from the study before randomization, and 10 failed to complete both study periods. Thus, 48 patients completed both phases of the study. The mean distance walked in six minutes was 22 percent greater with active pacing (399+/-100 m vs. 326+/-134 m, P<0.001), the quality-of-life score improved by 32 percent (P<0.001), peak oxygen uptake increased by 8 percent (P<0.03), hospitalizations were decreased by two thirds (P<0.05), and active pacing was preferred by 85 percent of the patients (P<0.001). Although it is technically complex, atriobiventricular pacing significantly improves exercise tolerance and quality of life in patients with chronic heart failure and intraventricular conduction delay.",2001.0,0,0
607,11262534,Lack of agreement between left ventricular volumes and ejection fraction determined by two-dimensional echocardiography and contrast cineangiography in postinfarction patients.,Y Bernard; N Meneveau; S Boucher; D Magnin; T Anguenot; F Schiele; A Vuillemenot; J P Bassand,"To assess the agreement between left ventricular (LV) volumes and ejection fraction (EF) determined by two-dimensional echocardiography (2-D echo) and by cineangiography in postinfarction patients. LV end-diastolic and end-systolic volumes indexed (EDVI and ESVI) to body surface area as well as EF were determined by both methods in all patients. Multicenter trial conducted in five university hospitals. 63 patients, 61 male, two female, mean age 55.5 +/- 10.4 years, suffering from a recent myocardial infarction. Eighty-one pairs of measurements were available. The results of biplane 2-D echo measures, using apical four-chamber (4C) and two-chamber (2C) views were compared to those of a 30 degrees right anterior oblique cineangiography projection, using either the apical method of discs or the area-length 2-D echo method. Moreover, eyeball EF was estimated at 2-D echo and cineangiography, and was compared to the conventional methods. The agreement between results was assessed by the Bland and Altman method. The agreement between 2-D echo and cineangiography results was poor. Mean differences (MD) were -21.8 (EDVI, ml/m(2)), -9.5 (ESVI, ml/m(2)), and -0.9 (EF, %), respectively for 2-D echo method of discs versus cineangiography, and -23.2, -9.3, and -5.7 for area-length 2-D echo versus cineangiography. For EF (%), MD was -3.6 for eyeball cineangiography versus cineangiography, -1.3 for eyeball 2-D echo versus method of discs, and +0.30 for eyeball 2-D echo versus area-length 2-D echo, respectively. Two-dimensional echo is likely to underestimate LV volumes compared to cineangiography, especially for largest volumes. Even for EF, discrepancies are large, with a lack of agreement of 21%-25% between conventional methods, but agreement is better between eyeball EF and usual methods. Even with modern echocardiographic devices, agreement between 2-D echo and cineangiography-derived LV volumes and EF remains moderate, and both methods must not be considered interchangeable in clinical practice.",2001.0,0,0
608,11263853,Management of asymptomatic left ventricular dysfunction.,G J Haas,Asymptomatic left ventricular dysfunction should be treated as an early stage on the continuum that is chronic heart failure. The author presents the clinical trial data on which current management with angiotensin-converting enzyme inhibitors and beta-blockers is based. Issues surrounding screening are also discussed.,2001.0,0,0
609,11265507,Pharmacologic considerations in the neonate with congenital heart disease.,I L Calligaro; C A Burman,"Advances in knowledge about the developing cardiovascular system and compensatory physiologic changes that occur in infants with congenital heart disease have led to new approaches in the management of cardiac failure and arrhythmias. Information about the pharmacologic effects, pharmacokinetics, and pharmacodynamics of newer agents used in the management of congenital heart disease have led to more appropriate use of these medications to prolong survival and improve outcomes.",2001.0,0,0
610,11267615,"Angiotensin-converting enzyme inhibitors reduce hemoglobin concentrations, hematocrit, and serum erythropoietin levels in renal transplant recipients without posttransplant erythrocytosis.",D Montanaro; M Gropuzzo; P Tulissi; G Boscutti; A Risaliti; U Baccarani; G Mioni,,2001.0,0,0
611,11268233,"Adverse drug effects, compliance, and initial doses of antihypertensive drugs recommended by the Joint National Committee vs the Physicians' Desk Reference.",J S Cohen,"Compliance problems are common causes of the inadequate treatment of hypertension, with 16% to 50% of patients quitting treatment within 1 year. Dose-related adverse drug events (ADEs) frequently cause compliance problems, and many ADEs occur with the initial doses of antihypertensive drugs. Thus, it is an established tenet to initiate antihypertensive therapy at low doses to avoid ADEs that diminish patients' quality of life and reduce compliance. However, what are the lowest effective doses of antihypertensive drugs? To compare the initial doses recommended in the Physicians' Desk Reference (PDR) with those recommended by the Sixth Report of the Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Review of the latest JNC VI report (1997) and the 1999 and 2000 editions of the PDR and the medical literature. The JNC VI recommends substantially lower initial doses for 23 (58%) of 40 drugs, compared with the PDR. In addition, for 37 (82%) of 45 drugs, PDR guidelines do not suggest lower initial doses for old or frail patients than for younger adults. Although the PDR is the drug reference most used by physicians, it does not reflect the lowest initial doses that are recommended by the JNC VI for many of the most prescribed antihypertensive drugs. Because avoidance of ADEs is essential to maintaining compliance with antihypertensive therapy, and because many antihypertensive ADEs are dose related, physicians must know the very lowest, effective, least ADE-prone doses. Patients and physicians would benefit by establishing mechanisms to make this information readily available to all practicing physicians.",2001.0,0,0
612,11273109,Exercise-induced ventricular arrhythmias in congestive heart failure and role of ACE inhibitors.,P K Hasija; S D Karloopia; B N Shahi; S S Chauhan,"Ventricular arrhythmias are considered to be related to left ventricular (LV) dysfunction. ACE inhibitors though improve LV function their beneficial role on exercise-induced ventricular arrhythmias is not established. To study the effects of ACE inhibitors on exercise capacity vis-a-vis their role on exercise-induced ventricular arrhythmias, 25 patients of congestive heart failure (CHF) of various etiologies in NYHA Class II and III were subjected to a prospective randomised controlled trial. The control group comprising of 12 patients received conventional treatment (digitalis and diuretics) and the test group was given enalapril/captopril in addition as tolerated. They were followed up for 3 months. Exercise testing on treadmill and monitoring of clinical and biochemical parameters were done at the beginning and end of study in all cases. Ventricular arrhythmias observed during exercise and post-exercise for 10 minutes was analysed using Lown's grading for frequency and severity of ventricular arrhythmia. The mean exercise duration showed significant improvement on ACE inhibitor as compared to the control group (p < 0.05) however there was no significant change in the grades of arrhythmia. Serum electrolytes and other bio-chemical parameter were within normal range. It is concluded that effect of ACE inhibitor on improving functional capacity in CHF is independent of it's any effect on exercise-induced ventricular arrhythmias.",2001.0,0,0
613,11273142,Evaluation of efficacy and safety of losartan potassium in the treatment of mild to moderate hypertension as compared to enalapril maleate.,J C Shobha; T R Kumar; B S Raju; S Kamath; M Rao; ; A Babu; J Bhaduri,"To study the effect of losartan potassium in the treatment of mild to moderate hypertension and to compare its efficacy and adverse effect profile with enalaparil maleate. One hundred and forty five patients with mild to moderate essential hypertension were enrolled in this randomized, double blind, controlled, parallel and multicentric study. Seventy two patients received losartan potassium 50 mg and seventy three received enalapril maleate 5 mg. Losartan potassium reduced the DBP to < 90 mm Hg in 59% of the patients at the end of 8 weeks compared to 45% in the enalapril maleate group. DBP was reduced by 10 or > than 10 mm Hg in 89% of the patients with losartan as compared to the baseline whereas it was 80% in the enalapril group. Percentage of side effects seen in losartan and enalapril groups were 12 and 22 respectively. Losartan potassium is an efficacious antihypertensive agent in mild to moderate hypertension. It also has fewer side effects when compared to enalapril maleate.",2001.0,0,0
614,11273316,Effect of enalapril therapy on ventilatory pulmonary function tests in hypertensive patients.,M Sabir; V K Tinna; A Rastogi; R P Agarwal,"Fifty newly diagnosed nonsmoker patients suffering from mild to moderate hypertension (diastolic BP 90 to 114 mmHg), randomly selected and not having respiratory or other systemic diseases which may affect pulmonary functions were subjected to thorough interrogation and clinical examination. Twenty five normal age and sex matched healthy volunteers served as control. All patients and controls were subjected to ventilatory pulmonary function tests (VPFT), done by computerized spirometer. Hypertensive patients were put on oral enalapril, doses were titrated and maintained on 2.5 to 10 mg once daily. Twenty percent of the total hypertensive patients reported mild to moderate dry cough and was more frequently observed among females (27%). Significant decline was observed in MEF 50% and MEF 25% of vital capacity values (p 0.0204 and 0.0001) after 10 days of enalapril therapy. These two VPFT parameters showed significantly higher decline among patients who developed cough as compared to patients who did not develop cough. Decline in VPFT parameters were directly related to doses of enalapril.",2001.0,0,0
615,11273348,An open clinical trial of benazepril--a new ACE inhibitor in mild-moderate hypertension.,N D Karnik; Y K Oza; S P Sane; R Kaushik; A D Bhatt; K P Chawla; A B Vaidya; V H Yajnik; R C Khokhani,"Benazepril hydrochloride, a new non-sulfhydryl ACE inhibitor (ACEI) was studied in a titrated dose of 10 mg-20 mg once a day for 6 weeks in 42 mild to moderate adult hypertensive patients with sitting diastolic blood pressure (SDBP) 95-114 mm Hg. The pre-drug SDBP(mean +/- SE) of 102.5 +/- 0.8 mm Hg showed a significant reduction to 87.5 +/- 0.93 mm Hg at the end of treatment. BP was controlled (SDBP < or = 90 mm Hg) in 34 (81%) patients and a drop of at least 10 mm Hg from the pre-treatment SDBP value was noted in 34 (81%) patients. Common adverse reaction was cough in 8(19%) patients. Clinically significant changes in laboratory evaluations were not seen in any patient. Study showed that benazepril in a dose range of 10 to 20 mg per day is an effective agent for treatment of mild to moderate hypertension.",2001.0,0,0
616,11279324,Is the tissue affinity of ACE inhibitors of relevance for the remodeling of the left ventricular wall following myocardial infarction? Estimations with cine magnetic resonance imaging.,M Konermann; B M Sanner; C Altmann; F Laschewski; B Rawert; H J Trappe,"Angiotensin-converting enzyme (ACE) inhibitors have been shown to be of value in the treatment of postinfarction remodeling. The question whether substances with a greater tissue affinity are associated with advantages for the acute and the chronic course is, however, still unclear. The aim of the present study was to investigate the influence of ACE inhibitors with differing tissue affinities on the remodeling of the left ventricular wall in patients recovering from myocardial infarction. 52 patients (17 women, aged 38-73 years) suffering their first acute myocardial infarction were randomized to receive a daily dose of either 25-75 mg captopril or 10-20 mg fosinopril, beginning on the 7th postinfarction day. 28 patients had an anterior wall infarction and 24 patients an inferior wall infarction. The size of the infarct was determined using the creatine kinase integral method. 50 patients were investigated by cine magnetic resonance imaging 1 and 26 weeks after the infarction. The following parameters were determined: infarct weight and diastolic diameter of the infarcted zone, systolic wall stress, muscle mass, diastolic and systolic diameters, systolic wall thickening, and motility of the noninfarcted myocardium. The infarct weight increased under captopril by 5.7% (p < 0.05) and under fosinopril by 6.1% (p < 0.05). The diastolic diameter of the infarcted zone decreased by 12% under captopril (p < 0.001) and by 11% under fosinopril (p < 0.001). The systolic wall thickness increased by 12.1% (p < 0.001) and the muscle mass by 12.7% (p < 0.001) under captopril and by 15.4% (p < 0.001) and 9.6% (p < 0.01), respectively, under fosinopril. Under captopril, the diastolic diameter increased by 2.3% (p < 0.05) and the systolic diameter by 17.8% (p < 0.01) and under fosinopril by 2.8% (n.s.) and 17.5% (p < 0.001), respectively. The systolic wall thickening increased by 73.9% under captopril (p < 0.001) and by 129.4% under fosinopril (p < 0.001). The motility decreased by 13.8% (p < 0.05) under captopril and by 6.0% (n.s.) under fosinopril. For all parameters, the results seen in anterior wall infarction were appreciably poorer than those seen in inferior wall infarction. All the differences between captopril and fosinopril were not significant. Captopril and fosinopril show no major differences in their influence on left ventricular wall remodeling following myocardial infarction. On the basis of the present results, the tissue affinity of an ACE inhibitor does not appear to be of a significant relevance for postinfarction treatment.",2001.0,0,0
617,11281082,Just the berries. Management of heart failure.,L Ruggles,,2001.0,0,0
618,11281234,"Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension.",J A Diamond; L R Krakoff; A Goldman; N Coplan; A Gharavi; K Martin; R Goldsmith; M J Henzlova; J Machac; R A Phillips,"Dihydropyridine and nondihydropyridine calcium channel blockers (CCB) differ in pharmacologic characteristics. Few clinical studies distinguish effects of CCB as monotherapy. We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension. Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were randomly assigned to either nifedipine-GITS or verapamil-SR. Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks. Clinic blood pressure (BP), 24-h ambulatory BP, exercise BP, left ventricular mass, systolic and diastolic function by echocardiography, and coronary flow reserve by split-dose thallium-201 imaging with adenosine were assessed at baseline, end of titration, 3 months and 6 months of treatment. Plasma renin activity, atrial natriuretic peptide, norepinephrine, and epinephrine were assayed. Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index. Compared to nifedipine-GITS, verapamil-SR produced a significantly lower resting and peak exercise heart rate. Nifedipine-GITS elicited a lower peak exercise systolic BP. At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels, no longer apparent by 6 months. Plasma norepinephrine was lower with verapamil-SR, also at end titration and at 3 months, but not at 6 months. Plasma epinephrine and plasma renin activity were unchanged by either drug. There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments. Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension. Differences in their hemodynamic profiles and neurohormonal responses are consistent with preclinical pharmacologic characteristics. The clinical implications of their similarities and differences remain to be fully evaluated in outcome studies.",2001.0,0,0
619,11281235,"ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension.",T O Morgan; A I Anderson; R J MacInnis,"The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; beta-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on beta-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP (P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on beta-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. beta-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.",2001.0,0,0
620,11281338,Verapamil versus amlodipine in proteinuric non-diabetic nephropathies treated with trandolapril (VVANNTT study): design of a prospective randomized multicenter trial.,R Boero; C Rollino; C Massara; G Vagelli; M Gonella; I M Berto; P Bajardi; P Perosa; U Malcangi; M P Giorgi; P M Ghezzi; M Borzumati; A M Baroni; C Cogno; G Triolo; D Angelini; A Antonelli; F Quarello,"Angiotensin converting enzyme inhibitors (ACEI) are the most effective antiproteinuric agents and should be used as first-line drugs in both diabetic and non-diabetic proteinuric nephropathies. The role of calcium channel blockers (CCB) is much more controversial. In diabetic patients verapamil and diltiazem seem more effective than dihydropyridines in reducing urinary protein excretion, and have additive effects with ACEI, but little is available on chronic treatment of non-diabetic nephropathies for non-dihydropyridine CCBs. To test whether the combination of verapamil 180 mg or amlodipine 5 mg with trandolapril 2 mg reduces urinary protein excretion more than trandolapril 2 mg alone, we planned a prospective, randomized, double-blind, multicenter trial. The secondary aims are to evaluate the effects of both treatments on the selectivity of proteinuria and check their safety. Consecutive patients aged between 18 and 70 years with non-diabetic proteinuria > or =2 g/24 h and plasma creatinine < 3 mg/dl or creatinine clearance > or = 20 ml/min are asked to participate. After a four-week run-in during which previous antihypertensive therapy is withdrawn, a single dose of trandolapril 2 mg is given once a day in open conditions for four weeks. At the end of this period patients are randomly assigned to receive once a day, in a double blind fashion, either trandolapril 2 mg and verapamil 180 mg [plus a placebo], or trandolapril 2 mg plus amlodipine 5 mg. They are monitored after one, two, five and eight months.",2001.0,0,0
621,11281339,Long term effect of nifedipine GITS and lisinopril on subclinical organ damage in patients with essential hypertension.,R Pontremoli; F Viazzi; M Ravera; G Leoncini; V Berruti; G P Bezante; M Del Sette; G Deferrari,"Preventing subclinical organ damage is currently a major issue in the management of patients with essential hypertension. Antihypertensive drugs which act through different pathophysiological mechanisms might confer specific target organ protection beyond what is already provided by their blood pressure lowering effect. Thirty-one patients with essential hypertension were randomized to receive long-term treatment with either a calcium channel blocker (nifedipine GITS, 90 mg/day) or an ACE-inhibitor (lisinopril, 20 mg/day). Blood pressure, left ventricular mass, carotid wall thickness and timed urinary albumin excretion were measured at baseline and over the course of 24 months of treatment. Both regimens significantly lowered mean blood pressure over the 24 months (from 124+/-2 to 103+/-2 mmHg in the lisinopril group and from 122+/-2 to 104+/-1 in the nifedipine group). Overall, end-organ damage improved with persistent blood pressure control. However, the two treatments had different specific effects. Lisinopril induced a more pronounced reduction of the left ventricular mass index (from 56+/-3 to 52+/-2 g/m2.7, P< 0.05) and urinary albumin excretion (from 34+/-15 to 9+/-2 microg/min, P< 0.01), while nifedipine achieved a greater reduction of carotid intima plus media thickness (from 0.8+/-0.06 to 0.6+/-0.06 mm, P< 0.01). Blood pressure control does help reduce the severity of organ damage in patients with essential hypertension. Different antihypertensive treatments may confer additional specific cardiorenal and vascular protection regardless of blood pressure control. These data could be useful when devising individualized therapeutic strategies in high-risk hypertensive patients.",2001.0,0,0
622,11282905,"Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm: effects of angiotensin-converting enzyme inhibitor and beta-blocker therapy.",C R Gibbs; A D Blann; R D Watson; G Y Lip,"To investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and beta-blockers would beneficially affect the measured indices. In the cross-sectional analysis, plasma viscosity (P=0.001), fibrinogen (P=0.02), vWF (P<0.0001), and soluble P-selectin (P<0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P<0.05). Plasma viscosity (P=0.009) and fibrinogen (P=0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III-IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P=0.016) and vWF (P=0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of beta-blocker therapy, apart from a rise in mean platelet count (P<0.001). Abnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of beta-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.",2001.0,0,0
623,11288383,Hypertension clinical guideline 2000.,Southern African Hypertension Society Executive Committee 2000,"Extensive data from many randomised controlled trials have shown the benefit of treating hypertension. The target blood pressure (BP) for antihypertensive management should be systolic < 140 mmHg and diastolic < 90 mmHg, with minimal or no drug side-effects. However, a lesser reduction will elicit benefit, although this is not optimal. The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 6 months. Stricter BP control is required for patients with end-organ damage, coexisting risk factors and co-morbidity, e.g. diabetes mellitus. Coexistent risk factors should also be controlled. Reduction in risk of stroke, cardiac failure, renal insufficiency and probably coronary artery disease. The major precautions and contraindications to each antihypertensive drug recommended are listed. Correct BP measurement procedure is described. Evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated. The total cardiovascular disease risk profile should be determined for all patients and this should inform management strategies. Lifestyle modification and patient education play an essential role in the management strategy. First line--low-dose diuretics; second line--add one of the following: reserpine, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers; third line--add another second-line drug or hydralazine or an alpha-blocker. The guideline includes management of specific situations, e.g. hypertensive emergency or urgency, severe hypertension with target organ damage and refractory hypertension (BP > 160/95 mmHg on triple therapy), hypertension in diabetes mellitus, etc. The guideline was developed by the Executive Committee of the Southern African Hypertension Society with consensus meeting endorsement, and is endorsed by the South African Medical Association Guideline Commitee.",2001.0,0,0
624,11288822,Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.,S M Voyaki; J A Staessen; L Thijs; J G Wang; A D Efstratopoulos; W H Birkenhäger; P W de Leeuw; G Leonetti; C Nachev; J L Rodicio; J Tuomilehto; R Fagard; Systolic Hypertension in Europe (Syst-Eur) Trial Investigators,"In the outcome trials that provided information on renal function in older hypertensive patients, diuretics and beta-blockers were mostly used as first-line drugs. The long-term renal effects of calcium-channel blockers remain unclear. To compare the changes in renal function in 2,258 treated and 2,148 untreated patients with isolated systolic hypertension, of whom 455 had diabetes mellitus and 390 had proteinuria. We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Active treatment was initiated with nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg, to less than 150 mmHg. The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault. Serum creatinine concentration at the time when participants were randomly allocated to study groups was less than 176.8 micromol/l (2.0 mg/dl), averaging 88 micromol/l. At the time of the last serum creatinine measurement, the blood pressure difference (P< 0.001) between the two groups was 11.6/4.1 mmHg. In the intention-to-treat analysis (11,427 patient-years), serum creatinine and the calculated creatinine clearance were not influenced by active treatment. However, in the patients assigned randomly to receive active treatment, the incidence of mild renal dysfunction (serum creatinine at least 176.8 mmol/l) decreased by 64% (P= 0.04) and that of proteinuria by 33% (P= 0.03). Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients: by 71%, compared with 20% (P= 0.04). In non-proteinuric patients, active treatment did not influence serum creatinine, whereas in patients with proteinuria at entry to the study, serum creatinine decreased on active treatment (P< 0.001). Furthermore, in on-randomized treatment comparison stratified for risk at baseline, serum creatinine concentration did not change (P= 0.98) in patients continuing to receive monotherapy with nitrendipine, whereas it increased by 6.73 mmol/l (P < 0.001) in patients who received hydrochlorothiazide alone or in combination with other study medication (P < 0.001 for difference in trends). In older patients with isolated systolic hypertension, antihypertensive treatment starting with the dihydropyridine calcium-channel blocker, nitrendipine, did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria, especially in diabetic patients.",2001.0,0,0
625,11288962,Angiotensin receptor blockers: evidence for preserving target organs.,P Carson; T Giles; M Higginbotham; N Hollenberg; W Kannel; H M Siragy,"Hypertension is a major problem throughout the developed world. Although current antihypertensive treatment regimens reduce morbidity and mortality, patients are often noncompliant, and medications may not completely normalize blood pressure. As a result, current therapy frequently does not prevent or reverse the cardiovascular remodeling that often occurs when blood pressure is chronically elevated. Blockade of the renin-angiotensin system (RAS) is effective in controlling hypertension and treating congestive heart failure. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) inhibit the activity of the RAS, but these two classes of antihypertensive medications have different mechanisms of action and different pharmacologic profiles. Angiotensin-converting enzyme inhibitors block a single pathway in the production of angiotensin II (Ang II). In addition, angiotensin I is not the only substrate for ACE. The ACE inhibitors also block the degradation of bradykinin that may have potential benefits in cardiovascular disease. Bradykinin is, however, the presumed cause of cough associated with ACE inhibitor therapy. Data from clinical trials on ACE inhibitors serve to support the involvement of the RAS in the development of cardiovascular disease. Angiotensin receptor blockers act distally in the RAS to block the Ang II type 1 (AT1) receptor selectively. Thus, ARBs are more specific agents and avoid many side effects. Experimental and clinical trials have documented the efficacy of ARBs in preserving target-organ function and reversing cardiovascular remodeling. In some instances, maximal benefit may be obtained with Ang II blockade using both ARBs and ACE inhibitors. This review describes clinical trials that document the efficacy of ARBs in protecting the myocardium, blood vessels, and renal vasculature.",2001.0,0,0
626,11289051,Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria: the European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT).,,"In the treatment of diabetic nephropathy, ACE inhibitor therapy reduces albumin excretion and slows the rate of decline in glomerular filtration rate (GFR). Our study was designed to investigate whether these effects lay in amelioration of the underlying glomerular structural abnormalities. A total of 54 type 1 diabetic patients with albuminuria and blood pressure (BP) <150/90 mmHg were randomized to receive 10 mg enalapril once daily, 10 mg nifedipine retard twice daily, or placebo in a multicenter double-blind study of 3 years' duration. Renal biopsy was performed at baseline and follow-up, and tissue was analyzed by standard morphometric methods. BP, GFR, albumin excretion rate (AER), and HbA1c were measured every 6 months. Enalapril lowered AER after 6 months by 26% (P < 0.05); however, this reduction was not sustained at 3 years. There was no significant effect of nifedipine or placebo on AER. GFR decreased by a similar average rate of 4.1 ml x min(-1) x year(-1) (95% CI 2.6-5.6) in all three groups. BP and HbA1c were unchanged throughout the study in all groups. At baseline, nearly all biopsies showed classic appearances of diabetic glomerulopathy. There was no detectable effect of enalapril compared with either nifedipine or placebo on renal structure over 3 years. However, we found that patients with increased AER have established glomerulopathy and a progressive average decline in GFR of 4.1 ml x min(-1) x year(-1) in the absence of overt hypertension, and baseline AER appeared predictive of subsequent mesangial volume fraction (r = 0.20, P = 0.0018). In this small cohort of nonhypertensive patients studied for 3 years, disease evolution appears unaffected by treatment with either enalapril or nifedipine.",2001.0,0,0
627,11293449,Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report.,A C Nunes; P Amaro; F Maç as; A Cipriano; I Martins; A Rosa; I Pimenta; A Donato; D Freitas,"We report a case of fosinopril-induced prolonged cholestatic jaundice and pruritus in a 61-year-old man, with no previous hepatobiliary disease, who presented with asthenia, jaundice and itching 3 weeks after starting fosinopril therapy. Other drugs taken by the patient were not considered probable causes. The diagnostic evaluation showed no biliary obstruction and other possible causes of intra-hepatic cholestasis were excluded. Liver biopsy showed cholestasis without bile duct damage. The disease ran a severe course during the 2 months of hospitalization, with prolonged itching for 6 months, eventually controlled with oral naltrexone. Jaundice subsided after 4 months, with anicteric cholestasis persisting for more than 18 months. Similar occurrences have been reported with other inhibitors of angiotensin-converting enzyme (mostly captopril), but this is the first case of an important adverse reaction to fosinopril.",2001.0,0,0
628,11293942,Angioedema and antihypertensive therapy.,M Binder; H Kittler,,2001.0,0,0
629,11294048,[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy].,J C Philips; L Weekers; A J Scheen,"The main objective of the CALM (Candesartan And Lisinopril Microalbuminuria) study is to assess the effect of a dual blockade of the renin-angiotensin system--using both an angiotensin converting enzyme inhibitor (ACE-I) and an angiotensin II type 1 receptor blocker--in patients with type 2 diabetes, high blood pressure and microalbuminuria. The study included 200 patients randomized to receive candesartan 16 mg or lisinopril 20 mg for 12 weeks, followed by 12 weeks of the same monotherapy or a combination treatment. Main outcomes are the reduction of microalbuminuria and blood pressure. All three of the treatments are effective, but the dual blockade is respectively 18%, 8 mmHg and 5 mmHg more effective in reducing microalbuminuria, systolic and diastolic blood pressure. No comparison is made between this ""new"" association and the more frequently used biotherapy (i.e. ACE-I plus thiazidic diuretic) and therefore its usefulness in regular practice is still to be determined.",2001.0,0,0
630,11295958,"Dose discrepancies between the Physicians' Desk Reference and the medical literature, and their possible role in the high incidence of dose-related adverse drug events.",J S Cohen,"Adverse drug events (ADEs) are a major cause of morbidity and mortality, and even minor ADEs may adversely affect patients' compliance with treatment. Because most ADEs are dose-related phenomena, adjusting drug dosages to account for individual patients' needs and tolerances is fundamental to good therapeutics. To determine whether the Physicians' Desk Reference (PDR), the leading source of drug information for physicians, provides the full range of effective drug doses, especially the lowest, least ADE-prone doses of medications, for physicians to consider in treating patients. Review of dosage guidelines and dose-response information in the PDR. Comparison with dose-response data obtained from articles listed in MEDLINE from 1966 to 2000. For many types of medications, physicians are frequently advised to use the lowest effective doses of drugs, especially initially. Yet, effective low doses determined in prerelease studies or in postrelease work are often omitted from the PDR, even when they have been recommended by expert panels. Optimal therapeutics depends on the availability of comprehensive information. However, the PDR contains only the limited dose information from package inserts. Because the PDR was originally developed as a promotional device, there is no mechanism by which all clinically relevant dose-response data or important postrelease discoveries are regularly and rapidly incorporated into it. Thus, a gap exists in the availability of current and comprehensive dose information for physicians. This article provides information on lower, effective doses for 48 major medications, with an extensive reference list-a compilation of low-dose information not previously published, to our knowledge, in the medical literature. Physicians must have a readily accessible source of current and complete dose-response information to individualize drug therapy and minimize the risks of ADEs.",2001.0,0,0
631,11295959,"Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa.",P Sareli; I V Radevski; Z P Valtchanova; E Libhaber; G P Candy; E Den Hond; C Libhaber; D Skudicky; J G Wang; J A Staessen,"Thiazides are recommended to initiate antihypertensive drug treatment in black subjects. To test the efficacy of this recommendation in a South African black cohort. Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen. While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P</=.03) vs 20 (39.9%) receiving verapamil, 21 (40.4%) receiving hydrochlorothiazide, and 11 (20.8%) receiving enalapril. At 13 months (n = 257), more patients (P<.001) continued receiving monotherapy with nifedipine (94/154 [61.0%]) or verapamil (22/35 [62.9%]) than hydrochlorothiazide (10/39 [25.6%]) or enalapril (1/29 [3.4%]). A sustained decrease of left ventricular mass (P<.001) with no between-group differences was achieved at 4 and 13 months. In contrast to current recommendations, calcium channel blockers are more effective than thiazides as initial treatment in black subjects with hypertension. If treatment is started with thiazides or converting-enzyme inhibitors, combination therapy is more likely to be required to control blood pressure and reduce left ventricular mass.",2001.0,1,1
632,11297201,Beneficial effects of nicorandil versus enalapril in chronic rheumatic severe mitral regurgitation: six months follow up echocardiographic study.,D K Gupta; A Kapoor; N Garg; S Tewari; N Sinha,"It is possible that vasodilator therapy may retard left ventricular (LV) dilatation and functional deterioration in chronic mitral regurgitation (MR). The study objectives were to evaluate comparatively the efficacy of nicorandil (a new, balanced vasodilator) and enalapril therapy on LV volume, mass and function in mildly symptomatic, chronic rheumatic severe MR. Eighty-seven mildly symptomatic rheumatic patients with severe MR were enrolled in this prospective, randomized study. All patients underwent serial echocardiography study at entry, and again at six months. Eighty patients completed the study. At six months, the nicorandil and enalapril patient groups each had a significant reduction in LV end-systolic volume index (57.4 +/- 24.8 versus 43.2 +/- 20.7 ml/m2, p = 0.003; 50.0 +/- 19.0 versus 40.4 +/- 14.2 ml/m2, p = 0.006, respectively) and LV mass index (218.0 +/- 88.0 versus 188.0 +/- 76.0 g/m2, p = 0.05; 217.2 +/- 48.0 versus 186.2 +/- 45.0 g/m2, p = 0.002 respectively). Both nicorandil and enalapril caused significant improvement in ejection fraction (63.8 +/- 7.0 versus 71.0 +/- 6.7%, p <0.0001; 63.2 +/- 6.9 versus 67.5 +/- 6.4%, p = 0.002, respectively) and a reduction in LV end-systolic stress (152.9 +/- 29.0 versus 126.0 +/- 25.0 dyne/cm2, p = 0.001; 150.0 +/- 30.2 versus 138.0 +/- 29.0 dyne/cm2, p = 0.002, respectively). However, nicorandil caused a greater reduction in absolute LV end-systolic volume index (13.3 +/- 10.1 versus 9.6 +/- 5.9 ml/m2, p = 0.02), and a greater improvement in absolute ejection fraction (7.2 +/- 4.7 versus 4.2 +/- 2.6%, p = 0.0005) than enalapril. It is concluded that nicorandil is equivalent to enalapril in improving LV volume, mass, end-systolic stress and ejection fraction in mildly symptomatic chronic rheumatic severe mitral regurgitation over a period of six months.",2001.0,0,1
633,11300425,Beneficial effects of ramipril on left ventricular end-diastolic and end-systolic volume indexes after uncomplicated invasive revascularization are associated with a reduction in cardiac events in patients with moderately impaired left ventricular function and no clinical heart failure.,L Kjøller-Hansen; R Steffensen; P Grande,"OBJECTIVES We sought to assess the effect of ramipril on left ventricular (LV) volumes, and the clinical significance thereof, in patients with moderate LV dysfunction and no clinical heart failure undergoing invasive revascularization for chronic stable angina. It is unsettled whether treatment with an angiotensin-converting enzyme inhibitor has an impact on LV volumes in this patient group, and, if so, whether this is associated with the clinical outcome. A total of 133 patients with a left ventricular ejection fraction (LVEF) between 0.30 and 0.50 and no clinical heart failure undergoing invasive revascularization for chronic stable angina were randomized to receive ramipril 10 mg once daily or placebo and were followed for a median of 33 months with echocardiography at baseline and 3, 12 and 24 months postoperatively. Repeated measures analysis of all time points showed that ramipril significantly reduced the end-diastolic volume index (EDVI) (p = 0.032) and end-systolic volume index (ESVI) (p = 0.006) as compared with placebo. Ramipril also reduced the incidence of the triple composite end point of cardiac death, acute myocardial infarction or development of heart failure (p = 0.046). Cox regression analysis, controlling for baseline LVEF and assignment to ramipril, revealed: 1) that increases in EDVI and ESVI up to three months predicted an increasing risk of a future adverse clinical outcome; and 2) that the benefit with ramipril on clinical outcome was partly dependent on a reduction in LV volumes. Even in this patient group, LV dilation may supervene and lead to an adverse clinical outcome. Ramipril reduces the postoperative increase in LV volumes and may thereby improve clinical outcome.",2001.0,0,1
634,11301961,A retrospective analysis comparing the costs and cost effectiveness of amlodipine and enalapril in the treatment of hypertension.,J Doyle; P Omvik; S Arikian; J Casciano; R Casciano; M A Gonzalez; R Arocho,"A comparison of treatment costs and cost effectiveness was performed retrospectively by using patient-level data from a randomized, controlled, one-year clinical trial of amlodipine and enalapril in the treatment of mild-to-moderate hypertension. Unit costs of amlodipine and enalapril were applied to the daily dosages of individual patients to calculate the total costs and average costs per patient in each treatment group in the clinical trial on an intent-to-treat basis. Efficacy rates were used to calculate the average treatment costs per success in blood pressure control. Although not statistically significant, amlodipine treatment resulted in a higher efficacy (89.5%) vs. enalapril (85.2%). The average costs per amlodipine-treated patient were consistently lower (-$112.30) than for the enalapril-treated patient by week 50. Treatment with amlodipine resulted in an average cost per success of $609 per patient compared with $772 per enalapril-treated patient. A sensitivity analysis revealed that, in the treatment of mild-to-moderate hypertension over the 50-week treatment period, amlodipine would remain less costly than enalapril, with a decrease in the cost of enalapril of up to 17%, and would remain more cost effective, with a 21% decrease in the cost of enalapril.",2001.0,0,0
635,11302283,Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.,C Bulpitt; A Fletcher; N Beckett; J Coope; B Gil-Extremera; F Forette; C Nachev; J Potter; P Sever; J Staessen; C Swift; J Tuomilehto,"A number of trials and meta-analyses have demonstrated clear benefits of blood pressure (BP) reduction in patients aged <80 years with regard to the reduction in stroke and cardiovascular events. However, a variety of studies have suggested that the positive relationship between BP and cardiovascular mortality is weakened or indeed reversed in the very elderly. Most intervention trials to date have either excluded or not recruited sufficient patients aged > or =80 years to determine whether there is a significant benefit from treatment in this age group. A meta-analysis of intervention trials that recruited patients aged > or =80 years has suggested a benefit in terms of stroke reduction but has also raised the possibility of an increase in total mortality. The benefit to risk ratio therefore needs to be clearly established before recommendations can be made for treating very elderly patients with hypertension. The Hypertension in the Very Elderly Trial (HYVET) pilot recruited 1283 patients aged > or =80 years and showed the feasibility of performing such a trial in this age group. It was a Prospective Randomised Open Blinded End-Points (PROBE) design but the main trial has additional pharmaceutical sponsorship to run a double-blind trial. Therefore, the main trial is a randomised, double-blind, placebo-controlled trial designed to assess the benefits of treating very elderly patients with hypertension. It compares placebo with a low dose diuretic (indapamide sustained release 1.5mg daily) and additional ACE inhibitor (perindopril) therapy if required. As in the pilot trial, the primary end-point is stroke events (fatal and non-fatal) and the trial is designed to determine whether or not a 35% difference occurs between placebo and active treatment. The main objective will be achieved with 90% power at the 1% level of significance. Secondary outcome measures will include total mortality, cardiovascular mortality, cardiac mortality, stroke mortality and skeletal fracture. 2100 patients aged > or =80 years are to be recruited and followed up for an average of 5 years. Entry BP criteria after 2 months of a single-blind placebo run-in period are a sustained sitting systolic BP (SBP) of 160 to 199mm Hg and a diastolic BP of 90 to 109mm Hg. The standing SBP must be >140mm Hg. The trial will be carried out in accordance with the principles of Good Clinical Practice. We describe in detail the protocol for the main trial and discuss the reasons for the changes from the pilot, the use of the drug regimen, and the BP criteria to be used in the trial.",2001.0,0,0
636,11304102,Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.,J F Mann; H C Gerstein; J Pogue; J Bosch; S Yusuf,"The cardiovascular risk associated with early renal insufficiency is unknown. Clinicians are often reluctant to use angiotensin-converting enzyme inhibitors in patients with renal insufficiency. To determine whether mild renal insufficiency increases cardiovascular risk and whether ramipril decreases that risk. Post hoc analysis. The Heart Outcomes and Prevention Evaluation (HOPE) study, a randomized, double-blind, multinational trial involving 267 study centers. 980 patients with mild renal insufficiency (serum creatinine concentration >/= 124 micromol/L [>/=1.4 mg/dL]) and 8307 patients with normal renal function (serum creatinine concentration < 124 micromol/L [<1.4 mg/dL]) Patients with a baseline serum creatinine concentration greater than 200 micromol/L (2.3 mg/dL) were excluded. The primary outcome measure was incidence of cardiovascular death, myocardial infarction, or stroke. Cumulative incidence of the primary outcome was higher in patients with renal insufficiency than in those without (22.2% vs. 15.1%; P < 0.001) and increased with serum creatinine concentration. Patients with renal insufficiency had a substantially increased risk for cardiovascular death (11.4% vs. 6.6%) and total mortality (17.8% vs. 10.6%) (P < 0.001 for both comparisons). The effect of renal insufficiency on the primary outcome (adjusted hazard ratio, 1.40 [95% CI, 1.16 to 1.69]) was independent of known cardiovascular risks and treatment. Ramipril reduced the incidence of the primary outcome in patients with and those without renal insufficiency (hazard ratio, 0.80 vs. 0.79; P > 0.2 for the difference). In patients who had preexisting vascular disease or diabetes combined with an additional cardiovascular risk factor, mild renal insufficiency significantly increased the risk for subsequent cardiovascular events. Ramipril reduced cardiovascular risk without increasing adverse effects.",2001.0,0,0
637,11304505,Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.,J G Wang; J A Staessen; R H Fagard; W H Birkenhäger; L Gong; L Liu,"We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.",2001.0,0,0
638,11315826,Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,J I Barzilay; C L Jones; B R Davis; J N Basile; D C Goff; J O Ciocon; M E Sweeney; O S Randall; Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Collaborative Research Group,"Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. The Antihypertensive and Lipid-Lowering high-risk hypertensive participants, ages > or = 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002. There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, treatments for the two study outcomes. The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.",2001.0,0,0
639,11317186,Blockade of the renin-angiotensin-aldosterone system with combination angiotensin receptor antagonist and ACE inhibitor therapy: observations from Val-HeFT and CALM.,B S Chin; G Y Lip,,2001.0,0,0
640,11317199,"A randomised, placebo-controlled, double-blind, crossover study of losartan and enalapril in patients with essential hypertension.",R Fagard; P Lijnen; K Pardaens; L Thijs; W Vinck,"The primary objective of this randomised, placebo- controlled, double-blind, crossover study, was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure (BP). After a 4-week placebo run-in period, nine patients with essential hypertension entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril 20 mg o.d. or losartan 50 mg o.d. Losartan and enalapril, taken between 07.00 and 08.00, reduced ambulatory BP throughout the 24-h period. Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan. Daytime BP averaged 157/101 mm Hg on placebo, and was significantly lower during enalapril (142/91 mm Hg) than during losartan treatment (147/95 mm Hg). Clinic BP, measured 2 to 4 hours after drug intake, was reduced to the same extent by both drugs. The losartan-induced BP changes were significantly related to those obtained with enalapril (0.63 < r < 0.93). Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients. The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone. In conclusion, losartan 50 mg o.d. and enalapril 20 mg o.d. lower BP to approximately the same extent, except for a more pronounced effect of enalapril on daytime ambulatory BP. The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP.",2001.0,0,0
641,11319567,Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men.,L S Williams; D Hill; J Davis; D T Lowenthal,"A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18 (78%) of the elderly hypertensive men in this study had an uncomplicated and beneficial response to either fosinopril or verapamil. There was a well-tolerated reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP). There were no significant adverse drug events. Only the sitting SBP and the sitting DBP were significantly lowered by fosinopril and verapamil SR. Because reduction in both SBP and DBP in elderly hypertensives has been shown to be beneficial, these findings take on further importance when considering the choice of medication for antihypertensive therapy in the elderly. The increase in norepinephrine in the fosinopril-treated patients may explain why patients treated with long-term angiotensin-converting enzyme inhibitors alone or in combination with diuretics rarely complain of orthostatic symptoms.",2001.0,0,0
642,11320070,Using computerized data to identify adverse drug events in outpatients.,B Honigman; J Lee; J Rothschild; P Light; R M Pulling; T Yu; D W Bates,"To evaluate the use of a computer program to identify adverse drug events (ADEs) in the ambulatory setting and to evaluate the relative contribution of four computer search methods for identifying ADEs, including diagnosis codes, allergy rules, computer event monitoring rules, and text searching. Retrospective analysis of one year of data from an electronic medical record, including records for 23,064 patients with a primary care physician, of whom 15,665 actually came for care. Presence of an ADE; sensitivity and specificity of computer searches for ADE. The computer program identified 25,056 incidents, which were associated with an estimated 864 (95 percent confidence interval [CI], 750-978) ADES. Thus, the ADE rate was 5.5 (CI, 5.2-5.9) per 100 patients coming for care. Furthermore, in 79 (CI, 68-89) ADEs, the patient required hospitalization, resulting in an estimated rate of 3.4 (CI, 2.7-4.3) admissions per 1,000 patients. The sensitivity of the search methods for identifying ADEs was estimated to be 58 (CI, 18-98) percent, and the estimated specificity was 88 (CI, 87-88) percent. The positive predictive value was 7.5 (CI, 6.5-8.5) percent, and the negative predictive value was 99.2 (CI, 95.5-99.98) percent. Compared with age and gender-matched controls with no positive screen, patients with ADEs had twice as many outpatient visits and were taking nearly three times as many drugs. Antihypertensives, ACE-inhibitors, antibiotics, and diuretics were associated with 56 (CI, 47-65) percent of ADES. Among ADEs, 23 (CI, 16-32) percent were life-threatening or serious, and 38 (CI, 29-47) percent were judged preventable. Computerized search programs can detect ADEs, and free-text searches were especially useful. Adverse drug events were frequent, and admissions were not rare, although most hospitals today do not identify them. Thus, such detection programs demonstrate ""value-added"" for the electronic record and may be useful for directing and assessing the impact of quality improvement efforts.",2001.0,0,0
643,11320369,ADEPT: Addition of the AT1 receptor antagonist eprosartan to ACE inhibitor therapy in chronic heart failure trial: hemodynamic and neurohormonal effects.,D R Murdoch; T A McDonagh; R Farmer; J J Morton; J J McMurray; H J Dargie,"Persistent activation of the renin-angiotensin-aldosterone-system (RAAS) is known to occur in patients with chronic heart failure (CHF) despite treatment with angiotensin-converting enzyme inhibitor (ACE) therapy. When added to ACE inhibitors, angiotensin II type 1 (AT1) antagonists may allow more complete blockade of the RAAS and preserve the beneficial effects of bradykinin accumulation not seen with AT1 receptor blockade alone. Thirty-six patients with stable New York Heart Association class II-IV CHF receiving ACE inhibitor therapy were randomly assigned in a double-blind manner to receive either eprosartan, a specific competitive AT1 receptor antagonist (400 to 800 mg daily, n = 18) or placebo (n = 18) for 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF) as measured by radionuclide ventriculography, and secondary measures were central hemodynamics assessed by Swan-Ganz catheterization and neurohormonal effects. There was no change in LVEF with eprosartan therapy (mean relative LVEF percentage change [SEM] +10.5% [9.3] vs +10.1% [5.0], respectively; difference, 0.4; 95% confidence interval [CI], -20.8 to 21.7; P =.97). Eprosartan was associated with a significant reduction in diastolic blood pressure and a trend toward a reduction in systolic blood pressure compared with placebo (-7.3 mm Hg [95% CI, -14.2 to -0.4] diastolic; -8.9 mm Hg [95% CI, -18.6 to 0.8] systolic). No significant change in heart rate or central hemodynamics occurred during treatment with eprosartan compared with placebo. A trend toward an increase in plasma renin activity was noted with eprosartan therapy. Eprosartan was well tolerated, with an adverse event profile similar to placebo, whereas kidney function remained unchanged. When added to an ACE inhibitor, eprosartan reduced arterial pressure without increasing heart rate. There was no change in LVEF after 2 months of therapy with eprosartan.",2001.0,0,1
644,11321866,The cost-effectiveness of doxazosin for the treatment of hypertension in type II diabetic patients in the UK and Italy.,J Casciano; J Doyle; R Casciano; Z Kopp; N Marchant; S Bustacchini; S Arikian; R Kim,"The objective of this analysis was to assess the cost-effectiveness of achieving 'tight control' versus 'less tight control' of blood pressure, as defined in the UK Prospective Diabetics Study 38, in type II diabetic patients in the UK and Italy. The effect of including doxazosin in a 'tight control' combination therapy was analysed. Given doxazosin's positive impact on lipid levels in addition to its antihypertensive effect, it is hypothesised that treatment including doxazosin will reduce the incidence of macrovascular complications. For each country, a Markov model was constructed to simulate macrovascular outcomes of patients on various drug combinations. Transitional probabilities were based on the risk rates presented in UKPDS 38. Risk rates were adjusted for the ageing of the cohort and the lipid-lowering properties of doxazosin using Framingham risk equations. Incremental cost-effectiveness ratios ranged from 2224 Pounds to 4867 Pounds (US$3225-7057) per life-year saved for the UK and from L1.8-9.3 million (US$818-4159) per life-year saved for Italy. Doxazosin is a cost-effective agent when included in a combination therapy in the treatment of hypertension in the diabetic populations of the UK and Italy.",2001.0,0,0
645,11322382,Angiotensin converting enzyme inhibitor-induced angioedema: report of a further case.,A Awan; D G Gill,,2001.0,0,0
646,11325669,Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria.,G Jerums; T J Allen; D J Campbell; M E Cooper; R E Gilbert; J J Hammond; J Raffaele; C Tsalamandris,"The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 microg/min for perindopril, 122 microg/min for nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8 mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2 mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in normotensive patients with type 1 diabetes and microalbuminuria.",2001.0,0,0
647,11327628,Effect of acute blood pressure reduction on endothelial function in the brachial artery of patients with essential hypertension.,L Ghiadoni; Y Huang; A Magagna; S Buralli; S Taddei; A Salvetti,"To evaluate the effect of acute blood pressure reduction on endothelium-dependent vasodilation in the peripheral circulation of essential hypertensive patients. A parallel group study; endothelial function measured in 64 essential hypertensive patients before and after (2 h) treatment with nifedipine (20 mg, n = 32) or captopril (50 mg, n = 32), p.o., randomly assigned. In hypertensive patients, we evaluated flow-mediated, endothelium-dependent dilation (FMD, high resolution ultrasound) of the brachial artery compared with endothelium-independent response to glyceryl trinitrate (GTN, 25 microg s.l.). Automatic computerized analysis was used to measure brachial artery diameter on end-diastolic frames acquired every second during the study. Sixty-six healthy normotensive subjects were also evaluated to assess the presence of endothelial dysfunction in hypertensive patients. Hypertensive patients showed a significantly (P< 0.01) lower FMD (5.9 +/- 2.5%) as compared to healthy controls (7.7 +/- 3.8%). The response to GTN was similar in normotensive subjects (7.5 +/- 3.1%) and hypertensive patients (7.2 +/- 6.5%). At baseline brachial artery diameter, FMD and response to GTN were similar in the nifedipine- and captopril-treated groups. Nifedipine and captopril similarly reduced blood pressure, but only nifedipine increased heart rate. Acute nifedipine, but not captopril, significantly (P< 0.01) increased brachial artery diameter, while FMD and response to GTN were not modified after nifedipine or captopril. Endothelial dysfunction in the brachial artery of essential hypertensive patients is not improved by acute blood pressure reduction.",2001.0,0,0
648,11329095,The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group.,S Sharma; D Deitchman; J S Eni; K Gelperin; J P Ilgenfritz; M Blumenthal,"The objective of this study was to evaluate the hemodynamic and clinical effects of fosinopril in patients with heart failure. This was a prospective, multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80 years of age who were receiving diuretics with a systolic blood pressure (SBP) > or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction < or = 40%, pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg, and a cardiac index (CI) < or = 2.6 L/min/m(2) were eligible. A total of 179 patients were randomized to a single, double-blind oral dose of placebo or fosinopril at 1, 20, or 40 mg, and hemodynamic monitoring was performed for 24 hours postdose; 155 patients with SBP > or = 90 mm Hg were re-randomized to 10 weeks of double-blind fosinopril at 1, 20, or 40 mg once daily. Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours postdose (trough) and continuing for 12 hours thereafter. Significant decreases in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases in CI and stroke volume index were observed after 10 weeks of treatment with fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and MABP at most time points and P < or = .05 v baseline for other parameters at most time points). Dose-related trends toward reduced supplemental diuretic use (P = .027) and reduced symptoms of dyspnea (P = .008) were observed with the 20-mg and 40-mg fosinopril dose groups. Once daily administration of fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of dyspnea, resulting in a reduced need for supplemental diuretic therapy.",2001.0,0,0
649,11329107,Effect of angiotensin-converting enzyme therapy on QT interval dispersion.,V Ranade; J Molnar; T Khokher; A Agarwal; A Mosnaim; J C Somberg,"Patients with chronic heart failure (CHF) have an increased risk for sudden death. This increased risk has been associated with increased QT dispersion (QTd), a reflection of the heterogeneity in ventricular repolarization. Angiotensin-converting enzyme (ACE) inhibitors have been reported to decrease heart size as well as decreasing morbidity and mortality in moderate-to-severe CHF. The aim of this study was to determine if ACE therapy is associated with a decrease in QTd, a marker for increased electrical instability. Ninety-seven patients were evaluated. The normalized QTd after 2 months of ACE therapy decreased from 16 +/- 4 to 12 +/- 3, a 25% reduction in dispersions. QTd also decreased from 61 +/- 14 to 47 +/- 12 (P < .001) and QTc dispersions decreased from 71 +/- 18 to 52 +/- 14 (P < .001). After 2 months of ACE inhibitor therapy, heart rate slowed significantly (RR intervals 765 +/- 198 before and 838 +/- 186 after ACE). There was a negative correlation between ejection fraction and QTd (r = -0.8; P < .001). The study also found no correlation between ACE level, percent converting enzyme inhibition, and QTd. The effects of ACE therapy appear early on in terms of repolarization changes. The reduction in QTd may explain the reduced sudden death mortality in patients with heart failure who are treated with ACE inhibitor therapy.",2001.0,0,0
650,11329119,University of Miami division of clinical pharmacology therapeutic rounds: issues in prescribing for geriatric patients and emerging practice guidelines.,A G Golden; M A Silverman; R A Preston,"The geriatric population accounts for over 12% of the United States population and consumes over 25% of all prescription medications. Polypharmacy and patient noncompliance are often encountered in caring for these patients. These issues along with a variety of age-related physiologic changes and the presence of multiple medical illnesses place the elderly at an increased risk for adverse drug reactions. Especially worrisome is the use of long-acting benzodiazepines and anticholinergic medications in this population. The problem of adverse drug reactions is a common clinical problem that is of great public concern as the number of older persons in the United States continues to grow. In response, a variety of proactive measures have been developed. These measures include the development of consensus criteria for inappropriate medications, federal government regulation, expansion of the role of clinical pharmacists, and computer-assisted prescribing protocols.",2001.0,0,0
651,11330885,"Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study.","R Asmar; J Topouchian; B Pannier; A Benetos; M Safar; Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study","To evaluate the ability of an antihypertensive therapy to improve arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large population of hypertensive patients. Sixty-nine healthcare centres, private and institutional (19 countries). Subjects aged 18-79 years, with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52% male) completed the study: mean age = 50 +/- 12 years; mean baseline systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. Patients were treated for 6 months, starting with perindopril (angiotensin converting enzyme (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). It was feasible to measure carotid-femoral PWV using the automatic device Complior at inclusion, 2 and 6 months, along with conventional BP assessments in a population of 1,703 patients. Significant decreases (P < 0.001) in BP (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. The Complior Study is the first study to show the feasibility of a large-scale intervention trial using PWV as the endpoint in hypertensive patients. Adequate results may be obtained using an automatic device and rigorous criteria for assessment. A long-term controlled intervention study is needed to confirm the results of the present uncontrolled trial.",2001.0,0,0
652,11331054,Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases.,H Schepkens; R Vanholder; J M Billiouw; N Lameire,"The beneficial effects of spironolactone are additive to those of ACE inhibitors among patients with heart failure and/or hypertension; however, it is essential to identify patients prone to develop serious hyperkalemia during combined treatment and to evaluate the associated morbidity and mortality. We studied 25 patients treated with ACE inhibitors and spironolactone who were admitted to the emergency room with a serum potassium level > 6 mmol/L. Patients were followed up for at least one month after admission. The mean age of the patients (11 males, 14 females) was 74 +/- 13 years. Five patients were diabetics. On admission, the serum potassium was 7.7 +/- 0.7 mmol/L and the serum creatinine was 3.8 +/- 1.8 mg/dL; these values were significantly higher than the most recent follow-up laboratory measurements (4.6 +/- 0.5 mmol/L and 1.9 +/- 1.2 mg/dL, respectively) obtained at 13 +/- 5 weeks before admission. The arterial pH on admission was 7.3 +/- 0.1 and the plasma bicarbonate was 18 +/- 5 mmol/L. The main causes for acute renal failure were dehydration (n = 12) and worsening heart failure (n = 9). The mean daily dose of spironolactone was 57 +/- 32 mg and 12 patients were concomitantly treated with other drugs that may cause hyperkalemia. Two patients died, and 2 patients were resuscitated but survived. Hemodialysis was necessary in 17 patients; 12 patients were admitted to the intensive care unit. The mean duration of hospitalization was 12 +/- 6 days. Two patients needed to be started on maintenance hemodialysis therapy. A combination of ACE inhibitors and spironolactone should be considered with caution and monitored closely in patients with renal insufficiency, diabetes, older age, worsening heart failure, a risk for dehydration, and in combination with other medications that may cause hyperkalemia. A daily spironolactone dose of 25 mg should not be exceeded.",2001.0,0,0
653,11331059,Formulating clinical strategies for angiotensin antagonism: a review of preclinical and clinical studies.,R Tabibiazar; A H Jamali; S G Rockson,"Extensive animal studies and a growing number of human clinical trials have now definitively demonstrated the central role of the renin-angiotensin-aldosterone system in the expression and modulation of cardiovascular disease. In contrast to the original hypothesis, the benefits of angiotensin antagonism do not emanate from the antihypertensive effect alone. Subsequent extensive investigations of angiotensin blockade suggest that the benefits of this approach may also result from the pharmacologic alteration of endothelial cell function and the ensuing changes in the biology of the vasculature. The more recent availability of direct antagonists of the AT(1) angiotensin receptor has introduced an element of doubt into this realm of clinical decision making. The receptor antagonists and the more widely studied converting-enzyme inhibitors share many endpoint attributes. Nevertheless, the partially overlapping mechanisms of action for the two classes of angiotensin antagonists confer distinct pharmacologic properties, including side effect profiles, mechanisms of action, and theoretic salutary effects upon the expression of cardiovascular disease. The current review will attempt to contrast the biology of angiotensin converting-enzyme inhibition with angiotensin II receptor antagonism. A discussion of the differential effects of these drug classes on endothelial cell function and on the modulation of vascular disease will be utilized to provide a theoretic framework for clinical decision making and therapeutics.",2001.0,0,0
654,11332334,"The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension.",A Himmelmann; S Keinänen-Kiukaanniemi; A Wester; J Redón; R Asmar; T Hedner; Effect Study Group,"To determine the antihypertensive efficacy, effect duration and safety of the angiotensin II type 1 receptor blocker candesartan cilexetil and the angiotensin converting enzyme inhibitor enalapril once daily in patients with mild to moderate hypertension. A multicenter, randomised, double-blind parallel group study was performed in Finland, France, the Netherlands, Spain and Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years with primary hypertension were randomised to an 8-week double-blind treatment period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood pressure was measured for 36 h at baseline and after 8 weeks. The primary efficacy variable was the change in mean diastolic and systolic ambulatory blood pressure 22-24 h post-dose. There was a significant difference in the adjusted mean difference for the change from baseline to week 8 between candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95% confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory diastolic blood pressure. There was a significant difference in adjusted mean daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both drugs were generally well tolerated. The results of the present study suggest that advantages may be attributed to the use of candesartan cilexetil, as compared to enalapril in the treatment of patients with essential hypertension. In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively lowered blood pressure at trough and in particular on the day following the day after the last dose.",2002.0,0,0
655,11333991,Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction.,D V Exner; D L Dries; M J Domanski; J N Cohn,"Black patients with heart failure have a poorer prognosis than white patients, a difference that has not been adequately explained. Whether racial differences in the response to drug treatment contribute to differences in outcome is unclear. To address this issue, we pooled and analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD) prevention and treatment trials, two large, randomized trials comparing enalapril with placebo in patients with left ventricular dysfunction. We used a matched-cohort design in which up to four white patients were matched with each black patient according to trial, treatment assignment, sex, left ventricular ejection fraction, and age. A total of 1196 white patients (580 from the prevention trial and 616 from the treatment trial) were matched with 800 black patients (404 from the prevention trial and 396 from the treatment trial). The average duration of follow-up was 35 months in the prevention trial and 33 months in the treatment trial. The black patients and the matched white patients had similar demographic and clinical characteristics, but the black patients had higher rates of death from any cause (12.2 vs. 9.7 per 100 person-years) and of hospitalization for heart failure (13.2 vs. 7.7 per 100 person-years). Despite similar doses of drug in the two groups, enalapril therapy, as compared with placebo, was associated with a 44 percent reduction (95 percent confidence interval, 27 to 57 percent) in the risk of hospitalization for heart failure among the white patients (P<0.001) but with no significant reduction among black patients (P=0.74). At one year, enalapril therapy was associated with significant reductions from base line in systolic blood pressure (by a mean [+/-SD] of 5.0+/-17.1 mm Hg) and diastolic blood pressure (3.6+/-10.6 mm Hg) among the white patients, but not among the black patients. No significant change in the risk of death was observed in association with enalapril therapy in either group. Enalapril therapy is associated with a significant reduction in the risk of hospitalization for heart failure among white patients with left ventricular dysfunction, but not among similar black patients. This finding underscores the need for additional research on the efficacy of therapies for heart failure in black patients.",2001.0,0,0
656,11336083,Effects on urinary albumin excretion and renal function changes by delapril and manidipine in normotensive type 2 diabetic patients with microalbuminuria.,C Deerochanawong; P Kornthong; S Phongwiratchai; S Serirat,"This study was designed to investigate the effect of delapril, an ACE inhibitor, and manidipine, a long action calcium antagonist, on persistent microalbuminuria in normotensive type 2 diabetic patients. Sixty type 2 diabetic patients were randomized to take delapril 30 mg/day or manidipine 10 mg/day for 48 weeks, in an open label design. Twenty eight of thirty subjects in the delapril group and twenty nine of thirty in the manidipine group completed the study. Urine albumin excretion as measured by the urinary albumin creatinine ratio decreased significantly in both groups (112.0+/-60.9 to 95.3+/-64.9 mg/g and 108.5+/-51.0 to 96.4+/-53.5 mg/g in the delapril and manidipine group respectively, p < 0.05, by paired t-test). Systolic and diastolic blood pressure were not significantly changed after treatment in the delapril group but significantly decreased in the manidipine group (130.9+/-7.1/80.2+/-6.1 to 127.2+/-7.1/78.0+/-5.3 mm/Hg, p < 0.05, by student's paired t-test). After 48 weeks of treatment, two patients in the delapril group and one patient in the manidipine group converted to normoalbuminuria (urinary albumin:creatinine ratio < 30 mg/g) and one patient in each group progressed to overt nephropathy (urinary albumin:creatinine ratio > 300 mg/g). There were no significant changes in fasting plasma glucose, HbA1c, serum fructosamine, creatinine, potassium and lipid profiles after 48 weeks of treatment in both groups. Two cases in the delapril group were withdrawn during the study because of an intolerable cough and one case in the manidipine group because of intolerable dizziness and headache. In conclusion, both delapril and manidipine are effective in the reduction of microalbuminuria in normotensive type 2 diabetic patients with persistent microalbuminuria.",2001.0,0,0
657,11336102,Reversal of pathophysiologic changes with long-term lisinopril treatment in isolated systolic hypertension.,W F Heesen; F W Beltman; A J Smit; J F May; P A de Graeff; J H Muntinga; T K Havinga; F H Schuurman; E van der Veur; B Meyboom-de Jong; K I Lie,"The purpose of this study was to evaluate in a prospective, double-blind, placebo-controlled study the effect of long-term (2-year) lisinopril treatment on cardiovascular end-organ damage in patients with previously untreated isolated systolic hypertension (ISH). All patients with ISH were derived from a population screening program. End-organ damage measurements, done initially and after 6 and 24 months of treatment, included measurements of aortic distensibility and echocardiographic left ventricular mass index (LVMI) and diastolic function. Blood pressure was measured by office and ambulatory measurements. Of the 97 subjects with ISH selected from the screening, 62 (30 lisinopril) completed the study according to protocol. Office blood pressure decreased in both groups, but ambulatory results significantly decreased with lisinopril-treatment only. Aortic distensibility increased significantly with lisinopril, as opposed to a decrease in placebo-treated subjects. The main effect of increased distensibility occurred between 6 and 24 months, whereas ambulatory blood pressure changed mainly in the first 6 months of treatment. LVMI decreased in both treatment groups, with a significantly higher reduction in lisinopril-treated subjects. Left ventricular diastolic function showed no significant changes in either group. The vascular pathophysiologic alterations of ISH-a decreased aortic distensibility-can be improved with long-term lisinopril treatment, whereas values deteriorate further in placebo-treated subjects. These results, in one of the first studies including subjects with previously untreated ISH only, indicate that lisinopril treatment might favorably influence the cardiovascular risk of ISH.",2001.0,0,0
658,11336577,Amlodipine/benazepril: fixed dose combination therapy for hypertension.,M A Faulkner; D E Hilleman,"Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel), Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.",2002.0,0,0
659,11336618,The current status of antihypertensive treatments: into the new millennium.,T C Hardman; M W Lunnon,"In this short review, we present a historical perspective of the treatment of hypertension, highlight some current issues and look to the possible future of antihypertensive therapy. The distribution of blood pressure within the population adopts a continuous, albeit somewhat skewed, distribution, so what constitutes hypertension? Conventionally, the disease has been defined as a level of blood pressure > 140/90 mmHg. Accepting this 'arbitrary' definition infers that approximately one quarter of the adult population in the US are hypertensive [1]. This has significant implications in terms of the impact upon public health. We know that treatment of hypertension can prevent the serious consequences of cardiovascular disease: stroke, myocardial infarction (MI), heart failure and renal disease. Thus, it is important that raised blood pressure is both detected and effectively lowered. To what level should blood pressure be reduced. Conventionally, a level of 120/80 mmHg has been used to define normotension but there are indications that under certain circumstances this should not be the target. The question also arises as to whether it matters how blood pressure is treated. The choice of agent may ultimately depend upon the presence of any concomitant condition and risk factors. Recent trial evidence has concluded that therapy selected to treat raised blood pressure should take into account the overall cardiovascular risk profile of the patient [2].",2002.0,0,0
660,11337444,What are the elements of good treatment for hypertension?,C D Mulrow; M Pignone,,2001.0,0,0
661,11343438,Epidemiologic review of the calcium channel blocker drugs. An up-to-date perspective on the proposed hazards.,J R Kizer; S E Kimmel,"In the setting of soaring popularity, postmarketing studies of calcium channel blockers came to suggest an increase in a variety of major adverse end points. The evidence, however, was largely observational, and large-scale trials capable of addressing the concerns were wanting. Clinical trials now support the safety and efficacy of the long-acting dihydropyridines for patients with both uncomplicated and diabetic hypertension, although conventional therapies and, in the latter case, angiotensin-converting enzyme inhibitors have superior proof of benefit. By contrast, short-acting dihydropyridines should be avoided. In the acute coronary syndromes, beta-blockers remain the treatment of choice; the evidence for nondihydropyridines remains inconclusive. Stable angina calls for beta-blockers as first-line therapy and nondihydropyridines as second-line therapy, whereas in ventricular dysfunction, safety data for nondihydropyridines are lacking. Initial reports of cancer, bleeding, and suicide have been contradicted by subsequent data, making the associations uncertain or unlikely. Remaining questions await completion of ongoing trials to better define the indications for these agents.",2001.0,0,0
662,11343737,"Effect of ACE inhibitors on angiographic restenosis after coronary stenting (PARIS): a randomised, double-blind, placebo-controlled trial.",T Meurice; C Bauters; X Hermant; V Codron; E VanBelle; E P Mc Fadden; J Lablanche; M E Bertrand; P Amouyel,"The DD genotype for the angiotensin-I converting enzyme (ACE I) deletion allele (D) polymorphism is a possible genetic risk factor for restenosis after coronary stent implantation. We aimed to establish whether or not blockade of ACE with high doses of ACE inhibitors could reduce this risk of angiographic restenosis. We characterised the ACE I/D polymorphism in 345 consecutive patients who were undergoing coronary stenting. 115 had the DD genotype. We assigned 91 of these 115 patients to quinapril 40 mg daily (n=46) or placebo (n=45). Treatment was started within 48 h after stent implantation and continued for 6 months. 79 patients complied with the protocol and underwent follow-up angiography after 6 months. Our primary endpoint of late loss in minimum lumen diameter (a quantitative index of restenosis) was significantly higher in the quinapril group than in the controls (mean 1.11 mm [SD 0.70] vs 0.76 mm [0.60]; p=0.018). Secondary endpoints also showed consistent trends towards increased angiographic restenosis in the treatment group. Contrary to our expectations, ACE inhibitor treatment did not reduce restenosis after coronary stent implantation in patients with DD genotype, but was associated with an exaggerated restenotic process when compared with administration of placebo.",2001.0,0,1
663,11347755,Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes.,M Bojestig; B E Karlberg; T Lindström; F H Nystrom,"To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. Ramipril was administered double blind at two different doses (1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo (n = 18) after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55; women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.",2001.0,0,0
664,11348602,The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function.,B Pitt; B O'Neill; R Feldman; R Ferrari; L Schwartz; H Mudra; T Bass; C Pepine; M Texter; H Haber; A Uprichard; L Cashin-Hemphill; R S Lees; QUIET Study Group,"Angiotensin-converting enzyme inhibitors improve endothelial function, inhibit experimental atherogenesis, and decrease ischemic events. The Quinapril Ischemic Event Trial was designed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events (the occurrence of cardiac death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary artery bypass grafting, coronary angioplasty, or hospitalization for angina pectoris) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction. A total of 1,750 patients were randomized to quinapril 20 mg/day or placebo and followed a mean of 27 +/- 0.3 months. The 38% incidence of ischemic events was similar for both groups (RR 1.04; 95% confidence interval 0.89 to 1.22; p = 0.6). There was also no significant difference in the incidence of patients having angiographic progression of coronary disease (p = 0.71). The rate of development of new coronary lesions was also similar in both groups (p = 0.35). However, there was a difference in the incidence of angioplasty for new (previously unintervened) vessels (p = 0.018). Quinapril was well tolerated in patients after angioplasty with normal left ventricular function. Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis. However, the absence of the demonstrable effect of quinapril may be due to several limitations in study design.",2001.0,0,1
665,11350567,Lisinopril reduces albuminuria during exercise in low grade microalbuminuric type 1 diabetic patients: a double blind randomized study.,P L Poulsen; E Ebbehøj; C E Mogensen,"Antihypertensive treatment is presently recommended in most type 1 diabetic patients with microalbuminuria. The long-term effect of angiotensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urinary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1 diabetic patients with low grade microalbuminuria is not well documented. In addition, the possible predictive effect of baseline E-UAE on the progression of overnight UAE remains to be clarified. In a randomized placebo controlled double blind study the effects of 2 years treatment with either lisinopril (20 mg o.d.) or placebo was evaluated in 21 normotensive type 1 diabetic patients with overnight UAE between 20 and 70 microg min-1. Determinations of E-UAE and E-BP were performed after exercise on an ergometercycle with a load of 70% of estimated maximal VO2 for 20 min. Patients in the placebo and lisinopril groups were similar with regard to age (35.8 +/- 11.3 vs. 29.3 +/- 8.6 years), duration of diabetes (19.4 +/- 8.2 vs. 16.8 +/- 5.3 years), and HbA1c (9.0 +/- 1.0 vs. 9.4 +/- 1.7%). At baseline, E-UAE was similar in the two groups (placebo: 150.1 x or divide 3.7, lisinopril: 96.8 x or divide 1.8 microg min-1 (geometric mean x or divide tolerance factor)). After 2 years treatment E-UAE had increased in the placebo group, whereas E-UAE was reduced in the lisinopril treated patients (placebo: 213.6 x or divide 6.9, lisinopril: 48.3 x or divide 3.1 microg min-1, P = 0.04). The relative increase in E-UAE (E-UAE/Pre-exercise UAE) was similar at baseline in both groups (3.7 x or divide 2.3 vs. 2.8 x or divide 2.0) but significantly higher in the placebo group after 2 years (4.4 x or divide 2.4 compared with 1.6 x or divide 1.7 in the lisinopril group, P < 0.01) These changes over two years in relative increase in E-UAE were significantly different (P = 0.03). Exercise blood pressure was similar in both groups at baseline and over 2 years increased in the placebo group (from 166.5 +/- 15.1-179.9 +/- 35.6 mmHg), in contrast to the lisinopril group where E-BP was slightly reduced (from 168.5 +/- 20.6-165.1 +/- 16.6 mmHg) but the difference in blood pressure over the 2 years did not reach statistical significance. Exercise urinary albumin excretion and E-BP were closely associated (correlation for year 2: r = 0.734, P < 0.001), and also changes over the 2 years in E-UAE and E-BP were positively correlated (r = 0.53, P = 0.01). At year 2, overnight UAE, pre-exercise UAE (pre-E-UAE), E-UAE and E-BP were all closely linked (r-values between 0.6 and 0.9, P-values < 0.01). In the prediction of changes in overnight UAE over 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory information in comparison with baseline overnight UAE and HbA1c. In type 1 diabetic patients with low-grade microalbuminuria, 2 years of ACE-i treatment with lisinopril significantly reduced E-UAE. Strong correlations were found between E-UAE and E-BP and also changes over 2 years in these parameters were significantly associated.",2001.0,0,0
666,11353877,"Early ACE-i intervention in microalbuminuric patients with type 1 diabetes: effects on albumin excretion, 24 h ambulatory blood pressure, and renal function.",P L Poulsen; E Ebbehøj; R Nosadini; P Fioretto; G Deferrari; G Crepaldi; C E Mogensen,"To study the effects of ACE-i in type 1 diabetic patients with early microalbuminuria with regard to: i) UAE, ii) 24 h AMBP, including the effect on diurnal BP variation, and iii) renal haemodynamics. 58 patients with urinary albumin excretion (UAE) between 20-70 microg/min were treated for two years with either the ACE inhibitor (ACE-i) lisinopril (20 mg od) or placebo in two randomised placebo controlled double blind studies. In a subgroup of patients (n=22) we performed 24 h ambulatory blood pressure measurements (AMBP) and renal function tests (constant infusion technique). i) Changes in UAE over the two years were significantly different (p<0.01) in the two groups with final UAE in the lisinopril group of 19.1 microg/min x/divide 2.5 (geometric mean x/divide tolerance factor) and 44.1 microg/min x/divide 2.8 in the placebo group. In the lisinopril group 20 patients (60.6%) reversed to normoalbuminuria compared to 6 patients (24%) in the placebo group (p<0.02). ii) Clinical BP measurements revealed no differences between groups, but by AMBP significant reductions were detectable in the lisinopril group, primarily in night AMBP (systolic/diastolic: - 6.9 +/- 8.6/- 6.0 +/- 5.3 mmHg, p<0.01) as opposed to increases in the placebo group (3.1 +/- 9.3/1.9 +/- 7.3 mmHg). iii) Changes in UAE and changes in filtration fraction (FF) were positively correlated in the intervention group (r=0.9, p<0.01), i.e. the patients who showed the greatest fall in UAE were the ones with the greatest fall in FF. ACE-i treatment in patients with low-grade microalbuminuria reduces 24 h AMBP without attenuating diurnal blood pressure variation, reduces UAE significantly, with changes in UAE being strongly associated with changes in FF. Furthermore, compared to placebo, ACE-i reverses micro- to normoalbuminuria in a significant fraction of patients.",2001.0,0,0
667,11368252,Treating hypertension in women of child-bearing age and during pregnancy.,L A Magee,"Hypertension is found among 1 to 6% of young women. Treatment aims to decrease cardiovascular risk, the magnitude of which is less dependent on the absolute level of blood pressure (BP) than on associated cardiovascular risk factors, hypertension-related target organ damage and/or concomitant disease. Lifestyle modifications are recommended for all hypertensive individuals. The threshold of BP at which antihypertensive therapy should be initiated is based on absolute cardiovascular risk. Most young women are at low risk and not in need of antihypertensive therapy. All antihypertensive agents appear to be equally efficacious; choice depends on personal preference, social circumstances and an agent's effect on cardiovascular risk factors, target organ damage and/or concomitant disease. Although most agents are appropriate for, and tolerated well by, young women, another consideration remains that of pregnancy, 50% of which are unplanned. A clinician must be aware of a woman's method of contraception and the potential of an antihypertensive agent to cause birth defects following inadvertent exposure in early pregnancy. Conversely, if an oral contraceptive is effective and well tolerated, but the woman's BP becomes mildly elevated, continuing the contraceptive and initiating antihypertensive treatment may not be contraindicated, especially if the ability to plan pregnancy is important (e.g. in type 1 diabetes mellitus). No commonly used antihypertensive is known to be teratogenic, although ACE inhibitors and angiotensin receptor antagonists should be discontinued, and any antihypertensive drugs should be continued in pregnancy only if anticipated benefits outweigh potential reproductive risk(s). The hypertensive disorders of pregnancy complicate 5 to 10% of pregnancies and are a leading cause of maternal and perinatal mortality and morbidity. Treatment aims to improve pregnancy outcome. There is consensus that severe maternal hypertension (systolic BP > or = 170mm Hg and/or diastolic BP > or = 110mm Hg) should be treated immediately to avoid maternal stroke, death and, possibly, eclampsia. Parenteral hydralazine may be associated with a higher risk of maternal hypotension, and intravenous labetalol with neonatal bradycardia. There is no consensus as to whether mild-to-moderate hypertension in pregnancy should be treated: the risks of transient severe hypertension, antenatal hospitalisation, proteinuria at delivery and neonatal respiratory distress syndrome may be decreased by therapy, but intrauterine fetal growth may also be impaired, particularly by atenolol. Methyldopa and other beta-blockers have been used most extensively. Reporting bias and the uncertainty of outcomes as defined warrant cautious interpretation of these findings and preclude treatment recommendations.",2001.0,0,0
668,11370797,Sexual dysfunction in hypertensive patients treated with losartan.,J L Llisterri; J V Lozano Vidal; J Aznar Vicente; M Argaya Roca; C Pol Bravo; M A Sanchez Zamorano; C M Ferrario,"Impaired erectile function in men is a component of the dysmetabolic syndrome of high blood pressure as well as a sequela of antihypertensive therapy. This prospective interventional study in men with uncontrolled hypertension (blood pressure > or =140/90 mm Hg) used a survey instrument to assay sexual dysfunction before and after therapy with losartan. We evaluated the influence of a 12-week therapy with losartan in 82 hypertensive subjects with (n = 82) and without (n = 82) a diagnosis of erectile dysfunction using a self-administered questionnaire validated in another 60 subjects with hypertension. From an initial sample of 323 hypertensive men and women, 82 men, aged 30 to 65 years, with sexual dysfunction underwent a 12-week regimen of losartan therapy (50-100 mg/day). Losartan treatment improved sexual satisfaction from an initial 7.3 to 58.5% (chi2; P = 0.001). Subjects reporting a high frequency of sexual activity improved from 40.5% initially to 62.3% after drug treatment, whereas the number of patients with low or very low frequency of sexual activity decreased significantly (chi2; P = 0.001). At the completion of the 12-week losartan regimen, only 11.8% of the treated subjects reported in improvement in sexual function. Improvement on quality of life was demonstrated in 73.7% of subjects medicated with losartan, 25.5% reported no changes, and only 0.8% felt worse. In the group without sexual dysfunction, losartan had a nonsignificant effect on sexual function. Our data suggest that losartan improved erectile function and both satisfaction and frequency of sexual activity. Because side effects are one of the most influential factors in the management of hypertension, an added benefit of losartan therapy may be its positive impact on quality of life.",2001.0,0,0
669,11376827,Effect of antihypertensive therapy using enalapril or losartan on haemostatic markers in essential hypertension: a pilot prospective randomised double-blind parallel group trial.,F L Li-Saw-Hee; D G Beevers; G Y Lip,"To test the hypothesis that the hypercoagulable state in hypertension is significantly altered by anti-hypertensive therapy, we conducted a pilot prospective randomised double-blind trial of 40 untreated hypertensive patients (30 males, mean age 59 years) who were treated with either enalapril (10-20 mg per day) or losartan (50-100 mg per day) for 8 weeks. Thrombogenicity was assessed by measurement of plasma fibrinogen, soluble P-selectin (an index of platelet activation), plasminogen activator inhibitor 1 (PAI-1, an index of fibrinolysis) and von Willebrand factor (an index of endothelial dysfunction). Baseline von Willebrand factor alone was significantly higher in untreated hypertensive patients compared to controls (P<0.001). Following 8 weeks treatment with enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day), there was a significant reduction in mean blood pressure from 169+/-11/94+/-8 mmHg (baseline) to 147+/-14/84+/-7 mmHg (post-treatment) (P<0.001). However, there were no statistically significant changes in the levels of haemostatic markers (von Willebrand factor, fibrinogen, s-Psel and PAI-1). Our pilot study confirms previous observations of endothelial dysfunction in hypertensives. However, plasma fibrinogen and indices of platelet activation, fibrinolysis or endothelial dysfunction were not significantly affected by antihypertensive treatment with enalapril or losartan, despite satisfactory blood pressure control.",2001.0,0,0
670,11377666,"Progression, remission, regression of chronic renal diseases.",P Ruggenenti; A Schieppati; G Remuzzi,"The prevalence of chronic renal disease is increasing worldwide. Most chronic nephropathies lack a specific treatment and progress relentlessly to end-stage renal disease. However, research in animals and people has helped our understanding of the mechanisms of this progression and has indicated possible preventive methods. The notion of renoprotection is developing into a combined approach to renal diseases, the main measures being pharmacological control of blood pressure and reduction of proteinuria. Lowering of blood lipids, smoking cessation, and tight glucose control for diabetes also form part of the multimodal protocol for management of renal patients. With available treatments, dialysis can be postponed for many patients with chronic nephropathies, but the real goal has to be less dialysis-in other words remission of disease and regression of structural damage to the kidney. Experimental and clinical data lend support to the notion that less dialysis (and maybe none for some patients) is at least possible.",2001.0,0,0
671,11380832,Add-on angiotensin receptor blockade with maximized ACE inhibition.,R Agarwal,"Prolonged angiotensin-converting enzyme (ACE) inhibitor therapy leads to angiotensin I (Ang I) accumulation, which may ""escape"" ACE inhibition, generate Ang II, stimulate the Ang II subtype 1 (AT1) receptor, and exert deleterious renal effects in patients with chronic renal diseases. We tested the hypothesis that losartan therapy added to a background of chronic (>3 months) maximal ACE inhibitor therapy (lisinopril 40 mg q.d.) will result in additional Ang II antagonism in patients with proteinuric chronic renal failure with hypertension. Sixteen patients with proteinuric moderately advanced chronic renal failure completed a two-period, crossover, randomized controlled trial. Each period was one month with a two-week washout between periods. In one period, patients received lisinopril 40 mg q.d. along with other antihypertensive therapy, and in the other, losartan 50 mg q.d. was added to the previously mentioned regimen. Hemodynamic measurements included ambulatory blood pressure monitoring (ABP; Spacelabs 90207), glomerular filtration rate (GFR) with iothalamate clearances and cardiac outputs by acetylene helium rebreathing technique. Supine plasma renin activity and plasma aldosterone and 24-hour urine protein were measured in all patients. Twelve patients had diabetic nephropathy, and four had chronic glomerulonephritis. The mean age (+/- SD) was 53 +/- 9 years. The body mass index was 38 +/- 5.7 kg/m(2), and all except two patients were males. Seated cuff blood pressure was 156 +/- 18/88 +/- 12 mm Hg. The pulse rate was 77 +/- 11 per min, and the cardiac index was 2.9 +/- 0.5 L/min/m(2). Mean log 24-hour protein excretion/g creatinine or overall ABPs did not change. Mean placebo subtracted, losartan-attributable change in protein excretion was +1% (95% CI, -20% to 28%, P = 0.89). Similarly, the change in systolic ambulatory blood pressure (ABP) was 4.6 mm Hg (-5.7 to 14.9, P = 0.95), and diastolic ABP was 1.5 mm Hg (-4.5 to 7.6, P = 0.59). No change was seen in cardiac output. However, there was a mean 14% increase (95% CI, 3 to 26%, P = 0.017) in GFR attributable to losartan therapy. A concomitant fall in plasma renin activity by 32% was seen (95% CI, -15%, - 45%, P = 0.002). No hyperkalemia, hypotension, or acute renal failure occurred in the trial. These results were not attributable to sequence or carryover effects. Add-on losartan therapy did not improve proteinuria or ABP over one month of add on therapy. Improvement of GFR and fall in plasma renin activity suggest that renal hemodynamic and endocrine changes are more sensitive measures of AT1 receptor blockade. Whether add-on AT1 receptor blockade causes antiproteinuric effects or long-term renal protection requires larger and longer prospective, randomized controlled trials.",2001.0,0,0
672,11381282,Trapped renal arteries: functional renal artery stenosis due to occlusion of the aorta in the arch and below the kidneys.,D G Hackam; L M Thain; A Abassakoor; F N McKenzie; J D Spence,"Acute renal failure is a well recognized complication from the use of angiotensin-converting enzyme inhibitors in patients with severe bilateral renovascular disease. A 54-year-old woman presented with acute pulmonary edema with intractable hypertension and a history of lower limb claudication. The addition of lisinopril to her antihypertensive regimen resulted, within 48 h, in the development of acute renal failure that remitted with cessation of the drug. She was found to have a heavily calcified occlusion of her aortic arch and another occlusion of the aorta below the renal arteries. Angiography and Doppler ultrasonography showed normal renal arteries. This is the first reported case of angiotensin-converting enzyme inhibitor-induced renal failure occurring in a patient with atherosclerotic occlusion of the aorta. The literature on suprarenal aortic occlusion is reviewed to determine the manner of presentation, prevalent risk factors and physical findings that typify this unique clinical entity.",2001.0,0,0
673,11383751,Pharmacoeconomics of hypertension management: the place of combination therapy.,E Ambrosioni,"Pharmacological treatment of hypertension has been shown to reduce the risk of stroke, coronary events, heart failure and progression of renal disease. However, rates of successful blood pressure control remain low among treated patients while antihypertensive medication represents a large and increasing proportion of healthcare expenditure in many countries. Several influential pharmacoeconomic analyses have confirmed the cost effectiveness of conventional antihypertensive treatments, usually involving monotherapy with diuretics or beta-blockers, compared with alternative strategies. Recent research has shown that a considerable proportion of the total cost of antihypertensive treatment in general practice is due to factors such as inadequate blood pressure control, poor compliance with therapy, discontinuation and switching between therapies. These factors operate to a much lesser extent in well-conducted clinical trials, and have not been fully incorporated into most economic studies. Some novel strategies, particularly low dose combinations of antihypertensive agents, may offer advantages in terms of efficacy, reduced adverse effects and improved compliance with treatment. There is therefore a need for comprehensive pharmacoeconomic analyses of novel strategies, taking these additional factors into account. Until such studies are available, the wider use of low dose combination therapy and other novel strategies should not be held back on the basis of earlier economic studies that have not included all relevant considerations.",2001.0,0,0
674,11384079,"Comparison of the first dose response of fosinopril and captopril in congestive heart failure: a randomized, double-blind, placebo controlled study.",B Eryonucu; L Koldas; F Ayan; N Keser; A Sirmaci,"The purpose of this study was to compare the safety and tolerability of recommended initial doses of fosinopril (FOS) with those of captopril (CAP), in diuretic-treated, salt depleted ""high risk"" patients with congestive heart failure. Thirty patients were randomized in a double blind fashion to receive a single dose of either FOS 10 mg, CAP 6.25 mg or placebo. CAP produced a significant early and brief fall in BP, while the first-dose hypotensive response with FOS did not differ significantly from placebo. Baseline plasma angiotensin converting enzyme (ACE) activity was similar in all groups. Only CAP showed an acute and significant fall in plasma ACE activity, whereas FOS and placebo did not change ACE activity. There was no correlation between mean arterial pressure or percentile change in mean arterial pressure and plasma ACE activity. Also no correlation was found between high or low ACE activity level and first dose hypotension. The practical importance of the results are: For patients with congestive heart failure. FOS and CAP have different effects on BP after the first dose, and this effect may be dependent on the plasma ACE activity level. FOS produces ACE inhibition and BP changes similar to placebo so it is the safer choice for the treatment of congestive heart failure.",2001.0,0,0
675,11386587,Chronic heart failure in Australian general practice. The Cardiac Awareness Survey and Evaluation (CASE) Study.,H Krum; A M Tonkin; R Currie; R Djundjek; C I Johnston,"To investigate the frequency and general practitioner awareness of patients with chronic heart failure (CHF), and to evaluate a cardiac algorithm and document cardiac investigations performed in establishing this diagnosis. Between March and August 1998, consecutive patients aged 60 years and older presenting to their GP were assessed. In patients previously diagnosed with CHF, aetiology and diagnostic assessments were documented. In patients with suspected CHF (by a standardised algorithm, based on World Health Organization guidelines), further investigations and GP diagnosis were recorded. 80 consecutive patients were assessed by each of 341 GPs throughout Australia, reflecting the Australian metropolitan/rural population mix of 1996. This provided a total of 22060 evaluable patients. Estimated numbers of patients with CHF in general practice (previously and newly diagnosed); major aetiological factors; use of ancillary diagnostic tests; drugs prescribed. CHF was diagnosed in 2905 of 22060 patients (13.2%) (2485 previously diagnosed and 420 newly diagnosed). Major aetiological factors were ischaemic heart disease and hypertension. Echocardiography had been performed in 64% of previously diagnosed patients, but was performed in only 22% of possible CHF patients. Angiotensin-converting enzyme (ACE) inhibitors were prescribed in 58.1% of patients with CHF. Patients with evidence of left ventricular dysfunction were more likely to have received ACE inhibitors. CHF appears to be very common in the elderly, based on GP diagnosis of the condition. Of 100 patients aged 60 years and over presenting to their GP, two new cases of CHF will be detected using a simple clinical algorithm in conjunction with appropriate diagnostic tests. ACE inhibitors appear to be underutilised.",2001.0,0,0
676,11386927,Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.,L Y Agodoa; L Appel; G L Bakris; G Beck; J Bourgoignie; J P Briggs; J Charleston; D Cheek; W Cleveland; J G Douglas; M Douglas; D Dowie; M Faulkner; A Gabriel; J Gassman; T Greene; Y Hall; L Hebert; L Hiremath; K Jamerson; C J Johnson; J Kopple; J Kusek; J Lash; J Lea; J B Lewis; M Lipkowitz; S Massry; J Middleton; E R Miller; K Norris; D O'Connor; A Ojo; R A Phillips; V Pogue; M Rahman; O S Randall; S Rostand; G Schulman; W Smith; D Thornley-Brown; C C Tisher; R D Toto; J T Wright; S Xu; African American Study of Kidney Disease and Hypertension (AASK) Study Group,"Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.",2001.0,0,1
677,11393342,A 24-week dose-titration study of the angiotensin-converting enzyme inhibitor imidapril in the treatment of mild-to-moderate essential hypertension in the elderly.,I Dews; M VandenBurg,"This multicentre, randomized, double-blind study compared the anti-hypertensive efficacy and safety of oral once-daily imidapril 5-20 mg and hydrochlorothiazide 12.5-50 mg in elderly patients with mild-to-moderate essential hypertension. After 24 weeks of treatment, there was a significant reduction in mean sitting diastolic blood pressure from 102.5 mmHg to 87.2 mmHg in the imidapril group (n = 226) and from 102.7 mmHg to 87.4 mmHg in the hydrochlorothiazide group (n = 123) (intent-to-treat population). There were corresponding reductions in sitting systolic blood pressure and standing blood pressure. At least one adverse event was reported by 46% of patients in the imidapril group and 53% of patients in the hydrochlorothiazide group. Imidapril 5-20 mg is as effective and well tolerated as hydrochlorothiazide in the treatment of mild-to-moderate hypertension in elderly patients.",2001.0,0,0
678,11393383,A randomized and double-blind comparison of isradipine and spirapril as monotherapy and in combination on the decline in renal function in patients with chronic renal failure and hypertension.,L J Petersen; J R Petersen; U Talleruphuus; M L Møller; S D Ladefoged; J Mehlsen; H A Jensen,"Treatment of hypertension in patients with chronic renal failure has been shown to postpone the decline in renal function. Treatment with an ACE inhibitor has been shown to be superior to conventional antihypertensive treatment, but it is not known how an ACE inhibitor compares to treatment with a calcium channel blocker or to treatment with a combination of these drugs. The aim of the study was to evaluate the rate of decline in GFR in patients with chronic renal failure and hypertension treated with isradipine and spirapril as monotherapy and in combination. Sixty patients with chronic renal failure and hypertension were enrolled in the study. After enrollment, patients were followed prospectively for 6 months in the outpatient clinic on their usual antihypertensive medication, and then randomized to a double-blinded comparison of either spirapril 6 mg daily, isradipine 5 mg daily or spirapril 3 mg and isradipine 2.5 mg daily. After randomization, patients were followed for 21 months or until the need for dialysis. Every 3 months before and 3.5 months after randomization the glomerular filtration rate was measured by 51Cr-EDTA clearance and the effective renal plasma flow evaluated using the renal clearance of paraaminohippuric acid. Blood pressure and the decline in glomerular filtration rate did not differ between the groups before randomization. After randomization, the mean decline in the glomerular filtration rate was -0.32 ml/(min x month x 1.73 m2) in the spirapril group, -0.58 ml/(min x month x 1.73 m2) in the isradipine group and -0.14 ml/(min x month x 1.73 m2) in the combination group (p = 0.38). Twelve patients, 4 in each group, reached end-stage renal failure. No significant difference was found with respect to diastolic (p = 0.10) or systolic blood pressure (p = 0.08) during the treatment period, but a trend towards a better blood pressure control in the combination group was present. During treatment, the rate of decline in renal plasma flow did not differ significantly between the groups (p = 0.09), neither did the changes in filtration fraction (FF) (p = 0.58) nor the mean FF (p = 0.22) during the treatment. Our study indicated differences between the 3 treatment modalities in favor of combined therapy with respect to both the rate of decline in GFR and blood pressure control, but the differences where insignificant. Thus, the treatments might differ, but we were unable to confirm this because of large variation in GFR and small sample size.",2001.0,0,0
679,11395222,Benefits of antihypertensive drug treatment in elderly patients with isolated systolic hypertension.,J G Wang; J A Staessen,"Isolated systolic hypertension affects over 15% of all people older than 60 years. In the elderly, systolic hypertension is a major modifiable cardiovascular risk factor. Systolic blood pressure is associated with higher risk of an adverse outcome, whereas diastolic blood pressure is inversely correlated with total mortality, independent of systolic blood pressure, highlighting the role of pulse pressure as risk factor. Three placebo-controlled outcome trials on antihypertensive drug treatment in older patients with isolated systolic hypertension have been published: the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in Europe (Syst-Eur) Trial and the Systolic Hypertension in China (Syst-China) Trial. These three trials demonstrated the benefit of antihypertensive drug treatment. A meta-analysis was performed by pooling the patients from these three trials with a subset of patients with isolated systolic hypertension from five other trials in the elderly. Antihypertensive treatment based on a calcium-channel blocker may provide additional benefits in diabetic patients and in the prevention of dementia and renal dysfunction. The pooled results of 15693 older patients with isolated systolic hypertension prove that antihypertensive drug treatment is justified if on repeated clinic measurements systolic blood pressure is 160 mmHg or higher.",2001.0,0,0
680,11397366,Comparison of effects of losartan versus enalapril on fibrinolysis and coagulation in patients with acute myocardial infarction.,H Soejima; H Ogawa; H Suefuji; K Kaikita; K Takazoe; S Miyamoto; I Kajiwara; H Shimomura; T Sakamoto; M Yoshimura; S Nakamura,,2001.0,0,0
681,11397368,Effect of quinapril versus nitrendipine on endothelial dysfunction in patients with systemic hypertension.,A Uehata; B Takase; T Nishioka; K Kitamura; T Akima; A Kurita; K Isojima,,2001.0,0,0
682,11397596,Androgenetic alopecia in men and women.,R D Sinclair; R P Dawber,,2001.0,0,0
683,11398915,Perindopril: an updated review of its use in hypertension.,M Hurst; B Jarvis,"Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Perindopril 4 to 8 mg once daily significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients. These reductions are maintained for at least 24 hours, as evidenced by trough/peak ratios of >50%. Vascular abnormalities associated with hypertension were improved or normalised during perindopril treatment. Perindopril 4 to 8 mg once daily significantly decreased carotid-femoral aortic pulse wave velocity (PWV), improved arterial compliance, reduced left ventricular mass index and, in patients with recent cerebral ischaemia and/or stroke, preserved cerebral blood flow despite significantly reducing SBP and DBP. Further research is needed to establish the significance of promising results showing that reductions in aortic PWV were associated with reduced mortality in patients with end-stage renal failure, a third of whom received perindopril. Response rates (numbers of patients with supine DBP < or = 90 mm Hg) were significantly higher with perindopril 4 to 8 mg once daily (67 to 80%) than with captopril 25 to 50 mg twice daily (44 to 57%) in 3 randomised double-blind trials. In other clinical trials, the antihypertensive effects of perindopril were similar to those of other ACE inhibitors (including enalapril) and calcium-channel antagonists. Combination treatment with perindopril and an antihypertensive agent from another treatment class provided additional benefits, either as first-line treatment or in patients failing to respond to monotherapy. Perindopril monotherapy was also effective in the elderly and in patients with hypertension and concomitant disease. Perindopril has a similar adverse event profile to that of other ACE inhibitors; cough is the most common event reported during treatment, and is also the most common adverse event responsible for treatment withdrawal. Perindopril is a well tolerated ACE inhibitor that is significantly better than captopril (in terms of response rates) in the treatment of hypertension, and as effective as other ACE inhibitors. Perindopril appears to reverse some of the vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy, although further research is needed to confirm promising results regarding its ability to decrease associated cardiovascular morbidity and mortality. Results from ongoing studies will help confirm the place of perindopril in the treatment of hypertension; currently, it is an effective and well tolerated treatment for patients with mild to moderate essential hypertension.",2001.0,0,0
684,11403364,"Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.",P S Sever; B Dahlöf; N R Poulter; H Wedel; G Beevers; M Caulfield; R Collins; S E Kjeldsen; G T McInnes; J Mehlsen; M Nieminen; E O'Brien; J Ostergren,"To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. Patients were recruited mainly from general practices. Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.",2002.0,0,0
685,11406907,Antihypertensive efficacy and tolerability of low-dose perindopril/indapamide combination compared with losartan in the treatment of essential hypertension.,X Chanudet; M De Champvallins,"The aim of the study was to evaluate the antihypertensive efficacy and tolerability of the low-dose combination of the angiotensin-converting enzyme inhibitor perindopril 2 mg plus the diuretic indapamide 0.625 mg (P/I) compared with the angiotensin II antagonist losartan 50 mg (L50) in the treatment of essential hypertension. Patients (n = 277) were randomised, double-blind and allocated to receive either P/I or L50 once daily for a period of 12 weeks. Responder and normalisation rates in the two groups were compared by a chi 2 test. Ambulatory blood pressure monitoring results were compared using the one-tailed Student's t-test. Normalisation rates were significantly greater in the P/I group (76.0%) than in the L50 group (60.0%) (p = 0.009). Responder rates were significantly higher in the P/I group (91.7%) than in the L50 group (81.8%) (p = 0.025). The average blood pressure reductions were: in sSBP (P/I-L50 = -2.4 mmHg; CI: 6.2; 1.3) and sDBP (P/I-L50 = -2.0 mmHg; CI: -4.2; 0.2). The average night-time SBP decrease (ABPM) was significantly greater in the P/I group (p = 0.041). The tolerability was comparable between the two groups in terms of emergent adverse events related to treatment (12.4% for P/I patients and 8.4% for L50 patients). Laboratory evaluations did not show any significant variations. It was concluded the low-dose P/I combination had significantly higher responder and normalisation rates than L50. This study also confirmed the good tolerability of both treatments.",2001.0,0,0
686,11410114,Lisinopril improves endothelial function in chronic cigarette smokers.,R Butler; A D Morris; A D Struthers,"Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38+/-12 years; mean+/-S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measurement of forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasodilators and an endothelial-dependent vasoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-L-arginine (L-NMMA) respectively] using venous occlusion plethysmography. Lisinopril significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12+/-0.37 (mean+/-S.E.M.); placebo, 2.58+/-0.25; P=0.02, 95% confidence intervals (CI) 0.09, 1.06] (values given are ratios of flow in the infused arm to that in the control arm); there was no effect on the response to sodium nitroprusside (lisinopril, 3.97+/-0.40; placebo, 3.92+/-0.39; P=0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to L-NMMA demonstrated a significant improvement (lisinopril, 0.77+/-0.06; placebo, 0.95+/-0.05; P<0.001; 95% CI -0.09, -0.27). In conclusion, these results indicate that ACE inhibition can improve endothelial function in cigarette smokers. We show that lisinopril improves both receptor-mediated and tonic NO release. The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release.",2001.0,0,0
687,11411737,Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators.,M R Weir; M A Weber; J M Neutel; J Vendetti; E L Michelson; R Y Wang,"A large-scale, 8-week, open-label, clinical experience trial evaluated the efficacy of the angiotensin II receptor (AT1 subtype) blocker candesartan cilexetil (16 to 32 mg once daily) either alone or as add-on therapy in 6465 hypertensive patients. The study population was 52% female and 16% African American with a mean age of 58 years. It included 5,446 patients who had essential hypertension (HBP) and 1,014 patients who had isolated systolic hypertension (ISH). These patients had either untreated or uncontrolled hypertension (systolic blood pressure [SBP] 140 to 179 mm Hg or diastolic blood pressure [DBP] 90 to 109 mm Hg inclusive at baseline) despite a variety of antihypertensive medications including diuretics, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, and alpha- or beta-blockers, either singly or in combination. The mean baseline blood pressure for the HBP group was 156/97 mm Hg. Candesartan cilexetil as monotherapy (in 51% of HBP patients) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg. As add-on therapy (in 49% of HBP patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.8/11.3 mm Hg), calcium antagonists (16.6/11.2 mm Hg), beta-blockers (16.5/ 10.4 mm Hg), ACE inhibitors (15.3/10.0 mm Hg), alpha-blockers (16.4/10.4 mm Hg). The mean baseline blood pressure for the ISH group was 158/81 mm Hg. Candesartan cilexetil, as monotherapy (in 34% of ISH patients), reduced SBP/DBP by 17.0/4.4 mm Hg. As add-on therapy (in 66% of ISH patients) to various background therapies, candesartan cilexetil consistently reduced mean SBP/DBP further, irrespective of the background therapy: diuretics (17.4/5.1 mm Hg), calcium antagonists (15.6/3.6 mm Hg), beta-blockers (14.0/4.8 mm Hg), ACE inhibitors (13.4/4.3 mm Hg), and alpha-blockers (11.6/4.5 mm Hg). The further blood pressure lowering effects of candesartan cilexetil as add-on therapy were seen regardless of age, sex, and race. Overall, 6.8% of the 6465 patients withdrew because of adverse events, most commonly headache (6.3%) and dizziness (5.0%). Orthostatic hypotension was infrequent; 0.2% with candesartan cilexetil alone, and 0.8% with candesartan cilexetil as add-on therapy. Thus, candesartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice settings.",2001.0,0,0
688,11413085,Differential effects of nifedipine and co-amilozide on the progression of early carotid wall changes.,A Simon; J Gariépy; D Moyse; J Levenson,"Common carotid artery intima-media thickness (IMT) progression was compared between 4 years of treatment with nifedipine and diuretic. This study, ancillary to the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), involved nifedipine 30 mg or co-amilozide (hydrochlorothiazide 25 mg and amiloride 2.5 mg) with optional subsequent titration. Among 439 randomized hypertensive patients, 324 had >/=1 year of follow-up (intent-to-treat group), and 242 completed follow-up (until-end-of-study group). Ultrasonography was performed at baseline, 4 months later, and then every year. Central computerized reading provided far-wall IMT, diameter, and cross-sectional area IMT (CSA-IMT). The primary outcome was IMT progression rate (slope of IMT-time regression). Secondary outcomes were changes from baseline (Delta) in IMT, diameter, and CSA-IMT. In the until-end-of-study population, between-treatment differences existed in IMT progression rate (P=0.002), Delta IMT (P=0.001), and Delta CSA-IMT (P=0.006), because IMT progressed on co-amilozide but not on nifedipine. In the intent-to-treat population, treatment differences existed in Delta IMT (P=0.004) and Delta CSA-IMT (P=0.04) but not in IMT progression rate (P=0.09). Patients with >/=2, 3, or 4 years of follow-up showed treatment differences in IMT progression rate (P=0.04, 0.004, 0.007, respectively), Delta IMT (P=0.005, 0.001, 0.005), and Delta CSA-IMT (P=0.025, 0.013, 0.015). Diameter decreased more on co-amilozide than on nifedipine in the intent-to-treat population (P<0.05), whereas blood pressure decreased similarly on both treatments. A difference in early carotid wall changes is shown between 2 equally effective antihypertensive treatments.",2001.0,0,0
689,11413935,Efficacy and safety of angiotensin II receptor blockers in elderly patients with mild to moderate hypertension.,C E Okereke; F H Messerli,"The role of the renin-angiotensin-aldosterone system in the pathogenesis of hypertensive disease has long been recognized, and the interruption of this cascade with angiotensin-converting enzyme-I has been beneficial in the management of hypertension. Recently, a new class of drugs, the angiotensin receptor blockers, emerged, enlarging the antihypertensive armamentarium. Since elderly patients are more prone to adverse drug reactions, in this paper we review several trials, most of which were of short duration, on the efficacy and safety of angiotensin receptor blockers in the geriatric population with mild to moderate hypertension. These studies established that the drugs are well-tolerated, safe, and in most instances as efficacious as other classes of antihypertensive medications. Combination therapy with angiotensin receptor blockers and hydrochlorothiazide was additive, without any significant effect on the safety profile.",2001.0,0,0
690,11416677,Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study.,G Bakris; A Gradman; M Reif; M Wofford; M Munger; S Harris; J Vendetti; E L Michelson; R Wang; CLAIM Study Investigators,"An 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study was conducted to evaluate the antihypertensive efficacy of candesartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were randomized to candesartan cilexetil 16 mg once daily, or losartan 50 mg once daily. Two weeks following randomization, patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks. At week 8, candesartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan (13.3/10.9 mm Hg with candesartan cilexetil vs. 9.8/8.7 mm Hg with losartan; p less than 0.001). At the same period, candesartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan (15.2 to 11.6 mm Hg with candesartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan; p less than 0.05). There were statistically significantly (p less than 0.05) higher proportions of responders and controlled patients in the candesartan cilexetil group (62.4% and 56.0%, respectively) than in the losartan group (54.0% and 46.9%, respectively). Both treatment regimens were well tolerated; 1.8% in the candesartan cilexetil group and 1.6% in the losartan group withdrew because of adverse events. In conclusion, this forced-titration study confirms that candesartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses. Both drugs were well tolerated. (c)2001 by Le Jacq.",2001.0,0,0
691,11416681,Choosing initial antihypertensive drug therapy for the uncomplicated hypertensive patient.,M A Moore,"Choosing the initial antihypertensive drug for the uncomplicated hypertensive patient is an important and frequent event for the primary care physician. Patients' first experience with antihypertensive drug therapy will likely affect their long-term perception of hypertension treatment. The choice should be made on the basis of sound scientific data and from the patient's perspective and needs. The drug should be taken once a day, should have proven efficacy in hypertension control and cardiovascular morbidity and mortality reduction, and should have as few side effects as possible. Low-dose thiazide diuretics meet this description, although the need to monitor electrolytes may make them less than ideal. The angiotensin II receptor antagonist class, with side-effects similar to those of placebo in controlled trials, is the most attractive from the patient's perspective, although outcome trial data do not yet exist proving that hypertension treatment with angiotensin II receptor antagonists reduces cardiovascular events. The angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists, with their low side-effect profiles and unique effects on vascular remodeling, are attractive second choices to combine with a diuretic if needed, although low-dose diuretic/Beta blocker combinations have also been shown to lower blood pressure with minimal side effects. At present, ensuring adequate long-term hypertension control is the most important aspect of hypertensive care, and which antihypertensive drug(s) the physician chooses can greatly affect the hypertensive patient's ability to achieve and to maintain long-term blood pressure control. (c)2001 by Le Jacq Communications, Inc.",2001.0,0,0
692,11416692,"Treating hypertension in the elderly--whom to treat, when, and with what?",M Moser; W Cushman; S Oparil; S Glasser,,2001.0,0,0
693,11416701,Emergency room management of hypertensive urgencies and emergencies.,D G Vidt,"Hypertensive crisis affects upward of 500,000 Americans each year. Although the incidence of hypertensive crisis is low, affecting fewer than 1% of hypertensive adults, more than 50 million adult Americans suffer from hypertension. Presentation of a patient with severe hypertension to the emergency room demands immediate evaluation, prompt recognition of a hypertensive emergency or urgency, and the prompt institution of appropriate therapeutic measures to prevent progression of target-organ damage and to avoid a catastrophic event. Hypertensive emergencies are severe elevations in blood pressure that are complicated by evidence of progressive target-organ dysfunction such as coronary ischemia, disordered cerebral function, a cerebrovascular event, pulmonary edema, or renal failure. Although therapy with parenteral antihypertensive agents may be initiated in the emergency department, these patients warrant prompt admission to an intensive care unit where continuous monitoring of blood pressure can be assured during therapy.",2001.0,0,0
694,11420767,A health perception score predicts cardiac events in patients with heart failure: results from the IMPRESS trial.,E P Havranek; P Lapuerta; T A Simon; G L'Italien; A J Block; J L Rouleau,"New York Heart Association (NYHA) class and treadmill exercise test variables are widely used for estimating prognosis and measuring the outcomes of treatment in patients with heart failure, but they do not take patients' perceptions into account. Five hundred forty-five patients enrolled in a multicenter 24-week comparison of the effects of omapatrilat and lisinopril on functional capacity in patients with heart failure reported a visual analog scale (VAS) score of their overall health perception at week 12 of the study. A total of 27 first events, defined as death or worsening heart failure (hospitalization, emergency room visit, or study discontinuation), occurred in the subsequent 12 weeks. The mean (+/-SD) health perception scores were 0.43 +/- 0.31 and 0.68 +/- 0.20 in patients with and without events, respectively (P =.0006). The risk ratio (RR) for an event associated with a decile change in the health perception score was 0.74 (95% confidence interval [CI], 0.61-0.88; P =.001). The RR was unaltered by adjustment for demographic variables, treadmill time, and NYHA functional class. Although the week 12 NYHA functional class was predictive of events (RR = 2.1; 95% CI, 1.2-4.6; P =.04), treadmill time was not (RR = 0.87; 95% CI, 0.73-1.03; P = 0.11). A patient-reported measure of perceived health predicts events in patients with heart failure.",2001.0,0,0
695,11422755,Long-term beneficial effect of ACE inhibition on diabetic nephropathy in normotensive type 1 diabetic patients.,H H Parving; E Hommel; B R Jensen; H P Hansen,"The purpose of this study was to assess whether long-term (8 years) inhibition of angiotensin-converting enzyme (ACE) protects kidney function in normotensive type 1 diabetic patients with diabetic nephropathy. We performed an open randomized follow-up study of normotensive type 1 diabetics with nephropathy either treated (N = 15) or not (N = 17) with captopril twice per day (average 74, range 12.5 to 125 mg/day). The main outcome measures were arterial blood pressure, albuminuria, and glomerular filtration rate (GFR; 51Cr-EDTA plasma clearance, twice yearly). Arterial blood pressure (mm Hg) was kept constant in the captopril group, at baseline (mean, SEM), 128/78 (3/2) and during follow-up 129/77 (4/1) but increased significantly in the control group from 127/79 (2/1) to 137/84 (5/2) (P < 0.01). Furthermore, 8 out of the 17 control subjects required treatment with blood pressure-lowering drugs because they developed hypertension. The fractional albumin clearance (x10-5) remained unchanged in the captopril group: baseline [10.8 (1.25) geometric mean and antilog (SEM)] during the eight years [11.8 (1.47)], while a significant rise occurred in control patients: 13.3 (1.23) to 26.2 (1.42) (P < 0.05). Baseline GFR was nearly identical: 111 (6) and 115 (4) mL/min/1.73 m2 in the captopril and control group, respectively. The median (range) rate of decline in GFR (mL/min/year) was 1.7 (10.7 to -2.0) in the captopril group versus 2.8 (17.7 to -2.6) in the control group (P = NS). The beneficial effect of captopril in arresting the rise in systemic blood pressure and albuminuria is long lasting. A loss in GFR is minimal in most patients with diabetic nephropathy if normotension is sustained by prospective treatment with ACE inhibitors or restored by implementation of other antihypertensive medications with the development of hypertension.",2001.0,0,0
696,11423299,Sternal dehiscence after cardiac surgery and ACE inhibitors [correction of ACE type 1 inhibition].,Q Abid; S R Podila; S Kendall,"We report two cases, which underwent surgery through Median sternotomy. They were on ACE inhibitors [corrected] pre-operatively. Both of these patients developed persistent dry cough post-operatively, which resulted in sternal wound dehiscence. They had no clinical or bacteriological evidence of sternal wound infection. Although one patient was overweight and had moderately impaired left ventricular function, there were no other associated risk factors. Both patients underwent rewiring of the sternum. Type II receptors inhibitor were introduced post-rewiring, which cured the persistent dry cough. Both the patients are enjoying a good quality of life at 2 year 6 months and 2 years post-rewiring of the sternum.",2001.0,0,0
697,11423708,Effects of chronic nitrate therapy on left-ventricular volume in patients with heart failure secondary to coronary disease already treated with captopril: a withdrawal study.,S Wieshammer; M Hetzel; J Hetzel; E Henze; V Hombach,"This randomized, double-blind, placebo-controlled study with treatment lasting 16 weeks and withdrawal lasting 6 weeks tried to determine whether stopping nitrates has an effect on left-ventricular end-systolic volume in patients with heart failure who were chronically treated with captopril and diuretics. The study group comprised 29 patients with previous myocardial infarction, symptoms of mild-to-moderate heart failure, ejection fraction below 40%, no exercise-induced angina and no electrocardiographic signs of ischemia. After all patients had been treated with captopril (target dose: 25 mg twice daily), diuretics and the study drug (target dose: 40 mg isosorbide dinitrate twice daily or placebo) for 16 weeks, the study drug was withdrawn. The patients were then maintained on captopril and diuretics at constant doses for a 6-week withdrawal period. Radionuclide ventriculography with right-heart catheterization was performed at rest and during supine bicycle exercise after 16 weeks of double-blind treatment and at the end of the 6-week withdrawal period. The changes in resting parameters following the withdrawal of the study drug were not different between the groups. At comparable maximum workload (placebo group 68 +/- 15 W, nitrate group 68 +/- 20 W), nitrate withdrawal caused a decrease in ejection fraction (placebo withdrawal: +0.8 +/- 4.0%; nitrate withdrawal: -2.7 +/- 4.3%, p < 0.02) and increases in left-ventricular end-diastolic volume (-9 +/- 35 vs. 23 +/- 48 ml, p < 0.02) and end-systolic volume (-9 +/- 33 vs. +24 +/- 47 ml; p < 0.01). The addition of nitrates to a baseline therapy with captopril and diuretics might reduce exercise-induced left-ventricular dilatation in patients with heart failure from coronary disease.",2001.0,0,0
698,11430394,A prospective comparison of four antihypertensive agents in daily clinical practice.,C Campo; J Segura; M L Fernández; L Guerrero; H Christiansen; L M Ruilope,,2001.0,0,1
699,11433130,Canadian valsartan study in patients with mild-to-moderate hypertension.,B H Lasko; A Laplante; D Hébert; S Bonnefis-Boyer,"This study was designed mainly to establish the rates of response to valsartan 80mg once daily (qd) and to valsartan 160mg qd given to non-responders to 80mg qd, as well as to determine the safety of valsartan and the blood pressure control achieved using valsartan over a period of 24 h or more, using ambulatory blood pressure monitoring (ABPM) devices. This was a single-blind, single-arm, multicenter study involving 256 out-patients with mild-to-moderate essential hypertension. After previous antihypertensive treatments had been 'washed out', the patients were entered into a 2-week placebo run-in period to confirm the diagnosis of mild-to-moderate hypertension. Patients who, at the end of the placebo run-in period, had a mean sitting diastolic blood pressure of between 95 and 115mmHg inclusive received valsartan 80mg qd for 4 weeks. Non-responders (those not demonstrating a diastolic blood pressure of less than 90mmHg or a decrease in diastolic blood pressure of 10mmHg or more compared with baseline) received valsartan 160mg qd for another 4 weeks. In selected centers, patients who agreed also had their blood pressure monitored for 24 h, provided their blood pressure was shown to be controlled. Of these patients, half skipped one dose of valsartan and were monitored for an additional 24h period. The rate of response to valsartan 80mg was 45.4%, and of those not responding to this dose, 36.3% responded to valsartan 160mg. The response rate to one or other dose was 63.2%. The ambulatory blood pressure data support a consistent reduction of blood pressure with valsartan over a 24h period and for up to 32 h after dosing in those who missed a dose. The overall incidence of adverse experiences per person-year, treatment related or otherwise, was 6.3 and 10.6 for the valsartan and placebo study periods respectively. Antihypertensive treatment with valsartan for 8 weeks produced a significant decrease in diastolic blood pressure in hypertensive patients. In addition, the drug may be safely administered, and the results of 24 h/48 h ambulatory monitoring demonstrate that valsartan is a true once-a-day antihypertensive.",2002.0,0,0
700,11434450,Monotherapy versus combination therapy as first line treatment of uncomplicated arterial hypertension.,M Ruzicka; F H Leenen,"Mild to moderate hypertension still remains poorly controlled. This relates to multiple factors including low antihypertensive efficacy of single drug therapies reluctance of primary care physicians to modify/titrate initially chosen therapy to obtain target blood pressure, and poor compliance with medication. Several guidelines for the treatment of high blood pressure now include combination therapy with low doses of 2 drugs as one of the strategies for the initial management of mild/moderate arterial hypertension. Evidence discussed in this article points to superior control of blood pressure by combinations of low doses of 2 drugs as compared with monotherapy in regular doses. This superior effectiveness of combined therapy relates to a better antihypertensive efficacy and higher response rates in the low range of doses as the result of complementary mechanisms of antihypertensive effects, better tolerance as a result of a lower rate of adverse effects in the low dose range, improved compliance from better tolerance and simple drug regimen, and lower cost. Whether increased use of fixed low dose combination therapies would translate to better control of arterial hypertension in the population and thereby further reduction of cardiovascular/cerebrovascular morbidity and mortality caused by hypertension remains to be assessed.",2002.0,0,0
701,11434453,Barnidipine.,H S Malhotra; G L Plosker,"Bamidipine is an antihypertensive drug belonging to the dihydropyridine (DHP) group of calcium antagonists. It is available in a modified-release formulation which has a gradual onset of action and is effective in a single daily oral dose of 10 to 20 mg. Bamidipine has selective action against cardiovascular calcium antagonist receptors and its antihypertensive action is related to the reduction of peripheral vascular resistance secondary to its vasodilatory action. The clinical antihypertensive efficacy of barnidipine is similar to that of other DHP calcium antagonists such as nitrendipine and amlodipine, and antihypertensives belonging to other drug classes such as atenolol and enalapril. Barnidipine has been found to be as efficacious and well tolerated as hydrochlorothiazide in the management of hypertension in elderly patients. Barnidipine is generally well tolerated. As with other DHP calcium antagonists, vasodilator adverse events such as headache, flushing and peripheral oedema account for most of the adverse events reported with its use and are usually transient. Oedema is less frequent than with amlodipine and nitrendipine. Its use is not associated with reflex tachycardia.",2002.0,0,0
702,11436209,The effects of ACE inhibitor therapy on left ventricular myocardial mass and diastolic filling in previously untreated hypertensive patients: a cine MRI study.,U Hoffmann; S Globits; T Stefenelli; C Loewe; K Kostner; H Frank,"Cardiac remodeling in case of hypertension induces hypertrophy of myocytes and elevated collagen content and, subsequently, impaired diastolic filling of the left ventricle. The purpose of this prospective study was to evaluate changes of left ventricular (LV) myocardial mass, as well as diastolic filling properties, in hypertensive patients treated with the ACE inhibitor fosinopril. Sixteen hypertensive patients with echocardiographically documented LV hypertrophy and diastolic dysfunction received fosinopril (10-20 mg daily). Measurements of LV myocardial mass and properties of diastolic filling (peak filling fraction (PFF); peak filling rate (PFR)) were performed prior to medication, as well as after 3 and 6 months of therapy using cine magnetic resonance imaging (MRI). Ten healthy subjects served as a control group. LV myocardial mass (g/m2) decreased continuously within 3-6 months of follow-up by 32% (148 +/- 40 vs. 120 +/- 26 vs. 101 +/- 22 g/m2; P < 0.0001/0.005). The extent of regression correlated to the severity of LV hypertrophy at baseline (r = 0.77; P < 0.004). Early diastolic filling increased significantly within 6 months of therapy (PFF (%): 36 +/- 6 vs. 61 +/- 7, P < 0.0001; PFR (mL/second): 211 +/- 48 vs. 282 +/- 48, P < 0.001). Cine MRI can be used to assess the time course of pharmacological effects on cardiac remodeling in the course of hypertension. ACE inhibitor therapy results in a significant reduction of LV mass within 3 months and is accompanied by a normalization of diastolic filling that is completed after 6 months.",2001.0,0,0
703,11437859,Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition.,N Chaturvedi; J H Fuller; F Pokras; R Rottiers; N Papazoglou; L P Aiello; EUCLID Study Group,"To determine whether circulating plasma vascular endothelial growth factor (VEGF) is elevated in the presence of diabetic microvascular complications, and whether the impact of angiotensin-converting enzyme (ACE) inhibitors on these complications can be accounted for by changes in circulating VEGF. Samples (299/354 of those with retinal photographs) from the EUCLID placebo-controlled clinical trial of the ACE inhibitor lisinopril in mainly normoalbuminuric non-hypertensive Type 1 diabetic patients were used. Albumin excretion rate (AER) was measured 6 monthly. Geometric mean VEGF levels by baseline retinopathy status, change in retinopathy over 2 years, and by treatment with lisinopril were calculated. No significant correlation was observed between VEGF at baseline and age, diabetes duration, glycaemic control, blood pressure, smoking, fibrinogen and von Willebrand factor. Mean VEGF concentration at baseline was 11.5 (95% confidence interval 6.0--27.9) pg/ml in those without retinopathy, 12.9 (6.0--38.9) pg/ml in those with non-proliferative retinopathy, and 16.1 (8.1--33.5) pg/ml in those with proliferative retinopathy (P = 0.06 for trend). Baseline VEGF was 15.2 pg/ml in those who progressed by at least one level of retinopathy by 2 years compared to 11.8 pg/ml in those who did not (P = 0.3). VEGF levels were not altered by lisinopril treatment. Results were similar for AER. Circulating plasma VEGF concentration is not strongly correlated with risk factor status or microvascular disease in Type 1 diabetes, nor is it affected by ACE inhibition. Changes in circulating VEGF cannot account for the beneficial effect of ACE inhibition on retinopathy.",2001.0,0,0
704,11441198,Angiotensin-converting enzyme inhibition with enalapril slows progressive intima-media thickening of the common carotid artery in patients with non-insulin-dependent diabetes mellitus.,N Hosomi; K Mizushige; H Ohyama; T Takahashi; M Kitadai; Y Hatanaka; H Matsuo; M Kohno; J A Koziol,"Whether angiotensin-converting enzyme (ACE) inhibitors have any clinically significant antiatherogenic effects in humans remains unproven. We undertook a prospective randomized clinical trial of 98 patients with non-insulin-dependent diabetes mellitus (NIDDM) to examine the efficacy of ACE inhibition with enalapril for preventing intima-media (IM) thickening of the carotid wall as measured ultrasonographically. Ninety-eight NIDDM patients were randomly assigned either to enalapril at 10 mg/d (n=48) or to a control group (n=50); the planned duration of the trial was 2 years. All patients were seen at baseline (study entry) and 2 subsequent formal annual evaluations, in addition to standard clinical management for NIDDM. IM thickening and vascular lumen diameters were determined for all patients on the basis of baseline and 2 subsequent annual evaluations with carotid ultrasonography. We performed an intent-to-treat analysis to assess changes in IM thickening over the course of the study. Annual IM thickening measurements of the right and left common carotid arteries were 0.01+/-0.02 and 0.01+/-0.02 mm/y in the enalapril-treated group and 0.02+/-0.03 and 0.02+/-0.02 mm/y in the control group, respectively (P<0.05). From regression analysis, annual IM thickening was found to be predicted by enalapril use, sex, and insulin use (F(3,94)=3.86, P=0.012). When we controlled for these other variables, enalapril use reduced annual IM thickening of right and left common carotid arteries by 0.01+/-0.004 mm/y relative to the control group over the course of this study. Long-term treatment with an ACE inhibitor (enalapril) slows progressive IM thickening of the common carotid artery in NIDDM patients.",2001.0,0,0
705,11444507,The kidney in congestive heart failure: renal adverse event rate of treatment.,C Delles; R E Schmieder,"In this paper we review the effect of medical treatment on renal function in patients with congestive heart failure. We have examined data from the large-scale heart failure studies with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-receptor blockers, an aldosterone antagonist, and a vasopeptidase inhibitor. Renal outcome was reported in almost all of the studies with angiotensin-converting enzyme inhibitors. Despite concern about renal adverse events with drugs in this class, they seem to be safe in patients with congestive heart failure. In contrast, we did not find any report about renal function in patients treated with beta-receptor blockers for congestive heart failure.",2002.0,0,0
706,11447306,Clinical experience with endothelin receptor antagonists in chronic heart failure.,A Seed; M P Love; J J McMurray,"Both ET(A) selective and dual, ET(A/B), receptor antagonists have favourable short- and longer-term haemodynamic actions in patients with acute and chronic heart failure. Their effect on neurohumoral measures is not yet fully determined. Two moderately large, medium-duration studies have examined the effect of dual ET(A/B) receptor antagonists on clinical status, reaching conflicting conclusions. One large scale, long-term, morbidity mortality evaluation is underway with bosentan.",2001.0,0,0
707,11448662,Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs.,M A Perazella; K Tray,,2001.0,0,0
708,11453706,Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.,T H Jafar; C H Schmid; M Landa; I Giatras; R Toto; G Remuzzi; G Maschio; B M Brenner; A Kamper; P Zucchelli; G Becker; A Himmelmann; K Bannister; P Landais; S Shahinfar; P E de Jong; D de Zeeuw; J Lau; A S Levey,"To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease. 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease. Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997. Data on 1860 nondiabetic patients were analyzed. Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d. Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.",2001.0,0,0
709,11453887,Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients.,E Bellissant; J F Giudicelli,"We compared the relationships between the plasma concentrations (C) of perindoprilat, active metabolite of the angiotensin I-converting enzyme inhibitor (ACEI) perindopril, and the effects (E) induced on plasma converting enzyme activity (PCEA) and brachial vascular resistance (BVR) in healthy volunteers (HV) and in congestive heart failure (CHF) patients after single oral doses of perindopril. Six HV received three doses of perindopril (4, 8, 16 mg) in a placebo-controlled, randomized, double-blind, crossover study whereas 10 CHF patients received one dose (4 mg) in an open study. Each variable was determined before and 6-12 times after drug intake. E (% variations from baseline) were individually related to C (ng ml(-1)) by the Hill model E=Emax x Cgamma/(CE50gamma + Cgamma). When data showed a hysteresis loop, an effect compartment was used. (means+/-s.d.) In HV, relationships between C and E were direct whereas in CHF patients, they showed hysteresis loops with optimal k(e0) values of 0.13 +/- 0.16 and 0.13 +/- 0.07 h(-1) for PCEA and BVR, respectively. For PCEA, with Emax set to -100%, CE50 = 1.87 +/- 0.60 and 1.36 +/- 1.33 ng ml(-1) (P = 0.34) and gamma = 0.90 +/- 0.13 and 1.11 +/- 0.47 (P = 0.23) in HV and CHF patients, respectively. For BVR, Emax= -41 +/- 14% and -60 +/- 7% (P = 0.02), CE50 = 4.95 +/- 2.62 and 1.38 +/- 0.85 ng ml(-1) (P = 0.02), and gamma = 2.25 +/- 1.54 and 3.06 +/- 1.37 (P = 0.32) in HV and CHF patients, respectively. Whereas concentration-effect relationships were similar in HV and CHF patients for PCEA blockade, they strongly differed for regional haemodynamics. This result probably expresses the different involvements, in HV and CHF patients, of angiotensinergic and nonangiotensinergic mechanisms in the haemodynamic effects of ACEIs.",2001.0,0,0
710,11464257,A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II.,D G Vidt; W B White; E Ridley; M Rahman; S Harris; J Vendetti; E L Michelson; R Wang; CLAIM Study Investigators,"An 8-week, multicentre (72 sites in the US), double-blind, randomised, parallel group, forced titration study compared the antihypertensive efficacy of candesartan cilexetil and losartan. A total of 611 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) were randomised initially to candesartan cilexetil 16 mg once daily or losartan 50 mg once daily. After 2 weeks of randomised treatment, the doses of candesartan cilexetil and losartan were doubled to 32 mg and 100 mg once daily and continued respectively for 6 weeks. At week 8, candesartan cilexetil lowered the blood pressure (BP) at 24 h (trough), 6 h (peak) and 48 h post dose to a significantly greater extent (P < 0.05) than losartan: candesartan cilexetil lowered trough BP by 13.4/10.5 mm Hg, peak BP by 15.5/12.9 mm Hg and 48-h BP by 10.5/9.9 mm Hg compared to a reduction of trough BP by 10.1/9.1 mm Hg, peak BP by 12.0/9.5 mm Hg, and 48-h BP by 5.9/7.0 mm Hg by losartan. The responder and control rates were numerically higher in the candesartan cilexetil group, but the differences did not reach statistical significance; the responder rates were 58.8% for the candesartan cilexetil group and 52.1% for the losartan group and control rates were 49.0% for the candesartan cilexetil group and 44.6% for the losartan group. Overall, both treatment regimens were well tolerated. A total of 15 of the 611 (2.5%) patients withdrew from the study due to an adverse event, including nine (2.9%) in the candesartan cilexetil group and six (2.0%) in the losartan group. In conclusion, this forced titration study confirms that candesartan cilexetil is more effective in lowering BP than losartan when compared at once daily maximum doses.",2001.0,0,0
711,11464260,Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone.,J Pool; P Kaihlanen; G Lewis; D Ginsberg; S Oparil; R Glazer; F H Messerli,"To compare the efficacy, tolerability, and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg, benazepril 10 mg, and placebo. Randomised, double-blind, placebo-controlled, parallel-group, multicentre trial. Twenty-two clinical centres, including private practice groups and academic research clinics. A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study, and 454 were randomised to treatment with amlodipine 5 mg/benazepril 10 mg, amlodipine 5 mg, benazepril 10 mg, or placebo for 8 weeks. Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg (P < 0.03), benazepril 10 mg (P < 0.001), and placebo (P < 0.001). The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group (66.4%) was better than that observed in the amlodipine 5-mg (50.0% P < 0.02), benazepril 10-mg (38.3% P < 0.001), and placebo (24.4% P < 0.001) groups. There was no significant difference in heart rate among the four groups. The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg (1.7%) group was somewhat less than that in the amlodipine 5-mg (4.5%) group. Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg, benazepril 10 mg, and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension.",2001.0,0,1
712,11465309,Cost effectiveness of ramipril in patients with non-diabetic nephropathy and hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN) Study for Germany from the perspective of statutory health insurance.,P K Schädlich; J G Brecht; M Brunetti; E Pagano; B Rangoonwala; E Huppertz,"In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF). To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension. Statutory Health Insurance (SHI) provider in Germany. Data from the REIN Study were used in a cost-effectiveness analysis (CEA). A modelling approach was used, which was based on secondary analysis of published data, and costs were those incurred by the SHI provider (i.e. SHI expenses). In the base-case analysis, average case-related SHI expenses were applied and PYCDA were quantified using the cumulative incidence of ESRF as observed in the REIN trial. The incremental cost-effectiveness ratios (ICERs) of ramipril varied between about -76,700 deutschmarks (DM) and -DM81,900 per PYCDA (DM 1 approximately equals 0.55 US dollars; 1999 values), according to the treatment periods of 1 year and 3 years, respectively. In the sensitivity,analysis, the robustness of the model and its results were shown when the extent of influence of different model variables on the base-case results was investigated. First, probabilities of ESRF and PYCDA were estimated according to the Weibull method. Second, the influence of the model variables on the target variable was quantified using a deterministic model. Third, the dependency of the target variable (ICER) on random variables was described in a simulation. The cost for chronic dialysis had by far the greatest impact on the target variable, which was 28 times greater than the impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of the 10,000 simulation steps resulted in savings of between DM69 500 and D94,600 per PYCDA after 3 years. Results from this evaluation show that ramipril offers enormous savings from the perspective of the SHI provider (third-party payer) in Germany when added to the conventional treatment of patients with non-diabetic nephropathy and hypertension.",2001.0,0,0
713,11465647,Effects of drug therapy on cardiac arrhythmias and ischemia in hypertensives with LVH.,S Novo; M G Abrignani; G Novo; E Nardi; L J Dominguez; A Strano; M Barbagallo,"Left ventricular hypertrophy (LVH) in hypertensive subjects is associated with an increased prevalence of ventricular arrhythmias. To evaluate the effect of antihypertensive treatment on cardiac arrhythmias (CA) and transient episodes of myocardial ischemia (TEMI), we studied 46 hypertensive patients with LVH, divided into four groups randomly treated with enalapril, hydrochlorothiazide (HCTZ), atenolol, or verapamil (SR-V) for 6 months. Office blood pressure and office heart rate values were recorded, in basal conditions, after 1 and 6 months of treatment, and all patients underwent echocardiography, electrocardiographic Holter monitoring, and stress testing. All drugs significantly lowered blood pressure, whereas left ventricular mass index was reduced by atenolol, enalapril, and SR-V, but not by HCTZ. Treatment induced a significant reduction in the number of patients with supraventricular arrhythmias (35 v 15, P < .034, and 28 v 8, excluding patients treated with HCTZ, P < .008). The number of patients with ventricular arrhythmias was also reduced (32 v 16 considering all groups, P < .08, and 24 v 9, excluding patients treated with HCTZ, P < .04). The number of TEMI during Holter monitoring significantly decreased from 47 to 23 (P = .043) in all patients, and from 39 to 14 (P = .013) excluding patients treated with HCTZ. In all groups, irrespective of treatment, a reduction of blood pressure, heart rate, and systolic blood pressure/heart rate product measured by exercise stress test was observed. The present study shows that in hypertensive patients with LVH, antihypertensive treatment with atenolol, enalapril and SR-V reduces LVH and decreases the prevalence of CA and TEMI. Treatment with HCTZ during the 6-month study did not alter LVH and did not appear to reduce CA and TEMI.",2002.0,0,0
714,11465651,Valsartan alone or with a diuretic or ACE inhibitor as treatment for African American hypertensives: relation to salt intake.,M R Weir; D H Smith; J M Neutel; M P Bedigian,"Previous clinical trials have demonstrated the important influence of ethnicity and dietary salt on the antihypertensive efficacy of drugs that block the renin angiotensin system. Angiotensin II receptor blockers are a new therapeutic entity that have not been widely studied in African American hypertensives, either alone, or in combination with other therapies such as diuretics or angiotensin converting enzyme inhibitors. We performed a pilot, prospective, open label, randomized design clinical trial to evaluate the effects of the angiotensin II receptor blocker valsartan (160 mg once a day) on systolic and diastolic blood pressure in hypertensive African Americans (n = 88) on a low salt (100 mEq Na+/day) for 2 weeks and the same diet supplemented by 100 mEq Na+ for 4 weeks. After this evaluation, while continuing the Na+ supplementation, patients were randomized to valsartan 320 mg/day (n = 28), or the addition of hydrochlorothiazide (HCTZ) 12.5 mg/day (n = 30), or benazepril 20 mg/day to the valsartan 160 mg/day for an additional 6 weeks. Valsartan (160 mg/day) lowered blood pressure significantly in African American patients on both low salt (-6.4/-4.8 mm Hg: P < .001) and a high salt diet (-4.9/-3.8 mm Hg: P = .01). The high salt diet attenuated the antihypertensive effect slightly (1.6/1.3 mm Hg, P = not significant). When comparing the efficacy of the three randomized therapeutic regimens while on the Na+ supplement, the valsartan 160 mg/HCTZ 12.5 mg was the most effective therapy with an incremental reduction in blood pressure of -10.5/-6.9 mm Hg (P < .01), compared to valsartan 160 mg/day alone. Doubling the dose of valsartan to 320 mg incrementally lowered blood pressure by -3.8/-3.3 mm Hg (P = not significant). The least effective approach was adding benazepril 20 mg/day to valsartan 160 mg/day with no incremental reduction in systolic blood pressure and diastolic blood pressure reduction of only 1.7 mm Hg (P = not significant). We conclude that in our open label pilot study, the antihypertensive activity of valsartan is not significantly attenuated by supplemented salt diet in hypertensive African Americans. Moreover, adding a low dose of HCTZ appears to be the most effective strategy in enhancing the antihypertensive activity of this angiotensin II receptor blocker in contrast to either doubling the dose or adding an angiotensin converting enzyme inhibitor.",2002.0,0,0
715,11465654,Does the antihypertensive response to angiotensin converting enzyme inhibition predict the antihypertensive response to angiotensin receptor antagonism?,G S Stergiou; I I Skeva; N M Baibas; C B Kalkana; L G Roussias; T D Mountokalakis,"To test the hypothesis that the antihypertensive response to angiotensin converting enzyme (ACE) inhibition can predict the response to angiotensin II type I receptor (AT1R) antagonism, 33 hypertensive patients were randomized to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks. Patients were then crossed-over to the alternative treatment for a second 5-week period. Twenty-four-hour ambulatory BP (ABP) was measured before randomization and on the final day of each period. The agreement in ABP response between the two drugs was assessed using the following approaches: Subjects were classified as responders and nonresponders using as a threshold an arbitrary level of response (ABP fall > or = 10 mm Hg systolic or > or = 5 mm Hg diastolic) or the median ABP response achieved by each of the drugs. Disagreement between the two drugs in the responders-nonresponders classification was expressed as the proportion of subjects whose ABP responded to one of the drugs only. Lisinopril was more effective than losartan in reducing ABP (mean difference 4.7+/-8.1/3.3+/-5.7 mm Hg, systolic/diastolic, P < .05). Disagreement in the antihypertensive response between the two drugs was found in 39%/33% of subjects for systolic/diastolic ABP using the arbitrary response criterion (33%/39% using the median response criterion). Significant correlations were found between the responses to lisinopril and losartan (r = 0.47/0.59, systolic/diastolic, P < .01). We conclude that in more than one third of hypertensive subjects, the BP response to ACE inhibition fails to predict the response to AT1R antagonism and vice versa. These data suggest that there are differences between these two drug classes that are not only of theoretical but also of practical significance.",2002.0,0,0
716,11465878,Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of hypertension.,A J Matheson; S M Cheer; K L Goa,"The fixed low-dose combination of the ACE inhibitor perindopril and the non-thiazide diuretic indapamide has been evaluated in the management of patients with mild to moderate hypertension. Combination therapy aims to improve overall therapeutic efficacy while minimising adverse effects. In well-designed multicentre clinical trials, perindopril/indapamide at doses ranging from 2/0.625 to 8/2.5 mg/day was significantly more effective than placebo in achieving adequate blood pressure (BP) control. A similar reduction in supine BP was observed when combined perindopril/indapamide 2/0.625 mg/day was compared with losartan 50 mg/day or atenolol 50 mg/day. Similar reductions in 24-hour ambulatory BP were also seen with perindopril/indapamide 2/0.625 mg/day and irbesartan 150 mg/day. However, response and normalisation rates were significantly higher with combination therapy than with losartan or irbesartan monotherapy. Combined perindopril/indapamide 2/0.625 mg/day therapy effectively reduced BP in elderly patients aged 65 to 85 years to a significantly greater extent than either atenolol 50 mg/day or placebo. Supine BP was also normalised in approximately two-thirds of patients in a small noncomparative trial in patients with hypertension and renal impairment. Low-dose perindopril/indapamide 2/0.625 mg/day was well tolerated in clinical trials; the most common adverse events were headache and cough. Hypokalaemia, associated with the use of diuretics, occurred with a higher incidence with combined perindopril/indapamide 2/0.625 mg/day therapy than with either atenolol 50 mg/day or placebo. Perindopril/indapamide 2/0.625 mg/day has shown efficacy in well designed comparative trials with atenolol, losartan and irbesartan including elderly patients and patients with renal impairment. Studies comparing this dosage of perindopril/ indapamide with other combination therapies would be beneficial in allowing the place of perindopril/indapamide to be more accurately determined. The fixed-low dose combination of perindopril/indapamide provides a promising and well tolerated treatment option in the management of patients with mild to moderate hypertension.",2002.0,0,0
717,11468010,Role of bradykinin and tachykinins in the potentiation by enalapril of coughing induced by citric acid in pigs.,B Moreaux; C Advenier; P Gustin,"Angiotensin-converting enzyme (ACE) inhibitors are among the first-choice drugs for treating hypertension and congestive heart disease. It has been reported, however, that these drugs could induce chronic cough and airway hyperresponsiveness. The aim of this work was to assess in pigs the effects of bradykinin and tachykinins on citric-acid-induced coughing after ACE inhibitor pretreatment. Coughing was induced by challenging pigs with an aerosol of 0.8 M citric acid over 15 min. Coughs were counted by a trained observer for 30 min. The animals underwent two cough induction tests two days apart (days 1 and 3), the first being taken as a control. All drugs were injected intravenously 30 min before the second challenge. In the control group, no difference was observed between days 1 and 3. The ACE inhibitor enalapril (7.5 and 15 microg/kg) caused the cough frequency to increase significantly. In contrast, a dose-related decrease was observed with Hoe140 (icatibant), a bradykinin B2 receptor antagonist (0.5 and 1 mg/kg). When both drugs were administered simultaneously (15 microg/kg for enalapril and 1 mg/kg for Hoe140), a significant increase was observed as compared with the control value obtained on day 1. When enalapril was combined with the three tachykinin receptor antagonists SR 140333 (NK1 receptor antagonist), SR 48968 (NK2 receptor antagonist) and SR 142801 (NK3 receptor antagonist), a significant decrease was observed as compared with control value obtained on day 1; the percentage of variation was also significantly different as compared with those observed in enalapril groups at both doses. These data suggest that ACE-inhibitor-induced enhancement of the cough reflex is mainly due to tachykinins and not to bradykinin in our pig model. Bradykinin, however, plays a major role in coughing induced by citric acid alone.",2002.0,0,0
718,11468446,Enalapril-induced eosinophilic gastroenteritis.,N Barak; J Hart; M D Sitrin,"Eosinophilic gastroenteritis is a rare disorder of unknown etiology. We describe a case of a 63-year-old woman with chronic diarrhea and eosinophilia. Small bowel biopsy revealed eosinophils in large clusters in the lamina propria with focal infiltration of the epithelium. The patient's diarrhea and eosinophilia started shortly after enalapril was prescribed. When the patient was instructed to stop taking that drug, her diarrhea promptly ceased, and the blood eosinophil level returned to normal. This is the first reported case of eosinophilic gastroenteritis associated with an angiotensin-converting enzyme inhibitor. Eosinophilic gastroenteritis should be entertained in the differential diagnosis of patients taking angiotensin-converting enzyme inhibitors who develop diarrhea or other gastrointestinal symptoms.",2001.0,0,0
719,11468543,Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive renal transplant recipients: a prospective randomized double-blind study.,K Midtvedt; H Ihlen; A Hartmann; P Bryde; B L Bjerkely; A Foss; P Fauchald; H Holdaas,"Cardiovascular disease is the dominant cause of death in renal transplant recipients. Left ventricular hypertrophy (LVH) is a known risk factor. After renal transplantation, persistent hypertension is an important determinant for the further evolution of LVH. The aim of the present study was to compare the effect of an angiotensin converting enzyme (ACE) inhibitor (lisinopril) with a calcium channel blocker (CCB) (controlled release nifedipine) in treatment of posttransplant hypertension focusing on changes in LVH. One hundred fifty-four renal transplant recipients presenting with hypertension (diastolic BP> or =95 mmHg) during the first 3 weeks after transplantation were randomized to receive double-blind 30 mg nifedipine or 10 mg lisinopril once daily. One hundred twenty-three patients completed 1 year of treatment. Good quality echocardiographic data were available in 116 recipients (62 nifedipine/54 lisinopril) 2 and 12 months posttransplant. Blood pressure was equally well controlled in the two groups throughout the study (mean systolic/diastolic+/-SD after 1 year: 140+/-16/87+/-8 mmHg with nifedipine and 136+/-17/85+/-8 mmHg with lisinopril). Left ventricular mass index was reduced by 15% (P<0.001) in both groups (from 153+/-43 to 131+/-38 g/m2 with nifedipine and from 142+/-35 to 121+/-34 g/m2 with lisinopril). There were no statistically significant differences between the two treatment groups at baseline or at follow-up. In hypertensive renal transplant recipients with well-controlled blood pressure, there is a regression of left ventricular mass after renal transplantation. The regression of left ventricular mass index is observed to a similar extent in patients treated with lisinopril or nifedipine.",2001.0,0,0
720,11468877,The dental implications of chronic use of acidic medicines in medically compromised children.,J H Nunn; S K Ng; I Sharkey; M Coulthard,"Liquid oral medicines form a significant proportion (11%) of the medicines used by the population as a whole, either prescribed or over the counter. The active agent, as well as some of the other ingredients, can pose a threat to oral health. Eight liquid oral medicines and two effervescent preparations routinely prescribed for long-term use by paediatric renal patients were assessed for titratable acidity and pH values. All of the medicines tested were acidic and the majority were well below the critical pH of 5.5 at which enamel demineralisation takes place. The titratable acidity values, at a pH of 6.7, ranged between 0.01 and 1.54 for the liquid preparations but were 8.4 and 10.6 for the two effervescent tablets tested. Surplus acid in effervescent preparations while ensuring palatability of medicines and thus compliance, may produce unwanted dental side effects in children who are already medically compromised.",2002.0,0,0
721,11469695,The juxtaglomerular apparatus in young type-1 diabetic patients with microalbuminuria. Effect of antihypertensive treatment.,C Gulmann; R Osterby; H J Bangstad; S Rudberg,"Our goal was to investigate the effect of antihypertensive drugs on the juxtaglomerular apparatus (JGA) in young type-1 diabetic patients with microalbuminuria. Twelve patients were allocated to treatment with either an angiotensin-converting enzyme inhibitor (group 1, six subjects) or a beta-receptor blocker (group 2, six subjects). A comparable group of nine patients without antihypertensive treatment provided reference values (group 3, nine subjects). Renal biopsies were taken at baseline and after a median of 40 months (groups 1 and 2) and 30 months (group 3). Using light microscopy with 1microm serial sections of the plastic-embedded biopsies, volumes of the JGA and glomerulus and areas of the macula densa and lumina of the afferent and efferent arterioles were obtained. A significant decrease of the volume of the JGA (P=0.026) and of the volume of the JGA relative to that of its corresponding glomerulus (P=0.0005) was noted in the reference group only. Negative correlations existed between the increase in the luminal area of the afferent arteriole and mean diastolic blood pressure in the study period in group 1 (P=0.024) and group 2 (P=0.032). Our results showed that a decrease in the size of the JGA is offset by antihypertensives. The negative correlation between the change in the luminal area of the afferent arteriole and mean diastolic blood pressure in groups 1 and 2 suggest that renal protection in antihypertensive treatment may be through a better constriction of the afferent arteriole protecting the glomerulus from systemic blood pressure.",2001.0,0,0
722,11472461,An economic evaluation of atenolol vs. captopril in patients with Type 2 diabetes (UKPDS 54).,A Gray; P Clarke; M Raikou; A Adler; R Stevens; A Neil; C Cull; I Stratton; R Holman; UKPDS Group,"To compare the net cost of a tight blood pressure control policy with an angiotensin converting enzyme inhibitor (captopril) or beta blocker (atenolol) in patients with Type 2 diabetes. A cost-effectiveness analysis based on outcomes and resources used in a randomized controlled trial and assumptions regarding the use of these therapies in a general practice setting. Twenty United Kingdom Prospective Diabetes Study Hospital-based clinics in England, Scotland and Northern Ireland. Hypertensive patients (n = 758) with Type 2 diabetes (mean age 56 years, mean blood pressure 159/94 mmHg), 400 of whom were allocated to the angiotensin converting enzyme inhibitor captopril and 358 to the beta blocker atenolol. Life expectancy and mean cost per patient. There was no statistically significant difference in life expectancy between groups. The cost per patient over the trial period was 6485 UK pounds in the captopril group, compared with 5550 UK pounds in the atenolol group, an average cost difference of 935 UK pounds (95% confidence interval 188 UK pounds, 1682 UK pounds). This 14% reduction arose partly because of lower drug prices, and also because of significantly fewer and shorter hospitalizations in the atenolol group, and despite higher antidiabetic drug costs in the atenolol group. Treatment of hypertensive patients with Type 2 diabetes using atenolol or captopril was equally effective. However, total costs were significantly lower in the atenolol group. Diabet. Med. 18, 438-444 (2001)",2001.0,0,0
723,11473571,Comparison of angiotensin II receptor antagonists.,W Kirch; B Horn; J Schweizer,"Nonpeptide orally active angiotensin II type 1 (AT1) receptor antagonists are the most specific means presently available to block the renin-angiotensin enzymatic cascade. Six of these drugs have already been licensed in Europe and in the United States for the treatment of high blood pressure, and additional candidates are in the pipeline. The World Health Organisation has also recently endorsed their use for this condition. Inasmuch as AT1 receptor antagonists have proven themselves the equals of angiotensin converting enzyme inhibitors with respect to antihypertensive efficacy, but demonstrated better safety profiles, this class of drugs may be considered to be a qualitative improvement in the treatment of essential hypertension. Interestingly, the six agents now on the market diverge considerably with respect to their pharmacokinetic and pharmacodynamic properties, although it is not certain whether such differences are clinically relevant. A considerable number of large, multicentre trials are in progress to ascertain the possible longer-term organoprotective effects of these substances on cardiovascular morbidity and mortality. Because of their noteworthy safety record to date, and simple once-a-day dosage regimen, AT1 receptor antagonists have the potential to improve compliance in patients with chronic hypertension.",2002.0,0,0
724,11474160,Efficacy and safety of imidapril in patients with essential hypertension: a double-blind comparison with captopril.,P J Huang; K L Chien; M F Chen; L P Lai; F T Chiang,"In this 12-week, double-blind, parallel-group, comparative trial, 57 adult patients with mild-to-moderate hypertension were randomly allocated to receive imidapril or captopril, initially at a dose of 5 mg once a day and 25 mg twice daily, respectively. After 4 weeks of therapy, the dose of each drug was increased twice if diastolic blood pressure (DBP) remained > or =90 mm Hg. Both treatments effectively lowered DBP in a comparable manner. Mean changes from baseline in DBP at 12 weeks were -9.9 mm Hg for imidapril and -8.8 mm Hg for captopril (p = 0.488). Responder rates in patients receiving active treatment for at least 6 weeks were 53.9% for imidapril and 48% for captopril (p = 0.676). Both treatments were well tolerated. Adverse drug reactions were observed in 20.7% (6/29) of the imidapril group and 46.4% (13/28) of the captopril group (p < 0.05). A cough was the most frequent side effect, reported in 13.8% of the imidapril group and 35.7% of the captopril group. The results indicate that imidapril is as effective as captopril in the treatment of hypertension. Imidapril produces less adverse effects compared with captopril.",2001.0,0,0
725,11476732,Atrial natriuretic peptide mimetics and vasopeptidase inhibitors.,G A Sagnella,"There is now substantial evidence supporting a role of the natriuretic peptides as a major defence mechanism against excess salt and water retention and high blood pressure. Because of this there has been considerable interest in the therapeutic potential of the natriuretic peptide system. Several approaches have been explored including the use of native peptides, the development of natriuretic peptides mimetics and targetting of endogenous clearance of natriuretic peptides. While ANP and BNP administration may be valuable in some circumstances, however, the limitations of the use of peptides especially for long-term treatment are well apparent. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides through inhibition of breakdown by neutral endopeptidase. This research has now led to the vasopeptidase inhibitors - dual inhibitors of both endopeptidase and angiotensin converting enzyme. These agents clearly provide a novel approach to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity and may lead to an important advance in the treatment of hypertension and of conditions associated with overt salt and water overload.",2001.0,0,0
726,11479247,Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.,G R Dagenais; S Yusuf; M G Bourassa; Q Yi; J Bosch; E M Lonn; S Kouz; J Grover; HOPE Investigators,"In trials of patients with left ventricular dysfunction or heart failure, ACE inhibitor use was unexpectedly associated with reduced myocardial infarction (MI). Using the Heart Outcomes Prevention Evaluation (HOPE) trial data, we tested prospectively whether ramipril, an ACE inhibitor, could reduce coronary events and revascularization procedures among patients with normal left ventricular function. In the HOPE trial, 9297 high-risk men and women, >/=55 years of age with previous cardiovascular disease or diabetes plus 1 risk factor, were randomly assigned to ramipril (up to 10 mg/d), vitamin E (400 IU/d), their combination, or matching placebos. During the mean follow-up of 4.5 years, there were 482 (10.4%) patients with clinical MI and unexpected cardiovascular death in the ramipril group compared with 604 (12.9%) in the placebo group [relative risk reduction (RRR), 21% (95% CI) (11,30); P<0.0003]. Ramipril was associated with a trend toward less fatal MI and unexpected death [4.0% versus 4.7%; RRR, 16% (-3, 31)] and with a significant reduction in nonfatal MI [5.6% versus 7.2%; RRR, 23% (9,34)]. Risk reductions in MI were documented in participants taking or not taking beta-blockers, lipid lowering, and/or antiplatelet agents. Although ramipril had no impact on hospitalizations for unstable angina [11.9% versus 12.2%; RRR, 3% (-9,14)], it reduced the risk of worsening and new angina [27.2% versus 30.0%; RRR, 12% (5,18); P<0.0014] and coronary revascularizations [12.5% versus 14.8%; RRR, 18%; (8,26) P<0.0005]. In this high-risk cohort, ramipril reduced the risk of MI, worsening and new angina, and the occurrence of coronary revascularizations.",2001.0,0,0
727,11480579,Exposure to hydroxyurea during pregnancy: a case series.,C Thauvin-Robinet; C Maingueneau; E Robert; E Elefant; H Guy; D Caillot; R O Casasnovas; S Douvier; A Nivelon-Chevallier,,2001.0,0,0
728,11487379,A single (investigator)-blind randomised control trial comparing the effects of quinapril and nifedipine on platelet function in patients with mild to moderate hypertension.,I F Islim; D Bareford; D G Beevers,"The effect of quinapril and nifedipine on platelet aggregation, vascular endothelial function and coagulation system activity, was compared in a parallel-group, investigator-blind study carried out on patients with mild to moderate hypertension but no other diseases or receiving medication which might affect platelet function, vascular endothelium or coagulation. Forty patients (two groups of 20 patients each) and 20 control subjects were recruited. Patients were randomised to receive either quinapril or nifedipine retard and the dose escalated to control hypertension. Platelet aggregation studies were assessed serially and beta-thromboglobulin, angiotensin-converting enzyme (ACE), von Willebrand factor (vWF) coagulation factors VIIIc, XII and fibrinogen were measured at the beginning and end of the 12-week period. Blood pressure was adequately controlled in all patients in both groups. Platelet function was impaired in certain parameters (slope of the reaction with ADP and collagen and maximum aggregation with collagen) in the patient group compared to controls before treatment and this improved in patients on quinapril but not on nifedipine; likewise beta-thromboglobulin was higher in the patient group and fell significantly in the quinapril group but not those on nifedipine. Measurements of endothelial function and coagulation were normal before treatment and showed no alteration during the study, except in the expected fall in plasma ACE in the quinapril group. The results indicate that the ACE inhibitor, quinapril, has a beneficial effect on platelet function unlike the calcium channel blocker, nifedipine.",2002.0,0,0
729,11487558,Angiotensin receptor blockade and portal hypertension: paradise gained and paradise lost.,A J Sanyal,,2001.0,0,0
730,11494784,"Potential risks and prevention, Part 3: Drug-induced threats to life.",K Marcellino; W N Kelly,"Potential risk factors for and the preventability of drug-induced threats to life were studied. Case reports of adverse drug events (ADEs) published in Clin-Alert during 1977-97 were the source of information on drug-induced life threats. Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed. Data were entered into a relational database for analysis. The data indicated 846 drug-induced life threats. Seventy-four percent of the cases were assessed as definite or probable. Patients received usual or below-usual dosages in 89% of the cases. Patients tended to be middle-aged and only moderately ill. The drug categories most frequently associated with life threats were antimicrobials and central-nervous-system agents. Plasma drug level monitoring should have been performed in 127 cases but occurred only in 31 cases (24%). Event types were distributed as adverse drug reactions (50%), allergic reactions (35%), drug interactions (11%), and medication errors (4%). A commercial reference classified almost half of the drug interactions associated with a life threat as posing minimal or no potential risk to the patient. Half of the life-threatening events were judged to have been preventable; about half of these could have been prevented by a pharmacist. Litigation was reported for only 1% of the cases of drug-induced threats to life; judgments and settlements averaged $1.2 million. A review of published case reports of ADEs for 1977-97 yielded information on possible risk factors for drug-induced life threats and on which events may have been preventable.",2002.0,0,0
731,11494785,"Potential risks and prevention, Part 4: Reports of significant adverse drug events.",W N Kelly,"A summary analysis of three descriptive studies of significant adverse drug events (ADEs) was conducted. Case reports of ADEs published in Clin-Alert during 1976-97 were the source of information on ADEs, including drug-induced deaths, disabilities, and threats to life. The results of the three studies were compared, and recommendations were made. During the 21-year period, 1520 significant ADEs were reported (29% resulting in death, 15% in permanent disability, and 56% in life threats). Event types were distributed as adverse drug reactions (52%), allergic drug reactions (25%), medication errors (15%), and drug interactions (8%). Only 12% of the drug interactions were classified as having highest significance by one drug information reference, while 32% of the drug interactions were unclassified. Typically, patients were 40-69 years old and relatively healthy or only moderately ill and had received usual dosages. However, 29% of the patients with a drug-induced permanent disability were less than 10 years old. Only 17% of the drugs that could have been monitored by blood level tests were so monitored. The drug categories most commonly involved in ADEs were central-nervous-system agents, antimicrobials, antineoplastics, and cardiovascular agents. The nervous, hematopoietic, cardiovascular, and respiratory systems were affected the most. Faulty prescribing was the most common reason for medication error, and wrong dosage was the most common type of error. A lawsuit was reported in 13% of the cases. Overall, 52% of the cases were judged to have been preventable; of these, 50% could have been prevented by a pharmacist. Litigation was reported for 13% of the cases; settlements and judgments averaged $3.1 million. A summary analysis of more than 1500 published case reports of ADEs for 1976-97 yielded information on possible risk factors for drug-related deaths, disabilities, and life threats and on which events may have been preventable.",2002.0,0,0
732,11496059,"Is there a place for combining angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists in the treatment of hypertension, renal disease or congestive heart failure?",A A Taylor,"Angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists have proven to be effective and well tolerated antihypertensive agents. They also exhibit unique cardioprotective and renoprotective properties in patients with comorbid conditions such as congestive heart failure and proteinuria or renal insufficiency. This benefit is observed most dramatically in diabetic persons. Although inconclusive, the results of a limited number of clinical trials support the notion that additive antihypertensive, cardioprotective, and renoprotective effects may be obtained with combined used of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 antagonists in some patients. More studies are needed to confirm the findings of these preliminary studies, and to define more clearly those subsets of patients who might derive the greatest benefit from angiotensin-converting enzyme inhibitor-angiotensin II receptor subtype 1 antagonist combination therapy.",2002.0,0,0
733,11497198,Effects of ACE inhibitor therapy on derived central arterial waveforms in hypertension.,A M Dart; C M Reid; B McGrath; Tonometry Study Group,"Large artery properties constitute an important component of left ventricular afterload in hypertension. The present study examined whether such properties were particularly responsive to angiotensin converting enzyme inhibitor therapy. A prospective, randomized, 12-week study in 138 previously treated hypertensive subjects, in 67 of whom usual treatment (UC) was replaced with perindopril (P) therapy. Large artery properties were assessed as central arterial pressure augmentation determined by applanation tonometry of the radial artery and a transfer function. At baseline both augmentation index (AI, %) and pressure (AP, mm Hg) were related to body size, heart rate, and gender. In addition AP was related to age and systolic blood pressure (BP). After 12 weeks of treatment AP decreased significantly in both perindopril and UC groups, whereas AI only decreased significantly (151.7%+/-2.3% to 144.9%+/-2.6%) in those treated with perindopril. Decreases in AP (-4.2+/-0.9 mm Hg v -1.9+/-0.7 mm Hg) and AI (-6.8%+/-2.2% v -2.2%+/-2.5%) from week 0 to week 12 were greater in the perindopril-treated group, but differences between groups failed to reach statistical significance (P = .05 and .09, respectively). The change in AI during the 12-week treatment period was dependent on the initial heart rate (P < .001), systolic BP (P < .05), weight (P < .001), and sex (P < .001), but not on treatment group (P > .5). Al at 12 weeks was negatively correlated with heart rate but regression slopes for the association were virtually identical for perindopril and UC groups. Perindopril treatment produces a greater decrease in AI than continuation with previous therapy, but this can be largely explained by hemodynamic changes rather than direct arterial effects.",2002.0,0,0
734,11497204,Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril.,J D Spence,,2002.0,0,0
735,11498653,Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists.,M A Weber; M R Weir,"Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of < 130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT(1) receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease. (c)2001 Le Jacq Communications, Inc.",2001.0,0,0
736,11498655,The African American Study of Kidney Disease and Hypertension (AASK): new findings.,D A Sica; J G Douglas,"In September, 2000, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health called an early halt to the amlodipine arm of the African American Study of Kidney Disease and Hypertension (AASK) trial after careful deliberation by an independent data and safety monitoring board. An interim analysis of the AASK at 3 years revealed a renoprotective effect of the angiotensin-converting enzyme inhibitor ramipril as compared to the dihydropyridine calcium channel blocker (DHP-CCB) amlodipine in patients with mild to moderate renal insufficiency. This differential effect was independent of the blood pressure (BP) levels reached and was evident in proteinuric patients and suggestive in patients with baseline proteinuria < 300 mg/d, but was not conclusive. The AASK trial data suggest that DHP-CCBs should be used cautiously in the presence of mild to moderate renal insufficiency. Judgment should be reserved for the use of other CCBs, such as verapamil or diltiazem, since these are fundamentally different CCBs with the potential for a different impact on hypertensive nephrosclerosis. The blinded observation period for AASK will be completed at the end of September, 2001, at which time additional, clinically useful information is expected to become available. (c)2001 Le Jacq Communications, Inc.",2001.0,0,0
737,11502994,Comparison of the effects of enalapril and losartan on posttransplantation erythrocytosis in renal transplant recipients: prospective randomized study.,A Yildiz; N Cine; V Akkaya; S Sahin; V Ismailoğlu; S Türk; S Bozfakioğlu; M S Sever,"The aim of this prospective randomized study was to compare the safety and efficacy of enalapril (E) and losartan (L) in the treatment of posttransplantation erythrocytosis and the effect of the ACE genotype on response to therapy. Twenty-seven (24 male and 3 female, mean age 34+/-8 years) renal transplant recipients with erythrocytosis were treated either with E (15 patients) (10 mg/day) or L (12 patients) (50 mg/day) for 8 weeks. The hemoglobin levels were significantly decreased in the L (17.1+/-0.7 to 15.9+/-1.3 g/dl, P=0.01) and E groups (17.4+/-1.1 to 14.9+/-2.2 g/dl, P=0.001). Among the responders who discontinued treatment, there was a trend for longer time to relapse in the L group (7.38+/-3.75 months; 95% confidence interval: 0.03-14.7) compared with the E group (2.75+/-0.70 (95% confidence interval: 1.37-4.13) (P=0.11). Decrease in hemoglobin was more prominent with E compared with L (-3.26+/-0.65 vs. -1.70+/-0.39 g/dl, P=0.05). Decrease in hemoglobin levels between DD and non-DD genotype groups was similar (-2.0+/-1.5 vs. -1.7+/-2.3 g/dl, P=0.69). Enalapril caused a greater decrease but faster relapse in hemoglobin levels compared with losartan in patients with posttransplantation erythrocytosis. The DD type polymorphism had no effect on response.",2001.0,0,0
738,11503000,Neutropenia after treatment of posttransplantation erythrocytosis with enalapril.,C Donadio; A Lucchesi,,2001.0,0,0
739,11503814,Perindopril + indapamide: new preparation.  Simple trick.,,"(1) The combination of perindopril 4 mg + indapamide 1.25 mg is approved for second-line treatment of hypertension after failure of perindopril alone.  (2) The other combination, of a low dose of an angiotensin-converting-enzyme inhibitor (2 mg of perindopril) and a diuretic (0.625 mg of indapamide), is being promoted as first-line treatment of hypertension.  (3) The clinical files for both preparations are limited to the strict minimum.  (4) A dose-finding study showed that the perindopril 4 mg + indapamide 1.25 mg dose combination offered the best risk-benefit ratio by comparison with combinations containing the same perindopril dose but other indapamide doses.  (5) A double-blind trial suggests that the antihypertensive activity of the perindopril 4 mg + indapamide 1.25 mg combination is equivalent to that of the captopril 50 mg + hydrochlorothiazide 25 mg and enalapril 20 mg + hydrochlorothiazide 12.5 mg combinations.  The safety profile was the same for the three combinations.  (6) The 2-mg perindopril combination has not been compared with perindopril monotherapy at the usual dose of 4 mg, or with indapamide monotherapy at a mean dose of 2.5 mg.  (7) The two combinations are costlier than their competitors.",2001.0,0,0
740,11503832,Flawed WHO recommendations on hypertension: WHO has damaged its reputation.,,"(1) The international expert group ignored the ground rules governing clinical assessment, and clinical trial data too, taking up a stance that favours drug manufacturers.",2001.0,0,0
741,11505744,[The comparison of hypotensive efficiency and tolerability of amlodipine and enalapril in patients with essential hypertension].,P Gryglas,"In this multicentre, double-blind trial in 176 patients with mild or moderate essential hypertension were randomized to amlodipine or enalapril monotherapy after 2-week period of placebo. Doses of amlodipine (2.5-10 mg once daily) and enalapril (5-20 mg once daily) were titrated to achieve office blood pressure below 140/90 mm Hg during 8 weeks of therapy. Both drugs were similarly effective in lowering blood pressure and goal blood pressure was achieved in 72.4% patients treated with amlodipine and 67.4% with enalapril. Also, degree of reduction of blood pressure was similar in both groups. Compared to initial values: systolic/diastolic blood pressure decreased by 23.5/14.9 mm Hg in amlodipine group and 23.2/14.0 mm Hg in subjects receiving enalapril. However, adverse effects, especially dry cough were more frequent in enalapril-treated patients. Both amlodipine and enalapril provide significant blood pressure reduction in stage I-II hypertension. Tolerance of short-term therapy was good in both groups however number of adverse events was significantly lower in amlodipine-treated patients.",2002.0,0,0
742,11506246,Prospective randomized controlled multicenter trial on steroids plus ramipril in proteinuric IgA nephropathy.,C Manno; L Gesualdo; C D'Altri; M Rossini; G Grandaliano; F P Schena,"Recent studies have shown that steroids improve renal survival and reduce proteinuria in IgA nephropathy (IgAN) patients with moderate urinary protein excretion and normal renal function. However, this effect seems to diminish over time. Moreover, it has been demonstrated that long-term use of ramipril reduces the risk of end-stage renal disease in proteinuric diabetic and non-diabetic chronic nephropathies. We have planned a long-term unblinded, prospective, centrally randomized, controlled, multicentric trial to assess whether combined treatment of steroids and ramipril is superior to ramipril alone in patients with progressive IgAN disease. A minimum of 134 patients with biopsy-proven IgAN, grade G3 or G4, daily proteinuria > 1.0 g and creatinine clearance > 50 mL/min will be enrolled during a 2-year recruitment period. The patients will be allocated randomly to receive a six-month course of oral prednisone (1.0 mg/Kg/day for 2 months, tapered by 0.2 mg/Kg/day every month) plus ramipril (2.5 mg/day for one month, increased by 1.25 mg/day every month to achieve and maintain a blood pressure less than 120-80 mm Hg and/or to reduce daily proteinuria to 1.0 g or less or by at least 50%) in the experimental group or ramipril alone in the control group. Ramipril will be administered during the whole 5-year follow-up period in both groups. The primary endpoint will be renal survival estimated by 50% increase in baseline serum creatinine; the secondary endpoints will be urinary protein and cytokine excretion and side-effects. Analyses will be done by intention to treat. A p <0.05 will be taken as significant.",2002.0,0,0
743,11508256,ACOG Practice Bulletin. Chronic hypertension in pregnancy. ACOG Committee on Practice Bulletins.,ACOG Committee on Practice Bulletins,"Chronic hypertension occurs in up to 5% of pregnant women; rates vary according to the population studied and the criteria used for confirming the diagnosis (1,2). This complication may result in significant maternal, fetal and neonatal morbidity and mortality. There has been confusion over the terminology and criteria used to diagnose this complication, as well as the benefit and potential harm of treatment during pregnancy. The purpose of this document is to review the effects of chronic hypertension on pregnancy, to clarify the terminology and criteria used to define and diagnose it during pregnancy, and to review the available evidence for treatment options.",2001.0,0,0
744,11509470,Iron supplementation inhibits cough associated with ACE inhibitors.,S C Lee; S W Park; D K Kim; S H Lee; K P Hong,"Dry cough is the most common limiting factor of ACE inhibitor (ACEI) use. Generation of NO, a proinflammatory substance on bronchial epithelial cells, is increased by ACEI. Using a randomized, double-blind, placebo-controlled trial, we tested the hypothesis that supplementing iron, an inhibitor of NO synthase, may reduce the cough associated with ACEI use. The subjects were 19 patients who had developed ACEI-induced cough. After a 2-week observation period, they were randomized to a daily morning dose of either 256-mg ferrous sulfate as a tablet or placebo for a treatment period of 4 weeks. The subjects were requested to fill out a cough diary by scoring the daily severity of the cough on a scale of 0 to 4. Mean daily cough scores for the last week of the observation and treatment period were compared. Changes in blood cell count and serum iron and ferritin concentration between the 2 periods were evaluated. Mean daily cough scores during the observation and treatment periods were 3.07+/-0.70 and 1.69+/-1.10, respectively, for the iron group and 2.57+/-0.80 and 2.35+/-1.22, respectively, for the placebo group, showing a significant reduction in cough scores with iron supplementation (P<0.01) but not with placebo. Three subjects in the iron group showed almost complete cough abolition. No significant changes in laboratory data were observed in either group. In conclusion, iron supplementation successfully decreases ACEI-induced cough. This effect may be related to the decrease of NO generation associated with the inhibition of NO synthase activity in bronchial epithelial cells.",2001.0,0,0
745,11509491,Effects of chronic clonidine administration on sympathetic nerve traffic and baroreflex function in heart failure.,G Grassi; C Turri; G Seravalle; G Bertinieri; A Pierini; G Mancia,"Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0+/-1.1 years (mean+/-SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (-46.8% and -26.7%, respectively; P<0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.",2001.0,0,0
746,11511120,"Geographic variation in patient and hospital characteristics, management, and clinical outcomes in ST-elevation myocardial infarction treated with fibrinolysis. Results from InTIME-II.",R P Giugliano; J Llevadot; R G Wilcox; E P Gurfinkel; C H McCabe; A Charlesworth; S L Thompson; E M Antman; E Braunwald; InTIME (Intravenous nPA for Treatment of Infarcting Myocardium Early) II Investigators,"We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction. We compared baseline characteristics, management, and outcomes in four regions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North America and Latin America (odds ratios (OR) [95% confidence intervals (CI)] compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2 [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10-fold but did not explain regional mortality differences. Germany and the U.K. had similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although invasive procedures were four- to 10-fold more common in Germany. Similarly the U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61-1.17]) despite three-fold higher use of invasive procedures in the U.S. Significant geographic variations in practice and adjusted mortality following fibrinolysis persist despite recent guidelines. These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations.",2001.0,0,0
747,11515986,Diabetics with hypertension not controlled with ACE inhibitors: alternate therapies.,T J Cleophas; B M van Ouwerkerk; J van der Meulen; A H Zwinderman,"If hypertension in patients with diabetes mellitus type II is not adequately controlled by angiotensin-converting enzyme inhibitors (ACE-i), a beta-blocker is frequently added as second-line therapy. Recently, large randomized trials demonstrated the beneficial effect of second-generation dihydropyridine calcium-channel blockers in these patients. These compounds are increasingly being used to replace beta-blockers. Withdrawal of beta-blockers may influence diabetic control and may cause rebound hypertension. Any rebound hypertension from beta-blocker withdrawal may not occur if the beta-blocker is replaced with a calcium-channel blocker. A calcium-channel blocker will influence vascular resistance (VR) and blood pressure differently than a beta-blocker. Thirty-four patients with diabetes mellitus type II and a resting diastolic blood pressure above 90 mm Hg despite enalapril 10 mg daily (or equipotent dosages of other ACE-i) for at least 3 months were treated in an open label sequential comparison with the same ACE-i in combination with the beta-blocker metoprolol 100 mg for 3 months, and, subsequently for 3 more months with the same ACE-i in combination with the dihydropyridine calcium-channel blocker lercanidipine 10 mg once daily. After 6 weeks, patients with a diastolic blood pressure above 90 mm Hg were titrated up to 200 mg metoprolol or 20 mg lercanidipine once daily. Patients were examined every 6 weeks during the trial, and after 2 weeks while receiving lercanidipine. In addition to blood pressure measurements, VR was measured by iridium strain gauge plethysmography and expressed in units (1 unit = 1 mm Hg/mL blood/100 mL tissue per minute). Two of 34 patients did not complete the protocol because of non-compliance with the lercanidipine treatment in the first 2 weeks of treatment. Their data are included in the analysis. No rebound hypertension 14 days after the change-over of therapies was observed. (Mean arterial pressures [MAPs] were not significantly different from the point of withdrawal of the beta-blockers.) However, heart rate rose from 69+/-7 to 94+/-10 beats/min (p < 0.001). After 3 months on lercanidipine, MAP fell by 6+/-10 mm Hg (p = 0.002) compared to the point of withdrawal of the beta-blocker. Vascular resistance fell by 6.28+/-11.91 units (p<0.01), while glucosylated hemoglobin (HbA1c) rose by 0.4+/-0.5% (p<0.001) and body weight rose by 0.6+/-0.6 kg (p < 0.01). Multiple regression analysis revealed significant associations between decrease in VR, increase in HbAlc, and decrease in MAP, and partial dependence of these variables on one another. In hypertensive patients with diabetes type II, replacement of ACE-i and metoprolol with ACE-i and lercanidipine does not appreciably influence metabolic control and does not cause rebound hypertension. Lercanidipine was more effective than metoprolol as a second-line antihypertensive drug in these patients. At least two mechanisms may be involved: withdrawal of a pressor effect from the beta-blocker, and calcium-channel-mediated vasodilation.",2001.0,0,0
748,11528233,Trans-tubular potassium gradient in patients with drug-induced hyperkalemia.,H Mayan; R Kantor; Z Farfel,"Trans-tubular potassium gradient (TTKG) is considered to reflect mainly aldosterone bioactivity with regard to its kaliuretic response. We determined both TTKG and aldosterone serum concentrations in patients with severe drug-induced hyperkalemia (DIH). Ten hyperkalemic patients with serum potassium of more than 5.5 mEq/l, and serum creatinine of less than 2.5 mg/dl (221 micromol/l) were studied prospectively. Two control groups of 10 patients each were used. Control 1 group with normal renal function, and control 2 group with normokalemia and renal failure of the same magnitude as that of the hyperkalemic patients. Serum osmolarity, electrolytes, creatinine, aldosterone and urine electrolytes and osmolarity were measured and TTKG calculated. DIH patients had lower TTKG values than control 1 patients (2.58 +/- 0.36 vs. 6.68 +/- 0.55, p < 0.001), and also lower than that of the control 2 patients (2.58 +/- 0.36 vs. 5.51 +/- 0.87, p < 0.01). Serum aldosterone concentration in the DIH group was higher than that of the control 1 group [24.30 +/- 5.0 vs. 7.4 +/- 2.1 pg/ml (674 +/- 139 vs. 205 +/- 58 pmol/l), p < 0.006] but not different from that of the control 2 group [24.3 +/- 5.0 vs. 15.3 +/- 3.8 pg/ml (674 +/- 139 vs. 424 +/- 106 pmol/l), respectively, p = 0.18]. Although there was some overlap in TTKG between DIH and control groups, 6 of 10 DIH patients had TTKG of less than 2.5, while none of the control patients had such a low value. DIH is characterized by lower TTKG values than those observed in patients with normal or mild-to-moderate renal failure. Other factors in addition to aldosterone seem to be involved.",2002.0,0,0
749,11529211,Prognostic importance of elevated jugular venous pressure and a third heart sound in patients with heart failure.,M H Drazner; J E Rame; L W Stevenson; D L Dries,"The independent prognostic value of elevated jugular venous pressure or a third heart sound in patients with heart failure is not well established. We performed a retrospective analysis of the Studies of Left Ventricular Dysfunction treatment trial, in which 2569 patients with symptomatic heart failure or a history of it were randomly assigned to receive enalapril or placebo. The mean (+/-SD) follow-up was 32+/-15 months. The presence of elevated jugular venous pressure or a third heart sound was ascertained by physical examination on entry into the trial. The risks of hospitalization for heart failure and progression of heart failure as defined by death from pump failure and the composite end point of death or hospitalization for heart failure were compared in patients with these findings on physical examination and patients without these findings. Data on 2479 patients were complete and analyzed. In multivariate analyses that were adjusted for other markers of the severity of heart failure, elevated jugular venous pressure was associated with an increased risk of hospitalization for heart failure (relative risk, 1.32; 95 percent confidence interval, 1.08 to 1.62; P<0.01), death or hospitalization for heart failure (relative risk, 1.30; 95 percent confidence interval, 1.11 to 1.53; P<0.005), and death from pump failure (relative risk, 1.37; 95 percent confidence interval, 1.07 to 1.75; P<0.05). The presence of a third heart sound was associated with similarly increased risks of these outcomes. In patients with heart failure, elevated jugular venous pressure and a third heart sound are each independently associated with adverse outcomes, including progression of heart failure. Clinical assessment for these findings is currently feasible and clinically meaningful.",2001.0,0,0
750,11529215,Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 26-2001. Hypertensive encephalopathy with impaired renal function in a 67-year-old woman with polymyositis.,,,2001.0,0,0
751,11532109,Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.,T H Jafar; P C Stark; C H Schmid; M Landa; G Maschio; C Marcantoni; P E de Jong; D de Zeeuw; S Shahinfar; P Ruggenenti; G Remuzzi; A S Levey; AIPRD Study Group. Angiotensin-Converting Enzymne Inhibition and Progression of Renal Disease,"Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients. Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease. Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion. The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.",2001.0,0,0
752,11532682,Plasma levels and metabolism of AcSDKP in patients with chronic renal failure: relationship with erythropoietin requirements.,Y Le Meur; V Lorgeot; L Comte; J C Szelag; J C Aldigier; C Leroux-Robert; V Praloran,"N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a physiological inhibitor of hematopoiesis that is maintained at stable levels in normal plasma. Its degradation in vivo and in vitro by angiotensin-converting enzyme (ACE) accounts for the high plasma concentrations of AcSDKP in patients treated with ACE inhibitors. Because ACE inhibitors can induce anemia in some patients, we measured plasma AcSDKP concentrations in 176 patients with chronic renal failure: 120 hemodialysis (HD) and 56 nondialysis (nD) patients, 39 of whom were administered ACE inhibitors. We studied the relationships between AcSDKP levels, hematologic parameters, and recombinant human erythropoietin (rHuEPO) requirements in these patients. AcSDKP levels were significantly greater in HD (10.3 +/- 3.9 pmol/mL) and nD (3.1 +/- 1.8 pmol/mL) patients not administered ACE inhibitors than controls (1.8 +/- 0.2 pmol/mL). In all patients, treatment with ACE inhibitors significantly increased these levels fourfold. HD sessions significantly decreased AcSDKP concentrations by 66% and reduced the predialysis in vitro half-life of AcSDKP (270 +/- 109 minutes) to values (182 +/- 67 minutes) not significantly different from those of controls or nD patients. Most HD patients treated with ACE inhibitors had AcSDKP levels greater than 24 pmol/mL (the greatest concentration found in other nD and HD patients). Only in this group of patients did weekly doses of rHuEPO correlate with AcSDKP levels. Our results show that renal function is essential to maintain stable AcSDKP plasma levels, and at high levels, AcSDKP acts as a uremic toxin causing partial resistance to erythropoietin and inhibiting erythropoiesis.",2001.0,0,0
753,11539066,Successful behavior changes in a man with hypertension.,N K Hollenberg,"Several years of stress, smoking, increased alcohol use, and weight gain accompanied hypertension in a young man with an ominous family history.  Aided by short-term drug therapy, he changed his ways and reduced his blood pressure for the long term.",2001.0,0,0
754,11546834,Cutaneous drug reactions.,C K Svensson; E W Cowen; A A Gaspari,"Cutaneous drug reactions are the most frequently occurring adverse reactions to drugs. Among hospitalized patients, the incidence of these reactions ranges from 1 to 3%. The frequency of cutaneous reactions to specific drugs may exceed 10%. These reactions may range from mildly discomforting to those that are life-threatening. Anti-infective and anticonvulsant agents are among the drugs most commonly associated with adverse reactions in the skin. We describe and illustrate the clinical morphology of the most common cutaneous drug reactions, as well as drugs that most commonly precipitate specific reactions. The varied nature of the reactions that do occur, even with specific agents, indicates a multiplicity of mechanisms available whereby cutaneous drug reactions may be initiated. Although a variety of terms have been proposed for categorizing cutaneous drug reactions, we propose that reactions are best defined based upon mechanisms, where known. In this review, we assess the current knowledge of four categories of cutaneous drug reactions: immediate-type immune-mediated reactions, delayed-type immune-mediated reactions, photosensitivity reactions, and autoimmune syndromes. Moreover, we describe evidence that viral infection is an important predisposing factor for the development of cutaneous drug reactions upon drug administration. Finally, we review the current knowledge of the type and mechanisms of cutaneous drug reactions to several categories of drugs.",2001.0,0,0
755,11548082,Renal artery stenosis: a disease worth pursuing.,S C Parker; A Hannah; M Brooks; W J Louis; C J O'Callaghan,"Consider renovascular hypertension (HT) when: Newly diagnosed hypertension presents with features that are atypical of essential hypertension; Resistant hypertension is associated with risk factors for atheroma; or Angiotensin-converting enzyme (ACE) inhibitor or angiotensin-II-receptor antagonist therapy is associated with increasing plasma creatinine levels. Atheromatous renovascular HT can often be managed medically, which includes intensive correction of cardiovascular risk factors. ACE inhibitors are probably second-line antihypertensives for patients with unilateral renal artery stenosis and two kidneys. First-line antihypertensives are diuretics, beta-blockers and calcium-channel blockers. Bilateral renal artery stenosis, or a unilateral stenosis in a patient with only one kidney, is an absolute contraindication to ACE inhibition.",2001.0,0,0
756,11548874,Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension.,A Ito; K Egashira; T Narishige; K Muramatsu; A Takeshita,"Endothelium-dependent/nitric oxide (NO)-mediated vasodilation is impaired in hypertensive individuals. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, is synthesized by many types of cells including vascular endothelial cells. The serum level of ADMA is elevated in patients with essential hypertension, but the mechanism for this increase is unknown. Therefore, the present study examined whether the renin-angiotensin system (RAS) is involved. Patients with essential hypertension [systolic blood pressure (BP) > 160 mmHg and/or diastolic BP > 95 mmHg] were randomized to an angiotensin-converting enzyme (ACE) inhibitor treatment group (perindopril, 4mg/day for 4 weeks, n = 7), an angiotensin II type 1 (AT1) receptor antagonist treatment group (losartan, 50 mg/day for 4 weeks, n = 7) or a beta-blocker treatment group (bisoprolol, 5 mg/day for 4 weeks, n = 7). Before and after the treatment, BP, serum concentration of ADMA and plasma concentration of von Willebrand factor (vWF, a biological marker of endothelial injury) were measured. Perindopril, losartan and bisoprolol decreased BP to a similar extent, and either perindopril or losartan, but not bisoprolol, significantly decreased serum ADMA and plasma vWF. These findings suggest that the RAS may contribute to the mechanism of increased serum ADMA as well as to the endothelial injury observed in hypertensive patients. The vasculoprotective actions of ACE inhibitors or AT1 receptor antagonists may be explained at least in part by amelioration of the endothelial injury through a decrease in the serum ADMA concentration.",2002.0,0,0
757,11550111,Effects of long-acting ACE inhibitor (temocapril) and long-acting Ca channel blocker (amlodipine) on 24-h ambulatory BP in elderly hypertensive patients.,K Eguchi; K Kario; K Shimada,"In a prospective randomised cross-over study, we compared the effects of ACE inhibitor temocapril and calcium channel blocker (CCB) amlodipine on ambulatory blood pressure in 59 asymptomatic elderly hypertensive patients (mean age 69 years). This study was performed in a cross-over fashion after a 2-week placebo period and 4 to 8 weeks each of treatment with temocapril and amlodipine. Of those 59 hypertensive patients, three patients with side effects and 10 patients whose office BPs did not achieve the target BPs were excluded, and the remaining 46 were analysed in this study: they consisted of 30 dippers, with a night time reduction in systolic BP (SBP) > or = 10% and 16 non-dippers, with reduction by < 10%. At the baseline, there were no significant differences in the office, 24-h or daytime BPs between the two groups (dippers and non-dippers). Though the office BPs and daytime BPs were successfully controlled to the same levels with both treatments and in both dipping groups, the antihypertensive effects were stronger with the CCB than with the ACE inhibitor in the night time and morning, especially in non-dippers. We conclude that even though office BPs were controlled successfully to almost the same levels, there is a possibility that these long-acting drugs have differential antihypertensive effects on night time and morning BPs among hypertensive patients with different night time BP dipping statuses.",2001.0,0,0
758,11551370,Clinical trials report. The effect of Ramipril versus Amlodipine on renal outcomes in hypertension nephrosclerosis.,D G Vidt,,2001.0,0,0
759,11551875,Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.,R B Devereux; V Palmieri; N Sharpe; V De Quattro; J N Bella; G de Simone; J F Walker; R T Hahn; B Dahlöf,"The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.",2001.0,0,0
760,11564390,Effects of omapatrilat on hemodynamics and safety in patients with heart failure.,M Klapholz; I Thomas; C Eng; B J Iteld; G A Ponce; A L Niederman; M Bilsker; J T Heywood; D Synhorst,"Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction < or = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.5, 5, 10, 25, or 50 mg, followed by hemodynamic assessment for 24 hours. At 4 to 6 hours after dosing, the 25- and 50-mg doses of omapatrilat, compared with placebo, reduced mean pulmonary capillary wedge pressure by approximately 6 mm Hg from 20 and 23 mm Hg at baseline to 14 and 16 mm Hg. The 50-mg omapatrilat dose maintained this effect compared with placebo with an approximately 2.5-mm Hg reduction in mean pulmonary capillary wedge pressure at 24 hours. Omapatrilat improved additional hemodynamic parameters, including cardiac index, systemic vascular resistance, stroke volume index, and mean arterial pressure. Additionally, by 2 hours after dosing with omapatrilat 25 and 50 mg, a trend in peak increases from baseline in plasma atrial natriuretic peptide (twofold) and cyclic guanosine monophosphate (nearly twofold) was observed. Moreover, omapatrilat was well tolerated. Thus, omapatrilat administered orally to patients with heart failure was safe and well tolerated and resulted in improved hemodynamic performance.",2001.0,0,0
761,11565517,Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.,E J Lewis; L G Hunsicker; W R Clarke; T Berl; M A Pohl; J B Lewis; E Ritz; R C Atkins; R Rohde; I Raz; Collaborative Study Group,"It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure. We randomly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups. We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration, the development of end-stage renal disease, or death from any cause. We also compared them with regard to the time to a secondary, cardiovascular composite end point. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006). The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups (P=0.07 for both comparisons). These differences were not explained by differences in the blood pressures that were achieved. The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine group (P=0.02). There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of the reduction in blood pressure it causes.",2001.0,0,0
762,11565518,Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.,B M Brenner; M E Cooper; D de Zeeuw; W F Keane; W E Mitch; H H Parving; G Remuzzi; S M Snapinn; Z Zhang; S Shahinfar; RENAAL Study Investigators,"Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy. A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo). Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.",2001.0,0,0
763,11570665,Angiotensin-converting-enzyme inhibitor administration must be monitored for serum amylase and lipase in order to prevent an acute pancreatitis: a case report.,M C Borgia; A Celestini; P Caravella; C Catalano,"Some clinical cases published in literature show that angiotensin-converting enzyme (ACE)-inhibitor administration may cause acute pancreatitis. In this work, the authors report a case of a patient affected by hypertension. Upon admission, the authors started antihypertensive therapy using captopril, which caused an important amylase and lipase rise within 13 days. When the ACE-inhibitor therapy was stopped, a rapid decrease of the serum enzyme was observed within 3 days. The high levels of serum amylase and lipase were linked to neutrophilia but were not associated with relevant symptomatic findings or features of pancreatopathy. The absence of the usual conditions that may cause pancreatitis, such as biliary stasis, hypercalcemia, or alcohol abuse, and the rapid decrease of serum enzyme levels after drug suspension suggested an ACE-inhibitor-induced pancreatitis. This is the first clinical report of an ACE-inhibitor-induced pancreatitis in which captopril administration was found after hospitalization. The drug suspension probably prevented other complications. This case report suggests that, when ACE-inhibitor administration is started, serum amylase and lipase should be monitored in order to prevent acute pancreatitis without waiting for clinical evidence of a pancreatopathy.",2001.0,0,0
764,11571256,AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology.,S C Smith; S N Blair; R O Bonow; L M Brass; M D Cerqueira; K Dracup; V Fuster; A Gotto; S M Grundy; N H Miller; A Jacobs; D Jones; R M Krauss; L Mosca; I Ockene; R C Pasternak; T Pearson; M A Pfeffer; R D Starke; K A Taubert,,2001.0,0,0
765,11571824,Management of hypertension by general practitioners: an Italian observational study.,F Mazzeo; G Motola; S Rossi; F Russo; M R Vitelli; A Capuano; F Rossi; A Filippelli,"Data on patients receiving antihypertensive therapy were collected from 20 general practitioners (GPs) in Campania, Italy, to determine the prescription of different antihypertensive classes and their use with other drugs for concomitant diseases, to investigate the main factors influencing antihypertensive choice, to document treatment outcome, and to assess adverse drug reactions (ADRs). Each GP completed a data card for each consultation that produced an antihypertensive prescription; 1900 cards were collected. The most frequently used antihypertensives were angiotensin-converting enzyme inhibitors (49.6%), calcium antagonists (24.8%), beta blockers (11.7%), angiotensin II-receptor blockers (5.5%), and alpha blockers (0.9%). In 82% of patients, blood pressure was reduced but did not reach normotensive levels. The choice of antihypertensive treatment was influenced by international guidelines (56%), clinical diagnosis (25%), concomitant diseases (8%), cost (4%), compliance (3%), and other factors (5%). ADRs--most often cough (35.7%), edema (22.7%), headache (13.3%), and tachycardia (7.8%)--occurred in 11.8% of patients.",2001.0,0,0
766,11574740,A comparison of selected antihypertensives and the use of conventional vs ambulatory blood pressure in the detection and treatment of hypertension.,D Ebbs,"This multicenter, randomized, double-blind, parallel group study was undertaken to determine the effectiveness of selected antihypertensives (doxazosin, amlodipine, enalapril, and bendrofluazide) in maintaining 24-hour control of blood pressure (BP). The predictive value of ambulatory (A)BP versus clinic (C)BP measurements as a method for detecting patients with hypertension was also evaluated. A total of 204 patients were screened and of these 110 were diagnosed as mild to moderately hypertensive with clinic diastolic BP 100-110 mm Hg (> or =95 mm Hg in patients with coronary heart disease risk factors). The 4 antihypertensives were all equally effective at controlling BP over 24 h, as shown by 24-hour ABP measurements. The incidence of adverse events was similar for all 4 treatment groups; headache was the most common event, being reported by 22 patients (20%). There was a clinically relevant reduction in total cholesterol for the doxazosin (-15.4 mg/dl) and amlodipine (-11.6 mg/dl) treatment groups in comparison with enalapril and bendrofluazide. Our results from ABP measurements suggest that the antihypertensives studied are effective first-line therapy in the regulation of hypertension and that ABP is a reproducible measure. ABP may also be useful in identifying patients with various types of high BP, for instance those with 'white coat' hypertension, enabling more accurate screening and diagnosis.",2002.0,0,0
767,11575266,A case of severe hypoglycemia due to pimobendan.,J Ako; M Eto; T Watanabe; Y Ouchi,,2001.0,0,0
768,11575979,The benefit of implementing a heart failure disease management program.,D J Whellan; L Gaulden; W A Gattis; B Granger; S D Russell; M A Blazing; M S Cuffe; C M O'Connor,"To handle the increasing complexity of congestive heart failure (CHF) care, several new models for the care of patients with CHF have been developed to replace traditional strategies. We undertook this study to evaluate the potential benefit of implementing a CHF disease management program at a tertiary care center, particularly in terms of beta-blocker use and cost to the health care system. After reviewing the literature regarding therapies and management strategies for patients with CHF, we developed the Duke Heart Failure Program. All enrolled patients had 1 of the following: recent CHF hospitalization, ejection fraction less than 20%, or symptoms consistent with New York Heart Association class III or IV. We compared preenrollment and postenrollment medication use and resource utilization. We enrolled 117 patients from July 1998 to April 1999. Mean enrollment time was 4.7 months. beta-Blocker use and dose significantly increased (52% vs 76% for beta-blocker, P<.01; 6% vs 13% of target dose, P<.01). The hospitalization rate decreased (1.5 vs 0 hospitalizations per patient-year, P<.01), while the number of clinic visits increased (4.3 vs 9.8 clinic visits per patient-year, P<.01). The Duke University Health System saved a median of $8571 per patient-year. Implementing a CHF disease management program was associated with improved CHF medication dosing and with decreased hospitalization for patients with CHF. A CHF disease management program is an effective method for a health care system to care for patients with CHF.",2002.0,0,0
769,11576319,Effective blood pressure treatment improves LDL-cholesterol susceptibility to oxidation in patients with essential hypertension.,A Quiñones-Galvan; A Pucciarelli; A Fratta-Pasini; U Garbin; F Franzoni; F Galetta; A Natali; L Cominacini; E Ferrannini,"LDL-cholesterol particles from hypertensive patients exhibit enhanced susceptibility to in vitro oxidation, an abnormality thought to increase cardiovascular risk. We tested whether blood pressure (BP) normalization can reverse this abnormality. Double-blind, randomized pharmacological intervention trial. Clinical research centre. Subjects. A total of 29 nondiabetic, normolipidaemic patients with essential hypertension (BP= 151 +/- 3/99 +/- 1 mmHg) and 11 normotensive controls (BP=125 +/- 3/85 +/- 1 mmHg) matched for gender, age, obesity, glucose tolerance and lipid profile. Intervention. Anti-hypertensive treatment for 3 months with a calcium-antagonist in randomized combination with either an ACE inhibitor or a beta-blocker. Lag phase of copper-induced LDL oxidation, cell-mediated (human umbilical vein endothelium) generation of malondialdehyde (MDA) by LDL and vitamin E content in LDL. At baseline in hypertensives versus controls, lag phase was shorter (89 +/- 3 vs. 107 +/- 6 min, P < 0.04), MDA generation was higher (5.8 +/- 0.1 vs. 5.1 +/- 0.2 nmol L(-1), P=0.002), and vitamin E was reduced (6.40 +/- 0.05 vs. 6.67 +/- 0.11 microg mg(-1), P=0.03). At 3 months, BP was normalized (124 +/- 3/81 +/- 1, P < 0.0001 vs. baseline, P=ns versus controls), lag phase was prolonged (to 98 +/- 3 min, P=0.0005), MDA generation was reduced (5.6 +/- 0.1 nmol L-1, P = 0.001), and vitamin E was increased (6.53 +/- 0.05 microg mg(-1), P=0.003), with no significant differences between the randomized groups. In nondiabetic, nonobese, normolipidaemic patients with essential hypertension, LDL susceptibility to copper- and cell-mediated oxidation is increased. BP normalization is associated with a significant improvement, but not a full reversal, of this abnormality.",2002.0,0,0
770,11579345,Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors.,J H Silber; A Cnaan; B J Clark; S M Paridon; A J Chin; J Rychik; A N Hogarty; M I Cohen; G Barber; M Rutkowsky; T R Kimball; C Delaat; L J Steinherz; H Zhao; M R Tartaglione,"The ACE Inhibitor After Anthracycline (AAA) study is a randomized, double-blind, controlled clinical trial comparing enalapril with placebo to determine whether treatment can slow the progression of cardiac decline in patients who screen positive for anthracycline cardiotoxicity. The primary outcome measure is the rate of decline, over time, in maximal cardiac index (in liters per minute per meters squared) at peak exercise; the secondary outcome measure is the rate of increase in left ventricular end systolic wall stress (in grams per centimeters squared). Patients >2 years off therapy and <4 years from diagnosis, aged 8 years and older, were eligible if they had received anthracyclines and had at least one cardiac abnormality identified at any time after anthracycline exposure. A total of 135 patients were randomized to enalapril or placebo. Baseline characteristics were similar across treatment groups. The AAA study will provide important information concerning the efficacy of using angiotensin-converting enzyme inhibitors to offset the effects of late anthracycline cardiotoxicity.",2002.0,0,0
771,11579362,"Reliability, validity, and responsiveness of the six-minute walk test in patients with heart failure.",C Demers; R S McKelvie; A Negassa; S Yusuf; RESOLVD Pilot Study Investigators,"Our purpose was to evaluate the reliability, validity, and responsiveness of the 6-minute walk test (6MWT) in patients with heart failure (HF) enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) pilot study. A total of 768 patients was enrolled in a multicenter randomized clinical trial evaluating the effect of candesartan, enalapril, and metoprolol on left ventricular ejection fraction (LVEF), 6MWT distance, neurohormones, and quality of life. The 6MWT was performed once at screening and twice at baseline, 18 weeks, and 43 weeks by a standardized method. Test-retest reliability at baseline (intraclass correlation coefficient [ICC] = 0.90), 18 weeks (ICC = 0.88), and 43 weeks (ICC = 0.91) was very good. Baseline 6MWT distance was weakly inversely correlated to the quality-of-life cumulative score (r = -0.26, P =.0001) and moderately inversely correlated to the New York Heart Association functional classification (NYHA-FC) (r = -0.43, P =.001). In the RESOLVD study, the 6MWT was not responsive to change when effect sizes and standardized response means were used. Disease-specific quality of life was responsive to change in patients treated with candesartan and enalapril and NYHA-FC was responsive to change in the candesartan and enalapril combination and for enalapril alone with small effect sizes. The 6MWT, NYHA-FC, and quality of life were not responsive to change during the metoprolol or placebo phase. The 6MWT is highly reproducible in patients with symptoms of HF. It is somewhat correlated to NYHA-FC and quality of life. Overall, quality of life was most responsive to change, whereas 6MWT and NYHA-FC were comparable but less responsive to change in the RESOLVD study.",2002.0,0,0
772,11579363,Regression of left ventricular remodeling in chronic heart failure: Comparative and combined effects of captopril and carvedilol.,R S Khattar; R Senior; P Soman; R van der Does; A Lahiri,"This study evaluated the independent and combined effects of captopril and carvedilol on left ventricular remodeling in chronic heart failure. Although angiotensin-converting enzyme inhibitors and b-blockers are known to attenuate the remodeling process in chronic heart failure, a direct comparison of these agents has not been performed. We investigated 57 patients with mild to moderate chronic heart failure (48 ischemic, 9 nonischemic) who were randomized in a double-blind fashion to treatment with carvedilol or captopril at maximum doses of 25 mg twice daily for 3 months, followed by 3 months of combined treatment. Serial echocardiography, right heart catheterization, and treadmill exercise testing were performed at baseline, 3 months, and 6 months. After exclusions, 49 patients were evaluated during monotherapy and 48 during combination therapy. Carvedilol monotherapy produced significant reductions in end-systolic volume, leading to a greater median increase in ejection fraction compared with captopril monotherapy (4.7% vs 1.5%, respectively; P <.05). Each drug caused similar reductions in left ventricular mass, chamber sphericity, and pulmonary artery wedge pressure during monotherapy and combined treatment. Adjunctive treatment with carvedilol produced a trend toward a greater increase in ejection fraction (4.3% vs 2.7%, respectively; P not significant) and significantly greater reductions in the wall thickening score index than with captopril (0.25 vs 0.08, respectively; P =.04). Although angiotensin-converting enzyme inhibitor therapy did not alter left ventricular volume, treatment with carvedilol was associated with reductions in chamber volume; both drugs reduced left ventricular mass and sphericity. These beneficial effects on remodeling may help to explain the relative prognostic benefits of these therapies.",2002.0,0,1
773,11580159,Hepatotoxicity induced by fosinopril.,M Romero-Gómez; E J Miralles; E García Díaz; A Robles; E Suárez; M Castro,,2002.0,0,0
774,11581138,Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril.,J Mathew; P Sleight; E Lonn; D Johnstone; J Pogue; Q Yi; J Bosch; B Sussex; J Probstfield; S Yusuf; Heart Outcomes Prevention Evaluation (HOPE) Investigators,"Electrocardiographic markers of left ventricular hypertrophy (LVH) predict poor prognosis. We determined whether the ACE inhibitor ramipril prevents the development and causes regression of ECG-LVH and whether these changes are associated with improved prognosis independent of blood pressure reduction. In the Heart Outcomes Prevention Evaluation (HOPE) study, patients at high risk were randomly assigned to ramipril or placebo and followed for 4.5years. ECGs were recorded at baseline and at study end. We compared prevention/regression and development/persistence of ECG-LVH in the two groups and related these changes to outcomes. At baseline, 676 patients had LVH (321 in the ramipril group and 355 in the placebo group) and 7605 patients did not have LVH (3814 in the ramipril group and 3791 in the placebo group). By study end, 336 patients in the ramipril group (8.1%) compared with 406 in the placebo group (9.8%) had development/persistence of LVH; in contrast, 3799 patients in the ramipril group (91.9%) compared with 3740 in the placebo group (90.2%) had regression/prevention of LVH (P=0.007). The effect of ramipril on LVH was independent of blood pressure changes. Patients who had regression/prevention of LVH had a lower risk of the predefined primary outcome (cardiovascular death, myocardial infarction, or stroke) compared with those who had development/persistence of LVH (12.3% versus 15.8%, P=0.006) and of congestive heart failure (9.3% versus 15.4%, P<0.0001). The ACE inhibitor ramipril decreases the development and causes regression of ECG-LVH independent of blood pressure reduction, and these changes are associated with reduced risk of death, myocardial infarction, stroke, and congestive heart failure.",2001.0,0,0
775,11583474,The pharmacokinetics of enalapril in children and infants with hypertension.,T Wells; R Rippley; R Hogg; A Sakarcan; D Blowey; P Walson; B Vogt; A Delucchi; M W Lo; E Hand; D Panebianco; W Shaw; S Shahinfar,"Forty children with hypertension between the age of 2 months and 15 years received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was administered orally as a novel extemporaneous suspension in children younger than 6 years of age and as tablets in older children. First-dose and steady-state pharmacokinetics were estimated in children ages 1 to 24 months, 25 months to < 6 years, 6 to < 12 years, and 12 to < 16 years. Maximum serum concentrations for enalapril occurred approximately 1 hour after administration. Serum concentrations of enalaprilat, the active metabolite of enalapril, peaked between 4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The area under the concentration versus time curve (AUC), adjusted for body surface area, did not differ between age groups. Based on comparison of first-dose and steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13- to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in children ages 12 to < 16 years. Urinary recovery for children ages 2 to < 6 years was 66.8%. The mean percentage conversion of enalapril to enalaprilat ranged from 64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The median effective half-life for accumulation ranged from 14.6 hours in children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years. There were two serious adverse events, neither of which was attributed to enalapril or resulted in discontinuation of the study drug. The extemporaneous suspension used in this study was tolerated well. The pharmacokinetics of enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with normal renal function appears to be similar to that previously observed in healthy adults.",2002.0,0,0
776,11586670,[Angiotensin-converting enzyme inhibitors after AMI].,C T Torp-Pedersen; L Køber; Trandolapril Cardiac Evaluation Study Group,The purpose of this study was to calculate the improvement in life expectancy by treating patients with left ventricular dysfunction after a myocardial infarction with an ACE inhibitor. Life expectancy was estimated as median lifetime and follow up in the TRACE study was prolonged until median lifetime could be calculated in both treatment groups. Median lifetime was reached in the placebo group after 4.6 years. In the trandolapril group median lifetime was increased by 15.3 months or 27% (7-51%). We conclude that the increase in lifetime by treatment of patients with left ventricular dysfunction after a myocardial infarction is substantial.,2001.0,0,0
777,11587159,Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women.,R Fogari; A Zoppi; P Preti; E Fogari; G Malamani; A Mugellini,"The aim of this study was to compare the effects of trandolapril and losartan on plasminogen activator inhibitor type 1 (PAI-1) levels and insulin sensitivity in hypertensive postmenopausal women. We studied 89 hypertensive (diastolic blood pressure >90 and <110 mm Hg) postmenopausal women, aged 51 to 60 years not taking any hormone replacement therapy. Diabetic, obese, and smoking patients were excluded. After a 4-week placebo period, they were randomized to receive 2 mg of oral trandolapril (n=45) or 50 mg of oral losartan (n=44) for 12 weeks according to a double-blind, parallel group design. At the end of the placebo and active treatment periods, blood pressure (BP) was measured, plasma samples were drawn to evaluate PAI-1 antigen levels, and insulin sensitivity was assessed. Both trandolapril and losartan reduced systolic BP (by a mean of 16.9 mm Hg and 15.2 mm Hg, respectively, P < .01 v placebo) and diastolic BP (by a mean of 13.1 mm Hg and 11.9 mm Hg, respectively, P < .01 v placebo) with no difference between the two treatments. The PAI-1 antigen levels were significantly decreased by trandolapril (from 36.9+/-21 ng/dL to 27.2+/-17 ng/dL, P < .05), but not by losartan (from 35.3+/-22 ng/dL to 37.1+/-23 ng/dL, P=not significant). Glucose infusion rate was significantly increased by trandolapril (from 6.67+/-0.56 mg/min/kg to 7.9+/-0.65 mg/min/kg, P < .05), but was not significantly modified by losartan (from 6.7+/-0.47 mg/min/kg to 6.9+/-0.50 mg/min/kg, P= not significant). In the trandolapril group the PAI-1 decrease correlated with glucose infusion rate increase (r=0.36, P=.045) These results provide evidence of different effects of angiotensin converting enzyme inhibitors and AT1 antagonists on fibrinolysis and suggest that the PAI-1 decrease induced by angiotensin converting enzyme inhibitors is related to their action on insulin sensitivity and is not dependent on angiotensin II antagonism but rather on other mechanisms. It remains to be seen whether these findings apply to other patient populations than postmenopausal women.",2002.0,0,0
778,11588522,Do arterial effects of antihypertensive drugs depend on subject's serum cholesterol?,J L Megnien; A Simon; E Mikaberidze; N Denarie; G Chironi; J Barra; R Armentano; J Levenson,"Effects of antihypertensive treatment on large arteries may be influenced by the type of drug and concomitant risk factors such as blood cholesterol. To explore these possibilities we investigated the common carotid artery of 20 subjects with low cholesterol and 19 subjects with high cholesterol, all with essential hypertension, randomly allocated to 3 months of treatment with nitrendipine (20 mg/d) or trandolapril (2 mg/d). Carotid parameters were determined by recording instantaneous pressure (applanation tonometry) and diameter (echotracking device) and by modeling the pressure-diameter loop to obtain the Peterson modulus, stiffness index, measured and isobaric compliances, and wall viscosity. Effects of drugs on carotid parameters did not differ, except on systolic and diastolic diameters (p < 0.01), which increased insignificantly under nitrendipine but decreased (p < 0.01) under trandolapril. Blood cholesterol status did not influence carotid effects of trandolapril, whereas patients with low and high cholesterol treated with nitrendipine exhibited significant differences in drug effects on (a) systolic and pulse pressures (p < 0.05), which decreased in patients with low cholesterol (p < 0.01, p < 0.05) but not in those with high cholesterol; (b) diastolic diameter (p = 0.05), which increased insignificantly in patients with low cholesterol but was unchanged in those with high cholesterol; and (c) wall viscosity (p < 0.01), which decreased in patients with low cholesterol (p < 0.05) but increased insignificantly in those with high cholesterol. Also, wall viscosity change under nitrendipine was positively related to the baseline blood cholesterol ( r = 0.64, p < 0.01). Thus, nitrendipine and trandolapril show noteworthy differences in their effects on the carotid artery, in particular with respect to the status of blood cholesterol, but these differences should be confirmed by larger studies.",2002.0,0,0
779,11588528,T-lymphocyte and plasma angiotensin-converting enzyme activity during enalapril and losartan administration in humans.,V V Petrov; R H Fagard; P J Lijnen,"This study evaluated the long-term effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on the angiotensin-converting enzyme activity in T lymphocytes and plasma in patients with essential hypertension. The study was a randomized, placebo-controlled, double-blind, crossover design. Nine patients with sitting blood pressure > or = 95 mm Hg and < or = 105 mm Hg at the end of a 4-week placebo run-in period entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril (20 mg, once daily), or losartan (50 mg, once daily) The angiotensin-converting enzyme activity in T lymphocytes was measured as the activity of the degradation of the substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu, which was quantified spectrofluorometrically. Enalapril but not losartan suppressed (p < or = 0.01) the angiotensin-converting enzyme activity in plasma, whereas it stimulated (p < or = 0.05) the angiotensin-converting enzyme activity in circulating T lymphocytes. Our data document induction of angiotensin-converting enzyme in human T lymphocytes during long-term treatment with the angiotensin-converting enzyme inhibitor enalapril. Angiotensin II receptor type 1 antagonism with losartan had no effect on plasma or lymphocytic angiotensin-converting enzyme.",2002.0,0,0
780,11588535,"Efficacy, tolerability, and impact on quality of life of long-term treatment with manidipine or amlodipine in patients with essential hypertension.",A Zanchetti; S Omboni; P La Commare; R De Cesaris; P Palatini,"This double-blind, multicenter trial compared antihypertensive efficacy, tolerability, and impact on quality of life of manidipine and amlodipine in patients with mild-to-moderate essential hypertension. Patients were randomly assigned to 48 weeks of once-daily manidipine, 10-20 mg, or amlodipine, 5-10 mg. Patients who did not respond to treatment after 12 weeks were also given enalapril, 10-20 mg, for the study's duration. The main efficacy end point was equivalence in sitting systolic (SiSBP) and diastolic (SiDBP) blood pressure reduction between the two drugs after 8 weeks (per protocol analysis). An intention-to-treat (ITT) analysis was performed in all patients with at least one efficacy determination during treatment. Quality of life was assessed by the ""Subjective Symptoms Assessment Profile"" (SSA-P) and ""General Well-being Schedule"" (GWBS), after 12 weeks of treatment. SiSBP reduction after 8 weeks was equivalent for manidipine (15.2 mm Hg, n = 227) and amlodipine (17.0 mm Hg, n = 219). The corresponding figure for SiDBP was 11.3 mm Hg for manidipine and 12.3 mm Hg for amlodipine. In the larger ITT population SiDBP was similarly and significantly reduced by manidipine (from 102 +/- 5 to 88 +/- 9 mm Hg, n = 241) and amlodipine (from 101 +/- 5 to 87 +/- 8 mm Hg, n = 240). Similar results were observed for SiSBP and standing SBP and DBP. Neither drug changed sitting or standing heart rate compared with baseline. SSA-P scores improved with manidipine but not amlodipine. GWBS total and partial scores increased more with manidipine than with amlodipine. Safety profile favored manidipine, which was associated with significantly less ankle edema than was amlodipine. This study shows for the first time that long-term treatment with the long-acting calcium channel blocker manidipine is as effective as treatment with amlodipine, has a better tolerability profile, and induces greater improvement in quality of life than amlodipine.",2002.0,0,0
781,11589855,Effective dose and cardiovascular effects of cilazapril in children with heart failure.,K Hazama; M Nakazawa; K Momma,,2002.0,0,0
782,11589932,"Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.",PROGRESS Collaborative Group,"Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease. However, there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients. The perindopril protection against recurrent stroke study (PROGRESS) was designed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack. 6105 individuals from 172 centres in Asia, Australasia, and Europe were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. The primary outcome was total stroke (fatal or non-fatal). Analysis was by intention to treat. Over 4 years of follow up, active treatment reduced blood pressure by 9/4 mm Hg. 307 (10%) individuals assigned active treatment suffered a stroke, compared with 420 (14%) assigned placebo (relative risk reduction 28% [95% CI 17-38], p<0.0001). Active treatment also reduced the risk of total major vascular events (26% [16-34]). There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups (all p<0.01). Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43% (30-54). Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke. This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack. Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone. Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack, irrespective of their blood pressure.",2001.0,0,0
783,11593107,Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout.,G Würzner; J C Gerster; A Chiolero; M Maillard; C L Fallab-Stubi; H R Brunner; M Burnier,"Losartan has been shown to increase urinary uric acid excretion and hence to lower serum uric acid levels. The purposes of the present study were: (1) to evaluate the effects of losartan on serum uric acid in hypertensive patients with hyperuricemia and gout, (2) to compare the effects of losartan with those of irbesartan, another angiotensin II receptor antagonist and (3) to evaluate whether losartan 50 mg b.i.d. has a greater impact on serum uric acid levels than losartan 50 mg once a day. Thirteen hypertensive patients with hyperuricaemia and gout completed this prospective, randomized, double-blind, cross-over study. Uric acid-lowering drugs were stopped 3 weeks before the beginning of the study. Patients were randomized to receive either losartan 50 mg or irbesartan 150 mg once a day, for 4 weeks. During this phase, a placebo was given in the evening. After 4 weeks, the dose was increased to losartan 50 mg b.i.d., or irbesartan 150 mg b.i.d. for another 4 week period. Subsequently, the patients were switched to the alternative treatment modality. Enalapril (20 mg o.d.) was given during the run-in period and between the two treatment phases. Serum and urinary uric acid were measured at the beginning and at the end of each treatment phase. Our results show that losartan 50 mg once daily decreased serum uric acid levels from 538 +/- 26 to 491 +/- 20 micromol/l (P < 0.01). Irbesartan had no effect on serum uric acid. Increasing the dose of losartan from 50 mg o.d. to 50 mg twice a day, did not further decrease serum uric acid. This may in part be due to a low compliance to the evening dose as measured with an electronic device. Indeed, whatever the prescribed drug, the mean compliance of the evening dose was always significantly lower than that of the morning dose. The uricosuric effect of losartan appears to decrease with time when a new steady state of lower serum uric acid is reached. In contrast to irbesartan, losartan was uricosuric and decreased serum uric acid levels. Losartan 50 mg b.i.d. did not produce a greater fall in serum uric acid than losartan once a day. Losartan might be a useful therapeutic tool to control blood pressure and reduce serum uric acid levels in hypertensive patients with hyperuricaemia and gout.",2002.0,0,0
784,11593109,A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.,R Marin; L M Ruilope; P Aljama; P Aranda; J Segura; J Diez; Investigators of the ESPIRAL Study. Efecto del tratamiento antihipertensivo Sobre la Progresión de la Insuficiencia RenAL en pacientes no diabéticos,"To investigate in a random comparison the capacity of an angiotensin converting enzyme inhibitor (fosinopril), and that of a long-acting dihydropiridine (nifedipine GITS) to modify the decay in renal function in patients with primary renal disease, exhibiting a progressive increase in serum creatinine during the previous 2 years. A randomized, open-label, multicenter study with a minimum follow-up of 3 years. A total of 241 patients were included in the study. All of them were hypertensive and had a 25% or at least 0.5 mg/dl increase in the value of serum creatinine during the 24 months prior to entering the study. Initial doses of fosinopril and nifedipine GITS were 10 and 30 mg respectively, and titration to 30 and 60 mg was performed if needed to obtain the expected blood pressure goal (< 140/90 mmHg). Furosemide, atenolol, and doxazosin were added as second, third, and fourth drugs if necessary, for blood pressure control. The primary end-point of the study was the appearance of double the serum creatinine values and/or the need to enter a dialysis programme. Secondary end-points were cardiovascular events, death, changes in 24 h proteinuria, and the evolution of serum creatinine. Data reflect the analysis performed by intention to treat. Mean age of the group was 54 +/- 14, and 59% were males. Primary glomerulonephritis (31%), nephrosclerosis (26%) and polycystic kidney disease (19%) were the three most frequent diagnostic findings. After 3 years of follow-up, 21% (27/127) of patients treated with fosinopril, and 36% (40/112) of those receiving nifedipine GITS presented a primary end-point, (OR 0.47, 95% confidence intervals 0.26-0.84, P = 0.01). Renal survival was significantly better when fosinopril constituted the first step therapy (P = 0.002). These results did not seem to be influenced by the type of primary renal disease. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving dihydropiridine. Blood pressure control did not differ among groups for diastolic values. During follow-up, however, the patients receiving ACEi showed systolic blood pressure values 4-6 mmHg lower. In patients with chronic renal failure and hypertension due to primary renal disease, fosinopril significantly differed from nifedipine GITS by its capacity to slow the progressive decay in renal function. The drugs also differed by their capacity to lower blood pressure. The better control, in particular of systolic blood pressure, in the fosinopril arm could have contributed in a relevant manner to the attainment of a better outcome when the ACEi was employed.",2002.0,0,0
785,11593526,Quality of life of patients with mild hypertension treated with captopril: a randomized double-blind placebo-controlled clinical trial.,Y Hu; J Zhu,"To determine the quality of life (QOL) of mild hypertensive patients treated with captopril as compared to placebo. This is a randomized, double-blind, placebo-controlled clinical trial held in the out-patient clinic of Zhong Shan Hospital. Adult patients aged from 28 to 75 years with mild hypertension defined as diastolic blood pressure from 90 to 105 mm Hg were the inclusion criteria of the study. There were 278 patients who were eligible to enter the study. They were randomized to receive captopril or placebo 25 to 50 mg bid for 12 weeks. Change of QOL was compared both quantitatively and qualitatively between captopril and placebo groups. Change of blood pressure and side effects were also compared. With intention-to-treat analysis, significantly more improved QOL patients could be found qualitatively in patients with captopril treatment (45.3% vs 23.7%, P = 0.0002 for physical health domain; 48.9% vs 26.6%, P = 0.0002 for mental health domain; 33.8% vs 11.5%, P = 0.0001 for general function domain). Quantitatively, the change of score of mental health, general function and total QOL of captopril (3.18 +/- 5.90; 1.65 +/- 4.43; 7.84 +/- 11.03) were significantly higher than those of placebo (1.32 +/- 5.13, P = 0.00004; 0.64 +/- 3.45, P = 0.0008; 4.19 +/- 10.33, P = 0.0025 respectively), and the change of score of physical health domain (3.01 +/- 5.26 vs 2.23 +/- 4.79, P = 0.044) was of borderline statistical significant difference. Blood pressure was significantly lowered by captopril than by placebo (P = 0.000). Compared with the placebo, captopril is not only effective in lowering blood pressure, as has been established, but also effective in improving QOL in mild hypertensives.",2002.0,0,0
786,11594254,What is the relevance of the HOPE study in general practice?,J Kennedy; C E Mogensen; S G Ball; A D Castaigne; P J Commerford; L Distiller; B M Fisher; J Gonzalez-Jaunatey; R Nosadini; A Novials; J Ostergren; J Palma-Gámiz; P Perrone-Filardi; J J Schipperheijn; J Senges; R Trevisan,"The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long-term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist--a cardiologist or a diabetologist--may ultimately be necessary.",2001.0,0,0
787,11596665,Study rationale and design of ADVANCE: action in diabetes and vascular disease--preterax and diamicron MR controlled evaluation.,ADVANCE Management Committee,"Patients with Type II (non-insulin-dependent) diabetes mellitus are at increased risk of macrovascular and microvascular disease, both of which are reduced by controlling raised blood pressure in hypertensive patients. Intensive glycaemic control has also been shown to reduce microvascular disease but the effects on macrovascular disease remain uncertain. This study will examine the hypotheses that lowering blood pressure with an ACE inhibitor-diuretic combination and intensively controlling gylcaemia with a sulphonylurea-based regimen in high-risk patients with Type II diabetes (both hypertensive and non-hypertensive) reduces the incidence of macrovascular and microvascular disease. The study is a 2 x 2 factorial randomised controlled trial that will include 10000 adults with Type II diabetes at high risk of vascular disease. Following 6 weeks on open label perindopril-indapamide combination, eligible patients are randomised to continued perindopril-indapamide or matching placebo, and to an intensive gliclazide MR-based glucose control regimen or usual guidelines-based therapy. Primary outcomes are, first, the composite of nonfatal stroke, non-fatal myocardial infarction or cardiovascular death and, second, the composite of new or worsening nephropathy or diabetic eye disease. The scheduled average duration of treatment and follow-up is 4.5 years. The study will be conducted in approximately 200 centres in Australasia, Asia, Europe and North America. ADVANCE is designed to provide reliable evidence on the balance of benefits and risks conferred by blood pressure lowering therapy and intensive glucose control therapy in high-risk diabetic patients, regardless of initial blood pressure or glucose concentrations.",2002.0,0,0
788,11596705,Counseling patients about drug allergies in the inpatient setting.,V Johnson; C Croft; V Crane,,2002.0,0,0
789,11597291,Ramipril and the development of diabetes.,S Yusuf; H Gerstein; B Hoogwerf; J Pogue; J Bosch; B H Wolffenbuttel; B Zinman; HOPE Study Investigators,"Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied. To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons. The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999. Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883). Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups. One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined. Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmation.",2001.0,0,1
790,11603173,[The comparison of clinical effectiveness of perindopril and acebutolol in the primary hypertension treatment].,W Pieniazek; P Franczuk; K Janicki,"Hypertension is one of the most important risk factors for ischaemic heart disease and stroke. The aim of our study was to assess the antihypertensive effect of angiotensine converting enzyme inhibitor (perindopril) versus beta blocker (acebutolol) in hypertensive patients. It was a double blind, placebo controlled study performed in the group of 31 patients (16 males, 15 females; mean age 46.6 +/- 8.7 years) with newly diagnosed (previously not treated) mild to moderate hypertension. Each patient in the wash-out period (two weeks) was given placebo and then was randomized to active treatment: perindopril (4 mg/day) or acebutolol (400 mg/day) for 3 weeks, following these drugs were cross matched (after one week wash out period). Blood pressure (BP) with mercury sphygmomanometer was measured three times: after 2 weeks of placebo treatment, after 3 weeks of perindopril and 3 weeks of acebutolol treatment. Both perindopril and acebutolol proved to be effective in monotherapy of hypertension. After 3 weeks of the treatment we observed BP systolic and diastolic normalization, but more patients had systolic BP normalization after perindopril treatment.",2002.0,0,0
791,11603905,Failing ageing hearts.,M C Petrie; C Berry; S Stewart; J J McMurray,,2002.0,0,0
792,11606149,Acute precipitants of congestive heart failure exacerbations.,R T Tsuyuki; R S McKelvie; J M Arnold; ; A C Barretto; A C Carvalho; D L Isaac; A D Kitching; L S Piegas; K K Teo; S Yusuf,"Few studies have prospectively and systematically explored the factors that acutely precipitate exacerbation of congestive heart failure (CHF) in patients with left ventricular dysfunction. Knowledge of such factors is important in designing measures to prevent deterioration of clinical status. The objective of this study was to prospectively describe the precipitants associated with exacerbation of CHF status in patients enrolled in the Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study. We conducted a 2-stage, multicenter, randomized trial in 768 patients with CHF who had an ejection fraction of less than 40%. Patients were randomly assigned to receive enalapril maleate, candesartan cilexetil, or both for 17 weeks, followed by randomization to receive metoprolol succinate or placebo for 26 weeks. Investigators systematically documented information on clinical presentation, management, and factors associated with the exacerbation for any episode of acute CHF during follow-up. A total of 323 episodes of worsening of CHF occurred in 180 patients during 43 weeks of follow-up; 143 patients required hospitalization, and 5 died. Factors implicated in worsening of CHF status included noncompliance with salt restriction (22%); other noncardiac causes (20%), notably pulmonary infectious processes; study medications (15%); use of antiarrhythmic agents in the past 48 hours (15%); arrhythmias (13%); calcium channel blockers (13%); and inappropriate reductions in CHF therapy (10%). A variety of factors, many of which are avoidable, are associated with exacerbation of CHF. Attention to these factors and patient education are important in the prevention of CHF deterioration.",2002.0,0,0
793,11607794,ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity?,H C Routledge; J N Townend,"Conventionally angiotensin-converting enzyme (ACE) inhibitors are contraindicated in patients with aortic stenosis. Abundant evidence is now available showing that angiotensin II has a central role in the development of left ventricular hypertrophy (LVH), myocardial contractile failure and diastolic dysfunction in response to pressure overload. In animal models, ACE inhibitors have been shown to attenuate these pathological responses. In humans there is no such evidence available, however uncontrolled studies have shown that these agents are not only tolerated but are associated with acute improvements in haemodynamics and diastolic function. Further studies are merited to assess the possible role of ACE inhibitors in aortic stenosis both before and after valve replacement. Potential benefits may include prevention of LVH, improved diastolic function, reduction of arrhythmias and preservation of left ventricular function.",2002.0,0,0
794,11607795,Resistance to antihypertensive medication as predictor of renal artery stenosis: comparison of two drug regimens.,B C van Jaarsveld; P Krijnen; F H Derkx; J Deinum; A J Woittiez; C T Postma; M A Schalekamp,"Renal artery stenosis is among the most common curable causes of hypertension. The definitive diagnosis is made by renal angiography, an invasive and costly procedure. The prevalence of renal artery stenosis is less than 1% in non-selected hypertensive patients but is higher when hypertension is resistant to drugs. To study the usefulness of standardised two-drug regimens for identifying drug-resistant hypertension as a predictor of renal artery stenosis. Prospective cohort study carried out in 26 hospitals in The Netherlands. Patients had been referred for analysis of possible secondary hypertension or because hypertension was difficult to treat. Patients < or =40 years of age were assigned to either amlodipine 10 mg or enalapril 20 mg, and patients >40 years to either amlodipine 10 mg combined with atenolol 50 mg or to enalapril 20 mg combined with hydrochlorothiazide 25 mg. Renal angiography was performed: (1) if hypertension was drug-resistant, ie if diastolic pressure remained > or =95 mm Hg at three visits 1-3 weeks apart or an extra drug was required, and/or (2) if serum creatinine rose by > or =20 micromol/L (> or =0.23 mg/dL) during ACE inhibitor treatment. Of the 1106 patients with complete follow-up, 1022 had been assigned to either the amlodipine- or enalapril-based regimens, 772 by randomisation. Drug-resistant hypertension, as defined above, was identified in 41% of the patients, and 20% of these had renal artery stenosis. Renal function impairment was observed in 8% of the patients on ACE inhibitor, and this was associated with a 46% prevalence of renal artery stenosis. In the randomised patients, the prevalence of renal artery stenosis did not differ between the amlodipine- and enalapril-based regimens. In the diagnostic work-up for renovascular hypertension the use of standardised medication regimens of maximally two drugs, to identify patients with drug-resistant hypertension, is a rational first step to increase the a priori chance of renal artery stenosis. Amlodipine- or enalapril-based regimens are equally effective for this purpose.",2002.0,0,0
795,11641292,"Pet ownership, but not ace inhibitor therapy, blunts home blood pressure responses to mental stress.",K Allen; B E Shykoff; J L Izzo,"In the present study, we evaluated the effect of a nonevaluative social support intervention (pet ownership) on blood pressure response to mental stress before and during ACE inhibitor therapy. Forty-eight hypertensive individuals participated in an experiment at home and in the physician's office. Participants were randomized to an experimental group with assignment of pet ownership in addition to lisinopril (20 mg/d) or to a control group with only lisinopril (20 mg/d). On each study day, blood pressure, heart rate, and plasma renin activity were recorded at baseline and after each mental stressor (serial subtraction and speech). Before drug therapy, mean responses to mental stress did not differ significantly between experimental and control groups in heart rate (94 [SD 6.8] versus 93 [6.8] bpm), systolic blood pressure (182 [8.0] versus 181 [8.3] mm Hg), diastolic blood pressure (120 [6.6] versus 119 [7.9] mm Hg), or plasma renin activity (9.4 [0.59] versus 9.3 [0.57] ng. mL(-1). h(-1)). Lisinopril therapy lowered resting blood pressure by approximately 35/20 mm Hg in both groups, but responses to mental stress were significantly lower among pet owners relative to those who only received lisinopril (P<0.0001; heart rate 81 [6.3] versus 91 [6.5] bpm, systolic blood pressure 131 [6.8] versus 141 [7.8] mm Hg, diastolic blood pressure 92 [6.3] versus 100 [6.8] mm Hg, and plasma renin activity 13.9 [0.92] versus 16.1 [0.58] ng. mL(-1). h(-1)). We conclude that ACE inhibitor therapy alone lowers resting blood pressure, whereas increased social support through pet ownership lowers blood pressure response to mental stress.",2001.0,0,0
796,11641310,"Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.",R G Asmar; G M London; M E O'Rourke; M E Safar; REASON Project Coordinators and Investigators,"International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic (DBP) but also systolic blood pressure (SBP). Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections. The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide (0.625 mg) and perindopril (2 mg) (Per/Ind) with the beta-blocking agent atenolol (50 mg) to determine whether Per/Ind decreases SBP and pulse pressure (PP) more than does atenolol and, if so, whether this decrease is predominantly due to reduction of aortic pulse wave velocity (PWV) (automatic measurements) and reduction of wave reflections (pulse wave analysis, applanation tonometry). In a double-blind randomized study, 471 patients with essential hypertension were followed for 12 months. For the same DBP reduction, Per/Ind decreased brachial SBP (-6.02 mm Hg; 95% confidence interval, -8.90 to -3.14) and PP (-5.57; 95% confidence interval, -7.70 to -3.44) significantly more than did atenolol. This difference was significantly more pronounced for the carotid artery than for the brachial artery. Whereas the 2 antihypertensive agents decreased PWV to a similar degree, only Per/Ind significantly attenuated carotid wave reflections, resulting in a selective decrease in SBP and PP. The very-low-dose combination Per/Ind normalizes SBP, PP, and arterial function to a significantly larger extent than does atenolol, a hemodynamic profile that is known to improve survival in hypertensive populations with high cardiovascular risk.",2001.0,0,0
797,11641316,"Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial.",W C Cushman; B J Materson; D W Williams; D J Reda,"Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined.",2001.0,0,0
798,11672450,Effects of blood pressure lowering with amlodipine or lisinopril on vascular structure of the common carotid artery.,A V Stanton; J N Chapman; J Mayet; P S Sever; N R Poulter; A D Hughes; S A Thom,"Increased intima-media thickness of the common carotid artery predicts increased risk of myocardial infarction and stroke. Preliminary evidence suggests that a decrease in blood pressure (BP) is associated with diminished wall thickness. It is not known if all classes of anti-hypertensive agents have similar protective effects. In this double-blind parallel-group clinical trial, 69 previously untreated patients with hypertension were allocated randomly to 1 year of treatment with either amlodipine (5-10 mg daily) or lisinopril (5-20 mg daily). Doxazosin and bendrofluazide were added if required to achieve BP control. After 12 months of treatment, clinic BP, ambulatory BP and cardiac mass were reduced similarly by the two treatment regimens. Common carotid artery intima-media thickness decreased by 0.048 mm (95% confidence intervals -0.066, -0.031 mm) in the amlodipine-treated group, but decreased by only 0.027 mm (-0.046, -0.007 mm) in the lisinopril-treated group (P<0.05 for difference between treatments). Common carotid artery lumen diameter declined significantly only in patients treated with lisinopril [amlodipine, -0.02 mm (-0.14, 0.10 mm); lisinopril, -0.21 mm (-0.32, -0.11 mm); P<0.02], while intima-media area declined similarly in the two treatment groups [amlodipine -1.32 mm(2) (-1.91, -0.74 mm(2)), lisinopril -1.26 mm(2) (-1.80, -0.72 mm(2)); not significant]. The results confirm that a decrease in BP causes regression of structural changes in the carotid artery in hypertensive patients. The nature of the structural regression differed markedly between the two treatment regimens, in spite of similar decreases in BP. The calcium channel blocker induced greater regression of common carotid artery intima-media thickness than the angiotensin-converting enzyme inhibitor. However, carotid artery wall mass, as indicated by intima-media area, was reduced to a similar extent by the two treatments. It remains to be established whether such differences confer a prognostic advantage.",2002.0,0,0
799,11674903,What is the best treatment for slowing the progression to end-stage renal disease (ESRD) in African Americans with hypertensive nephropathy?,J R McConaghy,,2002.0,0,1
800,11676305,Postdischarge adverse drug reactions in primary care originating from hospital care in France: a nationwide prospective study.,L Letrilliart; T Hanslik; M Biour; J P Fagot; M Guiguet; A Flahault,"To describe and estimate the incidence and preventability of postdischarge adverse drug reactions (ADRs) detected in primary care in France. Prospective study of patients referred to hospital by participating general practitioners (GPs). These GPs reported all cases of an adverse reaction to a drug instituted in hospital among patients who consulted them within 30 days of discharge. 305 general practices from all French regions. 7540 patients referred by GPs to private or public hospitals. The incidence for postdischarge ADRs in primary care, and their preventability. 30 cases of postdischarge ADR were detected in 29 re-consulting patients, yielding a minimal incidence for France of 0.4 per 100 admissions (95% confidence interval 0.3 to 0.6). The ADRs were assessed as serious in 60% of cases. The main drug classes implicated were cardiovascular drugs (8 ADRs), oral anticoagulants (6), psychoactive drugs (4), antidiabetics (3), and opioid analgesics (3). Patients experiencing a postdischarge ADR were older than patients not experiencing one (median age: 77 vs 68 years; p = 0.004). Detected ADRs were considered preventable in 59% of cases. Physicians and patients should be aware of the possible occurrence of postdischarge ADRs. Patient information in hospital, close postdischarge follow-up of patients at risk, and appropriate transmission of information between hospital physicians and GPs can help to prevent them.",2002.0,0,0
801,11677279,Drug related medical emergencies in the elderly: role of adverse drug reactions and non-compliance.,S Malhotra; R S Karan; P Pandhi; S Jain,"Adverse drug reactions and non-compliance are important causes of admissions in the elderly to medical clinics. The contribution of adverse drug reactions and non-compliance to admission by the medical emergency department was analysed. A total of 578 consecutive elderly patients admitted to the medical emergency department were interviewed to determine the percentage of admissions due to adverse drug reactions or non-compliance with medication regimens, their causes, consequences, and predictors. Eighty three (14.4%) of the 578 admissions were drug related: 39 (6.7%) caused by adverse drug reactions and 44 (7.6%) caused by non-compliance with medication. One hundred ninety two (33.2%) patients had a history of non-compliance. Factors associated with an increased risk of admission because of an adverse drug reaction were patients with diabetes or neoplasms, and patients using numerous different medications. Factors associated with a higher risk of hospitalisation because of non-compliance were poor recall of the medication regimen, seeing numerous physicians, female sex, polypharmacy, drug costs, and switching over to non-conventional forms of treatment. Many elderly admissions are drug related, with non-compliance accounting for a substantial fraction of these. Elderly people at high risk of suffering a drug related medical emergency are identified and suitable interventions may be planned by the healthcare policymakers to target them.",2002.0,0,0
802,11677377,Combination of hydrochlorothiazide or benazepril with valsartan in hypertensive patients unresponsive to valsartan alone.,B Waeber; R Aschwanden; L Sadecky; P Ferber,"The aim of this open multicentric study was to investigate the efficacy and safety of the addition of an angiotensin converting enzyme (ACE) inhibitor (benazepril, 10 mg/day) or a diuretic (hydrochlorothiazide, 12.5 mg/day) for 4 weeks in patients with mild to moderate essential hypertension having been treated for 4 weeks by an angiotensin II antagonist (valsartan, 80 mg/day) but still having a diastolic blood pressure (BP) > 90 mmHg on this medication given alone. A total of 327 patients were included in the trial and 153 patients (46%) had their diastolic BP </= 90 mmHg after 4 weeks of valsartan monotherapy. These patients continued the same treatment regimen for the next 4 weeks, but no further blood pressure reduction was observed. The remaining patients were randomized to either the valsartan-hydrochlorothiazide or the valsartan-benazepril combination. The two combinations induced an additional significant BP reduction, which was of similar magnitude for diastolic BP (-4.5 during valsartan-hydrochlorothiazide treatment and -3.3 mmHg during valsartan-benazepril treatment), but of greater magnitude for systolic BP during valsartan-hydrochlorothiazide (-6.77 mmHg) than during valsartan-benazepril co-administration (-3.2 mmHg). At the end of the trial, the BP of the responders to the valsartan monotherapy was lower than that of patients having required a combination therapy. Valsartan given alone or in association with hydrochlorothiazide or benazepril was well tolerated. These data therefore show that in patients not responding sufficiently to angiotensin II receptor blockade BP can be further and safely lowered by adding a small dose of a diuretic or an ACE inhibitor, with the diuretic-containing combination tending to being more effective in controlling systolic BP.",2002.0,0,0
803,11678523,Captopril-induced jaundice: report of 2 cases and a review of 13 additional reports in the literature.,A Schattner; N Kozak; J Friedman,"Two elderly patients, treated with captopril for left ventricular dysfunction and diabetes, developed severe cholestatic jaundice for which no alternative explanation could be found. The jaundice resolved completely after discontinuation of the drug. A review of the literature identifies a highly similar and distinctive clinical pattern in another 13 cases reported and suggests that hepatotoxicity is a well-established yet rare adverse effect of captopril. However, the very common use of this drug, together with the severity of the liver injury it may cause, calls for a high index of suspicion and increased awareness of this phenomenon.",2002.0,0,0
804,11684211,Cardiovascular protection and blood pressure reduction: a meta-analysis.,J A Staessen; J G Wang; L Thijs,"Whether antihypertensive drugs offer cardiovascular protection beyond blood pressure lowering has not been established. We aimed to investigate whether pharmacological properties of antihypertensive drugs or reduction of systolic pressure accounted for cardiovascular outcome in hypertensive or high-risk patients. In a meta-analysis we extracted summary statistics from published reports, and calculated pooled odds ratios for experimental versus reference treatment. We correlated across-trials odd ratios for differences in systolic pressure between groups. We analysed nine randomised trials comparing treatments in 62605 hypertensive patients. Compared with old drugs (diuretics and b-blockers), calcium-channel blockers and angiotensin converting-enzyme inhibitors offered similar overall cardiovascular protection, but calcium-channel blockers provided more reduction in the risk of stroke (13.5%, 95% CI 1.3-24.2, p=0.03) and less reduction in the risk of myocardial infarction (19.2%, 3.5-37.3, p=0.01). Heterogeneity was significant between trials because of high risk of cardiovascular events on doxazosin in one trial, and high risk of stroke on captopril in another; but systolic pressure differed between groups in these two trials by 2-3 mm Hg. Similar systolic differences occurred in a trial of diltiazem versus old drugs, and in three trials of converting-enzyme inhibitor against placebo in high-risk patients. Meta-regression across 27 trials (136124 patients) showed that odds ratios could be explained by achieved differences in systolic pressure. Our findings emphasise that blood pressure control is important. All antihypertensive drugs have similar long-term efficacy and safety. Calcium-channel blockers might be especially effective in stroke prevention. We did not find that converting-enzyme inhibitors or a-blockers affect cardiovascular prognosis beyond their antihypertensive effects.",2002.0,0,0
805,11686543,Effects of low-dose losartan treatment on persistent microalbuminuria in normotensive type 1 diabetic subjects.,O Açbay,"To examine the effect of low-dose losartan, an angiotensin II antagonist, on persistent microalbuminuria in normotensive Type 1 diabetes mellitus, 16 subjects with Type 1 diabetes were randomly assigned to two 2-month treatment periods, with either losartan (25 mg/day) or enalapril (5 mg/day) in a single-blind cross-over design. Urinary albumin excretion (UAE), blood pressures, lipids, glycemia, HbA1C, serum potassium and creatinine clearance were measured before and after each treatment period. The UAEs were similarly reduced after both treatments. The median UAE decreased by 27.8%, from 162 (range 65-250) to 117 (34-190) mg/day (p<0.01) after enalapril, and decreased by 25%, from 160 (60-246) to 120 (36-184) mg/day (p<0.01) after losartan. The systolic and diastolic blood pressures also decreased significantly (p<0.05), whereas serum levels of potassium increased (p<0.01) after both treatments. The levels of serum HbA1c, mean fasting glucose, total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol and creatinine clearances were not significantly (p>0.05 in all) changed by either the enalapril or losartan treatment. No significant differences were found between the effects of enalapril and losartan. In conclusion, losartan treatment reduces microalbuminuria as effectively as enalapril in normotensive Type 1 diabetic patients.",2002.0,0,0
806,11688766,"Efficacy, tolerability and influence on ""quality of life"" of nifedipine GITS versus amlodipine in elderly patients with mild-moderate hypertension.",A C Pessina; L Boari; E De Dominicis; C Giusti; M Marchesi; G Marelli; M Mattarei; L Mos; S Novo; A Pirrelli; M Santini; M Santonastaso; S Semeraro; E Uslenghi; M O Kilama,"The main purpose of this study was to compare efficacy, tolerability and influence on quality of life (QOL) of nifedipine gastrointestinal therapeutic system (NI) 30-60 mg once a day vs amlodipine (AM) 5-10 mg once a day in elderly patients with mild-moderate hypertension. This was a randomized, double-blind, parallel-group, multicenter study. After a 2-week single-blind placebo run-in, patients were randomized to either NI 30 mg or AM 5 mg. Responders continued on the same dosage for 16 additional weeks, while non-responders were titrated to 60 mg NI or 10 mg AM. Blood pressure was measured by mercury sphygmomanometer and efficacy equivalence of NI and AM tested by covariance analysis. Diastolic blood pressure (DBP) was the primary efficacy parameter, its baseline value being taken as covariate while centers effect and treatment interaction were included as fixed effects in the analysis model. The secondary efficacy variables systolic blood pressure (SBP) and scores for QOL were analyzed according to the same model. At the end of the study, overall mean DBPs, calculated as least-square means (LSMEANS), in the ""by protocol"" population were 87.5 mmHg for NI and 86.7 for AM (difference 0.8 mmHg with 90% CI -1.2 to 2.8 mmHg). In the ""by intention to treat"" (ITT) population LSMEANS were 87.6 mmHg for NI and 86.4 mmHg for AM (difference 1.2 mmHg with 90% CI -0.6 to 3.1 mmHg). SBP LSMEANS in the ""by protocol"" population were 147.7 mmHg for NI and 147.3 mmHg for AM (difference 0.3 mmHg, with 90% CI -3.7 to 4.3); corresponding values in the ""by ITT"" population were 148.0 mmHg for NI and 147.2 for AM (difference 0.8 mmHg, with 90% CI -2.8 to 4.6). Mean values for QOL parameters were not significantly different. A total of 173 episodes of adverse events were documented in 54 patients (26 NI and 28 AM), dropouts were 15 (20% of group) on NI and 21 (28%) on AM. NI 30-60 mg was shown to be as efficacious and safe as AM 5-10 mg in elderly patients with mild-moderate hypertension. QOL improved compared to baseline with no significant difference between the two drugs, thus confirming a positive class effect for calcium antagonists.",2002.0,0,0
807,11703440,Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus?,K E White; N Pinel; D J Cordonnier; R W Bilous; Diabiopsies Group,"To examine the effect of ACE inhibition on glomerular structure in Type 2 diabetic patients with nephropathy. Twenty-two patients were randomized to receive either perindopril (PE) or placebo (PO) and biopsied at baseline and after 2 years. Nineteen patients completed the study and data on interstitial changes, examined by light microscopy, have already been published. Only 11 patients (five PE, six PO) had sufficient tissue at baseline and follow-up to provide material for detailed electron microscopic examination. At baseline, mean +/- sd age (PE vs. PO) was 48 +/- 12 vs. 45 +/- 7 years; creatinine clearance 116 +/- 24 vs. 128 +/- 68 ml/min; median (range) proteinuria 0.7 (0.1-1.0) vs. 0.5 (0.07-3.9) g/24 h (P = NS for all). This cohort of 11 patients showed the same interstitial changes as the whole group. Between-group analysis showed that the change in interstitial volume fraction was significantly greater in the PO compared with PE group (0.10 +/- 0.07 vs. -0.001 +/- 0.04, P = 0.020). There were no significant changes in proteinuria or glomerular structural parameters (mesangial volume fraction PO 0.40 +/- 0.17 to 0.42 +/- 0.21; PE 0.29 +/- 0.08 to 0.28 +/- 0.14) in either treatment group. Interstitial changes appear to be more sensitive to ACE inhibition than glomerulopathy. Larger patient groups and longer treatment periods are necessary in order to detect any possible impact of ACE inhibition on the glomerular changes in Type 2 diabetes mellitus.",2002.0,0,0
808,11705355,New advances in severe adverse drug reactions.,J Revuz,"Every new drug has the potential for causing cutaneous adverse drug reactions. Usually the clinical pattern is well known and has been described in association with other drugs; new entities, however, are described frequently. This article reviews several of them.",2002.0,0,0
809,11705443,Liver failure in a patient treated with long-term rosiglitazone therapy.,H E Gouda; A Khan; J Schwartz; R I Cohen,,2002.0,0,0
810,11705582,Vasopeptidase inhibitors.,M A Weber,"Vasopeptidase inhibitors are a new class of cardiovascular drug that simultaneously inhibit both neutral endopeptidase and angiotensin-converting enzyme (ACE). They increase the availability of peptides that have vasodilatory and other vascular effects; they also inhibit production of angiotensin II. In animal models vasopeptidase inhibitors decrease blood pressure in low, medium, and high renin forms of hypertension, and they also appear to confer benefits in models of heart failure and ischaemic heart disease. Studies in human hypertension show that these agents are effective in decreasing blood pressure regardless of race or age. Experience with omapatrilat, the most clinically advanced of these drugs, has shown it to be more effective than currently available ACE inhibitors or other widely used antihypertensive agents. Studies with omapatrilat in congestive heart failure have shown beneficial effects on haemodynamics and symptoms. The vasopeptidase inhibitors appear to have safety profiles similar to ACE inhibitors, though the frequency of side-effects such as angio-oedema and cough remains to be established. Large trials with clinical endpoints, some already in progress, are needed to establish the place of this class of drug beside that of established therapies in conditions such as hypertension, heart failure, ischaemic heart disease, and nephropathy.",2002.0,0,0
811,11707687,Nitrendipine and enalapril combination therapy in mild to moderate hypertension: assessment of dose-response relationship by a clinical trial of factorial design.,A Roca-Cusachs; F Torres; M Horas; J Ríos; G Calvo; J Delgadillo; M Terán; Spanish Nitrendipine/Enalapril Collaborative Study Group,"Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality. Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required. As many as 50% of patients require the addition of a second agent to achieve satisfactory blood pressure control. The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension. A total of 496 patients were enrolled in a multicenter, randomized, double-blind, factorial-design, parallel-group clinical trial comparing placebo, nitrendipine (5, 10, and 20 mg) and enalapril (5, 10, and 20 mg) alone or in combination. After a single-blind, 2-week placebo run-in period, 414 patients whose diastolic blood pressure ranged between 90-109 mm Hg were randomly assigned to a treatment group. The combination of nitrendipine and enalapril, particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg, were significantly superior to both monotherapies; mean diastolic blood pressure reductions from baseline to last visit were -12.5 and -14.3 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy. All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups. In summary, the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses. The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg.",2002.0,0,0
812,11709807,"Prevention, protection, and the intrarenal renin-angiotensin systems.",D G Warnock,"The use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor antagonists, or aldosterone antagonists can have important beneficial effects on the progression of renal disease associated with glomerular and interstitial fibrosis, especially if the adverse side effects (eg, hyperkalemia) can be minimized. Because it appears that chronic renal insufficiency and proteinuria may well be cardiovascular risk factors, it is exciting to note that recent large scale epidemiologic studies (Heart Outcomes and Prevention Evaluation [HOPE]) have shown both cardioprotective and renoprotective effects of ACE inhibition. It appears paradoxic that such renoprotective effects are clearly evident in diabetes mellitus in which the plasma renin activity may be suppressed. Even in this setting, it appears that there is activation of the renal angiotensin system(s), and inhibitions of these intrarenal systems are involved in the renoprotective effects of these agents. Recent studies have identified nearly all of the components needed to generate angiotensin II in the renal luminal compartment, and suggest that there may be a direct effect through AT(1) receptors on NaCl transport in the distal nephron. The possibility that the components of this intraluminal renin-angiotensin system may be acutely regulated by variations in dietary salt intake provides an opportunity to better understand the normal maintenance of salt balance. Whether or not inhibition of these pathways is involved in the renoprotective effects of ACE inhibitors and angiotensin receptor antagonists is an important issue to be addressed.",2002.0,0,0
813,11710893,Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review.,K A Phillips; D L Veenstra; E Oren; J K Lee; W Sadee,"Adverse drug reactions are a significant cause of morbidity and mortality. Although many adverse drug reactions are considered nonpreventable, recent developments suggest these reactions may be avoided through individualization of drug therapies based on genetic information, an application known as pharmacogenomics. To evaluate the potential role of pharmacogenomics in reducing the incidence of adverse drug reactions. MEDLINE English-language only searches for adverse drug reaction studies published between January 1995 and June 2000 and review articles of variant alleles of drug-metabolizing enzymes published between January 1997 and August 2000. We also used online resources, texts, and expert opinion. Detailed inclusion criteria were used to select studies. We included 18 of 333 adverse drug reaction studies and 22 of 61 variant allele review articles. All the investigators reviewed and coded articles using standardized abstracting forms. We identified 27 drugs frequently cited in adverse drug reaction studies. Among these drugs, 59% are metabolized by at least 1 enzyme with a variant allele known to cause poor metabolism. Conversely, only 7% to 22% of randomly selected drugs are known to be metabolized by enzymes with this genetic variability (range, P =.006-P<.001). Our results suggest that drug therapy based on individuals' genetic makeups may result in a clinically important reduction in adverse outcomes. Our findings serve as a foundation for further research on how pharmacogenomics can reduce the incidence of adverse reactions and on the resulting clinical, societal, and economic implications.",2002.0,0,0
814,11717612,"Changes in vasoconstrictive hormones, natriuretic peptides, and left ventricular remodeling soon after anterior myocardial infarction.",M White; J L Rouleau; C Hall; M Arnold; F Harel; P Sirois; S Greaves; S Solomon; U Ajani; R Glynn; C Hennekens; M Pfeffer,"Our purpose was to study the changes in vasoconstrictive neurohormones, N-terminal proatrial natriuretic peptide (Nt-proANP), and brain natriuretic peptide (BNP) and their relationship with left ventricular (LV) remodeling soon after anterior myocardial infarction (MI). The Healing and Afterload Reducing Therapy (HEART) trial has shown that early use of ramipril improves left ventricular ejection fraction (LVEF) and attenuates LV remodeling when initiated soon after MI. This neurohumoral substudy of HEART investigates the changes in vasoconstrictive and natriuretic peptides and their relationship with LV remodeling. One hundred twenty-two patients had blood drawn for the measurement of catecholamines, endothelin-I, angiotensin II, Nt-proANP and BNP, and prostacyclins within 24 hours of an MI, and at 3, 14, and 90 days after the MI. Quantitative echocardiograms were performed at baseline and at 14 days. All neurohormones except angiotensin II (P =.12) and prostaglandins were significantly elevated at baseline. Vasoconstrictive neurohormones decreased significantly over time but remained elevated at 14 days. Both Nt-proANP and BNP were elevated within the first 14 days. BNP decreased significantly by 90 days, whereas Nt-proANP exhibited no change between 14 and 90 days. Ramipril decreased plasma levels of angiotensin II at 3 days but had no effect on the other neurohormones. Neurohumoral activation occurs and persists in patients with anterior MI and overall preserved LV function. Ramipril had only a modest impact on neurohormones despite its significant benefits on LV remodeling soon after MI.",2002.0,0,0
815,11718163,An ACE inhibitor to coronary patients: ramipril reduces mortality according to HOPE trial.,,"In a clinical trial mainly involving patients over 55 with coronary heart disease, ramipril reduced mortality while vitamin E had no preventive effect.",2002.0,0,1
816,11720604,Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group.,A H Gradman; A Lewin; B T Bowling; M Tonkon; P C Deedwania; A E Kezer; J D Hardison; D J Cushing; E L Michelson,"The antihypertensive efficacy and tolerability of the novel angiotensin-II (A-II) receptor blocker candesartan cilexetil and the prototype A-II receptor blocker, losartan, were compared in an 8-week, multicenter, double-blind, randomized, parallel-group, titration-to-effect study of 332 adults (42% women, 12% black) with systemic hypertension (sitting diastolic blood pressure [DBP] 95-114 mmHg, inclusive). In patients with a mean trough (24 +/- 3 hours after dose) sitting DBP of 90 mmHg or higher after 4 weeks of once daily administration of candesartan 16 mg or losartan 50 mg, dose was titrated up to candesartan 32 mg or losartan 100 mg once daily. The candesartan regimen was significantly more effective than the losartan regimen in reducing trough sitting DBP at week 8 (11.0 mmHg versus 8.9 mmHg). Candesartan also produced numerically greater reductions in secondary blood pressure parameters, including sitting systolic blood pressure (SBP), trough standing DBP and SBP, and peak (6 +/- 2.5 hours after dose) sitting and standing DBP and SBP. Responder rates (sitting DBP < 90 mmHg or reduction in blood pressure of > or = 10 mmHg) and control rates (sitting DBP <90 mmHg) were higher with candesartan (64% versus 54% and 54% versus 43%, respectively). A total of 1.9% of the patients taking candesartan and 6.5% of those taking losartan discontinued prematurely because of adverse events or lack of efficacy.",2002.0,0,0
817,11721319,Mechanical vs intrinsic components in the improvement of brachial arterial compliance. Comparison of the effects of atenolol versus ramipril in hypertensive patients.,R L Armentano; S Graf; A J Ramírez; J D Espinosa; L Brandani; H Baglivo; R Sánchez,"The aim of this study was to compare the mechanical and intrinsic effects of an angiotensin converting enzyme inhibitor, vs a beta-blocker, on brachial arterial compliance. In a double blind study, 34 essential hypertensive patients were treated for 3 months with either ramipril 2.5-5.0 mg daily (n = 17, age 57 +/- 7 y, 11 males) or atenolol 50-100 mg daily (n = 17, age 53 +/- 8 y, 11 males). Blood pressure (BP), brachial artery diameter (D), brachial-radial pulse wave velocity (PWV) and effective compliance (Ceff), were measured before and at the end of the study. Isobaric evaluation (Ciso) was performed in the entire population studied at an average mean BP of 110 mmHg. Ramipril significantly reduced BP from 155 +/- 16/94 +/- 6 mmHg to 140 +/- 15/85 +/- 7 mmHg (p < 0.001) without affecting heart rate (HR; 74 +/- 10 vs. 75 +/- 12 bpm). In addition, it significantly improved both PWV (18%; p < 0.001) and arterial compliance (45%; p < 0.001), from which 35% was related to a pressure independent effect (p < 0.01). Atenolol also induced a reduction in both BP (159 +/- 17/96 +/- 10 to 133 +/- 13/81 +/- 8 mmHg; p < 0.001) and HR (76 +/- 10 to 57 +/- 7 bpm; p < 0.001). In a similar way, PWV (11%; p < 0.05) and Ceff (30%; p < 0.05) were significantly improved without significant change in Ciso. This suggests that blood pressure reduction was responsible for compliance improvement. In conclusion, it is suggested that atenolol induces only hemodynamic changes, mediated mainly by BP reduction. In contrast, the improved brachial buffering function observed after ramipril involves not only hemodynamic changes, but also changes mediated by other mechanisms, such as modification of wall structures.",2002.0,0,0
818,11721652,Cutaneous drug reaction case reports. From the world literature.,,"Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International, Auckland, New Zealand) and Medline. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage).",2002.0,0,0
819,11722484,Relevance of skin tests with drugs in investigating cutaneous adverse drug reactions.,A Barbaud; P Trechot; S Reichert-Penetrat; N Commun; J L Schmutz,"Skin tests with drugs can be of value in investigating patients who have developed cutaneous adverse drug reactions (CADR), but their specificity and relevance remain to be determined. A false-positive result on skin testing can happen if it is not compared to results in control subjects. When performing intradermal tests (IDT), we have determined the lowest concentrations that induce false-positive results for many drugs, including betalactam antibiotics, cephalosporins, other antibiotics or non-steroidal anti-inflammatory drugs. Some drugs in their commercialized form contain sodium lauryl sulfate and can induce irritation when patch tested as such. When patch tested with colchicine at 10% in pet. or with a Cytotec pill (containing misoprostol) at 30% in pet., respectively, 80% of the 29 and 9 of the 10 negative controls developed false-positive results. Lastly, positive results of patch tests with drugs can be related to contact allergy to one of the components of the commercialized form of the drug, without any relevance to the investigation of a CADR, as observed in 2 cases with iodine or avocado oil.",2002.0,0,0
820,11723089,Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project.,L Niskanen; T Hedner; L Hansson; J Lanke; A Niklason; CAPPP Study Group,"The Captopril Prevention Project (CAPPP) evaluated the effects of an ACE inhibitor-based therapeutic regimen on cardiovascular mortality and morbidity in hypertension. One planned subanalysis of the CAPPP was to evaluate the outcome in the diabetic patient group. In the CAPPP, 572 (4.9% of 10,985 hypertensive patients) had diabetes at baseline and were studied according to a prospective, randomized, open, blinded, end point trial design. Patients aged 25-66 years with diastolic blood pressure > or =100 mmHg were included and randomized to receive either captopril or conventional antihypertensive treatment (diuretics and/or beta-blockers). The primary end point, fatal and nonfatal myocardial infarction and stroke as well as other cardiovascular deaths, was markedly lower in the captopril than in the conventional therapy group (relative risk [RR] = 0.59; P = 0.018). Specifically, cardiovascular mortality, defined as fatal stroke and myocardial infarction, sudden death, and other cardiovascular death, tended to be lower in the captopril group (RR = 0.48; P = 0.084), and no difference was observed between the study groups for stroke (RR = 1.02; P = 0.96). Myocardial infarctions were less frequent in the captopril group than in the conventional therapy group (RR = 0.34; P = 0.002). Furthermore, total mortality was lower in the captopril as compared with the conventional therapy group (RR = 0.54; P = 0.034). Patients with impaired metabolic control seemed to benefit the most from ACE inhibitor-based therapy. Captopril is superior to a diuretic/beta-blocker antihypertensive treatment regimen in preventing cardiovascular events in hypertensive diabetic patients, especially in those with metabolic decompensation.",2002.0,0,0
821,11723356,Beyond the usual strategies for blood pressure reduction: therapeutic considerations and combination therapies.,T D Giles; G E Sander,"Rapidly accumulating clinical data have repeatedly demonstrated not only the critical importance of even small increases in blood pressure as a pathophysiologic factor in the development of cardiovascular disease, particularly in individuals with diabetes mellitus, but also the therapeutic necessity of more aggressive blood pressure reduction and the achievement of progressively lower blood pressure targets in reducing cardiovascular event rates. JNC VI has defined optimal blood pressure as <or=120/80 mm Hg, and Stage 1 hypertension as >or=140/80 mm Hg. Target blood pressures are now <or=130/80 mm Hg in patients with diabetes and <125/75 mm Hg for patients with hypertensive renal disease with proteinuria of >1 gm/24 hours. Achieving such target pressures is increasingly difficult, particularly in diabetic patients with chronic renal disease, who require complex multidrug antihypertensive regimens. This review attempts to provide some suggestions for constructing such antihypertensive regimens, and provides considerations for the appropriate use of diuretics and the most effective drug combinations. Factors potentially contributing to drug resistant hypertension include such problems as failure to maximize drug dosing, suboptimal diuretic use, noncompliance, and possible confounding effects of such concomitant medications as nonsteroidal and anti-inflammatory drugs or decongestants. The issues underlying drug-resistant hypertension are listed, together with strategies for overcoming this problem.",2002.0,0,0
822,11724081,Prescribing patterns and therapeutic implications for diabetic hypertension in Bahrain.,K A Al Khaja; R P Sequeira; V S Mathur,"To determine drug prescription patterns and the extent of conformity with World Health Organization/international Society of Hypertension (WHO/ISH) guidelines in diabetic hypertension. Retrospective prescription-based survey. Seven primary-care health centers, comprising approximately one-third of primary-care health centers in Bahrain. Patients with type 2 diabetes and hypertension. The prescribing pattern of antihypertensive and antidiabetic drugs. Among a study sample of 1,463 patients with type 2 diabetes and hypertension, antidiabetic agents were prescribed as monotherapy in the following descending order: glyburide, gliclazide, insulin, and metformin. As combinations, sulfonylureas plus metformin was most popular, followed by metformin plus insulin, and sulfonylureas plus insulin. Sulfonylurea and metformin with insulin was rarely used. There was no significant difference in prescribing of glyburide and metformin between the elderly and young middle-aged diabetic patients; many patients older than 65 years were treated with a beta-blocker along with a long-acting sulfonylurea. Both as monotherapy and in overall use, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium-channel blockers were most often prescribed. Among 35.5% patients treated with antihypertensive combinations, various two- and three-drug combinations of beta-blockers, ACE inhibitors, calcium-channel blockers, and diuretics were often used. The proportion of patients taking atenolol 100 mg/d was higher with combination regimens. Hydrochlorothiazide 25 mg or equivalent thiazide diuretics were extensively used. The prescribing pattern of antihypertensives in diabetic hypertension differs in many instances from WHO/ISH guidelines, especially regarding the choice of antihypertensive drugs and their combinations. The appropriateness of antidiabetic drug choice is questionable in relation to the antihypertensive used.",2002.0,0,0
823,11727363,"Hypertension in menopausal women--a special case, for special treatment?",A Pines; E Z Fisman,"After the menopause the consequences of hypertension in women change. Their risks of myocardial infarction and stroke rise steeply, a rise that has been blamed in part on the loss of estrogen and the onset of menopausal metabolic syndrome, with endothelial dysfunction, hyperlipidemia, insulin resistance and derangement in coagulation. Hypertensive menopausal women have not had optimum treatment. They have poorer prognoses than men of the same age. Their antihypertensive management therefore merits special attention. Hormone replacement, aspirin prophylaxis and lipid-lowering drugs have their place. The antihypertensive drug chosen should not worsen the metabolic syndrome: angiotensin-II converting enzyme (ACE) inhibitors are therefore among the first-line drugs. Few drugs have been specifically aimed at menopausal hypertension and these are reviewed here.",2002.0,0,0
824,11728260,Aspirin does not interact with ACE inhibitors when both are given early after acute myocardial infarction: results of the GISSI-3 Trial.,R Latini; E Santoro; S Masson; L Tavazzi; A P Maggioni; M G Franzosi; S Barlera; L Calvillo; M Salio; L Staszewsky; V Labarta; G Tognoni; GISSI-3 Investigators,"Aspirin (ASA) and angiotensin-converting enzyme inhibitor (ACEi) therapy reduce mortality when administered early after the onset of myocardial infarction. ASA can antagonize some effects of ACEi therapy by inhibiting the synthesis of vasodilating prostaglandins; however, the evidence for this effect from large controlled trials is contradictory. The authors analyzed a database of 18,895 patients of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio-3 (GISSI-3) Trial in which patients were allocated either to receive lisinopril or not to receive lisinopril within 24 hours of the onset of symptoms of myocardial infarction. The aim of the study was to verify the possible negative interaction between ASA and the ACEi lisinopril in the postacute phase of acute myocardial infarction. Of 18,895 analyzable patients, 15,841 received ASA at entry. Overall lisinopril reduced 42-day mortality from 7.1% to 6.3%. In patients receiving ASA, mortality was reduced by lisinopril from 6.0% to 5.4%, and from 13.0% to 10.8% in patients not receiving ASA. The difference in proportional reductions of mortality corresponds to the fact that a more marked lisinopril effect is seen in patients at higher baseline risk across all study subgroups, one of which coincides with the no-ASA group. The analysis of the inhospital incidence of major clinical events did not reveal a potentially negative interaction between ASA and lisinopril. The same findings were obtained from the analysis of reinfarction at 42 days. The interaction between ASA and lisinopril was also tested by multivariate analysis adjusted for confounding variables at entry, and the interaction tests were not statistically significant. Serum creatinine levels at 42 days were significantly higher in lisinopril group than in the control group. Systolic and diastolic blood pressures in lisinopril group were significantly lower than controls at 42 days. The effect of lisinopril on creatinine and blood pressure did not differ between the ASA and no-ASA groups. ASA does not decrease the mortality benefit of early lisinopril after myocardial infarction, nor does it increase the risk of major adverse events. Lisinopril is safe and effective when given early after the onset of myocardial infarction, regardless of a concomitant administration of ASA started early and continued over a 6-week period.",2002.0,0,0
825,11728289,Evaluation of candesartan cilexetil in black patients with systemic hypertension: the ABC Trial.,Association of Black Cardiologists (ABC) Candesartan Study Group,"To assess the efficacy and tolerability of the angiotensin-II receptor blocker candesartan cilexetil, the Association of Black Cardiologists (ABC) coordinated a 12-week, multicenter, double-blind, placebo-controlled clinical trial in 304 black adults with a sitting diastolic blood pressure (DBP) of 91 to 105 mmHg, inclusive. The goal of the ABC Trial was to address previous reports suggesting that drugs that block the renin-angiotensin-aldosterone system may not be effective in controlling BP in hypertensive black individuals. Patients were randomized to receive candesartan cilexetil 16 mg (n = 156) or placebo (n = 148), once daily after a 4- to 5-week single-blind, placebo run-in period. Candesartan cilexetil and placebo doses were doubled if the trough (24 +/- 3 hours after dose) sitting DBP was 90 mmHg or higher after 4 weeks. If the DBP was 90 mmHg or higher at week 8, hydrochlorothiazide 12.5 mg was added to both placebo or candesartan cilexetil 32 mg. Candesartan cilexetil was significantly more effective than placebo in reducing trough sitting systolic BP (SBP) and DBP at week 8 (6.4/5.1 mmHg versus 1.3/2.7 mmHg) and at week 12 (9.3/7.5 mmHg versus 5.7/5.2 mmHg). Hydrochlorothiazide was added in 27 and 50% of patients in the candesartan cilexetil and placebo groups, respectively. Control and responder rates were consistently higher in the candesartan cilexetil treatment group at weeks 8 and 12. Discontinuation and adverse event rates were similar in the two groups. Candesartan cilexetil once daily was effective in reducing BP in a substantial proportion of an exclusively black hypertensive population. The combination of candesartan cilexetil plus hydrochlorothiazide demonstrated additional efficacy while maintaining an excellent tolerability profile.",2002.0,0,0
826,11728290,Effects of candesartan cilexetil on health-related quality of life in black patients with systemic hypertension in the ABC Trial.,T M Zyczynski; N K Leidy; B W Kong; C T Helaszek; E L Michelson; Association of Black Cardiologists (ABC) Candesartan Study Group,"Tolerability is an important consideration in evaluating a new antihypertensive agent. This can be assessed informally by conventional patient interviews or more formally with the use of validated health-related quality of life (HRQL) measures assessing the patient's perception of the agent's tolerability. HRQL was a secondary end point of a 12-week, multicenter, double-blind, randomized, placebo-controlled study of the efficacy and tolerability of candesartan cilexetil in black patients with systemic hypertension. HRQL was evaluated using the generic Medical Outcomes Study 36-Item Short Form (SF-36) and population- and condition-specific Vital Signs Quality of Life Questionnaire (VSQLQ). Data were gathered via face-to-face interviews at screening, baseline, and weeks 8 and 12. Of the 304 patients randomized, 268 were evaluable for the HRQL analysis. Clinical results, reported in the companion article, found that candesartan cilexetil initiated at 16 mg once daily and titrated to 32 mg once daily as needed, with the subsequent addition of hydrochlorothiazide 12.5 mg as needed, was effective for lowering diastolic and systolic blood pressure and was well tolerated based on office interviews. Analyses of patients' perceptions of tolerability found that HRQL was maintained during the 12-week study period, with no significant differences between treatment and placebo groups at the end of double-blind treatment. These results indicate that the HRQL of black patients with systemic hypertension is maintained during treatment with candesartan cilexetil.",2002.0,0,0
827,11729254,ACE inhibitors to prevent end-stage renal disease: when to start and why possibly never to stop: a post hoc analysis of the REIN trial results. Ramipril Efficacy in Nephropathy.,P Ruggenenti; A Perna; G Remuzzi; Gruppo Italiano di Studi Epidemiologici in Nefrologia,"In this post hoc, secondary analysis of the Ramipril Efficacy In Nephropathy (REIN) trial, an angiotensin-converting enzyme (ACE) inhibition risk/benefit profile was assessed in 322 patients with nondiabetic, proteinuric chronic nephropathies and different degrees of renal insufficiency. The rate of GFR decline (Delta GFR) and the incidence of end-stage renal disease (ESRD) during ramipril or non-ACE inhibitor treatment were compared within three tertiles of basal GFR. Delta GFR was comparable in the three tertiles, whereas the incidence of ESRD was higher in the lowest tertile than in the middle and highest tertiles. Ramipril decreased Delta GFR by 22%, 22%, and 35% and the incidence of ESRD by 33% (P < 0.05), 37%, and 100% (P < 0.01) in the lowest, middle, and highest tertiles, respectively. Delta GFR reduction was predicted by basal systolic (P < 0.0001), diastolic (P = 0.02), and mean (P < 0.001) BP and proteinuria (P < 0.0001) but not by basal GFR (P = 0.12). ESRD risk reduction was predicted by basal proteinuria (P < 0.01) and GFR (P < 0.0001) and was strongly dependent on treatment duration (P < 0.0001). Adverse events were comparable among the three tertiles and within each tertile in the two treatment groups. Thus, disease progression and response to ACE inhibition do not depend on severity of renal insufficiency. The risk of ESRD and the absolute number of events saved by ACE inhibition is highest in patients with the lowest GFR. However, renoprotection is maximized when ACE inhibition is started earlier and when long-lasting treatment may result in GFR stabilization and definitive prevention of ESRD.",2002.0,0,0
828,11730276,Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment.,S Margassery; B Bastani,"We present a 77-year-old male with moderate chronic renal insufficiency from diabetic nephropathy who developed severe metabolic acidosis and life threatening hyperkalemia on treatment with regular dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for urinary tract infection. The metabolic acidosis and hyperkalemia resolved upon appropriate medical intervention and discontinuation of TMP-SMZ. While hyperkalemia has commonly been reported with high dose of TMP-SMZ, severe metabolic acidosis is quite uncommon with regular dose TMP-SMZ. We emphasize that patients with renal tubular acidosis (RTA), renal insufficiency, aldosterone deficiency, old age with reduced renal mass and function, and angiotensin converting enzyme (ACE)-inhibitor therapy are at high risk of developing these severe and potentially life threatening complications.",2002.0,0,0
829,11737121,Efficacy of nifedipine or lisinopril in the treatment of hypertension after renal transplantation: a double-blind randomised comparative trial.,K Midtvedt; A Hartmann; H Holdaas; P Fauchald,"Calcium channel blockers and angiotensin converting enzyme-inhibitors are commonly used in the treatment of hypertensive renal transplant recipients. The purpose of this study was to investigate if the response rate to treatment differs with these drugs in this setting. A single centre, prospective, randomised, double-blinded, comparative study to address the efficacy of controlled release nifedipine or lisinopril in the treatment of hypertension (diastolic blood pressure > or =95 mmHg) in cyclosporin (CsA)-treated renal transplant recipients was performed. Recipients were randomised to receive either lisinopril (10 mg once daily) or controlled release nifedipine (30 mg once daily). The dose was doubled on indication. The number of responders (diastolic blood pressure <90 mmHg on monotherapy) were addressed during the early post-transplant phase (first 3 months) and during a late post-transplant phase (from 3 to 12 months after renal transplantation) in the same patient population. One hundred and fifty-four patients (nifedipine=78, lisinopril=76) with untreated hypertension (diastolic blood pressure> or =95 mmHg) were randomised within 3 wk after renal transplantation. One hundred and twenty-three patients (nifedipine=69, lisinopril=54) completed the study. Fourteen (20%) nifedipine-treated recipients responded during the early, and 26 (38%) during the late post-operative phase (months 4-12 after renal transplantation). Eleven (20%) lisinopril-treated recipients responded during the early, and 18 (33%) during the late post-transplant phase. Non-responders were, on average, 8.5+/-1.5 kg heavier both in the early phase and after 1 yr of treatment (p<0.01), and 6.1+/-0.9 yr older than responders (p<0.05). In conclusion, these results indicate that both controlled release nifedipine and lisinopril are equally efficient in the treatment of post-transplant hypertension. As monotherapy, both drugs show a ""response rate"" of 20-38%, depending on time interval after transplantation.",2002.0,0,0
830,11738123,Participant recruitment in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,S Pressel; B R Davis; G T Louis; P Whelton; H Adrogue; D Egan; M Farber; G Payne; J Probstfield; H Ward; ALLHAT Research Group,"The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a practice-based, randomized, multicenter clinical trial in 42,419 high-risk hypertensive patients aged 55 years and older; 10,356 of these patients are also in a lipid-lowering trial component. The purpose of the antihypertensive component is to determine whether the occurrence of fatal coronary heart disease and/or nonfatal myocardial infarction differs between patients randomized to diuretic (chlorthalidone) and those randomized to either calcium antagonist (amlodipine), angiotensin-converting enzyme inhibitor (lisinopril), or alpha-adrenergic blocker (doxazosin) therapy. (The doxazosin arm has been discontinued.) The purpose of the lipid-lowering component is to determine whether lowering low-density lipoprotein cholesterol with a 3-hydroxymethyl-glutaryl coenzyme A reductase inhibitor (pravastatin) in moderately hypercholesterolemic patients will reduce all-cause mortality compared to a control group receiving ""usual care."" ALLHAT recruited patients from a variety of practice settings from February 1994 through January 1998. Sites were paid for randomizations and are paid for completed follow-up visits and documented study events. Communication and monitoring were facilitated by nine regional coordinator teams. It was recognized from the outset that patient recruitment would be a very large task because of the number of participants (> 40,000) needed, the ambitious nature of the goal for recruitment of African-Americans (> 55%), and the knowledge that many investigators had limited experience recruiting participants for clinical trials. Multiple adjustments in the initial ALLHAT overall recruitment plan facilitated achievement of sample size goals for both components of the trial. The experience obtained from this large trial should be valuable for the planning and implementation of successful recruitment in future trials.",2002.0,0,0
831,11738213,Should all patients with heart failure now receive an ACE inhibitor.,S G Ball,,2002.0,0,0
832,11740389,Sustained improvement of renal graft function for two years in hypertensive renal transplant recipients treated with nifedipine as compared to lisinopril.,K Midtvedt; A Hartmann; A Foss; P Fauchald; K P Nordal; K Rootwelt; H Holdaas,"Treatment of posttransplant hypertension is still a matter of debate. Calcium antagonists may ameliorate renal side effects of cyclosporin. Angiotensin converting enzyme- (ACE) inhibitors may be more effective in sustaining renal function in native chronic renal disease. We prospectively compared the effect of controlled release nifedipine and lisinopril on long-term renal function in hypertensive kidney transplant patients treated with cyclosporin. A total of 154 renal transplant patients presenting with hypertension (diastolic blood pressure >or=95 mmHg) during the first 3 weeks after transplantation were randomised to receive double-blind nifedipine 30 mg or lisinopril 10 mg once daily. A total of 123 patients completed 1 year of treatment (69 nifedipine, 54 lisinopril) and 64 patients completed 2 years of double-blind treatment (39 nifedipine, 25 lisinopril). Baseline glomerular filtration rate was measured as 99 mTc-diethylene-triaminepentaacetate clearance in a stable phase 2 to 5 weeks after inclusion and repeated at 1 and 2 years. Baseline glomerular filtration rates were similar (46+/-16 ml/min with nifedipine, 43+/-14 ml/min with lisinopril). The changes in glomerular filtration rates from baseline were statistically significant between the groups after 1 year (9.6 ml/min mean treatment difference (95% confidence interval [CI]s 5.5-13.7 ml/min, P=0.0001) and remained statistically significant also after 2 years (10.3 ml/min mean difference (95% CIs 4.0-16.6], P=0.0017). After 1 year glomerular filtration rates averaged 56+/-19 ml/min in the nifedipine group and 44+/-14 ml/min in the lisinopril group. Both nifedipine and lisinopril were safe and effective in treatment of hypertension in renal transplant patients treated with cyclosporin. Patients receiving nifedipine but not lisinopril improved kidney transplant function over a period of 2 years.",2002.0,0,0
833,11750440,Is losartan as effective as enalapril on posttransplant persistent proteinuria?,M R Altiparmak; S Trablus; S Apaydin; O Başar; M Sariyar; K Serdengeçti; E Erek,,2002.0,0,0
834,11751648,Are angiotensin II receptor blockers indicated in chronic heart failure?,M Komajda,,2002.0,0,0
835,11751715,Omapatrilat versus lisinopril: efficacy and neurohormonal profile in salt-sensitive hypertensive patients.,V M Campese; K C Lasseter; C M Ferrario; W B Smith; M C Ruddy; C E Grim; R D Smith; R Vargas; M F Habashy; O Vesterqvist; C L Delaney; W C Liao,"Omapatrilat, a vasopeptidase inhibitor, simultaneously inhibits neutral endopeptidase and ACE. The efficacy and hormonal profile of omapatrilat and lisinopril were compared in salt-sensitive hypertensive patients. On enrollment, antihypertensive medications were withdrawn, and patients received a single-blind placebo. On day 15, salt-sensitivity determinations were made. Salt-sensitive hypertensive patients returned within 5 to 10 days for baseline evaluations of ambulatory diastolic blood pressure, ambulatory systolic blood pressure, and atrial natriuretic peptide. Salt-sensitive hypertensive patients were randomized to receive double-blind omapatrilat (n=28) or lisinopril (n=33) at initial doses of 10 mg for 1 week, increasing to 40 and 20 mg, respectively, for an additional 3 weeks. Ambulatory blood pressure and urinary atrial natriuretic peptide were assessed at study termination. Both omapatrilat and lisinopril significantly reduced mean 24-hour ambulatory diastolic and systolic blood pressures; however, omapatrilat produced significantly greater reductions in mean 24-hour ambulatory diastolic blood pressure (P=0.008), ambulatory systolic blood pressure (P=0.004), and ambulatory mean arterial pressure (P=0.005) compared with values from lisinopril. Both drugs potently inhibited ACE over 24 hours. Omapatrilat significantly (P<0.001) increased urinary excretion of atrial natriuretic peptide over 0- to 24-hour (3.8-fold) and 12- to 24-hour (2-fold) intervals; lisinopril produced no change. Omapatrilat significantly (P<0.001) increased urinary excretion of cGMP over the 0- to 24- and 4- to 8-hour intervals compared with that from lisinopril. Neither drug had a diuretic, natriuretic, or kaliuretic effect. In conclusion, in salt-sensitive hypertensive patients, omapatrilat demonstrated the hormonal profile of a vasopeptidase inhibitor and lowered ambulatory diastolic and systolic blood pressures more than lisinopril.",2002.0,0,0
836,11751733,Chronic ACE inhibition enhances the endothelial control of arterial mechanics and flow-dependent vasodilatation in heart failure.,R Joannides; C Bizet-Nafeh; A Costentin; M Iacob; G Derumeaux; A Cribier; C Thuillez,"Reduced conduit arteries flow-dependent dilatation and altered compliance have been described during heart failure. However, the role of shear stress, the relation between endothelial dysfunction and mechanics, and the effect of chronic ACE inhibition on this relationship have not been investigated. The present study was designed to evaluate in heart failure patients the relationship between flow-dependent dilatation and radial artery mechanics at known shear stress levels and to assess the effect of chronic ACE inhibition. Sixteen stable congestive heart failure patients, who had never been treated with ACE inhibitors, participated in the study. Arterial pressure, cardiac output (bioimpedance), radial artery diameter (echo tracking) and flow (Doppler), total blood viscosity, and mean artery wall shear stress were assessed before and during a gradual increase in the forearm blood flow in response to gradual distal hand skin heating. Cross-sectional radial artery compliance and distensibility indexes were calculated at 34 degrees C, 40 degrees C, and 44 degrees C. The endothelium-independent vasodilatation was evaluated by use of glyceryl trinitrate. All parameters were assessed before and 24 hours after the last administration of perindopril (4 mg once daily) or placebo in a 2-month double-blind randomized study. Before treatment, there was no difference between the 2 groups for all parameters. After chronic ACE inhibition, systolic arterial pressure decreased at baseline from 126+/-11 to 118+/-10 mm Hg (P<0.05). During heating, the increase in diameter in response to shear stress was higher after ACE inhibition than after placebo (time/treatment interaction, P<0.05). Moreover, in contrast to placebo, at the same shear stress, there was a significant increase in compliance (3.23+/-0.79 x 10(-7) to 6.82+/-2.47 x 10(-7) m(2)/kPa, P<0.05) and distensibility (5.71+/-1.35 x 10(-3) to 8.87+/-1.88 x 10(-3)/kPa, P<0.05) during heating after ACE inhibition. The effect of glyceryl trinitrate did not change. The present study demonstrates that chronic administration of the ACE inhibitor perindopril increases the magnitude of the flow-dependent dilatation and restores the flow-dependent increase in compliance and distensibility of the radial artery evaluated at stable shear stress. In addition, the decrease in baseline systolic arterial pressure after ACE inhibitor suggests an associated increase in the distensibility of the proximal elastic conduit arteries.",2002.0,0,0
837,11751734,Radial artery flow-mediated dilatation in heart failure patients: effects of pharmacological and nonpharmacological treatment.,C Giannattasio; F Achilli; A Grappiolo; M Failla; E Meles; G Gentile; I Calchera; A Capra; J Baglivo; A Vincenzi; L Sala; G Mancia,"Congestive heart failure (CHF) is associated with an impaired flow-mediated vasodilation that reflects an impaired endothelial function. Limited information is available, however, on whether and to what extent this impairment is improved by pharmacological or nonpharmacological treatment. We measured radial artery diameter and blood flow by an echo-tracking Doppler device both at baseline and after 4 minutes of hand ischemia, which increases diameter through NO secretion mediated by an increase in flow and shear stress. Data were collected from 44 CHF patients (New York Heart Association class I to III) under standard treatment (diuretic, digitalis, and enalapril, 20 mg/d), in whom CHF severity was assessed by a cardiopulmonary stress test, and from 16 age- and sex-matched controls. CHF patients were then randomized to maintain for (A) 2 months of standard treatment (n=11), (B) treatment with double the ACE inhibitor dose (n=11), (C) standard treatment with an angiotensin II antagonist (losartan, 50 mg/d; n=11), or (D) standard treatment with bicycle training for 30 minutes, 3 times a week (n=11). At baseline, radial artery diameter and flow were similar in CHF patients and controls; CHF patients had a modest although significant impairment in flow increase (-36%) and a striking impairment (-78%) in diameter increase following the 4 minutes of ischemia. After 2 months, baseline diameter and flow remained unaltered in the 4 groups. After the 4 minutes of ischemia, radial artery flow and diameter increased as before in the group under standard treatment (A), whereas in the other 3 groups, the increase was significantly (P<0.05) and, for diameter, markedly (B, 83%; C, 92%; and D, 95%) greater. The vasodilatation induced by trinitroglycerin was similar in CHF and control subjects and not affected by treatments. In CHF, radial artery shows a marked reduction in flow-mediated vasodilation, reflecting impairment of endothelial function. This impairment can be markedly improved by treatments that effectively block the renin-angiotensin system either at ACE or at ACE plus angiotensin receptor level. This is the case also with nonpharmacological treatment of CHF.",2002.0,0,0
838,11752035,Contribution of volume overload and angiotensin II to the increased pulse wave velocity of hemodialysis patients.,J L Tycho Vuurmans; Walther H Boer; Willem-Jan W Bos; Peter J Blankestijn; Hein A Koomans,"Aortic compliance is decreased in patients with end-stage renal disease. This malfunction contributes to high aortic systolic pressures and thus to the development of left ventricular hypertrophy. It was hypothesized that besides structural vascular changes, functional changes as a result of hypervolemia and increased vasoconstrictor activity, in particular angiotensin II, play a role in decreasing aortic compliance. Nineteen hemodialysis patients were studied before and 24 h after they had been dialyzed to dry weight. Applanation tonometry of peripheral arteries was used to estimate aortic pulse wave velocity (PWV), known to depend on aortic compliance, and aortic systolic pressure augmentation (augmentation index [Aix]). Predialysis aortic PWV was increased in the dialysis patients compared with matched healthy subjects (9.9 +/- 3.1 versus 7.5 +/- 1.1 m/s; P < 0.05). The AIx was also increased (35 +/- 6 versus 25 +/- 10; P < 0.05). Volume reduction with dialysis had no significant effect on PWV (9.3 +/- 1.5 m/s), but the AIx decreased (28 +/- 7; P < 0.05). A subset of 10 patients were restudied after 1 wk of angiotensin-converting enzyme inhibition (ACEi) with enalapril 5 mg once daily. ACEi decreased both predialysis as postdialysis BP but had no effect on pulse pressure and heart rate, which remained elevated compared with healthy subjects. ACEi also decreased predialysis aortic PWV, from 11.0 +/- 3.5 to 9.1 +/- 2.1 m/s (P < 0.05) but had no significant effect on AIx. During treatment with ACEi, the same volume reduction with dialysis decreased aortic PWV further to 8.0 +/- 1.4 m/s (P < 0.05), a figure not different from PWV in healthy subjects. AIx decreased to an even slightly subnormal value (12 +/- 23; P < 0.05). It was concluded that volume overload and angiotensin II both contribute to elevated PWV and AIx in dialysis patients. Volume reduction and ACEi both improve the aortic PWV and AIx. Combined volume reduction and ACEi has an enhanced effect that, in the present patients, was so large that PWV and AIx were no longer elevated. Monitoring and correcting of arterial pressure waves is feasible and may be an important tool in the treatment of patients with end-stage renal disease.",2002.0,0,0
839,11753189,Angiotensin-converting enzyme inhibitor angioedema in a pediatric patient: a case report and discussion.,E C Quintana; M W Attia,,2002.0,0,0
840,11755289,Neurohormonal and clinical responses to high- versus low-dose enalapril therapy in chronic heart failure.,W H Wilson Tang; Randall H Vagelos; Yin Gail Yee; Claude R Benedict; Kathy Willson; Charles L Liss; Michael B Fowler,"We sought to compare the neurohormonal responses and clinical effects of long-term, high-dose versus low-dose enalapril in patients with chronic heart failure (CHF). Examination of neurohormonal and clinical responses in patients receiving different doses of angiotensin-converting enzyme (ACE) inhibitors may provide insight into the potential for additional suppression with angiotensin II (AT-II) or aldosterone antagonists. Seventy-five patients with CHF were randomized to receive either high-dose (40 mg/day, n = 37) or low-dose (5 mg/day, n = 38) enalapril over six months. The results from exercise testing, echocardiography, tissue-specific ACE activity and monthly pre- and post-enalapril neurohormonal levels were compared. Despite greater intra-group improvements in plasma renin activity and serum aldosterone levels in the high-dose group, no statistically significant differences were observed between the two groups in all variables, except for serum ACE activity at the end of study. Elevated serum aldosterone and plasma AT-II levels were observed in 35% and 85% of patients, respectively, at 34 weeks, an inter-group difference that was not statistically significant. A trend toward higher levels of tissue-specific ACE activity in the high-dose group compared with the low-dose group at the end of study was observed (p = 0.054). A predefined composite end point of clinical events had a trend toward better improvement in the high-dose group. This study could not demonstrate a difference between high- and low-dose enalapril in terms of serum aldosterone and plasma AT-II suppression, despite a dose-dependent reduction in serum ACE activity. Even at maximal doses of enalapril, elevated serum aldosterone and plasma AT-II levels were frequently observed.",2002.0,0,0
841,11759645,A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.,J N Cohn; G Tognoni; Valsartan Heart Failure Trial Investigators,"Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs. We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to standard therapy for heart failure. A total of 5010 patients with heart failure of New York Heart Association (NYHA) class II, III, or IV were randomly assigned to receive 160 mg of valsartan or placebo twice daily. The primary outcomes were mortality and the combined end point of mortality and morbidity, defined as the incidence of cardiac arrest with resuscitation, hospitalization for heart failure, or receipt of intravenous inotropic or vasodilator therapy for at least four hours. Overall mortality was similar in the two groups. The incidence of the combined end point, however, was 13.2 percent lower with valsartan than with placebo (relative risk, 0.87; 97.5 percent confidence interval, 0.77 to 0.97; P=0.009), predominantly because of a lower number of patients hospitalized for heart failure; 455 (18.2 percent) in the placebo group and 346 (13.8 percent) in the valsartan group (P<0.001). Treatment with valsartan also resulted in significant improvements in NYHA class, ejection fraction, signs and symptoms of heart failure, and quality of life as compared with placebo (P<0.01). In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme (ACE) inhibitors or beta-blockers, valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs. Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure, when added to prescribed therapy. However, the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan, an ACE inhibitor, and a beta-blocker raises concern about the potential safety of this specific combination.",2002.0,0,0
842,11759959,Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.,,"Angiotensin Converting Enzyme Inhibitors (ACEIs) have been clearly proven to be effective in blood pressure control and haemodynamic control in heart failure patients. Moreover, there is evidence that ACEIs, both in animal models and in humans, also possess the ability to reduce remodeling in cardiovascular structures. Therefore, the reduction of the occurrence of arterial stiffness, leading to an increase in distensibility, is also anticipated. Other than physically measuring arterial wall, the assessment of Pulse Wave Velocity (PWV) is also a widely used index of arterial distensibility, which deteriorates through the course of remodeling. To determine the efficacy of a particular ACEI, perindopril, in increasing arterial distensibility, thus reducing PWV, a 6-month multi-center study was conducted in 146 patients with mild to moderate hypertension. The study population consisted of 70 men and 76 women, aged 56.36 (SD 9.4, range 28-73) years. 73 patients were newly diagnosed, 65 were treated patients but the blood pressure was not controlled, and 8 were treated patients with their blood pressure controlled but with adverse effects in need of switching treatment regimens. Mean blood pressure at the beginning of the study was 164.25/97.49 mmHg and 11.71 m/s (SD 2.29 range 7.35-20.12 m/s) in mean PWV. Perindopril was prescribed tritrating from 4 mg/day to 8 mg/day and adding a diuretic. 106 patients completed the study with 76.4 per cent of patients having their blood pressure controlled (Mean Blood pressure 138.6/85.18 mmHg, SD 11.34 and 7.10 Range 110-170/70-110 mmHg) (p<0.05). Mean PWV reduced to 10.56 m/s (-9.89%) (SD 1.84 range 7.27-15.96 m/s) (p<0.05). Anti-hypertensive treatment with perindopril for 6 months was effective in controlling blood pressure and reducing Pulse Wave Velocity reflecting the increase of arterial distensibility.",2002.0,0,0
843,11762556,Omapatrilat: neurohormonal and pharmacodynamic profile when administered with furosemide.,H Uderman; O Vesterqvist; J Manning; I Ferreira; C Delaney; W C Liao,"Pharmacodynamic effects of combination therapy with omapatrilat and furosemide were evaluated. Two groups of 13 healthy subjects each received furosemide 20 mg dailyfor 15 days coadministered with either placebo on days 6 to 15 or omapatrilat 10 mg on days 6 to 10 and 25 mg on days 11 to 15. In the omapatrilat group, urinary excretion of atrial natriuretic peptide increased, and greater blood pressure reductions were seen compared with placebo. Concomitant omapatrilat treatment did not affect the acute diuresis, natriuresis, and kaliuresis observed with chronic administration of furosemide. Neither effective renal plasma flow nor glomerularfiltration rate changed in either treatment group. No clinically significant safety issues were observed. Daily coadministration of omapatrilat 10 or 25 mg with furosemide 20 mg does not affect the pharmacodynamics offurosemide at steady state.",2002.0,0,0
844,11772299,Novel angiotensin II inhibitors in cardiovascular medicine.,M Burnier,"Blockade of the renin-angiotensin-aldosterone cascade is now recognised as a very effective approach to treat hypertensive, heart failure and high cardiovascular risk patients and to retard the development of renal failure. The purpose of this review is to discuss the state of development of currently available drugs blocking the renin-angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II receptor antagonists, with a special emphasis on the results of the most recent trials conducted with AT(2) receptor antagonists in heart failure and Type 2 diabetes. In addition, the future perspectives of drugs with dual mechanisms of action, such as NEP/ACE inhibitors, also named vasopeptidase inhibitors, are presented.",2002.0,0,0
845,11772908,Dual blockade of the renin-angiotensin system in diabetic nephropathy: a randomized double-blind crossover study.,Kasper Rossing; Per K Christensen; Berit R Jensen; Hans-Henrik Parving,"Many patients with diabetic nephropathy (DN) have levels of albuminuria > 1 g/day and blood pressure >135/85 mmHg, despite antihypertensive combination therapy, including recommended doses of ACE inhibitors, e.g., lisinopril/enalapril at 20 mg daily. We tested the concept that such patients might benefit from dual blockade of the renin-angiotensin system (RAS). We performed a randomized double-blind crossover study of 2 months treatment with candesartan cilexetil 8 mg once daily and placebo in addition to previous antihypertensive treatment. We included 18 type 2 diabetic patients with DN fulfilling the above-mentioned criteria. All received recommended doses of ACE inhibitor and, in addition, 15 patients received diuretics, 11 received a calcium channel antagonist, and 3 received a beta-blocker. At the end of each treatment period, we measured the glomerular filtration rate (GFR), 24-h blood pressure, albuminuria, and IgGuria. The addition of candesartan to usual antihypertensive therapy induced a mean (95% CI) reduction in albuminuria of 25% (2-58), P = 0.036 (geometric mean [95% CI] from 1,764 mg/24 h [1,225-2,540] to 1,334 mg/24 h [890-1,998]). It also produced a mean reduction of 35% (9-53) in the fractional clearance of albumin (P = 0.016), a reduction of 32% (1-54) in fractional clearance of IgG (P = 0.046), a reduction in 24-h systolic blood pressure of 10 mmHg (2-18) (P = 0.019) (mean +/- +/- SE) from 148 +/- 3 to 138 +/- 5 mmHg, and a mean reduction in GFR of 5 ml. min(-1). 1.73 m(-2) (0.1-9) (P = 0.045). Dual blockade of the RAS reduces albuminuria and blood pressure in type 2 diabetic patients with DN responding insufficiently to previous antihypertensive therapy, including ACE inhibitors in recommended doses.",2002.0,0,0
846,11773939,"An update: women, hypertension and therapeutic efficacy.",C A Jones; S Nagpal,"One in five Canadians has high blood pressure. The prevalence is as high as 58% in women between the ages of 65 and 74 years. Approximately 40% of stroke cases, 39% of myocardial infarction cases and 28% of end stage renal diseases are attributable to hypertension. Despite the burden that hypertension places on women, the effect of antihypertensive therapy on cardiovascular complications has not been well established. To address this knowledge gap, two meta-analyses with sex-specific results, including the most current randomized, controlled trials to evaluate hypertension treatment, were reviewed. The Individual Data Analysis of Antihypertensive (INDANA) intervention trials group and Quan and colleagues analyzed treatment benefits in 23,000 women and 19,975 men according to subgroup meta-analyses from 12 randomized, controlled trials that compared antihypertensive drug therapy with placebo. The meta-analyses demonstrated a statistically significant treatment benefit for all of the reported clinical outcomes in men of all ages and in black women. In women over the age of 54 years, antihypertensive treatment was associated with a significant reduction of fatal and nonfatal stroke, cardiovascular events and cardiovascular mortality. Overall, there was no significant difference in the relative treatment benefit in women and men; however, the absolute treatment benefit was lower in women than in men. Thus, the number needed to treat for the end points of fatal stroke, nonfatal stroke and cardiovascular events was one- to threefold higher for women than for men. Furthermore, white women between the ages of 30 and 54 years showed no treatment benefit or harm. Data from the 6.7-year follow-up in the Hypertension Detection and Follow-up Program (HDFP) trial suggested that this group of younger women might benefit from a longer duration of treatment. Indications for pharmacological intervention seem quite clear for all subgroups, excluding these younger women. Until further evidence is available for this low risk subgroup, the current recommendations for lifestyle modification cannot be challenged.",2002.0,0,0
847,11773949,"ACE inhibitor-induced angioedema of the intestine: Case report, incidence, pathophysiology, diagnosis and management.",G Oudit; N Girgrah; J Allard,"A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE) inhibitor-induced angioedema of the intestine (AIAI) occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound) is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.",2002.0,0,0
848,11773984,"ACE inhibitors in vascular disease: some PROGRESS, more HOPE.",G Y Lip; D G Beevers,,2002.0,0,0
849,11773985,The protective effect of blocking angiotensin in both type I and type II diabetics with nephropathy.,D G Beevers; G Y Lip,,2002.0,0,1
850,11773987,"Effect of two antihypertensive combinations on metabolic control in type-2 diabetic hypertensive patients with albuminuria: a randomised, double-blind study.",R Fernández; J G Puig; J C Rodríguez-Pérez; J Garrido; J Redon; TRAVEND Study Group,"The objective of this study was to compare, at equal blood pressure (BP) reduction, the effect of two different combinations on metabolic control and albuminuria in type 2 diabetic hypertensive patients with albuminuria. This was a prospective, randomised, double-blind, parallel, controlled trial carried out in 11 Spanish hospitals. A total of 103 type 2 diabetic patients with stable albuminuria and BP not controlled on monotherapy were randomised of which 93 finished the study. After a 4-week single-blind placebo period, patients were randomised to verapamil SR/trandolapril 180/2 mg (VT) or to enalapril/hydroclorothiazide 20/12.5 mg (EH). Treatment duration was 6 months. The main outcome measures were changes in BP, 24-h albuminuria, blood glucose and glycated haemoglobin. Overall BP was significantly reduced from 157.3 +/- 12.0/98.3 +/- 6.4 mm Hg to 140.5 +/- 14.5/86.1 +/- 8.2 mm Hg (P < 0.001) and albuminuria significantly decreased from 508.6 +/- 693.8 mg/24 h to 253.4 +/- 517.2 mg/24 h (P < 0.001), both without significant differences between treatments. Glycated haemoglobin was not modified on VT: baseline, 5.91 +/- 1.43%; end of treatment, 5.94 +/- 1.62%, but increased on EH: baseline, 5.96 +/- 1.25%; final, 6.41 +/- 1.51%, (ANOVA interaction P = 0.040). At the end of the study, a blood glucose <126 mg/dL was attained in 72.7% of the VT group-improving in 29.5% and worsening in 6.8% of patients (P = 0.021)-and in 50% of the EH group, 13.6% of patients improved and 11.4% worsened (P = 1.000). There were no changes in body weight, serum creatinine, uric acid, potassium, cholesterol, tryglicerides and serum albumin. In hypertensive type 2 diabetic patients not controlled on monotherapy, both treatments similarly reduced albuminuria. The combination verapamil/ trandolapril seems to allow a better metabolic control than enalapril/hydroclorothiazide.",2002.0,0,0
851,11773988,Comparison of quality of life and cough on eprosartan and enalapril in people with moderate hypertension.,E Breeze; E C Rake; M D Donoghue; A E Fletcher,"The objective of this study was to compare quality of life and incidence of dry persistent cough among patients treated with eprosartan and enalapril for mild-moderate hypertension. This was a randomised 26-week double-blind controlled trial carried out in clinics in nine countries of North America, Europe and South Africa. A total of 529 patients aged 18 and over with diastolic blood pressure between 95 mm Hg and 114 mm Hg were studied. Treatment comprised of eprosartan or enalapril monotherapy for 12 weeks with the option of hydrochlorothiazide addition for the remaining 14 weeks. The primary outcome measures were cough and the Psychological General Wellbeing Index (PGWB) total and subscales (anxiety, self-control, depression, general health, positive wellbeing and vitality). The results were that 17.8% of enalapril patients and 13.2% of eprosartan patients withdrew from randomised treatment. Those on enalapril were twice as likely to have gained a definite or possible cough by study end point as those on eprosartan (7.6% vs 3.2%) P = 0.099. At monotherapy end point the differences were greater (9.9% vs 2.1%) and of statistical significance, P = 0.001. Patients treated with enalapril, however, had small but significant improvements in measures of self-control and total PGWB compared with those on eprosartan. The effect sizes of 0.2 or less indicated that there were small differences. In conclusion eprosartan was associated with fewer coughs than enalapril but it performed less well on some aspects of quality of life.",2002.0,0,0
852,11773989,"Quality of life and cough on antihypertensive treatment: a randomised trial of eprosartan, enalapril and placebo.",E C Rake; E Breeze; A E Fletcher,"The objective of this study was to compare the quality of life and incidence of dry cough with the angiotensin II antagonist eprosartan, the ACE-inhibitor enalapril, and placebo, in hypertensive patients with a history of ACE-inhibitor cough. The study was a multicentre, randomised, double-blind, parallel group controlled trial. A total of 136 patients judged to have ACE-inhibitor cough during single-blind enalapril treatment which was lost during a subsequent placebo washout phase, were randomised to receive either eprosartan 300 mg twice daily, or enalapril 20 mg once daily, or placebo for 6 weeks. Self-completion questionnaires assessing quality of life and cough were examined at baseline and end of study. At study end point 23% of patients in the enalapril group and 5% in the eprosartan and placebo groups reported cough (which included definite, probable and possible coughs) (P = 0.02). After adjusting for multiple comparisons, the eprosartan group was not significantly different from either placebo or enalapril. There were no significant differences in the Psychological General Wellbeing Index (PGWB). In conclusion the incidence of self-reported cough on eprosartan was similar to that on placebo, and lower than on enalapril but this difference was not significant when adjustments were made for multiple comparisons. There were no differences in quality of life.",2002.0,0,0
853,11773991,ACE-inhibitor therapy with spirapril increases nocturnal hypotensive episodes in elderly hypertensive patients.,I Kantola; A Terént; M Kataja; E Breig-Asberg,"The purpose of this double-blind, randomised trial with a 4-week placebo run-in period followed by an active treatment period using either spirapril 3 mg or 6 mg once a day was to clarify the existence of hypotensive episodes in elderly hypertensive patients treated by an ACE-inhibitor. Forty hypertensive patients aged 60-76 years underwent 24-h ABPM at the end of the run-in (week 4) and active treatment (week 9) periods. The mean 24-h systolic blood pressure (SBP) decreased from 161.9 (26.7) mm Hg to 150.6 (29.9) mm Hg (P < 0.001) and diastolic blood pressure (DBP) from 91.70 (14.7) mm Hg to 84.2 (17.3) mm Hg (P < 0.001). No episodes of mean arterial pressure (MAP) <50 mm Hg were seen during the placebo period. Instead 11 episodes were observed during the antihypertensive treatment (one in the 3 mg group and 10 in the 6 mg group, P < 0.01 between the two treatment groups). Fifty-four episodes of MAP <70 mm Hg were observed during the placebo period and 117 during the treatment period (P < 0.001). During the placebo period low MAPs were observed only during night time. During the treatment period they were seen also from 11 am to 4 pm. In conclusion, ACE-inhibitor therapy with spirapril significantly increased hypotensive episodes in elderly hypertensive patients which may worsen their cerebral and myocardial circulation.",2002.0,0,0
854,11776939,"Sixteenth annual meeting of the American Society for Hypertension, San Francisco, CA, USA, May 15-19, 2001.",A Scriabine,,2002.0,0,0
855,11777285,Secondary prevention of stroke: PROGRESS and the evidence for blood pressure reduction.,G Jackson,,2002.0,0,0
856,11777296,Meta-analysis of studies using selective alpha1-blockers in patients with hypertension and type 2 diabetes.,M Glanz; A J Garber; G Mancia; M Levenstein,"This meta-analysis of published studies evaluated the effect of selective alpha1-blockers on lipid and carbohydrate profiles and blood pressure (BP) as well as tolerability in patients with hypertension and type 2 diabetes. Publications identified via MEDLINE were used. Text and bibliographies of retrieved articles were examined for additional references. Clinical trials with a randomised comparative structure (placebo and active treatment arms) and controlled studies with other structures were included. Of the 27 citations identified, 22 studies were selected for inclusion, and five were rejected. Efficacy and safety data, lipid and carbohydrate profiles, and study and patient characteristics were extracted by two investigators independently. The mean pooled results showed beneficial effects of selective alpha1-blockers on total serum cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and systolic and diastolic BP. The results also showed doxazosin had beneficial effects on fasting glucose levels, insulin sensitivity, TC, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, HDL/TC ratio, and systolic and diastolic BP. The risk difference was equivalent between the alpha1-blocker group and the control group for postural hypotension or syncope. This meta-analysis demonstrates a number of favourable effects of therapy with selective alpha1-blockers in hypertensive patients with type 2 diabetes. These agents provide an effective modality for reducing BP, with favourable effects on lipid, no deterioration in glycaemic control, and little risk of orthostatic hypotension.",2002.0,0,1
857,11779516,Relation of antibiotic use to risk of myocardial infarction in the general population.,José A Luchsinger; Ariel Pablos-Méndez; Charles Knirsch; Daniel Rabinowitz; Steven Shea,"There are conflicting reports of an association between Chlamydia pneumoniae (C. pneumoniae) infection and coronary artery disease (CAD); randomized trials of antibiotics for the secondary prevention of CAD are currently underway. Physicians may be tempted to believe that their choice of antibiotic class in treating any infection may alter the risk of CAD. Our objective was to determine if the use of antibiotics with antichlamydial activity in the general population reduces the risk of myocardial infarction. A healthcare claims database with 354,258 patients with continuous health and pharmacy coverage for at least 2 years between January 1, 1991 and December 31, 1997 was used for the analyses. Hazard ratios were derived from proportional hazards models with time-dependent covariates, relating antibiotic prescription to first claim related to incident first myocardial infarction during the observation period, adjusting for previous CAD, age, sex, diabetes, hypertension, hyperlipidemia, and chronic obstructive pulmonary disease. There were a total of 1,684,091 person-years of observation and 16,139 incident myocardial infarctions. The adjusted hazard ratios were 1.10 (95% confidence intervals [CI] 1.04 to 1.16) for macrolides, 1.20 (95% CI 1.13 to 1.26) for quinolones, 1.10 (95% CI 0.96 to 1.21) for cephalosporins, 1.00 (95% CI 0.96 to 1.06) for tetracyclines, 1.01 (95% CI 0.96 to 1.06) for penicillins, and 1.13 (95% CI 0.98 to 1.30) for trimetroprim-sulfamethoxazole. The hazard ratios for individual antibiotics with activity against C. pneumoniae within each group were similar. Use of antibiotics with activity against C. pneumoniae does not reduce the risk of myocardial infarction in the general population.",2002.0,0,0
858,11780187,Long-term mortality in patients with myocardial infarction: impact of early treatment with captopril for 4 weeks.,L Liu; Chinese Cardiac Study (CCS-I) Collaborative Group,"In an earlier interim report of the Chinese Cardiac Study (CCS-1) trial, 15,000 patients up to 36 hours after the onset of suspected acute myocardial infarction (AMI) were randomized to receive either oral captopril or matching placebo for one month. Results showed that captopril was associated with a non-significant reduction in 4-week mortality (681 [9.1%] captopril-allocated vs 730 [9.7%] placebo-allocated deaths; 2P = 0.19), but the long-term effects remained uncertain. The present study reports on the long-term effect of early captopril treatment on mortality and other major events in AMI patients of the earlier CCS-1 trial. Long-term follow-up was carried out in those hospitals which had recruited more than 20 cases in the CCS-1 trial. 8000 patients with MI were thus selected for long-term follow-up. Data on 6749 patients (84.4%) were available. Patient characteristics were comparable between the treatment group (n = 3391) and the placebo group (n = 3358). Average follow-up time was 23.4 +/- 16.9 months; average age was 63.6 +/- 10.6 years, and 76.2% were male. At the end of the follow-up time, cardiac function of NYHA III-IV was 9.0% in the treatment group and 9.8% in the placebo group; the reinfarction rate was 5.6% vs. 6.0%; total cardiovascular events were 32.9% vs. 34.3%. Total mortality was 11.9% (n = 404) vs 13.8% (n = 463), with a 13.8% reduction in the captopril group (P = 0.03). Cardiovascular mortality was 10.0% vs. 11.8% (P = 0.01), death due to heart failure was 4.1% vs. 5.5% (P = 0.01). From the above results, it is estimated that early treatment with captopril can save 19 lives per 1000 patients treated; patients with systolic blood pressure (SBP) > or = 100 mm Hg at entry would have a long-term mortality 12.4% in the treatment group vs. 13.8% in the placebo group (P = 0.04) and patients with a heart rate (HR) > or = 60/minute at entry would have a long term mortality 12.0% in captopril groups vs. 14.5% in the placebo group (P = 0.01). Early treatment with captopril during AMI for 4 weeks can significantly reduce long-term total mortality.",2002.0,1,1
859,11780330,Relationship between age and effect of early and long-term captopril treatment in patients with acute myocardial infarction.,X Cai; W Shen; L Gong,"To analyse the relationship between age and treatment with captopril after acute myocardial infarction (AMI). In a randomized trial, 822 patients with a first AMI received conventional medical treatment, including intravenous thrombolytic therapy and oral aspirin or metoprolol, and then were randomly allocated to captopril [dosage from the first 6.25 mg to 25 mg/t.i.d, 209 younger patients (< or = 64 years), 269 elderly patients (65-75 years)] or conventional treatment only (131 younger patients, 213 elderly). Survival in the four groups was calculated with the Kaplan-Meier method. Multivariate analysis was performed to understand the degree that multi-variables (including age) affect survival in patients taking captopril in the hospital or during long term follow-up. The survival of patients who took captopril correlated significantly with age (P < 0.001). The survival of the elderly patients on captopril treatment did increase (P < 0.0001), but not of the younger ones (P > 0.05) during hospitalization. During follow-up, the survival of patients who took captopril correlated insignificantly with age (P > 0.05), but both the elderly and the younger patients have good survival rates (all P < 0.01) and lower cardiac events (all P < 0.01) when they took captopril. Captopril exerts a weak effect on the younger patients but a beneficial effect on the elderly patients during hospitalization after AMI. However, there is no difference between the younger and the elderly in the prognosis, both having good survival and lower cardiac events when they take captopril long term during follow-up.",2002.0,0,0
860,11780682,"Antinuclear antibody-negative, drug-induced lupus caused by lisinopril.",J D Carter; J Valeriano-Marcet; K S Kanik; F B Vasey,"The clinical symptoms of drug-induced lupus (DIL) are similar to those of idiopathic systemic lupus erythematosus. The literature indicates that in patients with DIL, sera generally contain antinuclear antibodies (ANAs); however, ANA-negative DIL has been reported. The list of medications implicated as etiologic agents in DIL continues to grow. This list includes two different types of angiotensin-converting enzyme inhibitors--captopril and enalapril. We report the first case of DIL caused by lisinopril. Our patient had negative results on ANA testing and had histone antibodies (IgG anti-[H2A-H2B]-DNA) mirroring the disease course. Antibodies to the (H2A-H2B)-DNA complex are seen in more than 90% of patients with active DIL, excluding those with DIL due to hydralazine. Thus, it is important to recognize the clinical significance of IgG anti-(H2A-H2B)-DNA antibodies and that negative ANA test results do not preclude the diagnosis of DIL.",2002.0,0,1
861,11782734,Type IV renal tubular acidosis presenting as dyspnea in two older patients taking angiotensin-converting enzyme inhibitors.,J Scott Bomann; Bradley F Peckler,"The evaluation of dyspnea most often leads to a cardiac or pulmonary diagnosis. In the elderly, however, the cause is commonly multifactorial. The emergency physician should always consider noncardiopulmonary etiologies when treating such patients. We present 2 cases of new-onset type IV renal tubular acidosis (RTA) in older patients taking lisinopril who presented to the emergency department as dyspnea. Both patients had chronic cardiopulmonary illnesses and were initially diagnosed as having either congestive heart failure, asthma exacerbations, or both. The laboratory results for RTA are specific and the diagnosis can be made in the ED.",2002.0,0,0
862,11783600,Treatment of IgA nephropathy with angiotensin converting enzyme inhibitors: design of a prospective randomized multicenter trial.,R Coppo; M Chiesa; L Peruzzi; A Amore,"Although several in vitro studies and clinical observations suggest that ACE-inhibitors (ACE-I) are a promising treatment for IgA nephropathy (IgAN), meta-analysis of published data is not yet conclusive. Therefore, a European double-blinded, prospective, randomized therapeutic trial was designed to evaluate ACE-I treatment benefits in young IgAN patients (<35 years old) with persistent moderate proteinuria (>1<3.5 g/day/1.73 m2) and fair renal function (creatinine clearance >50 mL/min/1.73 m2). Patients enrolled are randomly assigned to benazepril (0.2 mg/kg/day) or placebo. Patients should be enrolled within a five year recruitment period (end on December 2003) for a total duration of follow-up of six years (end on December 2004). Hypertension and some genetic, histological and immunological factors will be evaluated to clarify their eventual role in the final response to ACE-I treatment.",2002.0,0,0
863,11788293,Sternal dehiscence after cardiac surgery and ACE type 1 inhibition.,B Nyawo; P Sarkar,,2002.0,0,0
864,11790173,Treatment of scleroderma.,Allen N Sapadin; Raul Fleischmajer,"The treatment of systemic sclerosis (scleroderma) is difficult and remains a great challenge to the clinician. Because the cause is unknown, therapies are directed to improve peripheral blood circulation with vasodilators and antiplatelet aggregation drugs, to prevent the synthesis and release of harmful cytokines with immunosuppressant drugs, and to inhibit or reduce fibrosis with agents that reduce collagen synthesis or enhance collagenase production. The purpose of this review is to critically analyze conventional and new treatments of systemic sclerosis and localized scleroderma. The therapeutic options discussed for the treatment of systemic sclerosis include the use of (1) vasodilators (calcium channel blockers [nifedipine], angiotensin-converting enzyme inhibitors [captopril, losartan potassium], and prostaglandins [iloprost, epoprostenol]), (2) immunosuppressant drugs (methotrexate, cyclosporine, cyclophosphamide, and extracorporeal photopheresis), and (3) antifibrotic agents (D-penicillamine, colchicine, interferon gamma, and relaxin). The treatment options reviewed for localized scleroderma include the use of corticosteroids, vitamin D analogues (calcitriol, calcipotriene), UV-A, and methotrexate. Preliminary reports on new therapies for systemic sclerosis are also considered. These include the use of minocycline, psoralen-UV-A, lung transplantation, autologous stem cell transplantation, etanercept, and thalidomide.",2002.0,0,0
865,11790290,Progress in secondary prevention of stroke with PROGRESS. The perindopril protection against recurrent stroke study.,Ernesto L Schiffrin,,2002.0,0,0
866,11790925,Management of heart failure in the elderly.,Michael W Rich,"The management of chronic heart failure in elderly patients is often complicated by the presence of multiple comorbid conditions, polypharmacy, psychosocial and financial concerns, and difficulties with adherence to complex medication and dietary regimens. In addition, few patients over 80 years of age have been enrolled in clinical trials, so that the efficacy of current heart failure therapies remains uncertain in this age group. Taken together, these factors contribute to the persistently high hospitalization and mortality rates as well as the poor quality of life associated with chronic heart failure in the elderly. In this article, nonpharmacologic aspects of care and the pharmacotherapy of systolic heart failure in elderly patients are reviewed. Optimal management requires a systematic approach comprising 5 key elements: coordination of care across disciplines, patient and caregiver education, enhancement of self-management skills, effective followup, and the judicious use of medications. However, it must be recognized that even with ""best practice"" interventions, the prognosis for established heart failure remains poor. Future research must therefore be directed at developing more effective strategies for the prevention of heart failure in our aging population.",2002.0,0,0
867,11791032,Effects of losartan and its combination with quinapril on the cardiac sympathetic nervous system and neurohormonal status in essential hypertension.,Kazuyuki Sakata; Hiroshi Yoshida; Kazuhiko Obayashi; Joji Ishikawa; Hiromichi Tamekiyo; Ryuzo Nawada; Osamu Doi,"Sympathetic nervous and renin-angiotensin systems play important roles in essential hypertension. This study was aimed at assessing the effects of losartan or its combination with quinapril on the cardiac nervous system and neurohormonal status in essential hypertension. Randomized, comparative study of 105 patients with mild essential hypertension, carried out at Shizuoka General Hospital. In phase 1, 40 hypertensives were allocated randomly into the losartan (50 mg) group or the quinapril (10 mg) group. In phase 2, 65 hypertensives, after 3 months 10 mg quinapril monotherapy, were allocated randomly into groups with 50 mg losartan (n = 32) or 5 mg amlodipine (n = 33) added to quinapril, and were treated for a further 3 months. All patients underwent [(123)I]metaiodobenzylguanidine (MIBG) imaging and neurohormonal measurements before and 3 months after treatment. Both monotherapies significantly increased renin activity, while losartan monotherapy also increased angiotensin II (AII) concentration. In both the losartan and quinapril groups, the washout rate was significantly decreased (18.1 +/- 11.4 versus 13.9 +/- 11.0%, P < 0.0002 and 13.3 +/- 9.3 versus 12.3 +/- 9.1%, P < 00001, respectively) without changes in the heart to mediastinum ratio (H/M ratio). Both combined therapies lowered blood pressure to similar levels. A combination therapy with losartan and quinapril significantly increased the H/M ratio (1.93 +/- 0.29 and 2.02 +/- 0.29, P < 0.01) and decreased the washout rate (17.6 +/- 11.0 and 15.3 +/- 9.2%, P < 0.02) without affecting AII concentration, whereas a combination therapy with amlodipine and quinapril therapy did not affect the scintigraphic parameters with an increase in the AII concentration. With a usual antihypertensive dose, both losartan and quinapril had a little suppressive effect on the cardiac sympathetic activity in essential hypertension. In contrast, the combination therapy with losartan and quinapril, which results in a higher degree of inhibition of the renin-angiotensin system, could suppress the cardiac sympathetic activity effectively.",2002.0,0,0
868,11792333,Comparison of perindopril versus captopril for treatment of acute myocardial infarction.,Chu Pak Lau; Hung Fat Tse; William Ng; Kwok Keung Chan; Shu Kin Li; Kin Kwan Keung; Yuk Kong Lau; Wai Hong Chen; Yuen Wai Tang; Sum Kin Leung,"Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with acute myocardial infarction (AMI), but these benefits might be limited by acute hemodynamic changes and difficulties in titrating to recommended doses. The objective of this study was to compare the hemodynamic changes and tolerability of perindopril with captopril after AMI. We randomized 212 patients to receive either captopril (n = 102) or perindopril (n = 110) within 72 hours of AMI. Captopril was given as an initial dose of 6.25 mg, and then 50 mg/day on day 1 and 100 mg/day thereafter. The corresponding doses of perindopril were 2, 4, and 8 mg/day. Acute hemodynamic changes, the percentage of patients who reached target doses, and in-hospital and 6-month cardiovascular events were monitored. Baseline clinical characteristics of the 2 groups were identical, but patients randomized to perindopril were in a higher Killip class (1.4 +/- 0.6 vs 1.2 +/- 0.5, p = 0.05). During the first 6 hours, treatment with perindopril resulted in higher minimal systolic (97 +/- 15 vs 91 +/- 14 mm Hg, p <0.01) and diastolic blood pressure (BP) (57 +/- 11 vs 54 +/- 10 mm Hg, p <0.02), later occurrence of minimal BP (3.6 +/- 0.2 vs 2.7 +/- 0.1 hour, p <0.001), and a lower incidence of persistent hypotension with systolic BP < 90 mm Hg for > or =1 hour (5% vs 16%; p < 0.01) compared with captopril. At initial administration, target doses of perindopril and captopril were attained in 97% and 82% of the patients, respectively (p < 0.01). After 6 months, there were no differences between patients treated with perindopril and captopril in mortality rates (6% vs 13%, p = 0.16) and need for revascularization (20% vs 21%, p = 0.9). Thus, in patients during AMI, perindopril treatment showed better short-term tolerance than treatment with captopril, with significantly less acute hemodynamic changes and fewer withdrawals.",2002.0,1,1
869,11793859,Cyclosporin A treatment for idiopathic membranous nephropathy.,X Yao; H Chen; Q Wang; Z Tang; W Hu; G Yin; Z Liu; L Li,"To evaluate the efficacy of cyclosporin A (CSA) in the treatment of idiopathic membranous nephropathy (IMN), a prospective controlled clinical study was performed. This study included a group of 30 IMN patients, among them 15 were treated with CSA and 15 with captopril (CAP). The diagnosis of IMN was made with exclusion of secondary forms of membranous nephropathy by extensive clinical and pathological studies. No patients received steroids or cytotoxic agents for six months prior to enrollment. In the CSA group, CSA was given at an initial dosage of 5 mg.kg-1.d-1, gradually tailed off over the first three months and maintained at 2 mg.kg-1.d-1 for 12 months. In the CAP group, CAP was given at a dosage of 37.5 mg/day. In the first three months, 6 (6/15) complete remissions (CR) and 2 (2/15) partial remissions (PR) were observed in the CSA group while only 2 (2/15) PRs were observed in the CAP group. Before the end of the 15-months, 8 patients in the CSA group experienced CR and 4 patients experienced PR. One CR patient relapsed as the dosage of CSA was reduced, so 7 patients remained in CR at the end of the first 15-months. No additional CR or PR was observed in the CAP group during late follow-up. At the last visit (an average follow-up time of 44 months) in the CSA-group, another 2 CR patients had relapsed and 1 CR patient shifted to PR after stopping the CSA treatment, so 4 CR and 5 PR remained in the CSA group. In the CAP group, 3 spontaneous CRs occurred beyond 1.5 year's follow-up, with 3 CR and 2 PR at the last visit. No difference was found between the averages of the initial and the last serum creatinine levels in either group. No serious adverse effects were found during CSA treatment. Re-biopsy data of three patients responsive to CSA treatment showed that no pathological improvement of glomerular basement membrane was observed, even in cases at remission. Tubulointerstitial fibrosis was found in 1 relapsed CR patient, whose serum creatinine increased above the normal range, but not in the other 2 patients whose serum creatinine remained in the normal range. CSA therapy at a dosage of 5 mg.kg-1.d-1 is effective in inducing remission of nephrotic syndrome in adult IMN patients within three months, with a response rate of 80%. A relatively high rate of relapse (50%) was observed within 2 years after the withdrawal of CSA treatment.",2002.0,0,0
870,11794033,[Angiotensin II antagonists versus ACE inhibitors in the treatment of raised blood pressure].,R S Andersen; S Christensen,"Blockade of the renin-angiotensin system has proved an important principle in the pharmacotherapy of cardiovascular diseases. There is now overwhelming documentation on the beneficial effect of angiotensin converting enzyme inhibitors (ACE inhibitors) on mortality and morbidity in patients with cardiovascular risk factors. Such documentation is still lacking for the angiotensin II receptor antagonists which, in 1999, sold for 77% of the amount spent on ACE inhibitors in Denmark. This review assesses the therapeutic effects of angiotensin II antagonists compared with the ACE inhibitors in patients with uncomplicated essential hypertension. From 21 comparative studies with a duration of up to one year, it can be concluded that the lowering of the blood pressure with the two classes is similar. Both showed relatively few side effects, the only difference being a higher incidence of cough after ACE inhibitors. Until larger comparative long-term studies on mortality and morbidity have been conducted, angiotensin II antagonists should only be used in hypertensive patients experiencing unacceptable side effects with ACE inhibitors.",2002.0,0,0
871,11794428,A review of vasopeptidase inhibitors: a new modality in the treatment of hypertension and chronic heart failure.,Surakit Nathisuwan; Robert L Talbert,"Vasopeptidase inhibitors are a group of agents capable of inhibiting neutral endopeptidase and angiotensin-converting enzymes, which leads to potentiation of natriuretic peptide actions and suppression of the renin-angiotensin-aldosterone system. With this distinctively characteristic mechanism, these agents have emerged as a new drug class for management of hypertension and heart failure. Several vasopeptidase inhibitors are under clinical investigation. Omapatrilat is the most studied agent in this class. Clinical studies of omapatrilat in hypertension have consistently shown the agent's effectiveness in a variety of patient populations. In patients with heart failure, omapatrilat significantly improved neurohormonal and hemodynamic status. Long-term effects of omapatrilat in patients with heart failure recently were compared with those of conventional therapy in a large phase II trial. Results of the study appear promising. Large clinical trials are ongoing, and additional information regarding safety and efficacy from these studies may help define the place in therapy for this agent.",2002.0,0,0
872,11800061,"Eprosartan versus enalapril in elderly patients with hypertension: a double-blind, randomized trial.",L Ruilope; B Jäger; B Prichard,"To compare the efficacy and safety of eprosartan and enalapril to lower systolic blood pressure in elderly patients with essential hypertension. 334 patients >65 years with sitting systolic blood pressure (sitSBP) > or = 160 mmHg and diastolic blood pressure (sitDBP) 90-114 mmHg were randomized to 12 weeks of double-blind treatment with eprosartan, 600-800 mg once daily (o.d.) or enalapril (5-20 mg o.d.), with flexible dose titration to lower systolic blood pressure below 140 mmHg. The primary outcome measure was change in sitSBP at endpoint. Least-squares mean changes from baseline in sitSBP were -18.0 and -17.4 mmHg in the eprosartan and enalapril groups, respectively (difference eprosartan-enalapril -0.6, 95% confidence interval, CI, -4.1 to 3.0, p = 0.76). The corresponding figures for sitDBP were -9.4 and -9.6 mmHg (difference eprosartan-enalapril 0.2, 95% CI -1.7 to 2.0, p = 0.84). Normalization and response rates were also similar in the two groups. Adverse events were recorded in 61 (35.7%) patients on eprosartan (one with dry cough) and 83 (50.9%) patients on enalapril (10 with dry cough). Eprosartan and enalapril were equally effective in reducing sitSBP and sitDBP in elderly patients with predominantly systolic hypertension. Eprosartan was better tolerated and, in particular, lacked the propensity of enalapril to cause dry cough.",2003.0,0,0
873,11805530,Effects of alcohol on the heart.,C D Spies; M Sander; K Stangl; J Fernandez-Sola; V R Preedy; E Rubin; S Andreasson; E Z Hanna; W J Kox,"Some evidence suggests that light to moderate alcohol consumption protects against cardiovascular diseases. However, this cardioprotective effect of alcohol consumption in adults is absent at the population level. Approximately 20 to 30% of patients admitted to a hospital are alcohol abusers. In medical practice, it is essential that patients' levels of consumption are known because of the many adverse effects that might result in the course of routine care. Ethanol damage to the heart is evident if alcohol consumption exceeds 90 to 100 g/d. Heavy ethanol consumption leads to increased risk for sudden cardiac death and cardiac arrhythmias. In patients with coronary heart disease, alcohol use was associated with increased mortality. An early response to drinking was an increased ventricular wall thickness to diameter ratio, possibly proceeding with continuous drinking to alcoholic cardiomyopathy, which had a worse outcome compared with idiopathic dilative cardiomyopathy if drinking was not stopped or at least reduced (< 60 g/d). In the ICU, patients with chronic alcoholism have more cardiac complications postoperatively. These complications probably are caused by biventricular dysfunction, particularly with the occurrence of severe infections or septic shock, events that are three to four times more frequent among chronic alcoholics than occasional drinkers or nondrinkers. To prevent further complications from drinking and for long-term management of drinking, patients with alcohol abuse and heart failure should be treated in brief intervention and follow-up programs. Prognosis is good even in patients with New York Heart Association class IV heart failure caused by cardiomyopathy if complete abstinence is accomplished. Noncompliance to smoking and alcohol restrictions, which are amenable to change, dramatically increases the risk for hospital readmissions among patients with heart failure.",2002.0,0,0
874,11815428,Fosinopril versus amlodipine comparative treatments study: a randomized trial to assess effects on plasminogen activator inhibitor-1.,Marco Pahor; Lonneke V Franse; Steven R Deitcher; William C Cushman; Karen C Johnson; Ronald I Shorr; Kandice Kottke-Marchant; Russell P Tracy; Grant W Somes; William B Applegate,"ACE inhibitors and calcium antagonists may modulate fibrinolysis. We conducted a randomized controlled trial to assess the effects of these drugs on plasminogen activator inhibitor-1 (PAI-1) antigen, an inhibitor of fibrinolysis. Participants with hypertension and type 2 diabetes mellitus (n=96, 51% black) were randomized after an initial 4 weeks of placebo to double-blind 20 or 40 mg fosinopril or 5 or 10 mg amlodipine daily for 4 weeks in a fixed-dose regimen. After 4 weeks of placebo washout, the patients received 4 weeks of crossover treatments. After treatment with placebo, systolic and diastolic blood pressure were 143+/-2 and 86+/-1 mm Hg and plasma PAI-1 was 43.4+/-2.3 ng/mL. Amlodipine achieved a greater systolic and diastolic blood pressure reduction than fosinopril (10 mm Hg versus 8 mm Hg, P=0.029, and 5 mm Hg versus 3 mm Hg, P=0.040, respectively) but tended to increase PAI-1, whereas fosinopril tended to decrease PAI-1 (5.4+/-3.6 versus -3.8+/-2.5 ng/mL, P=0.045). The PAI-1 changes depended on drug dose (6.5+/-6.1 and 3.4+/-3.9 ng/mL with amlodipine 10 and 5 mg, respectively, and -0.4+/-3.1 and -7.4+/-4.0 ng/mL with fosinopril 20 and 40 mg, respectively, P for trend 0.024). No significant differences between fosinopril and amlodipine were found for short-term changes in tissue plasminogen activator antigen, fibrinogen, C-reactive protein, and interleukin-6. The findings were similar in black and white participants. Short-term treatment with fosinopril significantly reduced PAI-1 compared with amlodipine in a dose-dependent fashion. This effect, which was independent of blood pressure reduction, may account for the improved clinical outcomes achieved with ACE inhibitors compared with calcium antagonists.",2002.0,0,0
875,11817974,Treatment of heart failure in patients with diabetes mellitus.,Steven J Lavine; Steven D Gellman,"Patients with diabetes mellitus have an increased morbidity and mortality from cardiovascular disease. Both coronary artery disease and congestive heart failure (CHF) are largely responsible for the increased cardiovascular adverse events in patients with diabetes. This review discusses the pathophysiology of CHF, the mechanisms of left ventricular (LV) dysfunction and the neurohormonal mechanisms involved in both LV dysfunction and CHF. Diabetes with and without hypertension is an important cause of LV dysfunction and CHF. Diabetes may be responsible for the metabolic and ultrastructural causes of LV dysfunction, while hypertension may be responsible for the marked fibrotic changes that are found. Experimental induction of diabetes in animals has shed light on the biochemical and ultrastructural changes seen. The role of insulin to reverse both metabolic and structural changes is reviewed both from experimental data and with the limited amount of clinical data available. The therapy of CHF in patients with diabetes is similar to that of patients without diabetes, with therapy directed toward the use of beta-blockers and angiotensin converting enzyme (ACE) inhibitors. As the morbidity and mortality are higher in patients with diabetes, several studies have pointed out the importance of this subgroup where the opportunity to make a significant clinical impact exists. A significant opportunity exists to reduce morbidity and mortality with beta-blockers and ACE inhibitors when ischaemia and CHF are both present. However, studies in patients diabetes have been limited to post hoc subgroup analyses and rarely as predefined subgroups. Clinical trials involving patients with diabetes with and without hypertension and LV dysfunction are clearly needed in the future to adequately address the needs of this high risk subgroup.",2002.0,0,0
876,11817979,Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders.,Christine R Culy; Blair Jarvis,"Quinapril is rapidly de-esterified after absorption to quinaprilat (the active diacid metabolite), a potent angiotensin converting enzyme (ACE) inhibitor. Quinapril produces favourable haemodynamic changes, and improves ventricular and endothelial function in patients with various cardiovascular disorders; these effects are mediated through the binding of quinaprilat to both tissue and plasma ACE. Quinapril 10 to 40 mg/day provided effective blood pressure control in most patients with essential hypertension in clinical trials, but some patients required dosages of 80 mg/day and/or concomitant diuretic therapy. In general, quinapril provided similar blood pressure control to other standard antihypertensive therapies including other ACE inhibitors, calcium antagonists and beta-adrenoceptor antagonists in comparative clinical trials. Combined therapy with quinapril and hydrochlorothiazide had a significantly greater antihypertensive effect than either drug as monotherapy in two well designed studies. Quinapril has also been shown to reduce microalbuminuria in patients with hypertension and/or diabetes mellitus. In patients with congestive heart failure, quinapril <or=40 mg/day produced beneficial haemodynamic and echocardiographic changes and improved exercise tolerance, symptoms and functional class. Effects of quinapril on survival have not been investigated, but quinapril 10 to 20 mg/day showed comparable efficacy to captopril 25 to 50mg twice daily in two well designed trials. In patients with coronary artery disease, quinapril 40 mg/day significantly reduced the incidence of ischaemic events after coronary artery bypass grafting (CABG) in a well controlled study (n = 148). However, a lower dosage of quinapril (20 mg/day) showed no effect on ischaemic events or atherosclerotic progression with 3 years of treatment in a similarly designed study involving 1750 patients undergoing coronary angioplasty. The tolerability of quinapril is similar to that of other ACE inhibitors. In placebo-controlled trials, cough occurred in 2 and 4.3% and hypotension occurred in <1 and 2.9% of quinapril recipients with hypertension or congestive heart failure, respectively. No increase in adverse events was observed when the dosage was increased from 10 to 40 mg/day. Quinapril is now firmly established as an effective and well tolerated ACE inhibitor for the treatment of patients with hypertension and congestive heart failure. Quinapril 40 mg/day also significantly reduced the incidence of ischaemic events in patients undergoing CABG in one study; however, a lower dosage of quinapril (20 mg/day) had no effect on ischaemic events in patients undergoing coronary angioplasty in another trial. Additional trials in patients with coronary artery disease receiving optimal dosages of quinapril (40 mg/day) would be useful.",2002.0,0,0
877,11817991,Antihypertensive treatment with and without benazepril in patients with chronic renal insufficiency: a US economic evaluation.,Thomas J Hogan; William J Elliott; Arnold H Seto; George L Bakris,"To conduct an economic analysis in the US of antihypertensive treatment with and without benazepril in patients with chronic renal insufficiency. A four-state Markov model, using clinical data obtained from a 3-year randomised clinical trial [the Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency (AIPRI) study] plus its extension study (median 3.6 years), and cost data obtained from published US sources. The period of analysis was 7 years following randomisation. Healthcare payer. Clinical data were obtained from multiple medical centres in three European countries as described in the published studies. Key economic data were obtained from the US Healthcare Financing Administration's End Stage Renal Disease programme. In the clinical studies on which this economic analysis was based, patients with chronic renal insufficiency of various aetiologies were randomised to antihypertensive therapy with or without concomitant benazepril. Over 7 years of analysis, patients randomised to antihypertensive treatment with concomitant benazepril therapy incurred on average USD12991 (1999 values) lower medical costs than patients prescribed antihypertensive treatment without benazepril, and obtained an additional 0.091 quality-adjusted life years (QALYs). Costs and QALYs were greater for the benazepril arm than the placebo arm for all years of analysis after the first. Rank order stability of results favouring the benazepril therapy arm was found in sensitivity analyses of changes in key model parameters. Additional economic and health benefits favouring patients receiving benazepril would be seen if underlying model rates of dialysis and transplantation were increased, as may be appropriate to reflect treatment practice differences in the US relative to European countries. Benazepril therapy as a component of antihypertensive treatment of persons with chronic renal insufficiency initially costs money, but investment costs are recouped quickly and return on investment continues to grow. The impact of end-stage renal disease on patient health and healthcare costs is great. Thus, the quality-adjusted survival benefits and overall cost savings seen in benazepril recipients over a prolonged period (2 to 7 years) indicate that the strategy of prescribing benazepril to reduce progression of renal disease in patients with renal insufficiency is both clinically and economically beneficial compared with current antihypertensive regimens without ACE inhibition.",2002.0,0,0
878,11818701,Changes in renal resistive index and urinary albumin excretion in hypertensive patients under long-term treatment with lisinopril or nifedipine GITS.,Giovanna Leoncini; Carlo Martinoli; Francesca Viazzi; Maura Ravera; Denise Parodi; Elena Ratto; Simone Vettoretti; Cinzia Tomolillo; Lorenzo E Derchi; Giacomo Deferrari; Roberto Pontremoli,"Increased renal vascular resistance and microalbuminuria are associated with hypertensive target organ damage and may be predictors of hypertensive nephrosclerosis. We investigated changes in renal resistive index (RI) and urinary albumin excretion (UAE) in a group of patients with primary hypertension before and during long-term antihypertensive treatment. Thirty-two patients were randomized to receive antihypertensive treatment with either a calcium channel blocker (nifedipine GITS, up to 90 mg/day, n = 16) or an ACE inhibitor (lisinopril, up to 20 mg/day, n = 16), alone or in association with a diuretic (chlortalidone, 25 mg/day). Blood pressure, renal resistive index (by US Doppler) and UAE (mean of three nonconsecutive timed urinary collections, microg/min) were evaluated at baseline and over the course of 24 months of treatment. Both regimens effectively lowered blood pressure (mean blood pressure from 123 +/- 1.8 at baseline to 103 +/- 1.5 mm Hg at 24 months in the lisinopril group and from 122 +/- 1.9 at baseline to 104 +/- 0.8 at 24 months in the nifedipine group, p < 0.001 for both groups). Overall, blood pressure decrease was associated with a reduction in UAE and no change in RI throughout the study. However, despite similar blood pressure reduction, the two regimens showed different specific effects. Lisinopril was associated with a significant decrease in both UAE (33.8 +/- 16.2 at baseline and 9.1 +/- 2.1 at 24 months, p < 0.01) and renal RI (0.61 +/- 0.02 at baseline and 0.56 +/- 0.04 at 24 months, p < 0.05) while nifedipine GITS did not significantly influence UAE (35.7 +/- 12.2 at baseline and 31.2 +/- 12.1 at 24 months, n.s.) or RI (0.61 +/- 0.01 at baseline and 0.59 +/- 0.02 at 24 months, n.s.). Effective blood pressure control over a long period of time reduces the severity of organ damage, namely UAE while maintaining renovascular resistance in patients with essential hypertension. Different classes of antihypertensive agents might convey additional specific renal protection beyond blood pressure control. These data could be useful in devising individualized therapeutic strategies in hypertensive patients at increased renal risk.",2002.0,0,0
879,11821634,Psychological characteristics and responses to antihypertensive drug therapy.,Samuel J Mann; Linda M Gerber,"The objective of this study was to explore the relationship between psychological characteristics and responses to antihypertensive drug therapy. Twenty-two hypertensive subjects underwent psychological evaluation and treatment with 1) a diuretic, hydrochlorothiazide (HCTZ); 2) an angiotensin-converting enzyme (ACE) inhibitor, quinapril; and 3) combined alpha + beta blockade (doxazosin + betaxolol). Anger-Out scores on the State-Trait Anger Expression Inventory were positively correlated with the HCTZ-induced fall in systolic blood pressure (p<0.01); Anger-In was negatively correlated with the quinapril-induced fall in systolic pressure (p<0.05). The target systolic blood pressure (130 mm Hg) was achieved with either HCTZ or quinapril in 79% of subjects without, vs. 25% of subjects with, childhood trauma (p=0.03). Responses to doxazosin + betaxolol were not correlated with psychological characteristics. The authors conclude that both inhibited anger expression and childhood trauma are associated with reduced response to a diuretic or ACE inhibitor. Combined alpha/beta blockade may be preferable to an ACE inhibitor or diuretic in treating selected hypertensive patients. Further studies should include examination of psychological factors in terms of the response to combined ACE inhibitor + diuretic therapy.",2002.0,0,0
880,11821637,Blood pressure reduction in those with cerebrovascular disease prevents secondary stroke.,Jan N Basile,,2002.0,0,0
881,11821721,Withdrawal from treatment in the Syst-Eur Trial.,Christopher J Bulpitt; Nigel S Beckett; Astrid E Fletcher; Lutgarde Thijs; Jan A Staessen; Dan L Dumitrascu; Francoise Forette; Gastone Leonetti; Choudomir Nachev; Jaakko Tuomilehto; Robert H Fagard; Syst-Eur investigators,"To investigate the reasons for withdrawal from double-blind randomized trials, and the reasons for changing treatment within a randomized therapeutic group. The Syst-Eur trial, in which 4695 older patients with systolic hypertension were randomized to active or placebo treatment. The reasons for withdrawal from the trial were examined, both for patient-initiated and investigator-initiated withdrawals. In addition, the reasons for stopping the first-line treatment (nitrendipine), the second-line treatments (enalapril and hydrochlorothiazide) and the corresponding placebos, were determined. A total of 135 patients (6%) were withdrawn by the investigators from placebo treatment because their blood pressure was too high, and, similarly, 36 (1.6%) through patient initiation. The corresponding results for the actively treated patients were 14 (0.6%) and 7 (0.3%). Very few patients were withdrawn from the trial because of the adverse effects of treatment. However, 39 (4%) stopped taking active nitrendipine because of ankle oedema, compared with 4 (0.5%) on placebo. Similarly, 28 versus three stopped due to flushing. Forty-one (10%) stopped taking enalapril because of cough, against eight (2%) for enalapril placebo. In all, 15.0% stopped active nitrendipine, 20.2% enalapril and 6.3% hydrochlorothiazide, versus placebo 7.1, 9.1 and 5.1%. The numbers withdrawn from the trial for adverse treatment consequences were small in comparison to the cardiovascular benefits. Nevertheless the numbers stopping individual treatments were higher than expected.",2002.0,0,0
882,11822537,The renin-angiotensin system in the twenty-first century.,M G Nicholls; J I Robertson; T Inagami,,2003.0,0,0
883,11823085,Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials.,Philip Jong; Catherine Demers; Robert S McKelvie; Peter P Liu,"We sought to determine the effect of angiotensin receptor blockers (ARBs) on mortality and hospitalization in patients with heart failure (HF). There is uncertainty regarding the efficacy of ARBs as substitute or adjunctive therapy to angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of HF. We conducted a meta-analysis of all randomized controlled trials that compared ARBs with either placebo or ACEIs in patients with symptomatic HF. The pooled outcomes were all-cause mortality and hospitalization for HF. Seventeen trials involving 12,469 patients were included. Overall, ARBs were not superior to controls in the pooled rates of death (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.23) or hospitalization (0.86; 0.69 to 1.06). Stratified analysis, however, showed a non-significant trend in benefit of ARBs over placebo in reducing mortality (0.68; 0.38 to 1.22) and hospitalization (0.67; 0.29 to 1.51) when given in the absence of background ACEI therapy. When compared directly with ACEIs, ARBs were not superior in reducing either mortality (1.09; 0.92 to 1.29) or hospitalization (0.95; 0.80 to 1.13). In contrast, the combination therapy of ARBs and ACEIs was superior to ACEIs alone in reducing hospitalization (0.74; 0.64 to 0.86) but not mortality (1.04; 0.91 to 1.20). This meta-analysis cannot confirm that ARBs are superior in reducing all-cause mortality or HF hospitalization in patients with symptomatic HF, particularly when compared with ACEIs. However, the use of ARBs as monotherapy in the absence of ACEIs or as combination therapy with ACEIs appears promising.",2002.0,0,0
884,11824861,"A comparative trial of controlled-onset, extended-release verapamil, enalapril, and losartan on blood pressure and heart rate changes.",George Bakris; Dominic Sica; Venkata Ram; Timothy Fagan; Paul T Vaitkus; Robert J Anders,"The excess morning risk of myocardial infarction and stroke may be attributable to the rapid rise in blood pressure (BP) and heart rate in the hours after awakening. The aim of this randomized, double-blinded, placebo-controlled, multicenter study was to compare once-daily, controlled-onset, extended-release (COER-24) verapamil to enalapril and losartan on BP and heart rate during the postawakening morning phase as well as throughout the 24-h period. A total of 406 patients were randomized to an 8-week forced-titration period with one of the following: 1) COER-24 verapamil 240 mg/day titrated to 360 mg/day; 2) enalapril 10 mg/day titrated to 20 mg/day, 3) losartan 50 mg/day titrated to 100 mg/day, or 4) placebo. Office BP and heart rate and ambulatory 24-h BP monitoring was performed at baseline, 4 weeks, and 8 weeks. Each active treatment, as compared with placebo, lowered BP both during the morning hours as well as the entire 24-h period. COER-24 verapamil was more effective in lowering morning systolic (-16.6 mm Hg) and diastolic (-11.9 mm Hg) BP than either enalapril or losartan (P < .001). For the entire 24-h period, the effects of COER-24 verapamil (-11.6/-8.4 mm Hg) were comparable to enalapril (- 13.4/-8.3 mm Hg; P = NS). Losartan achieved a similar 24-h effect on systolic pressure (-9.3 mm Hg) but was less effective on diastolic pressure (-5.4 mm Hg; P = .004 v COER-verapamil). Unlike losartan or enalapril, COER-24 verapamil was the only treatment to lower the heart rate over both the 24-h period (-4.6 beats/min; P < .001) and during waking hours (-4.6 beats/min; P < .001). A blunted rate of rise in BP, heart rate, and rate-pressure product occurred during the postawakening period with COER-verapamil (P = .03) but not with either of the other treatment arms. Lastly, the decline in BP at night was similar for COER-verapamil and losartan and greater with enalapril (P = .014) COER-24 verapamil produces changes in BP and pulse that more closely match the normal circadian hemodynamic rhythms than either do enalapril or losartan.",2002.0,0,0
885,11825317,Angiotensin II receptor blockers for the treatment of hypertension.,S See,"The rising incidence of stroke, congestive heart failure (CHF) and end stage renal disease (ESRD) has signalled a need to increase awareness, treatment and control of hypertension. There continues to be a need for effective antihypertensive medications since hypertension is a major precursor to various forms of cardiovascular disease. The renin-angiotensin (AT) aldosterone system (RAAS) is a key component to the development of hypertension and can be one target of drug therapy. Angotensin II (ATII) receptor blockers (ARBs) are the most recent class of agents available to treat hypertension, which work by by inhibiting ATII at the receptor level. Currently, national consensus guidelines recommend that ARBs should be reserved for hypertensive patients who cannot tolerate angiotensin converting enzyme (ACE) inhibitors (ACEIs). ARBs, however, are moving to the forefront of therapy with a promising role in the area of renoprotection and CHF. Recent trials such as the The Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Trial (IDNT), the Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes (IRMA2), and The Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL) study have demonstrated the renoprotective effects of ARBs in patients with Type 2 diabetes. The Valsartan Heart Failure Trial (Val-HeFT) adds to the growing body of evidence that ARBs may improve morbidity and mortality in CHF patients. As a class, ARBs are well tolerated and have a lower incidence of cough and angioedema compared to ACEIs. This article reviews the differences among the ARBs, existing efficacy data in hypertension, and explores the role of ARBs in CHF and renal disease.",2002.0,0,0
886,11825318,Pharmacotherapy of hypertension in patients with diabetes mellitus.,P C Deedwania,"The co-existence of hypertension and diabetes dramatically and synergistically increases the risk of microvascular and macrovascular complications. Overwhelming evidence supports aggressive treatment of hypertension in diabetic patients. However, only a small percentage of diabetic hypertensive patients reach their treatment goal of blood pressure (BP) < 130/80 mmHg. Tight BP control is not only cost-effective but also more rewarding than glycaemic control. The optimal goal of BP control in diabetics should be 130/80 mmHg. In subjects with diabetes and renal insufficiency, the BP should be lowered to 125/75 mmHg to delay the progression of renal failure. The choice of an antihypertensive agent should be based on proven effects on morbidity and mortality rather than on surrogate parameters such as lipid or glucose. Limited data suggests that an angiotensin converting enzyme inhibitor (ACEI) is the agent of choice, especially in those with proteinuria or renal insufficiency. beta-blockers (betaBs) can be the first-line agent in diabetics with coronary heart disease, while thiazide diuretics (TD) and calcium-channel blockers (CCBs) are the second-line drugs. Angiotensin II-receptor blockers (ARBs) may be proven to be as effective as ACEIs in diabetics with hypertension. alpha-adrenergic antagonists (AAAs) should be avoided. Most hypertensive patients require more than one agent to control their BP. There is no evidence to support one combination regimen over others; nevertheless, a combination of an ACEI with a TD or a betaB may be the most cost-effective regimens compared to other combinations.",2002.0,0,0
887,11831455,Usefulness of patch tests for diagnosing selective allergy to captopril.,P Gaig; M M San Miguel-Moncin; J Bartra; A Bonet; P García-Ortega,"Captopril, enalapril, and lisinopril are angiotensin-converting enzyme (ACE) inhibitors widely prescribed for hypertension and heart failure. Cutaneous side effects of captopril include angio-edema, anaphylactoid reactions, maculopapular eruptions, pitiryasis rosea-like rash, toxic erythema, and exfoliative dermatitis. Some of the immunological captopril-induced cutaneous adverse reactions have been diagnosed in recent years by patch tests. A case of a cutaneous immune adverse reaction to captopril with tolerance to enalapril and lisinopril demonstrated both by patch tests and double-blind challenge tests is reported for the first time. A 71-year-old nonatopic woman suffered a generalized pruriginous maculopapular rash. Two months earlier, she had started oral treatment with captopril 50 mg t.i.d and glibenclamide 5 mg daily. After the rash appeared, she stopped both drugs and the reaction cleared. A skin biopsy from one of the lesions showed perivascular lymphocytic infiltrate of the upper dermis. Skin prick tests with captopril and glibenclamide and patch tests with enalapril, lisinopril, and glibenclamide at 1% and 10% pet., and with mercaptobenzothiazole (a sulfhydryl group-containing chemical at 1% pet were negative. Only patch tests with captopril at 1% and 10% concentrations were positive at 48 h. Oral double-blind challenge tests with glibenclamide, enalapril, lisinopril, and placebo showed good tolerance. The patient was advised to avoid only captopril. Because captopril is the only ACE inhibitor containing a sulfhydryl group and has occasionally been implicated in complex immunological diseases, this chemical group has been considered the culprit of allergic reactions to captopril. The lack of cross-reactivity between captopril, enalapril, and benazepril has been demonstrated in a few patients by patch tests. In our patient, patch tests identified captopril as the drug responsible for a probably immune adverse reaction not due to the sulfhydryl group. Patch tests are useful and safe in the diagnostic work-up of allergic drug reactions and in studies of cross-sensitivity among ACE inhibitors.",2002.0,0,0
888,11833827,"A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL).",Antonio Coca; Carlos Calvo; Juan García-Puig; Blas Gil-Extremera; Maria T Aguilera; Alejandro de la Sierra; Alberto Martín-Hidalgo; Rafael Marín; MAPAVEL Investigators (Monitorizacíon Ambulatoria Presión Arterial APROVEL),"When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension. This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values. A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.",2002.0,0,0
889,11834188,Dermatitis to captopril.,J C Martínez; M J Fuentes; A Armentia; J M Vega; A Fernández,"reports on delated cutaneous reactions to captopril have been seldom reported. Captopril is an angiotensin-converting enzyme (ACE) inhibitor and their cutaneous side-effects are documented, but little has been published concerning the usefulness of patch test when they occur. We presented the case of a patient who developed a cutaneous reaction induced by captopril with positive patch test. patch testing was performed with captopril, other ACE (enalapril, lisinopril ramipril), and European standard series. Following, we performed a double-blind oral challenge test with drugs who results was negative. Positive reaction were obtained to captopril at 4 days and the others test being negative. The same test were negative in five control patients. The patient tolerated enalapril, and lisinopril without problems. the allergological studies confirmed sensitisation to captopril and tolerance to lisinopril, and enalapril. When patch test are performed with several drugs of the same family, results seem to indicate an absence of cross-sensitivity, but in several patients, oral provocation test were needed because patch test gave no conclusive information.",2002.0,0,0
890,11835029,"Early ST-segment recovery, infarct artery blood flow, and long-term outcome after acute myocardial infarction.",John K French; Jacqueline Andrews; Samuel O M Manda; Ralph A H Stewart; John J C McTigue; Harvey D White,"Early resolution of ST-segment deviation (ST recovery) on the postthrombolytic electrocardiograms and restoration of ""normal"" blood flow in the infarct-related artery are associated with improved outcomes after myocardial infarction (MI). To evaluate the relationships between ST recovery, infarct-related artery flow, and late survival we studied 766 patients with electrocardiograms recorded at a median of 167 minutes after thrombolytic therapy. Angiography was performed at 3 weeks, and follow-up was done at a median of 6.3 years (interquartile range [IQR] 5.0-8.4). At 10 years, the survival rates were 55% (95% CI 43-70) in patients with <30% ST recovery in the single lead with maximum ST elevation, 71% (95% CI 64-79) in those with 30% to 70% ST recovery, and 74% (95% CI 68-82) in those with >70% ST recovery (P =.0005), whereas ST recovery measured as the sum of voltage changes of either ST deviation (elevation or depression) or ST elevation was not associated with 10-year survival (log-rank test, P =.06 and P =.34, respectively). In patients with Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow, ST recovery of >70% (vs <30% and 30% to 70%) in the lead with maximum ST elevation was associated with increased late survival (P =.04). On multivariate analysis, the predictors, at admission, of 5-year survival were age (P <.001), ST recovery (measured as a continuous variable, P =.001), diabetes (P =.003) and female gender (P =.02). When the ejection fraction (P =.003) and TIMI flow grade (P =.02) at 3 weeks were included in the analysis, the P value for ST recovery was.08. ST recovery measured in the single lead with maximum ST elevation was a predictor of late survival, even in patients with TIMI grade 3 flow but ST recovery measured as the sum of voltage changes in all leads with ST deviation was not. This simple electrocardiographic parameter can identify patients with a reduced chance of survival who might benefit from additional therapies.",2002.0,0,0
891,11835037,Acute blood pressure response to trandolapril and captopril in patients with left ventricular dysfunction after acute myocardial infarction.,Simon Weber; Laurent Vaur; Zine Ounnoughene; Jacques Schwob; Isabelle Dubroca; JeanPierre Normand; Sylvie Etienne; Bernard Charbonnier,"Our purpose was to compare the blood pressure response to short-term treatment with captopril or trandolapril in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). A multicenter, randomized, double-blind, double-dummy, parallel group study was performed. Treatment was initiated 3 to 10 days after the onset of symptoms. On day 1, patients received a single dose of captopril 6.25 mg, trandolapril 0.5 mg, or placebo in the morning. Treatment was then titrated upward over the next 5 days. Blood pressure was monitored with an automated device for the first 12 hours after dosing on day 1. Conventional blood pressure measurements were performed throughout the study. Of 205 patients treated in the study, 193 patients were evaluated for first-dose effects. In the captopril group, the maximum decrease in blood pressure occurred after 2 hours, and the magnitude of this decrease was significantly greater than in the other 2 groups: 8.8 +/- 12/6.3 +/- 8 mm Hg (captopril) versus 5.4 +/- 10/3.1 +/- 8 mm Hg (trandolapril) versus 2.4 +/- 9/1.4 +/- 7 mm Hg (placebo) (P <.01). In the trandolapril group, the maximum decrease occurred after 7 hours and the magnitude of this effect was similar in all 3 groups: 5.9 +/- 11/3.6 +/- 8 mm Hg (trandolapril) versus 4.3 +/- 10/3.5 +/- 8 mm Hg (captopril) versus 3.1 +/- 11/2.8 +/- 8 mm Hg (placebo) (not significant). Although there was a higher incidence of hypotension on day 1 in the captopril group, the overall incidence of hypotension during the study period was similar in both active treatment groups. Because of differences in initial blood pressure response profiles, short-term treatment with trandolapril tended to be better tolerated than captopril in post-AMI patients with LV dysfunction.",2002.0,0,1
892,11840224,Sibutramine is safe and effective for weight loss in obese patients whose hypertension is well controlled with angiotensin-converting enzyme inhibitors.,F G McMahon; S P Weinstein; E Rowe; K R Ernst; F Johnson; K Fujioka; Sibutramine in Hypertensives Clinical Study Group,"Sibutramine treatment in obesity results in significantly greater weight reduction compared with placebo, although weight loss with sibutramine may be accompanied by small but statistically significant mean increases in blood pressure (BP). This 52-week, placebo-controlled, double-blind, randomised study investigated the effects of sibutramine 20 mg once daily or placebo on body weight in 220 obese (body mass index (BMI) 27-40 kg/m2), hypertensive patients. At randomisation, hypertension was well controlled (< or = 95 mm Hg diastolic blood pressure (DBP)) with an angiotensin-converting enzyme (ACE) inhibitor, with or without concomitant thiazide diuretic therapy. Therapy for hypertension continued for the 52 weeks of the study. Sibutramine 20 mg produced significantly greater weight loss compared with placebo: 4.5 kg with sibutramine compared with 0.4 kg with placebo (last observation carried forward (LOCF); P < or = 0.05). A total of 62 patients (42.8%) treated with sibutramine lost < or = 5% of their body weight compared with six patients (8.3%) treated with placebo; 19 patients (13.1%) treated with sibutramine lost > or = 10% of their body weight compared with two patients (2.8%) treated with placebo (LOCF; P < or = 0.05 for both comparisons). Hypertension remained well controlled for the 52 weeks of the study with both sibutramine and placebo treatment. After 52 weeks, the differences between placebo treatment and sibutramine treatment for both mean supine systolic blood pressure (SBP) and DBP were approximately 3 mm Hg: mean DBP was 82.8 mm Hg with placebo treatment compared with 85.5 mm Hg with sibutramine treatment (LOCF; P = 0.004) and mean SBP was 130.4 mm Hg with placebo compared with 133.1 mm Hg with sibutramine (LOCF; P = 0.0497; both comparisons, sibutramine vs placebo). The mean increases in SBP and DBP did not appear to change the overall risk category for coronary heart disease end points. Changes in pulse rate at week 52 were a decrease of 0.3 beats per minute (bpm) for placebo treatment compared with an increase of 5.7 bpm for sibutramine treatment (P < 0.001). Mandated withdrawals from the study due to protocol-defined changes in BP were not statistically different between the two treatment groups. Greater favourable changes in lipid profile, serum glucose, and uric acid could be accounted for by greater weight losses occurring in the sibutramine treatment group. Sibutramine was well tolerated. This study indicates that in obese patients whose hypertension is well controlled at the outset with an ACE inhibitor, with or without concomitant thiazide diuretic therapy, sibutramine safely and effectively achieves weight loss without compromising good BP control.",2002.0,0,0
893,11841077,Gynaecomastia.,I R Daniels; G T Layer,"Gynaecomastia is the commonest benign condition of the male breast. Management consists primarily of taking a complete history and making a thorough clinical examination. Ultrasound is recommended as the first-line imaging investigation although mammography may be added to confirm the diagnosis. The results of fine-needle aspiration cytology may be poor as an adequate yield of pathological specimens is low, and it should be reserved for suspected malignant lesions. Endocrine evaluation of gynaecomastia is rarely productive and such testing is best done selectively. Many patients can be treated simply with reassurance about the benign nature of the condition. In those patients in whom a stimulus has been identified modification of treatment may improve symptoms. Hormonal manipulation may be appropriate in younger patients, but a testicular neoplasm must be excluded. Operations should be reserved for those who fail to respond to hormones and in those with severe cosmetic deformities.",2002.0,0,0
894,11845579,"[Reversible impairment of renal function during treatment with lisinopril, an ACE-inhibitor (case report)].",N Lakusić; D Mahović; N Ciglenecki; R Kurnik; D Cerovec; M Majsec,"ACE inhibitors are group of drugs whose use over the last ten years has largely expanded. New members of this group of drugs are developed and registered and today in Croatia exist a dozen ACE inhibitors from different pharmaceutical companies like lisinopril, cilazapril, ramipril, trandolapril, enalapril etc. Notable side effects of ACE inhibitors are: hypotension, dry cough, rash, angioneurotical edema, impaired renal function and acute renal failure. The aim of the article was to present a 72 year old patient with reversible impairment of renal function during treatment with ACE inhibitor lisinopril.",2002.0,0,0
895,11845604,Dihydropyridine calcium-channel blockers for antihypertensive treatment in older patients--evidence from the Systolic Hypertension in Europe Trial.,J A Staessen; L Thijs; H Celis; J Gasowski; J G Wang; R H Fagard; Systolic Hypertension in Europe Trial Investigators (the Syst-Eur Trial),"The Syst-Eur study investigated whether active antihypertensive treatment could reduce cardiovascular complications in elderly patients with isolated systolic hypertension. Randomised, placebo-controlled, double-blind outcome trial. Hypertension clinics or general practitioners' surgeries in 198 centres in 23 Western and Eastern European countries. Patients aged > or = 60 years with sitting systolic blood pressure (BP) 160-219 mmHg and sitting diastolic BP < 95 mmHg during run-in phase. Four thousand, six hundred and ninety-five patients were randomly assigned to active treatment (N = 2,398), i.e. nitrendipine, with the possible addition of enalapril and hydrochlorothiazide, or to matching placebos (N = 2,297). In the intention-to-treat analysis, the between-group difference in blood pressure (BP) amounted to 10.1/4.5 mmHg (P < 0.001). Active treatment reduced the incidence of fatal and non-fatal stroke (primary endpoint) by 42% (P = 0.003). On active treatment all cardiac endpoints decreased by 26% (P = 0.03) and all cardiovascular endpoints by 31% (P < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, P = 0.07), but all-cause mortality was not influenced (-14%, P = 0.22). For total (P = 0.009) and cardiovascular mortality (P = 0.09), the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic BP at entry (P = 0.05). The benefits of active treatment were not independently related to sex or to the presence of cardiovascular complications at entry. The antihypertensive regimen was more effective in patients with diabetes than in those without diabetes at entry. Further analyses also suggested benefit in patients who were taking nitrendipine as the sole therapy. The per-protocol analysis largely confirmed the intention-to-treat results. Active treatment reduced all strokes by 44% (P = 0.004), all cardiac endpoints by 26% (P = 0.05) and all cardiovascular endpoints by 32% (P < 0.001). Total mortality was reduced by 26% (P = 0.05), but a similar reduction in cardiovascular mortality did not reach statistical significance in this analysis. Compared with placebo, active treatment also reduced the incidence of dementia by 50%. Stepwise antihypertensive drug treatment, starting with the dihydropiridine calcium-channel blocker nitrendipine, improves prognosis in elderly patients with isolated systolic hypertension.",2002.0,0,0
896,11849464,"Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes.",Robert W Schrier; Raymond O Estacio; Anne Esler; Philip Mehler,"Although several important studies have been performed in hypertensive type 2 diabetic patients, it is not known whether lowering blood pressure in normotensive (BP <140/90 mm Hg) patients offers any beneficial results on vascular complications. The current study evaluated the effect of intensive versus moderate diastolic blood pressure (DBP) control on diabetic vascular complications in 480 normotensive type 2 diabetic patients. The current study was a prospective, randomized controlled trial in normotensive type 2 diabetic subjects. The subjects were randomized to intensive (10 mm Hg below the baseline DBP) versus moderate (80 to 89 mm Hg) DBP control. Patients in the moderate therapy group were given placebo, while the patients randomized to intensive therapy received either nisoldipine or enalapril in a blinded manner as the initial antihypertensive medication. The primary end point evaluated was the change in creatinine clearance with the secondary endpoints consisting of change in urinary albumin excretion, progression of retinopathy and neuropathy and the incidence of cardiovascular disease. The mean follow-up was 5.3 years. Mean BP in the intensive group was 128 +/- 0.8/75 +/- 0.3 mm Hg versus 137 +/- 0.7/81 +/- 0.3 mm Hg in the moderate group, P < 0.0001. Although no difference was demonstrated in creatinine clearance (P = 0.43), a lower percentage of patients in the intensive group progressed from normoalbuminuria to microalbuminuria (P = 0.012) and microalbuminuria to overt albuminuria (P = 0.028). The intensive BP control group also demonstrated less progression of diabetic retinopathy (P = 0.019) and a lower incidence of strokes (P = 0.03). The results were the same whether enalapril or nisoldipine was used as the initial antihypertensive agent. Over a five-year follow-up period, intensive (approximately 128/75 mm Hg) BP control in normotensive type 2 diabetic patients: (1) slowed the progression to incipient and overt diabetic nephropathy; (2) decreased the progression of diabetic retinopathy; and (3) diminished the incidence of stroke.",2002.0,0,0
897,11850305,"Heart failure in older people: causes, diagnosis and treatment.",Ahmed H Abdelhafiz,"Congestive heart failure affects >5% of those aged 65-75 and 10-20% of those aged >80 in the UK, and levels are likely to rise in the wake of improved therapies for hypertension and myocardial infarction. It is often multifactorial in this group. The most common causes are hypertension and coronary heart disease, with valvular heart disease playing an increasing role. The most common precipitant of pre-existing heart failure is non-compliance with medication or diet; non-steroidal anti-inflammatory drugs are particularly likely to exacerbate the condition. Diagnosis may be difficult since typical signs are often absent or masked in older people, but plasma levels of brain natriuretic peptide appear to be a reliable indicator and may provide diagnostic test in the future. Systolic heart failure is managed by conventional therapy (diuretics, angiotensin-converting enzyme inhibitors and beta-blockers). The management of diastolic heart failure is less well defined, but symptoms should be managed, ischaemia prevented and the underlying causes identified and treated. Nurse-directed, multidisciplinary intervention (including education of patient and family, social support, review of medication, dietary modification and weight monitoring) have resulted in improvements in event-free survival and quality of life.",2002.0,0,0
898,11850763,Fixed dose combination therapy in the treatment of hypertension.,T Stanton; J L Reid,,2002.0,0,0
899,11850771,Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients.,M L De Rosa; P Cardace; M Rossi; A Baiano; A de Cristofaro,"The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure, echocardiographically calculated left ventricular mass, renal function evaluated by glomerular filtration rate and quality of life. The renin-angiotensin-aldosterone system is of importance for cardiovascular growth. There is substantial experimental documentation in animals that the angiotensin II antagonist, losartan, decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload. However, data in humans is scarce. This is a 3-year, randomised, double-blind study with parallel group design in 50 patients with essential hypertension. The results show that both drugs reduced blood pressure equally effectively, and also left ventricular mass (P < 0.001). After 3 years of treatment glomerular filtration rate significantly increased with losartan (P < 0.005). Serum uric acid fell modestly although significantly, dose-dependent in losartan patients compared with an increase in enalapril patients. A fall in serum potassium from the pre-study period was observed in all patients. There was no difference between treatments in terms of patient satisfaction on quality of life. Both drugs have relatively similar hormonal and haemodynamic effect, with an excellent tolerability profile; they appear to induce comparable blood pressure falls in hypertensive patients in particular, therapy based on specific Ang II blockade may offer advantages in high risk hypertensives if left ventricular hypertrophy is present. Both enalapril and losartan, in improving the renal function attenuating the intrarenal effects of angiotensin II, might be able to reverse the pathophysiology of essential hypertensive kidney disease, and should be first-choice drugs in the treatment of essential hypertension.",2002.0,0,0
900,11854123,Relationship between treatment-induced changes in left ventricular mass and blood pressure in black african hypertensive patients: results of the Baragwanath Trial.,Daniel Skudicky; Pinhas Sareli; Elena Libhaber; Geoffrey Candy; Ivo Radevski; Zdravska Valtchanova; Elizabeth Tshele; Lutgarde Thijs; Ji-Guang Wang; Jan A Staessen,"In a single-center study, we compared to what extent changes in conventional and ambulatory blood pressure (BP) predicted regression of left ventricular mass (LVM) index in response to antihypertensive treatment in previously untreated and treated patients with sustained hypertension. We enrolled 173 black African patients who, off treatment, had a daytime diastolic BP ranging from 90 to 114 mm Hg. Antihypertensive drugs were titrated and combined to reduce the daytime diastolic BP below 90 mm Hg. Echocardiograms were obtained at baseline and follow-up. Mean systolic/diastolic clinic BP, 24-hour BP, and LVM index were similar in previously untreated (n=64) and previously treated (n=109) patients and averaged 171/102 mm Hg, 151/97 mm Hg, and 118 g/m2, respectively. At 4 months, these values had decreased (P<0.001) by 26/12 mm Hg, 23/14 mm Hg, and 14 g/m2 in previously untreated patients and by 22/9 mm Hg, 21/13 mm Hg, and 19 g/m2 in previously treated patients. In the previously untreated patients, the regression in LVM index correlated to a similar degree (P=0.09) with the decreases in the conventional (r=0.34; P=0.005) and the 24-hour (r=0.26; P=0.04) systolic BP. In the previously treated patients, the corresponding correlations were 0.02 (P=0.82) and -0.10 (P=0.32), respectively. Compared with the 24-hour systolic BP, automated oscillometric measurements of systolic BP obtained at the clinic yielded similar results. In previously untreated patients with sustained hypertension followed at a single center, reductions in clinic and ambulatory systolic pressure in response to antihypertensive treatment equally predicted the regression in LVM index.",2002.0,0,0
901,11855793,Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study.,N B Tütüncü; A Gürlek; O Gedik,"We compared the efficacy of treatment protocols with an angiotensin converting enzyme (ACE) inhibitor alone (enalapril, 5 mg) or angiotensin II (ATII) receptor blocker (losartan, 50 mg) or both enalapril plus losartan in patients with microalbuminuria in a prospective, randomized clinical trial. Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study. Patients were grouped randomly into one of the protocols which consisted of treatment with 5 mg enalapril daily (group 1; n=12), 50 mg losartan daily (group 2; n=12) or both drugs (group 3; n=10). They were reevaluated with regard to HbA1c levels, lipid profiles, blood pressure and urinary albumin excretion rates (UAER) at 3-month intervals for 12 months. Mean age, duration of diabetes, body mass index, plasma lipid profiles and blood pressure levels were similar at the initial visit. In group 1, UAER returned to normal levels in 10 patients. Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3, respectively. Percentage of reduction in UAERs at the end of 12 months were 58%, 59% and 60% (p=0.0001; p=0.0002; p=0.0003, respectively). The amount of reduction in UAER did not differ significantly among the three groups (p=0.346). ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria, and the combination of the two drugs does not add any further benefit.",2002.0,0,0
902,11856403,A brief analysis of clinical pharmacy interventions undertaken in an Australian teaching hospital.,C P Alderman; C Farmer,"Selected clinical pharmacy interventions undertaken during a 30-day data capture period were analysed, seeking to gain a greater understanding of the nature of the drug-related problems involved. Pharmacists were asked to record only interventions that were of potentially major significance. A total of 67 interventions were submitted for analysis. In 28 cases (41.7% of the initial total) the intervention reports were excluded from further analysis after initial review. For the remaining 39 interventions, 20 patients (51%) were under the care of a medical unit, and cardiovascular/antithrombotic agents accounted for 17 reports (43.5%). The majority of interventions were implemented at the time of inpatient medication order review by the clinical pharmacist (n=25, 64%). The most common category of drug-related problem addressed in the interventions related to the prescription of inappropriately high doses of the correct drug for the patient (n=17, 43.6%). Deficiencies in technical knowledge accounted for less than 25% of all cases.",2002.0,0,0
903,11863083,Diabetic renal disease in African Americans.,Errol D Crook,"Diabetic nephropathy (DN) is the No. 1 cause of end-stage renal disease in the United States and is highly prevalent in African Americans. Almost all DN in African Americans is caused by type 2 diabetes. Glycemic control and control of blood pressure are essential to prolong renal survival and to protect against cardiovascular events. Among African Americans, diabetic nephropathy seems to affect women more than men, which may be related to increased rates of obesity and diabetes in African American women. In addition to gender, the development of albuminuria, family history, and possibly birth weight are factors that predict progression of renal disease in African Americans with DN. The impact of glycemic control, appropriate antihypertensives, and the optimal level of blood pressure control in African Americans with advanced DN require further study. This article will review the clinical characteristics, risk factors, predictors of disease progression, and treatment of diabetic nephropathy in African Americans.",2002.0,0,0
904,11867945,"Angiotensin II type 1 receptor antagonist, losartan, causes regression of left ventricular hypertrophy in end-stage renal disease.",Yasunoba Shibasaki; Hiroya Masaki; Takashi Nishiue; Mitsushige Nishikawa; Hiroaki Matsubara; Toshiji Iwasaka,"Left ventricular hypertrophy (LVH) commonly occurs in patients with end-stage renal disease (ESRD) and is an independent risk factor for cardiovascular events. Angiotensin II type 1 receptor (AT1-R) antagonists may be able to reverse LVH independent to the hypotensive effect in the ESRD setting. Thirty chronically hemodialyzed uremic patients with hypertension were randomly assigned to receive the AT1-R antagonist losartan (n = 10), the angiotensin-converting enzyme (ACD) inhibitor enalapril (n = 10), or calcium antagonist amlodipine (n = 10). Left ventricular mass (LVM) index was measured by echocardiography before and 6 months after treatment. The baseline demographic and clinical characteristics did not differ between the three groups. The mean baseline LVM index also did not differ in the three groups. After 6 months of treatment, losartan treatment significantly reduced the LVM index (-24.7 +/- 3.2%) than amlodipine (-10.5 +/- 5.2%) or enalapril (-11.2 +/- 4.1%) therapy. All three groups had a similar decrease in the mean blood pressure with treatment. The plasma angiotensin II concentration increased 5-fold with losartan treatment. In contrast, the plasma angiotension II concentration did not change with enalapril and only increased 2-fold with amlodipine. Thus, the present study indicates that losartan more effectively regresses LVH in patients with ESRD than do enalapril and amlodipine despite a comparable depressor effect between the three drugs.",2002.0,0,0
905,11869839,Gradual reactivation over time of vascular tissue angiotensin I to angiotensin II conversion during chronic lisinopril therapy in chronic heart failure.,Colin A J Farquharson; Allan D Struthers,"This study was designed to fully characterize vascular tissue angiotensin I (AI)/angiotensin II (AII) conversion changes over time in vivo in humans during chronic angiotensin-converting enzyme (ACE) inhibitor therapy. Plasma AII does not remain fully suppressed during chronic ACE inhibitor therapy. However, the plasma renin angiotensin system (RAS) might be dissociated from the vascular tissue RAS. We therefore set out to characterize the time course of vascular RAS reactivation during chronic ACE inhibitor therapy. Vascular AI/AII conversion was studied in patients with chronic heart failure (CHF) taking chronic lisinopril therapy by the differential infusion of AI and AII into the brachial artery. A cross-sectional study was done to see whether there were differences in vascular AI/AII conversion according to New York Heart Association (NYHA) class. A second longitudinal study followed 28 patients with NYHA I to II CHF serially over 18 months to see whether vascular ACE inhibition was progressively lost with time despite ACE inhibitor therapy. A third study examined whether increasing the dose of lisinopril affected subsequent vascular ACE inhibition. In the cross-sectional study, vascular AI-to-AII conversion was significantly reduced in NYHA class III compared with class I/II (p < 0.05). In the longitudinal study, vascular ACE inhibition was significantly reduced at 18 months as compared with baseline (p < 0.001), suggesting gradual reactivation of vascular ACE in CHF over time. In the third study, tissue ACE inhibition could be restored by increasing the ACE inhibitor dose. Vascular AI/AII conversion reactivates over time during chronic ACE inhibitor therapy even if the CHF disease process is clinically stable. It also occurs as the CHF disease process progresses. Even if vascular AI/AII conversion has reactivated, it can be suppressed by increasing the dose of the ACE inhibitor.",2002.0,0,0
906,11871625,Mortality associated with the quality of care of patients hospitalized with congestive heart failure.,Jean-Christophe Luthi; William M McClellan; Dawn Fitzgerald; Harlan M Krumholz; Richard J Delaney; Dale W Bratzler; Kurt Elward; Charles B Cangialos; David J Ballar; Multi-State Collaborative Congestive Heart Failure Study Group,"This study examined the association between use of angiotensin converting enzyme inhibitors (ACEIs) and risk of death in elderly patients hospitalized with left ventricular systolic dysfunction (LVSD). Retrospective cohort study. Despite evidence showing the benefit of treating LVSD with ACEI, elderly patients with LVSD are often not treated with an ACEI. Concern that the risk of ACEI treatment might exceed the benefits in elderly patients is a possible reason. We abstracted records from 2943 Medicare beneficiaries hospitalized for congestive heart failure in 69 hospitals in five states. The presence of LVSD was determined from recorded ejection fractions or a narrative description of ventricular function. Discharge medications and dosages were abstracted. Mortality was tracked for one year using Health Care Finance Administration MEDPRO files. There were 621 patients aged 65 years or older with LVSD. The mean age (SD) was 77.4 years (7.0). At discharge 79% were prescribed an ACEI and, of these, 47% were discharged at the dose recommended by clinical practice guidelines. There were 195 deaths (31.4%) during the year of follow-up. Compared with patients discharged at a recommended ACEI dose, patients not prescribed an ACEI at discharge had an adjusted hazard ratio for death (95% CI) of 1.63 (1.02, 2.60) and patients prescribed an ACEI at a less than recommended dose had a hazard ratio of 1.30 (0.86, 1.97). Our results show that ACEI use at discharge in elderly patients with LVSD is associated with decreased risk of death.",2002.0,0,0
907,11875316,Changes in pain perception during treatment with angiotensin converting enzyme-inhibitors and angiotensin II type 1 receptor blockade.,Luigina Guasti; Danilo Zanotta; Alessio Diolisi; Deborah Garganico; Cinzia Simoni; Giovanni Gaudio; Anna M Grandi; Achille Venco,"Besides the well-known role of the angiotensin system in blood pressure control, an interaction of angiotensin and pain perception has been suggested. This study sought to investigate whether an angiotensin converting enzyme inhibitor, which facilitates bradykinins, algesic peptides, and/or an AT1 receptor antagonist may modify hypertension-related hypoalgesia in humans. The study was approved by the ethical committee of our Department. A total of 22 hypertensive patients were submitted to dental pulp stimulation to obtain the dental pain threshold and tolerance, and to 24 h blood pressure monitoring together with a control group of 55 normotensives. Then the hypertensives were randomized to enalapril or losartan treatment and were re-evaluated (dental pain perception and ambulatory monitoring) after 8 weeks of the first treatment and after an additional 8 weeks of the second treatment. Untreated hypertensives showed a reduced perception to painful stimuli when compared with normotensives. A significant reduction of both pain threshold and tolerance was observed during the anti-hypertensive treatments (Friedman test: P = 0.007 and P = 0.006, respectively). Pain sensitivity was similar during the two treatments and it did not differ from pain sensitivity values of normotensive controls. ANCOVAs were computed to evaluate the relationship between anti-hypertensive agents and pain sensitivity, after controlling for blood pressure. A 24 h mean pressure served as covariate, removing any effect of blood pressure; a significant difference was observed entering both pain threshold and tolerance as dependent variables (F = 5.28, P = 0.0076; F = 8.16, P = 0.0007, respectively). Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.",2002.0,0,0
908,11875324,Twenty-four hour ambulatory blood pressure in the International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT).,Giuseppe Mancia; Stefano Omboni; Gianfranco Parati; Investigators of the INSIGHT ABPM substudy,"The International Nifedipine GITS Study Intervention as a Goal in Hypertension Treatment (INSIGHT) showed, by means of office blood pressure measurements, that long-term treatment with nifedipine GITS is as effective as diuretics in preventing cardiovascular and cerebrovascular complications. However, since office blood pressure measurements reflect to a limited extent blood pressure outside the office, a side-arm INSIGHT study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring was also performed. The study had a randomized, double-blind, parallel group design. After 4 weeks of placebo, mild-to-moderate essential hypertensive patients were randomized to nifedipine GITS 30 mg or amiloride 2.5 + hydrochlorothiazide 5 mg for 3.1 years. Dose titration was performed by dose doubling and addition of atenolol 25-50 mg or enalapril 5-10 mg, or other drugs when needed. Analysis was carried out by intention-to-treat and included computation of 24 h, day and night ambulatory blood pressure and heart rate values. Additional analyses included computation of the trough-to-peak ratio and the smoothness index (the ratio between the average of the 24-hourly blood pressure reductions after treatment and its standard deviation). A total of 151 patients were recruited and 149 were valid for analysis: 78 patients had 24 h ambulatory recordings both at baseline and during treatment and 134 during treatment. Office, 24 h and day and night blood pressures were all significantly and similarly reduced by both treatments. Office and ambulatory heart rate was left unchanged by diuretics, while it was slightly reduced by nifedipine. Median trough-to-peak ratios were always > 0.5 and superimposable between the two treatment groups. Similarly, smoothness indices of systolic and diastolic blood pressures were comparably high for nifedipine and diuretics, thus demonstrating a similar well-balanced antihypertensive response to both drugs. No significant differences were observed between the two treatment groups in the number of cardiovascular events (17 in the nifedipine-based and 26 in the diuretics-based treatment group). In the INSIGHT study, the long-term antihypertensive effect on 24 h blood pressure and the cardiovascular protection of nifedipine was similar to that of diuretics.",2002.0,0,0
909,11875587,Vasopeptidase inhibition: a novel approach to cardiovascular therapy.,John S Floras,"Omapatrilat was designed to inhibit simultaneously angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP). The ubiquitous involvement of the renin-angiotensin-aldosterone system, originally conceived as an axis of sodium and fluid metabolism in inflammation, thrombosis and cardiac and smooth muscle hypertrophy, is a major factor in disease progression for conditions as diverse as hypertension, heart failure, coronary artery disease and diabetes. Interruption of angiotensin II generation and bradykinin degradation by ACE inhibition is a major therapeutic advance in the management of these diseases. NEP metabolizes both bradykinin and the natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide, c-type natriuretic peptide and adrenomedullin). These peptides counter the adverse effects of angiotensin II by their vasodilator, natriuretic, diuretic and autonomic neural actions; by their antitrophic effects; and by suppressing plasma renin activity. These two systems can be considered key components of a cardiorenal axis that maintains blood pressure and cardiopulmonary blood volume within a stable range. This balance is compromised in the setting of heart failure and primary hypertension. The combination of ACE and NEP inhibition should augment the beneficial hemodynamic and tissue effects of bradykinin and the natriuretic peptides. Vasopeptidase inhibition, therefore, is a novel approach to cardiovascular therapy, with implications for hypertension, heart failure, renal function and ischemic heart disease.",2002.0,0,0
910,11877580,"Effects of losartan or enalapril on hemoglobin, circulating erythropoietin, and insulin-like growth factor-1 in patients with and without posttransplant erythrocytosis.",Angela Yee Moon Wang; Alex Wai Yin Yu; Christopher Wai Kei Lam; Ly Mee Yu; Philip Kam Tao Li; Juliana Goh; Siu Fai Lui,"Both angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists reduce hemoglobin (Hb) levels in patients with posttransplantation erythrocytosis (PTE). However, their effects in transplant recipients without PTE are not certain, and the mechanism by which they reduce Hb levels in patients with PTE remains unclear. This study evaluated the effects of losartan and enalapril on Hb levels in relation to serum erythropoietin (EPO) and insulin-like growth factor-1 (IGF-1) levels in 8 patients with PTE and 10 patients without PTE. All 18 patients were treated sequentially with 24 weeks of losartan therapy, followed by 24 weeks of enalapril therapy; the two treatment phases were separated by a washout period. Patients with PTE showed significantly greater baseline Hb and IGF-1 concentrations compared with patients without PTE before both losartan and enalapril treatments. Baseline serum EPO levels were similar for patients with and without PTE. Baseline Hb level correlated significantly with IGF-1 level (r = 0.517; P = 0.002), but not with EPO level. Treatment with enalapril, 5 mg, reduced Hb levels more markedly than treatment with losartan, 50 mg, in patients with PTE. In patients without PTE, enalapril, 5 mg, mildly reduced Hb levels, whereas losartan, 50 mg, had no significant Hb-lowering effect. The reduction in Hb levels with enalapril therapy in patients with PTE was associated with a significant reduction in circulating IGF-1 levels, but not EPO levels, whereas losartan reduced Hb levels with no significant change in circulating IGF-1 and EPO levels. In patients without PTE, no significant change was noted in serum EPO and IGF-1 levels with either treatment. The differential Hb-lowering effect with losartan and enalapril treatment in patients with and without PTE suggests that the pathogenesis for PTE is complex and heterogeneous. Different erythropoietic mechanisms may be involved in patients with and without PTE. Further large-scale study is needed to determine the exact interaction between the renin-angiotensin system and regulation of IGF-1 and EPO synthesis and define the exact mechanism by which losartan and enalapril reduce Hb levels.",2002.0,0,0
911,11879862,Angiotensin-converting-enzyme inhibition therapy in altitude polycythaemia: a prospective randomised trial.,"Raul Plata; Arturo Cornejo; Carla Arratia; Agustina Anabaya; Annalisa Perna; Borislav D Dimitrov; Giuseppe Remuzzi; Piero Ruggenenti; Commission on Global Advancement of Nephrology (COMGAN), Research Subcommittee of the International Society of Nephrology","Angiotensin-converting-enzyme (ACE) inhibitors reduce packed cell volume and haemoglobin concentration in polycythaemia that follows renal transplantation, which, like altitude polycythaemia, is an erythropoietin-dependent form of polycythaemia. We aimed to establish the effect of ACE-inhibitor treatment in people with altitude polycythaemia. We did a prospective randomised study in 26 people with altitude polycythaemia (packed cell volume > or = 55%) and 24-h rate of urinary protein excretion greater than 150 mg, who had been referred to the Renal Disease Project in La Paz, Bolivia. 13 participants were assigned 5 mg/day enalapril for 2 years (study group), and 13 no treatment (controls). Blood pressure, packed cell volume and haemoglobin concentration, proteinuria, and renal function were compared by intention-to-treat analyses. Baseline packed cell volume and haemoglobin concentration were positively correlated with bodyweight (p=0.02), systolic (p=0.01) and diastolic (p=0.04) blood pressure, serum creatinine (p=0.009), blood urea (p=0.008), and proteinuria (p=0.003). Systolic and diastolic blood pressure remained stable in the study group, but increased in controls. In study patients, mean (SD) packed cell volume, haemoglobin concentration, and proteinuria fell from 63.5% (4.9) to 56.8% (4.1), p<0.0001; 207 (18) to 164 g/L (13), p<0,0001; and from 358.6 (260.3) to 247.7 mg/24-h (208.2), p<0.002, respectively, but did not change significantly in controls. At 12 and 24 months of follow-up, packed cell volume, haemoglobin concentration, and proteinuria differed significantly between the groups (p<0.0001 for each comparison). In study patients, follow-up changes in packed cell volume (r=0.88, p<0.0001) or haemoglobin concentration (r=0.83, p<0.0001) and proteinuria were strongly correlated. Enalapril was well tolerated by all patients. ACE-inhibition therapy effectively and safely ameliorates altitude polycythaemia and reduces proteinuria.",2002.0,0,0
912,11881062,Discordant responses to two classes of drugs acting on the renin-angiotensin system.,P S Sever; C L Chang,"Marked heterogeneity characterises blood pressure (BP)responses to antihypertensive drugs. The efficacy of drugs acting on the renin-angiotensin-aldosterone system(RAAS) is predicted (albeit weakly) by plasma renin activity (PRA) and it has been assumed that, within individuals, there would be concordance in efficacy between drugs acting at different sites to block the RAAS. The present study was a randomised, double-blind,two-way, crossover study designed to evaluate intra-individual BP responses to an angiotensin II AT -receptor blocker (ARB), candesartan cilexetil, and anangiotensin-converting enzyme inhibitor (ACE-I), lisinopril, and to identify potential phenotypic characteristics of patients' responses to the drugs. 92 patients with essential hypertension, (mean systolic/diastolic BP 160/101 mmHg) entered the trial,of whom 76 patients completed both treatments. There was marked heterogeneity in response to the two drugs. 50% of patients responded (fall in diastolic BP of>10 mmHg or achieved diastolic pressure <90 mmHg)to both drugs; 16% were non-responders to both drugs; 20% responded to the ACE-I but not the ARB and 15% responded to the ARB but not to the ACE-I. Individual responses to the two drugs were poorly correlated (for diastolic pressure: r=0.19, p=0.11; for systolic pressure: r=-0.01, p=0.92). For the ACE-I, the fall in both systolic and diastolic BP was related to pre-treatment PRA (for diastolic pressure: r=0.31, p=0.008; for systolic pressure: r=0.24, p=0.04). In the case of the ARB, no relationship between the fall in BP and PRA was observed. These observations suggest that more complex mechanisms may be involved in BP reduction with ARBs than with ACE-I.",2002.0,0,0
913,11881131,"Evaluation of the safety and efficacy of telmisartan and enalapril, with the potential addition of frusemide, in moderate-renal failure patients with mild-to-moderate hypertension.",T Hannedouche; J Chanard; B Baumelou; French Collaborative Telmisartan Study Group,"The effect on renal function and efficacy of the angiotensin II AT1-receptor blocker (ARB), telmisartan, were compared with those of the angiotensin-converting enzyme inhibitor, enalapril, for the treatment of mild-to-moderate hypertension (diastolic blood pressure [DBP] 95-114 mmHg) in the presence of moderate renal failure (creatinine clearance [Ccr] 30-80 ml/minute). The study was multicentre, double-blind, double-dummy and active-controlled in design, with patients randomised in a 2:1 ratio to receive telmisartanor enalapril. After a two-week placebo run-in period, the 71 eligible patients received either telmisartan, 40 mg, orenalapril, 10 mg, once-daily for four weeks. Thereafter, doses were titrated to telmisartan 80 mg or enalapril 20 mg once-daily if supine trough DBP was still > or =90 mmHg. After a further four weeks, dose titration was again performed, as required, to telmisartan, 80 mg,or enalapril, 20 mg, or frusemide was given in addition if the double dose was already being administered. Mean Ccr decreases of 4.6% for telmisartan and 2.8% forenalapril were not clinically significant. Adverse events occurred in 12 (26.7%) telmisartan-treated patients and in 12 (46.2%) patients receiving enalapril. The mean reduction in supine trough DBP from baseline to the last available value was 12.5 mmHg for telmisartan,compared with 11.9 mmHg for enalapril. A full (reduction of >or=10 mmHg) or partial (reduction of 7-9 mmHg) response occurred in 78% of telmisartanpatients and 65% of enalapril patients. In the enalapril group, 43% of patients required frusemide, compared with 29% of those in the telmisartan group. In conclusion, telmisartan lacks detrimental effect on renal function, is effective in the treatment of mild-to-moderate hypertension in patients with moderate renal failure,and is comparable to enalapril.",2002.0,0,0
914,11882098,Family physicians' and general practitioners' approaches to drug management of diabetic hypertension in primary care.,Khalid A J Al Khaja; Reginald P Sequeira; Vijay S Mathur; Awatif H H Damanhori; Abdul Wahab M Abdul Wahab,"To compare the pharmacotherapeutic approaches to diabetic hypertension of family physicians (FPs) and general practitioners (GPs). A retrospective prescription-based study was conducted in 15 out of a total of 20 health centres, involving 115 primary care physicians--77 FPs and 38 GPs, representing 74% of the primary care physicians of Bahrain. Prescriptions were collected during May and June 2000 to comprise a study population of 1266 diabetic-hypertensive patients. As monotherapy, angiotensin-converting enzyme (ACE) inhibitors (37.9%) and beta-blockers (38.3%) were the most commonly prescribed classes of antihypertensives by FPs and GPs, respectively. Calcium channel blockers (CCBs) were ranked third by both categories of physicians. For two-drug combinations, a beta-blocker and an ACE inhibitor was the combination of choice for both physician categories. Patients managed by the FPs were more likely to receive a beta-blocker-CCB combination (17.4 vs. 14.9%) or a diuretic-ACE inhibitor combination (16.7 vs. 11.4%) and less likely to receive a beta-blocker-diuretic combination (11.8 vs. 16.7%) than those managed by the GPs. The proportion of patients receiving antihypertensive combinations was 40.6 and 38.5% for FPs and GPs, respectively. While the GPs prescribed CCB as a monotherapy to the elderly most often, the FPs choice was a beta-blocker. Diuretics were less preferred by both FPs and GPs. Beta-blocker-ACE inhibitor was again the most preferred combination of both FPs and GPs. FPs prescribed CCB-beta-blocker combinations more often than GPs (P = 0.01), whereas CCB-ACE inhibitor combinations were less preferred (P = 0.09). A trend towards excessive use of short-acting nifedipine as monotherapy for elderly patients, both by FPs and by GPs, was noticed. Glibenclamide, alone or in combination with metformin, was the foremost antidiabetic drug prescribed by FPs and GPs. Middle-aged (45-64 years) patients seen by GPs were more likely to receive glibenclamide than those treated by FPs (P = 0.001) and less likely to receive gliclazide (P = 0.01). Combinations of a beta-blocker with either glibenclamide or insulin were prescribed considerably more often by GPs. Within the same practice setting, a substantial difference was observed between FPs and GPs in terms of preference for different classes of drugs in the management of diabetic hypertension. The compliance of both FPs and GPs was suboptimal; overall, the compliance of the FPs was closer to the recommended guidelines, however. Educational programmes should specifically address these inadequacies in order to improve the quality of health care.",2002.0,0,0
915,11887299,Effect of various antihypertensive drugs on plasma fibrinogen levels in patients with essential hypertension.,J Bhatia; P Mahajan; M Sikka; O P Kalra,"In recent years, substantial evidence has accumulated to unambiguously implicate high plasma fibrinogen levels as a major cardiovascular risk factor. An open prospective and randomised pilot study was therefore undertaken in mild to moderate hypertensives to evaluate the effect of various antihypertensive drugs viz enalapril, felodipine and prazosin on the blood pressure and plasma fibrinogen levels. The systolic and diastolic blood pressures were determined at 0, 4 and 8 weeks whereas plasma fibrinogen assays were done at baseline and at the end of the 8th week of treatment in all the drug-treated groups. It was observed that although all the three drugs effectively controlled blood pressure, only enalapril significantly reduced plasma fibrinogen levels. Due to this additional effect, enalapril has potential to control two major cardiovascular risk factors--hypertension and high plasma fibrinogen levels--simultaneously.",2002.0,0,0
916,11889886,Practice tips. Treating persistent cough. Try a nebulized mixture of lidocaine and bupivacaine.,Roni Peleg; Liat Binyamin,,2002.0,0,0
917,11890357,Omapatrilat. Bristol-Myers Squibb.,R Tabrizchi,"Bristol-Myers Squibb (BMS) is developing the vasopeptidase inihibitor, omapatrilat, a dual inhibitor of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), for the potential treatment of cardiovascular diseases such as hypertension and heart failure [306287]. An NDA for the use of omapatrilat in hypertension was filed with the FDA and the regulatory authorities in the EU in December 1999 [351207], [353287]. In April 2000, BMS voluntarily withdrew the NDA in response to questions raised by the FDA regarding the comparative incidence and severity of an infrequent side effect (angioedema) reported within the NDA database. Prospective controlled clinical studies in patients with hypertension and heart failure were to continue. In May 2001, BMS reported that its blinded omapatrilat hypertension study was continuing and, pending supportive results from a data analysis anticipated in late summer/early autumn 2001, the company expected to refile an NDA with the FDA [409203]. In July 2000, BMS reported that it planned to conduct a multinational, 25,000 patient study (OCTAVE - Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) to compare the efficacy and safety of omapatrilat against enalapril in the treatment of hypertension [374909]. The OCTAVE trial was expected to generate data by mid-2001, which could allow for a launch by early 2002 [380280]. Phase III trials for hypertension had commenced by January 1998 [273646]. In January 2001, Merrill Lynch expected BMS to refile its NDA with the FDA in the second half of 2001 [395423]. In February 2001, Credit Suisse First Boston made a similar prediction, adding that it believed BMS would launch the drug in late 2002 or early 2003. The analysts also predicted peak sales for the drug of $585 million in 2005 [399484]. In May 2001, Merrill Lynch estimated sales of $1.8 billion in 2005 [411811].",2002.0,0,0
918,11890606,Blood pressure reduction after the first dose of captopril and perindopril.,P A Jansen; O O De Vries; S E De Rooy; J A Raymakers,,2002.0,0,0
919,11894644,The growing burden of heart failure.,Naomi Rapeport,,2002.0,0,0
920,11895062,Role of race in the pharmacotherapy of heart failure.,James S Kalus; Jean M Nappi,"To review the literature assessing the differences in response to angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in black patients compared with the response in non-black patients in the management of systolic heart failure. A MEDLINE search (January 1966-May 2001) was performed using heart failure, blacks, Negroid race, adrenergic beta-antagonists, and angiotensin-converting enzyme inhibitors as key words. English-language articles were identified. Additional pertinent articles were identified from review of the references of these articles. All identified references were reviewed. All articles deemed relevant to the subject of this article were included. It has been suggested that the antihypertensive effect of ACE inhibitors and beta-blockers may be less in black patients than in other racial groups. Retrospective reanalyses of major heart failure trials have suggested that black patients may not realize a significant benefit in morbidity or mortality when heart failure is managed with ACE inhibitors or beta-blockers. It has also been suggested that black patients may respond more favorably than non-black patients to the combination of hydralazine and isosorbide dinitrate. Published reanalyses of ACE inhibitor and beta-blocker trials in heart failure provide weak data to support a lack of benefit in black patients. The published literature on this topic is limited by its retrospective nature. Firm conclusions regarding the influence of race on effectiveness of ACE inhibitors and beta-blockers cannot be made until prospective trials, with planned analysis of the effect of race, have been performed.",2002.0,0,0
921,11896502,Is there an epidemic of primary aldosteronism?,J M C Connell,,2002.0,0,0
922,11896508,"Impact of an ACE inhibitor and calcium antagonist on microalbuminuria and lipid subfractions in type 2 diabetes: a randomised, multi-centre pilot study.",G L Bakris; A C Smith; D J Richardson; E Hung; R Preston; R Goldberg; M Epstein,"Microalbuminuria (MA) is associated with increased cardiovascular risk and lipid abnormalities in people with type 2 diabetes. ACE inhibitors and calcium channel blockers (CCBs) reduce MA and are neutral on total cholesterol and triglycerides. The effect of ACE inhibitors and CCBs on lipid subfractions such as Lp(a), apolipoprotein (apo) A1, apo B, and others, however, is unclear. The current study tests the hypothesis that a fixed-dose combination of an ACE inhibitor, benazepril (B) with the dihydropyridine CCB, amlodipine (A), will further reduce arterial pressure and reduce atherogenic lipid fractions compared to either agent alone. A multicentre, randomised, open-label, parallel group design was used to study 27 participants with type 2 diabetes. Measurements for total cholesterol, high- and low-density lipoprotein (HDL and LDL), triglycerides, apo A1, apo B, Lp(a), MA, arterial pressure and creatinine clearance were obtained at baseline and at 12-week intervals during the 36 week study. Arterial pressure was significantly reduced at 36 weeks in all three groups (P = 0.0078 for A, P = 0.0039 for B, and P = 0.0313 for A+B). MA was lowered in all groups with relatively greater reductions in the B (P < 0.05) and A+B groups (P < 0.03) vs A. An increase in mean HDL-cholesterol from baseline was noted in the B and A+B groups; P < 0.05), but not in the A group. A trend was also observed between the rise in HDL-cholesterol and the reduction in MA in the B and A+B groups. Additionally, only the B group exhibited a decrease in the median value of Lp(a) (P < 0.05). These data support the concept that ACE inhibition with B reduces the atherogenic profile by decreasing Lp(a) and increasing HDL-cholesterol, the latter being correlated with reductions in MA. While A+B exhibited similar trends in lipid subfractions and MA as B, this group had the greatest reduction in systolic blood pressure of the three groups. Thus, use of A+B offers the benefits of a decreased atherogenic profile with a higher probably of achieving goal blood pressure as recommended by national guidelines.",2002.0,0,0
923,11897766,Factors related to the occurrence of microalbuminuria during antihypertensive treatment in essential hypertension.,Josep Redon; Eduardo Rovira; Amparo Miralles; Raul Julve; Jose M Pascual,"The objective of the study was to assess the factors related to the occurrence of microalbuminuria during the follow-up of a young adult group with essential hypertension that had not been previously treated. Normo-albuminuric essential hypertensives, <50 years old, who had not been previously treated with antihypertensive drugs and who did not have diabetes mellitus were included. After the initial evaluation, patients were treated using only nonpharmacological measures (n=62), beta-blockers (n=38), ACE inhibitors (n=64), calcium channel blockers (n=8), and several classes (n=15). Measurements were taken for office blood pressure, biochemical profile, and 24-hour urinary albumin excretion at the beginning of the study and were measured yearly during an average of 2.7+/-1.2 years of follow-up. Among the 187 patients included, 22 (11,7%) developed microalbuminuria (progressors, 4.4/100 patients/y). No differences were present between progressors and those who remained normo-albuminuric (nonprogressors) in terms of age, gender, body mass index, disease duration, blood pressure values, biochemical profile, familial history of diabetes or hypertension, smoking habits, or the presence of EKG left ventricular hypertrophy. The group with the lowest progression rate was the patients treated with ACE inhibitors (n=5; 2.9/100 patients/y), followed by the diet group (n=5; 3.3/100 patients/y) and the beta-blockers group (n=5; 4.1/100 patients/y). When we excluded patients treated with calcium channel blockers or those who changed over time between different classes of treatment, no significant differences in the incidence of microalbuminuria were observed among the groups. Progressors showed higher slopes of fasting glucose (4.78+/-11.4 versus 0.50+/-6.8 mg/y, P<0.02) and uric acid (0.58+/-0.93 versus 0.05+/-1.10 mg/y, P<0.03) compared with the slopes of nonprogressors. Both the slopes for glucose and systolic blood pressure over time were associated independently with the slope of the logarithm of urinary albumin excretion when adjusted for age, gender, and treatment groups. Cox proportional hazard model for progression of microalbuminuria showed that baseline urinary albumin excretion (risk ratio [RR]=1.06; confidence interval [CI] 95%, 1.01 to 1.11), slope for systolic blood pressure (RR=1.11; CI 95%, 1.03 to 1.20), and slope for glucose (RR=1.08; CI 95%, 1.03 to 1.14) were independently associated to the development of microalbuminuria. In conclusion, in a group of young adults with essential hypertension that had not been previously treated, the main factors influencing the occurrence of microalbuminuria during antihypertensive treatment were the values of microalbuminuria at baseline and the slopes for systolic blood pressure and fasting glucose.",2002.0,0,0
924,11903350,A prospective evaluation of the angiotensin-converting enzyme D/I polymorphism and left ventricular remodeling in the 'Healing and Early Afterload Reducing Therapy' study.,R Y L Zee; S D Solomon; U A Ajani; M A Pfeffer; K Lindpaintner; Heart investigators,"The D/I (deletion, D, insertion, I) polymorphism of the angiotensin-converting enzyme (ACE) gene has been extensively studied for its association with a number of cardiovascular and other disease states. However, its potential association with differential clinical efficacy of ACE inhibitors (ACE-I) administered to patients who had suffered a myocardial infarction (MI), i.e. the prevention of left ventricular (LV) remodeling, has so far not been specifically studied. The aim of the study was to investigate whether the D/I polymorphism of the ACE gene is associated with the incidence of post-MI LV remodeling in patients drawn from the 'Healing and Early Afterload Reducing Therapy' (HEART) Study. The ACE D/I polymorphism was characterized by the polymerase chain reaction (PCR) in 265 subjects from the 'Healing and Early Afterload Reducing Therapy' Study, a double-blind, placebo-controlled trial with the objective of determining whether early or delayed administration of the ACE-I, ramipril, in patients with acute anterior wall MI would be optimal in reducing LV enlargement. Selected frequencies for the ACE D and I alleles were 0.59 and 0.41 (placebo-high dose group), 0.56 and 0.44 (low dose-low dose group), and, 0.60 and 0.40 (high dose-high dose group), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for an association between genotype and outcome regarding LV size or function, nor with the initial blood pressure response after ACE-I administration (adjusted for covariates). Our data provide no evidence for an association of the ACE D/I polymorphism with the risk of LV remodeling post-MI in the presence of ACE-I therapy, and therefore do not suggest that differential clinical efficacy of ACE-inhibitors is related to this genetic marker.",2002.0,0,0
925,11907286,Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.,Arthur J Moss; Wojciech Zareba; W Jackson Hall; Helmut Klein; David J Wilber; David S Cannom; James P Daubert; Steven L Higgins; Mary W Brown; Mark L Andrews; Multicenter Automatic Defibrillator Implantation Trial II Investigators,"Patients with reduced left ventricular function after myocardial infarction are at risk for life-threatening ventricular arrhythmias. This randomized trial was designed to evaluate the effect of an implantable defibrillator on survival in such patients. Over the course of four years, we enrolled 1232 patients with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned in a 3:2 ratio to receive an implantable defibrillator (742 patients) or conventional medical therapy (490 patients). Invasive electrophysiological testing for risk stratification was not required. Death from any cause was the end point. The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups. During an average follow-up of 20 months, the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group. The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 (95 percent confidence interval, 0.51 to 0.93; P=0.016). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, ejection fraction, New York Heart Association class, and the QRS interval. In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.",2002.0,0,0
926,11909785,Use of ramipril in preventing stroke: double blind randomised trial.,Jackie Bosch; Salim Yusuf; Janice Pogue; Peter Sleight; Eva Lonn; Badrudin Rangoonwala; Richard Davies; Jan Ostergren; Jeff Probstfield; HOPE Investigators. Heart outcomes prevention evaluation,"To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke. Randomised controlled trial with 2x2 factorial design. 267 hospitals in 19 countries. 9297 patients with vascular disease or diabetes plus an additional risk factor, followed for 4.5 years as part of the HOPE study. Stroke (confirmed by computed tomography or magnetic resonance imaging when available), transient ischaemic attack, and cognitive function. Blood pressure was recorded at entry to the study, after 2 years, and at the end of the study. Reduction in blood pressure was modest (3.8 mm Hg systolic and 2.8 mm Hg diastolic). The relative risk of any stroke was reduced by 32% (156 v 226) in the ramipril group compared with the placebo group, and the relative risk of fatal stroke was reduced by 61% (17 v 44). Benefits were consistent across baseline blood pressures, drugs used, and subgroups defined by the presence or absence of previous stroke, coronary artery disease, peripheral arterial disease, diabetes, or hypertension. Significantly fewer patients on ramipril had cognitive or functional impairment. Ramipril reduces the incidence of stroke in patients at high risk, despite a modest reduction in blood pressure.",2002.0,0,0
927,11910310,Dissociation between blood pressure reduction and fall in proteinuria in primary renal disease: a randomized double-blind trial.,PROCOPA Study Group,"Guidelines recommend lower threshold and goal blood pressure (BP) for patients with proteinuria. BP reduction could be accompanied by a different fall in proteinuria depending of the antihypertensive drug. The objective was to compare proteinuria reduction when BP is lowered to the same level with different drugs. Prospective, randomized, double-blind, controlled trial. 12 Spanish centres. A total of 119 patients with primary renal disease, blood pressure > 130/85 mmHg, proteinuria > 1 g/day, and creatinine clearance > or = 50 ml/min. After a 4-week run-in placebo period, patients were randomized to: atenolol 50 mg/day; trandolapril 2 mg/day; verapamil 240 mg/day or verapamil 180 + trandolapril 2 mg/day combination; forced double-dose titration was carried out at the 4th week. Treatment duration was 6 months. Changes in BP, 24 h proteinuria, serum albumin and calcium. BP was significantly reduced with the four treatments [SBP/DBP (mmHg]: atenolol 12.2/9.9; trandolapril 12.9/9.3; verapamil 8.2/7.9 and verapamil + trandolapril 13.6/11.3) without differences between them. A significant fall in proteinuria was seen in the trandolapril, 40.2% [95% confidence interval (CI) 24.3-56.2%], and verapamil + trandolapril groups, 48.5% (95% CI, 31.7-64.3%) accompanied with increases in serum albumin (trandolapril: from 3.86 +/- 0.64 to 4.03 +/- 0.67 g/dl; verapamil + trandolapril: from 4.15 +/- 0.58 to 4.40 +/- 0.51 g/dl). In patients with proteinuric primary renal disease, adequate dose titration of antihypertensive drugs may provide a substantial BP reduction. Only angiotensin-converting enzyme inhibitor (trandolapril) treatment, alone or better combined with verapamil, reduces proteinuria and increases serum albumin.",2002.0,0,0
928,11910315,"Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs.",Alison J Deary; Anne L Schumann; Helen Murfet; Stephen F Haydock; Roger S-Y Foo; Morris J Brown,"Hypertension guidelines recommend initial treatment with a beta-blocker or diuretic and adding the other drug where blood pressure is not controlled. We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient's response, and suggest a more rational approach to choosing best treatment. Thirty-four young hypertensives (age 28-55, median 47) rotated in a double-blind, Latin-square, crossover fashion through 6 weeks of treatment each with amlodipine, doxazosin, lisinopril, bisoprolol, bendrofluazide and placebo. Blood pressure was measured at each visit. 'Best' drug, defined by efficacy and tolerability, was repeated at the end. Rotation doubled the number of patients reaching target blood pressure (systolic < 140 mmHg) on one drug (P = 0.03). All five drugs were represented among the 'best' drugs. In six patients, the blood pressure on 'best' drug was at least 10 mmHg lower than on any other. Response to the 'best' drug was highly correlated (r = 0.79) with its previous administration. By contrast, there were only weak correlations between responses to pairs of drugs, except for angiotensin-converting enzyme (ACE) inhibitor (A) with beta-blocker (B), and calcium blocker (C) with diuretic (D) - each r = 0.71, P < 0.005). In these young patients, the majority of patients (23/34) responded best to a drug suppressing the renin system (A and B). Patients vary reproducibly in their response to initial treatment, and switching among drugs can increase the efficacy of monotherapy. The results support an AB/CD scheme for choosing therapy, in which the first drug is taken from one of these pairs, and uncontrolled patients switch to one of the other pair.",2002.0,0,0
929,11912272,ACE inhibitors versus AT(1) receptor antagonists in patients with chronic renal disease.,Karl F Hilgers; Johannes F E Mann,,2002.0,0,0
930,11918132,Reversal of left ventricular hypertrophy with the ACE inhibitor moexipril in patients with essential hypertension.,Roland Asmar; Fady Sayegh; Wiesława Tracz; Marta Hlawaty; Maria Olszowska; Michel Jourde; Marc Vincent; Bernard Goujoun; Joao Maldonado,,2002.0,0,0
931,11918155,Additional effects of irbesartan when compared to captopril in the prevention of post-infarction left ventricular dilatation.,Alexander N Parkhomenko; Oleg I Irkin; Sergey P Kushnir; Zhanna V Bryl; Oksana Soliarik; Lilia V Shkliar,,2002.0,0,0
932,11918753,Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension.,Christian Delles; Johannes Jacobi; Stefan John; Ingrid Fleischmann; Roland E Schmieder,"Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent. Enalapril and eprosartan, alone and in combination, were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension. Twenty male, white patients (27 +/- 1 years) with mild essential hypertension (143 +/- 11/95 +/- 6 mm Hg) were included in a double-blind, randomized, placebo-controlled, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or combination of both drugs (10 and 300 mg/day, respectively) each over a one week period followed by a two-week washout phase. After each study phase the glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined. Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). After one week of therapy, the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo (P < 0.01). Neither enalapril alone (-2 +/- 2/1 +/- 2 mm Hg, NS vs. placebo) nor eprosartan alone (-1 +/- 1/0 +/- 2 mm Hg, NS vs. placebo) had a clear-cut significant effect on casual blood pressure. In the combination phase, RPF increased by 123 +/- 36 mL/min (P < 0.01). Neither enalapril alone (+59 +/- 46 mL/min, P = 0.21) nor eprosartan alone (+113 +/- 51 mL/min, P = 0.06) had a clear-cut significant effect on RPF. Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination (r = 0.70, P < 0.01) and eprosartan phase (r = 0.86, P < 0.001), but not in the enalapril phase (r = -0.44, P = 0.10). Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase. GFR was unaffected by any treatment. In contrast to the effects of either substance alone, a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion. The effects of eprosartan on RPF are mediated, at least in part, by an increased bioavailability of nitric oxide in the renal vasculature.",2002.0,0,0
933,11926863,Is there proof that captopril causes proteinuria?,Karl Engelman,,2002.0,0,0
934,11927797,Treating hypertension in the patient who has had a stroke.,Borut Cizman; Raymond R Townsend,,2002.0,0,0
935,11933575,Assessment of platelet numbers and morphology in the peripheral blood smear.,Alvaro Moreno; David Menke,"Automated systems are currently in widespread use for the assessment of patients' complete blood counts. The evaluation of the peripheral blood smear, however, still constitutes a pivotal tool in the evaluation of patients with hematologic disorders. This article focuses on disorders affecting the number or morphology of platelets as assessed by evaluation of a peripheral blood smear and also outlines some of their important clinical findings.",2002.0,0,0
936,11934344,Treatment options for renovascular hypertension.,J David Spence,"Renovascular hypertension is usually caused by atherosclerotic narrowing of the origin of the renal artery and is much more common than is thought among patients with peripheral vascular disease, carotid stenosis or heart failure. Renovascular hypertension must be distinguished from renal artery stenosis. In true renovascular hypertension, the kidney takes charge of the blood pressure and will do what it takes to push blood pressure high enough to force blood through the blocked artery. This can be diagnosed with functional tests that measure glomerular filtration rate before and after blockade of the renin-angiotensin system with angiotensin converting enzyme inhibitors or antagonists of the AT(1) subtype of the angiotensin receptor. There is insufficient data on which to make evidence-based recommendations on the management of renovascular hypertension. Only two randomised trials exist of angioplasty versus medical therapy and of these the larger was severely contaminated by angioplasty among the group initially assigned to medical therapy. Only one trial exists of angiotensin converting enzyme inhibition versus alternative medical therapy. The drugs that are most effective in medical management of renovascular hypertension--angiotensin converting enzyme inhibitors and angiotensin receptor-1 blockers--tend to be avoided because of fear of a very rare complication (acute renal failure in patients with severe stenosis of both renal arteries, or the artery to a single remaining kidney). This fear is misplaced not only because it is rare (< 5% of patients with renovascular hypertension) but because it is reversible and treatable by revascularisation. Patients with renovascular hypertension should be evaluated by nuclear medicine differential glomerular filtration rate, enhanced by blockers of the renin-angiotensin system. If medical therapy is ineffective or causes severe impairment of renal function, revascularisation is required. Some experts favour surgical revascularisation because of occasional angioplasty failure and the risk of deterioration of renal function after angioplasty.",2003.0,0,0
937,11935151,Angiotensin converting enzyme inhibiting therapy is associated with lower vitreous vascular endothelial growth factor concentrations in patients with proliferative diabetic retinopathy.,I M Hogeboom van Buggenum; B C P Polak; J W M Reichert-Thoen; W A E J de Vries-Knoppert; V W M van Hinsbergh; G J Tangelder,"Vascular endothelial growth factor (VEGF) is thought to be instrumental in the progression of diabetic retinopathy. Indications exist that the renin-angiotensin system is involved in VEGF overexpression. We assessed the vitreous VEGF concentrations in patients and related them to anti-hypertensive treatment, with special interest in the use of ACE-inhibitors. Samples of vitreous fluid (10-80 microl) were obtained from 39 patients both with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus and 11 non-diabetic patients undergoing intra-ocular surgery. The VEGF-A concentrations were assessed by immunoassay. Control patients and patients without proliferative diabetic retinopathy ( n = 8) had low and comparable VEGF concentrations (medians < 50 pg/ml). In contrast, patients with proliferative diabetic retinopathy ( n = 31) had high vitreous VEGF concentrations (median 1134 pg/ml), which showed a negative correlation with the use of ACE inhibiting medication (Spearman rank-R = - 0.54; p = 0.002, n = 13). Diastolic and systolic blood pressure did not differ significantly between the two subgroups with proliferative diabetic retinopathy, i. e. those patients receiving ACE-inhibition (medians 88/160 mm Hg, respectively) and the others (90/160). For the mostly used ACE-inhibitor in the proliferative diabetic retinopathy group, i. e. enalapril ( n = 8), a linear dose-effect relation was observed (-20 +/- 4 pg x ml(-1) x mg(-1) x day(-1); p = 0.024; coefficient +/- SEM). Treatment with ACE-inhibitors attenuates retinal overexpression of VEGF-A in patients with proliferative diabetic retinopathy, probably by interference with a local effect of angiotensin II.",2002.0,0,0
938,11937741,Fosinopril as a possible pemphigus-inducing drug.,A Parodi; E Cozzani; G Milesi; M Drosera; A Rebora,"Fosinopril has recently been added to the angiotensin-converting enzyme inhibitors inducing pemphigus. The observation of a patient in whom pemphigus vulgaris (PV) worsened after taking fosinopril prompted us to study an experimental way to assess its responsibility. Slices of normal human skin (NHS) were simultaneously incubated for 2, 6, 12 and 24 h at 4 degrees C with progressively diluted fosinopril and captopril solutions and used as indirect immunofluorescence (IIF) substrates for 2 sera containing anti-desmoglein-3 (anti-Dsg3) antibodies at a dilution of 1/160. With captopril, IIF was negative, irrespective of dilution and time of incubation. Only at 1/40,000 dilution was IIF positive. With fosinopril, IIF was negative for the 2- and 6-hour-long incubations but turned positive after 12 h and so remained with all other solutions and incubation times. IIF negativity with captopril suggests that anti-Dsg3 antibodies contained in the PV sera were unable to find molecules in NHS to bind to. Captopril would therefore induce acantholysis by blocking the adhesion molecules. With fosinopril, instead, a partial block of the adhesion molecules was seen only with the very concentrated solution, unlikely to occur in vivo. Fosinopril, therefore, is probably unable to block the adhesion molecules in vivo. Our method might be used to verify the acantholytic properties of a drug.",2002.0,0,0
939,11940105,Vasopeptidase inhibitors and their potential role in diabetes.,T A Chowdhury; T Khan,,2002.0,0,0
940,11950623,Vasopeptidase inhibitors: a new class of dual zinc metallopeptidase inhibitors for cardiorenal therapeutics.,Giuseppe Molinaro; Jean-Lucien Rouleau; Albert Adam,"Vasopeptidase inhibitors are a new class of drugs that simultaneously inhibit angiotensin-I-converting enzyme and neutral endopeptidase 24.11, two metallopeptidases responsible for the breakdown of different vasoactive peptides. At least ten vasopeptidase inhibitors are in various stages of development and results obtained in preclinical and clinical studies indicate a promising future for the treatment of hypertension, heart failure and renal disease. However, like angiotensin-I-converting-enzyme inhibitors, vasopeptidase inhibitors are characterized by acute and chronic side-effects that need to be clarified.",2002.0,0,0
941,11950625,Current treatment and future directions in heart failure.,Gretchen Wells; William C Little,"Recent research in the pathophysiology of congestive heart failure has focused on the blockade of neurohormonal systems. Large clinical trials have clearly demonstrated morbidity and mortality benefits of angiotensin-converting-enzyme inhibitors and beta blockers. Indeed, all patients with heart failure should be treated with these agents unless there is a specific contraindication otherwise. Despite this treatment, however, mortality from heart failure remains high. Current investigation is now focused on other pathophysiological mechanisms and the interruption of these pathways.",2002.0,0,0
942,11955029,Chronic renal diseases: renoprotective benefits of renin-angiotensin system inhibition.,Giuseppe Remuzzi; Piero Ruggenenti; Norberto Perico,"Progression to renal parenchymal damage and end-stage renal disease, which seems to be largely independent of the initial insult, is the final common pathway for chronic, proteinuric nephropathies in animals and humans. The key event is enhanced glomerular capillary pressure; this impairs glomerular permeability to proteins and permits excessive amounts of proteins to reach the lumen of the proximal tubule. The secondary process of reabsorption of filtered proteins can contribute to renal interstitial injury by activating intracellular events, including upregulation of the genes encoding vasoactive and inflammatory mediators. Both interstitial inflammation and progression of disease can be controlled by such drugs as angiotensin-converting enzyme inhibitors, which strengthen the glomerular permeability barrier to proteins and thereby limit proteinuria and filtered protein-dependent inflammatory signals. Clinical data strongly suggest that remission can now be achieved in some patients with chronic renal disease. Because of the current lag time between starting treatment and remission, however, a substantial proportion of patients still progress to end-stage renal disease before renal function begins to stabilize. A multimodal approach that centers on reducing or removing all risk factors associated with the progression of renal disease may decrease the time to remission of the disease for most patients with proteinuric nephropathies.",2002.0,0,0
943,11959056,Nonchemotherapy drug-induced agranulocytosis in elderly patients: the effects of granulocyte colony-stimulating factor.,Emmanuel Andrès; Jean Emmanuel Kurtz; Catherine Martin-Hunyadi; Georges Kaltenbach; Martine Alt; Jean Christophe Weber; Jean Sibilia; Jean Louis Schlienger; Patrick Dufour; F rédéric Maloisel,"Elderly patients with nonchemotherapy drug-induced agranulocytosis present commonly with severe infections, and have a mortality of at least 20%. We studied whether granulocyte colony-stimulating factor (G-CSF), a hematopoietic growth factor that shortens the duration of neutropenia, is useful in these patients. We studied 54 patients > or =65 years of age who had drug-induced agranulocytosis, some of whom had been treated with G-CSF. We determined the times until hematologic recovery (defined as a neutrophil count >1.5 x 10(9)/L), tolerance of G-CSF, and clinical outcomes. Of the 54 patients, 20 received G-CSF. Two patients who had not been treated with G-CSF died of uncontrolled septic shock and extensive pneumonia. The mean (+/- SD) time until hematologic recovery was significantly less in patients treated with G-CSF (6.6 +/- 3.9 days vs. 8.8 +/- 4.9 days, P <0.04). Compliance with G-CSF therapy was good; only mild flu-like symptoms and transient bone pain were reported in 12 patients. Our findings suggest that G-CSF therapy may be beneficial in the management of drug-induced agranulocytosis in elderly patients.",2002.0,0,0
944,11959345,"Double-blind, crossover, comparative study of doxazosin and enalapril in the treatment of hypertension in renal transplant patients under cyclosporine immunosuppression.",A Martínez-Castelao; M Hueso; V Sanz; J Rejas; J Sarrias; J Alsina; J M Grinyó,,2002.0,0,0
945,11967252,Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors.,William B White; Jeffrey Kent; Addison Taylor; Kenneth M Verburg; James B Lefkowith; Andrew Whelton,"Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.",2002.0,0,0
946,11967807,Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction.,M de Gasparo; P Hess; B Nuesslein-Hildesheim; P Bruneval; J P Clozel,"There is increasing evidence to suggest endothelial dysfunction as a critical factor in vascular diseases. Genetically predisposed spontaneously hypertensive rats (SHR) treated with inhibitors of nitric oxide (NO) synthase, develop a severe hypertensive nephrosclerosis without the necessity for surgical reduction in renal mass, nephrectomy, renal infarction or nephrotoxic drugs. In these animals, endothelial dysfunction is considered a valid model for assessment of the efficacy of cardiovascular therapy. SHR were treated with either the angiotensin-converting enzyme inhibitor enalapril or the angiotensin II (Ang II) AT(1)-receptor antagonist (AIIA) valsartan at sub-hypotensive doses and the effects on survival rates, cardiac and renal changes were monitored. Rats treated with valsartan, alone or in combination with enalapril, showed markedly higher survival rates (67-85%, respectively) than untreated animals (37%) or those treated with enalapril alone (55%). Valsartan at a dose which attenuated blood pressure increase led to even greater survival rates (95%). Despite these improved survival rates, at non-hypotensive doses the drugs had no effect on histological appearance, nor was kidney function improved. Plasma creatinine levels were reduced by valsartan, alone or in combination with enalapril, but proteinuria persisted with all treatments over the 12 weeks of the study. Aldosterone levels were significantly reduced by all treatments. The results suggest a beneficial role for endothelium in hypertension. Reduced renal perfusion pressure probably underlies the beneficial renal effects of high-dose valsartan.",2002.0,0,0
947,11967825,Should the use of short acting angiotensin-converting enzyme inhibitors be abandoned?,A Erman; G Boner; D J van Dijk,"Angiotensin-converting enzyme inhibitors (ACE-I) have different modes of action and different durations of inhibition. The effects of ACE-I on the various components of the renin-angiotensin system (RAS) at trough hours were studied in patients with diabetes mellitus receiving long-term ACE-I treatment. Out of 86 Type 1 and 2 diabetic patients, 49 were untreated, 25 received captopril and 12 received enalapril as chronic treatment. Blood for the determination of plasma renin activity (PRA), serum ACE activity and plasma angiotensin II (Ang II) was drawn in the morning (0700-0900 hours) after an overnight fast, about 12 hours after the last dose. PRA and Ang II were measured by RIA and serum ACE activity was assayed by a radiometric assay using (3)H-hippuryl-glycyl-glycine as a substrate. Mean age was significantly greater in the enalapril-treated patients. Systolic and diastolic blood pressures were not different between the captopril-treated and untreated groups. Serum ACE activity in the captopril-treated diabetic patients was 101.5+/-42.5 nmol/mL/min, values obtained in untreated diabetic patients (101.4+/-25.2 nmol/mL/min). In contrast, ACE activity in the enalapril-treated patients was significantly reduced (5.5+/-7.5 nmol/mL/min) compared with untreated and captopril-treated patients (p<0.00001). PRA values in the ACE-I treated patients were significantly increased. Plasma Ang II levels were significantly increased in the captopril-treated vs. untreated patients (65.1+/-50.2 vs. 36.2+/-31.7 pg/mL, p=0.006), whereas the values in the enalapril-treated patient were slightly, but not significantly, reduced (23.8+/-21.4 pg/mL). CONCLUSIONS Trough serum ACE activity is not suppressed in diabetic patients receiving captopril, compared with those receiving enalapril and we thus question the use of short acting ACE-I in these patients.",2002.0,0,0
948,11973410,Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition.,Yukihito Higashi; Shota Sasaki; Keigo Nakagawa; Masashi Kimura; Satoshi Sasaki; Kensuke Noma; Keiko Hara; Hideo Matsuura; Chikara Goto; Tetsuya Oshima; Kazuaki Chayama,"The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and severe, n = 17 randomly assigned to treatment with either imidapril or amlodipine for 24 weeks in a double-blind fashion during reactive hyperemia and after sublingual administration of nitroglycerin. Imidapril augmented the FBF response to reactive hyperemia after 24 weeks of treatment in the mild and moderate hypertensive groups, but not in the severe hypertensive group. The augmentation of the FBF response to reactive hyperemia induced by imidapril was significantly greater in the moderate hypertensive group than in the mild hypertensive group. Amlodipine did not alter the FBF response to reactive hyperemia. The increase in FBF after the sublingually administered nitroglycerin was similar in all groups. The infusion of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, abolished the enhancement of reactive hyperemia in the mild and moderate hypertensive groups treated with imidapril. These findings suggest that the effects of imidapril on endothelial function are affected by the severity of hypertension and that angiotensin-converting enzyme inhibitor-induced augmentation of reactive hyperemia may be due to increased nitric oxide production.",2002.0,0,0
949,11975824,Lercanidipine: a novel dihydropyridine calcium-channel blocker.,M Epstein,"Calcium-channel blockers (CCBs) have been used for the treatment of hypertension for more than 20 years, and recent clinical trials support the efficacy and safety of long-acting dihydropyridine (DHP) CCBs for a wide spectrum of hypertensive patients, including diabetic hypertensive patients. DHP CCBs are effective agents overall and are particularly effective when used in combination with other agents. Lercanidipine is a novel DHP CCB effective for the treatment of mild-to-moderate hypertension. Compared with other DHP CCBs, lercanidipine has a molecular design that imparts greater solubility within the arterial cellular membrane bilayer, membrane-controlled kinetics, and a high cholesterol tolerance factor. These favorable membrane-controlled kinetics impart a gradual onset of vasodilation and a long duration of action. Further, the unique pharmacokinetic and pharmacodynamic properties of lercanidipine appear to contribute to its efficacy and favorable safety profile. In clinical trials in the treatment of mild-to-moderate hypertension, lercanidipine was administered at a starting dose of 10 mg once daily, and increased to 20 mg once daily for nonresponders. Studies have shown that lercanidipine has a 24-hour antihypertensive effect and causes no significant increase in heart rate. Lercanidipine has been shown to be effective in a wide range of hypertensive patients, including mild-to-moderate hypertension, severe hypertension, the elderly, and those with isolated systolic hypertension. It is associated with a low rate of adverse events. Because of its efficacy and favorable safety profile, lercanidipine has the potential to improve blood pressure control in a wide range of patients, including those who have not responded to, or who have been unable to tolerate, other antihypertensive agents.",2002.0,0,0
950,11978224,"In patients with diabetes and hypertension, should treatment start with an ACE inhibitor instead of a diuretic or beta blocker?",Paula S Mackrides; Allen F Shaughnessy,,2002.0,0,0
951,11980521,Timing of new black box warnings and withdrawals for prescription medications.,Karen E Lasser; Paul D Allen; Steffie J Woolhandler; David U Himmelstein; Sidney M Wolfe; David H Bor,"Recently approved drugs may be more likely to have unrecognized adverse drug reactions (ADRs) than established drugs, but no recent studies have examined how frequently postmarketing surveillance identifies important ADRs. To determine the frequency and timing of discovery of new ADRs described in black box warnings or necessitating withdrawal of the drug from the market. Examination of the Physicians' Desk Reference for all new chemical entities approved by the US Food and Drug Administration between 1975 and 1999, and all drugs withdrawn from the market between 1975 and 2000 (with or without a prior black box warning). Frequency of and time to a new black box warning or drug withdrawal. A total of 548 new chemical entities were approved in 1975-1999; 56 (10.2%) acquired a new black box warning or were withdrawn. Forty-five drugs (8.2%) acquired 1 or more black box warnings and 16 (2.9%) were withdrawn from the market. In Kaplan-Meier analyses, the estimated probability of acquiring a new black box warning or being withdrawn from the market over 25 years was 20%. Eighty-one major changes to drug labeling in the Physicians' Desk Reference occurred including the addition of 1 or more black box warnings per drug, or drug withdrawal. In Kaplan-Meier analyses, half of these changes occurred within 7 years of drug introduction; half of the withdrawals occurred within 2 years. Serious ADRs commonly emerge after Food and Drug Administration approval. The safety of new agents cannot be known with certainty until a drug has been on the market for many years.",2002.0,0,0
952,11981287,Renal aspects of the term and preterm infant: a selective update.,Alfred Drukker; Jean-Pierre Guignard,"This review discusses new aspects of normal and abnormal renal development that expand insight into the adaptation of the neonatal kidneys to the stress of extrauterine life. Highlighted are some pitfalls in measuring glomerular filtration rate in the neonate mainly caused by postnatal fluctuations in serum creatinine levels. Serum creatinine levels are correlated with the authors' recent finding of tubular reabsorption of creatinine in the immature neonatal kidney. Renal maldevelopment in premature and small-for-date babies has been shown related to serious medical problems in adult life, including hypertension. This finding presents the pediatrician with a new role in the time-honored vocation of preventing disease. Mutations in several genes may be responsible for most cases of congenital or hereditary renal aberrations. Two renal disorders, congenital nephrotic syndrome and neonatal acute renal failure, and one form of treatment modality of newborn infants, renal replacement therapy, are discussed in detail. These conditions are rare in general pediatric practice, but they illustrate some of the new developments in the renal care of the newborn. A word of caution is offered about the use of nonsteroidal anti-inflammatory drugs during pregnancy and the newborn period. All nonsteroidal anti-inflammatory drugs administered indirectly to the unborn fetus and directly to the young newborn impair renal structure (fetus) and function (both fetus and newborn). The new data have been obtained with genetic and molecular biology techniques and with established methods of developmental renal physiology. A better understanding of the pathogenesis of neonatal renal disorders will result in new diagnostic procedures and improved preventive and therapeutic possibilities relevant to the neonate with a renal disorder.",2002.0,0,0
953,11981289,Pediatric hypertension: recent literature.,Umbereen S Nehal; Julie R Ingelfinger,"This article reviews selected recent literature specifically concerning pediatric hypertension, much of which has focused on measurement and monitoring of blood pressure, as well as on evaluating antihypertensive medications. Normative data for blood pressure in children have been widely available for some time, based upon seated in-office measurements. In recent years, ambulatory blood pressure monitoring (ABPM), facilitated by user-friendly instrumentation, has become more commonplace, though norms are not based on large populations. However, ABPM has important uses in assessing blood pressure as well as in monitoring antihypertensive. This review discusses issues involved in determining blood pressure, as well as the utility of ABPM in several situations. Recent developments concerning pediatric antihypertensive therapy are considered, as well as new information relevant to the diagnosis, course and treatment of hypertension in children and adolescents.",2002.0,0,0
954,11984065,Perindopril: possible use in cancer therapy.,Hitoshi Yoshiji; Shigeki Kuriyama; Hiroshi Fukui,"Since angiogenesis is essential for the growth of any solid tumor, emerging efforts are being made to develop antiangiogenic therapy. To date, however, no antiangiogenic agent has become widely available for the clinical setting. Angiotensin I-converting enzyme (ACE) inhibitors are commonly used as antihypertensive agents and it has recently been suggested that they decrease the risk of cancer. Studies have found that an ACE inhibitor, perindopril, is a potent inhibitor of experimental tumor development and angiogenesis at a clinically comparable dose. The potent angiogenic factor, vascular endothelial growth factor (VEGF), is significantly suppressed by perindopril and also inhibits VEGF-induced tumor growth. In vitro studies showed that perindopril is not cytotoxic to either tumor cells or endothelial cells. Since perindopril is already in widespread clinical use without serious side effects, it may represent a potential new strategy for anticancer therapy.",2002.0,0,0
955,11989138,Tinnitus: an update.,D Roy; R Chopra,"Tinnitus is the perceived sensation of sound in the absence of acoustic stimulation. It is the commonest otological disorder referred to either the general practitioner or ear-nose-throat surgeon. This short review examines prevalence, aetiology, associated clinical symptoms, investigations and management. Despite current usage of a vast number of treatment modalities there remains no specific cure for the condition. However, there is currently great emphasis on tinnitus retraining therapy (TRT) in its management. The applications and results of TRT have, indeed, been encouraging--and are also briefly discussed here.",2002.0,0,0
956,11990112,Enalapril in the treatment of chronic mountain sickness.,M Vargas; F Leon-Velarde; C Monge-C; E Orozco; L Rey,,2002.0,0,0
957,11991216,Losartan and perindopril effects on plasma plasminogen activator inhibitor-1 and fibrinogen in hypertensive type 2 diabetic patients.,Roberto Fogari; Amedeo Mugellini; Annalisa Zoppi; Luca Corradi; Paola Preti; Pierangelo Lazzari; Giuseppe Derosa,"This study compared the effects of losartan and perindopril on plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in hypertensive type 2 diabetic patients. We studied 85 nonsmoking outpatients, aged 46 to 64 years, with mild to moderate essential hypertension (diastolic blood pressure [BP] > 90 and < 110 mm Hg) and well controlled type 2 diabetes mellitus. After a 4-week washout placebo period, patients were randomized to received perindopril 4 mg once daily (n = 42) or losartan 50 mg once daily (n = 43) for 12 weeks according to a double-blind, parallel-group design. At the end of the placebo and active treatment periods, BP was measured and plasma PAI-1 and fibrinogen were evaluated. Both perindopril and losartan reduced systolic and diastolic BP values (-16/15 mm Hg and -15/14, respectively; P < .001 v placebo), with no difference between the two treatments. Plasma PAI-1 was reduced by perindopril (-10 ng/dL, P = .028 v placebo) but not by losartan (+4 ng/dL, NS), the difference between the two treatments being statistically significant (P < .01). Plasma fibrinogen showed no significant change with both drugs, although a decreasing trend was noted with perindopril. These findings indicate that perindopril but not losartan decreases PAI-1 in hypertensive type 2 diabetic patients, which suggests that the PAI-1 lowering effect is unrelated with AT, receptor blockade and could rather be due to the fact that the endothelial receptors that mediate PAI-1 expression in response to angiotensin II are not type 1 receptor subtypes. Different effects of the two drugs on the bradykinin system might also be implicated.",2002.0,0,0
958,11991217,Reduction in arterial stiffness with angiotensin II antagonist is comparable with and additive to ACE inhibition.,Azra Mahmud; John Feely,"We measured the effects of angiotensin II blockade on arterial stiffness, augmentation index (AI%), pulse wave velocity (PWV), and blood pressure (BP) in 12 hypertensive patients (mean 49 +/- 11 years) in a 4-week, randomized, cross-over study comparing valsartan 160 mg/day with captopril 100 mg/day, with a 2-week washout period. Subsequently both therapies were combined. Reductions in PWV and AI% remained significant when corrected for BP. Combined therapy reduced PWV and AI% (P < .05) more than monotherapy, even when corrected for BP. The study shows that angiotensin receptor antagonists reduce arterial stiffness in hypertension comparable with and possibly additive to angiotensin converting enzyme inhibition.",2002.0,0,0
959,11996200,"How to prevent, recognize, and treat drug-induced nephrotoxicity.",Xiaoqing Guo; Chike Nzerue,"Many drugs can injure the kidneys, but they cause renal injury via only a few common mechanisms. Many patients who develop renal injury after drug exposure have identifiable risk factors that could be modified or that should preclude the use of these drugs in the first place.",2002.0,0,0
960,11996651,Angiotensin II Type 1 receptor antagonists in chronic heart failure.,Petra A Thürmann; D Collette,"Angiotensin II Type 1 receptor antagonists share most but not all of their pharmacological actions with angiotensin-converting enzyme inhibitors. The latter belong to standard heart failure therapy, with proven benefit in terms of morbidity and mortality. Promising data have been provided for angiotensin II Type 1 receptor antagonists in experimental models of heart failure. In patients with hypertension and those with diabetic nephropathy, favourable results have been observed with regards to blood pressure control, reversibility of structural changes or prevention of progression of disease. The currently available clinical trials in heart failure patients with angiotensin II Type 1 receptor antagonists suggest that they may be equivalent to angiotensin-converting enzyme inhibitors, but superiority has not been proven. There is no doubt about their effectiveness with regards to symptoms; however, their effect on hospitalisation and mortality is not unequivocally demonstrated. Further trials are warranted, particularly to define their role in comparison with and in addition to angiotensin-converting enzyme inhibitors and to further characterise heart failure patient populations who derive benefit from angiotensin II Type 1 receptor blockers above and beyond angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone.",2002.0,0,0
961,11999264,Does lowering blood pressure prevent recurrent stroke?,Andrew M Tonkin,,2002.0,0,0
962,11999634,Recent advances in the treatment of heart failure.,Ayan R Patel; Marvin A Konstam,"Treatment strategies for patients with heart failure and left ventricular systolic dysfunction continue to evolve as the complex pathophysiology of this disease is better understood. A number of advances have been made in recent years, most notably the addition of beta-receptor antagonists. In addition, recent studies have provided important information regarding the utility of angiotensin receptor antagonists, aldosterone receptor antagonists, and natriuretic peptides in the management of heart failure. Nonpharmacologic advances include resynchronization therapy, which appears to confer symptomatic improvement in some patients, and improvements in ventricular assist device technology. As the importance of neurohormonal activation in the progression of heart failure becomes increasingly apparent, new therapeutic strategies targeting these neurohormonal systems are being investigated.",2002.0,0,0
963,12002704,ACE inhibition is superior to angiotensin receptor blockade for renography in renal artery stenosis.,Georgios Karanikas; Alexander Becherer; Karoline Wiesner; Robert Dudczak; Kurt Kletter,"Angiotensin converting enzyme (ACE) inhibitors as well as angiotensin II receptor antagonists are able to prevent the vasoconstrictive effect of angiotensin II on the efferent renal vessels, which is believed to play an important role in renovascular hypertension. This effect is assumed to be essential for the demonstration of renovascular hypertension by captopril renography. In this study, renographic changes induced by captopril and the AT1 receptor antagonist valsartan were compared in patients with a high probability for renovascular hypertension. Twenty-five patients with 33 stenosed renal arteries (grade of stenosis >50%) and hypertension were studied. Captopril, valsartan and baseline renography were performed within 48 h using technetium-99m mercaptoacetyltriglycine. Blood pressure was monitored, plasma renin concentration before and after intervention was determined and urinary flow was estimated from the urinary output of the hydrated patients. Alterations in renographic curves after intervention were evaluated according to the Santa Fe consensus on ACE inhibitor renography. Captopril renography was positive, indicating renovascular hypertension, in 25 of the 33 stenosed vessels, whereas valsartan renography was positive in only ten. Blood pressure during captopril and valsartan renography was not different; reduction in blood pressure was the same after valsartan and captopril. Plasma renin concentration was comparable for valsartan and captopril studies, showing suppressed values after intervention in as many as 12 of the 25 patients. Urinary flow after valsartan was higher than after captopril (P<0.05). However, this difference could not explain the markedly higher sensitivity of captopril compared with valsartan in demonstrating renal artery stenosis. In 14 of the 25 patients, blood pressure response to revascularisation was monitored, showing a much better predictive value for captopril renography. It is concluded that captopril renography is much more sensitive than valsartan renography in detecting a clinically significant renal artery stenosis. Furthermore, our data suggest that other effects, such as that on the prostaglandin-bradykinin system, are of at least similar importance to ACE inhibition for the high diagnostic sensitivity of captopril renography regarding renovascular hypertension.",2002.0,0,0
964,12003698,Effect of ramipril versus amlodipine on renal outcomes in hypertensive nephrosclerosis.,John M Flack,,2002.0,0,0
965,12008175,Effects of perindopril on aldosterone production in the failing human heart.,Yuji Mizuno; Hirofumi Yasue; Michihiro Yoshimura; Hiromi Fujii; Nobuyasu Yamamoto; Masafumi Nakayama; Eisaku Harada; Tomohiro Sakamoto; Shota Nakamura; Teruhiko Ito; Yukio Shimasaki; Hisao Ogawa; Yoshihiko Saito; Kazuwa Nakao,"The present study was designed to examine whether the production of aldosterone from the heart is suppressed by angiotensin-converting enzyme (ACE) inhibition in patients with heart failure. Forty-one patients with left ventricular systolic dysfunction were randomly divided into either the perindopril group (n = 21, perindopril 4 mg/day) or the placebo group (n = 20). Plasma levels of aldosterone and ACE activity were measured in the anterior interventricular vein, coronary sinus, and aortic root during cardiac catheterization. The levels of aldosterone as well as ACE activity were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root in the placebo group (aldosterone: 92.1 +/- 9.0 vs 70.6 +/- 8.3 pg/ml [p <0.001]; 90.3 +/- 9.2 vs 70.6 +/- 8.3 pg/ml [p <0.001], respectively; ACE activity: 13.6 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], 13.4 +/- 0.8 vs 12.2 +/- 0.7 IU/L [p <0.001], respectively). On the other hand, there were no differences in the levels of aldosterone or ACE activity between the anterior interventricular vein and aortic root or between the coronary sinus and aortic root (aldosterone: 68.1 +/- 8.4 vs 69.9 +/- 9.4 pg/ml [p = NS]; 67.3 +/- 8.9 vs 69.9 +/- 9.4 pg/ml [p = NS], respectively; ACE activity: 9.7 +/- 0.8 vs 9.9 +/- 0.8 IU/L [p = NS]; 9.8 +/- 0.8 vs 9.9 +/- 0.8 IU/L, respectively) in the perindopril group. The levels of aldosterone as well as ACE activity were significantly lower at the anterior interventricular vein and coronary sinus in the perindopril group than in the placebo group. The difference in the level of aldosterone between the anterior interventricular vein and aortic root (Delta aldosterone [anterior interventricular vein - aortic root]) had a significant positive correlation with that of ACE activity (Delta ACE [anterior interventricular vein - aortic root]) (r = 0.536, p <0.001), whereas ACE activity in the aortic root had no significant correlation with either the aldosterone levels in the aortic root or Delta aldosterone (anterior interventricular vein - aortic root). Perindopril suppressed cardiac aldosterone production by mainly suppressing cardiac ACE activity in patients with heart failure. Thus, aldosterone production is activated in the failing ventricle and is suppressed by perindopril mainly via the suppression of cardiac ACE activity in patients with heart failure.",2002.0,0,0
966,12011663,Effect of indomethacin on the antihypertensive efficacy of valsartan and lisinopril: a multicentre study.,Roberto Fogari; Annalisa Zoppi; Renzo Carretta; F Veglio; Antonio Salvetti; Italian Collaborative Study Group,"To compare the effect on antihypertensive efficacy produced by the addition of indomethacin to the angiotensin II (Ang II) antagonist, valsartan, or to the angiotensin-converting enzyme inhibitor, lisinopril, in hypertensive patients with chronic osteoarthritis. One hundred and twenty-eight patients (52 men and 76 women) aged 25-82 years (mean age 55.7 years), with diastolic blood pressure (DBP) > 100 mmHg at the end of a 2-week placebo washout period were allocated randomly to groups to receive valsartan (80-160 mg once daily) or lisinopril (10-20 mg once daily). At the end of 10 weeks of treatment, patients with DBP < 90 mmHg, while continuing to receive valsartan or lisinopril treatment, were allocated randomly to groups to receive either indomethacin (50 mg three times a day) or the corresponding placebo for 2 weeks, with a 1-week washout period between the two treatments, according to a double-blind, crossover design. After the initial washout period, patients were examined at the end of the 4th, 8th and 10th weeks of randomized treatment with valsartan and lisinopril, at the end of the first crossover period and then at the beginning and at the end of the second crossover period. At each visit, sitting and standing blood pressure were measured by standard mercury sphygmomanometer. The addition of indomethacin blunted the blood pressure-decreasing effect of both antihypertensive drugs. Although indomethacin produced greater increases in both systolic and DBP values in the lisinopril-treated patients (5.45/3.22 mmHg) than in the valsartan-treated ones (2.12/1.87 mmHg), no significant difference between the two drugs was found. From a theoretical standpoint, these findings suggest that prostaglandins may play a part in the antihypertensive action of Ang II antagonists. From a practical standpoint, hypertensive patients treated with valsartan or with lisinopril should be monitored to detect changes in blood pressure control while receiving indomethacin.",2002.0,0,0
967,12011664,Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy.,Alberto Zanchetti; Lennart Hansson; Gastone Leonetti; Karl-Heinz Rahn; Luis Ruilope; Ingrid Warnold; Hans Wedel,"It has been reported that aspirin (ASA) may interfere with the blood pressure (BP)-lowering effect of various antihypertensive agents and attenuate the beneficial effects of angiotensin-converting enzyme (ACE) inhibitors in patients with congestive heart failure. Data from the Hypertension Optimal Treatment (HOT) Study, in which 18 790 intensively treated hypertensive patients were randomized to either ASA 75 mg daily or placebo for 3.8 years (with a 15% reduction in cardiovascular events and a 36% reduction in myocardial infarction in ASA-treated patients), were reanalysed for the whole group of patients and for various subgroups with particular attention to the possible effects of ASA on BP and renal function. In ASA-treated and placebo-treated patients: (1) systolic blood pressure (SBP) and diastolic blood pressure (DBP) values achieved with antihypertensive treatment were superimposable, with clinically irrelevant differences; (2) these superimposable SBP and DBP were achieved with antihypertensive therapies, that were quantitatively and qualitatively similar, and (3) changes in serum creatinine and in estimated creatinine clearance and the number of patients developing renal dysfunction were also similar. Furthermore, the cardiovascular benefits of ASA were of the same magnitude in hypertensive patients receiving or not receiving ACE-inhibitors. Even long-term, low-dose ASA does not interfere with the BP-lowering effect of antihypertensive agents, including combinations with ACE inhibitors, or with renal function. No negative interaction occurs between ACE inhibition and the cardiovascular benefits of small dose of ASA. Our conclusions cannot be extended to larger doses of ASA, or to patients with congestive heart failure.",2002.0,0,0
968,12013487,Benefits of electronic pillboxes in evaluating treatment compliance of patients with mild to moderate hypertension.,J M Mallion; C Dutrey-Dupagne; L Vaur; N Genes; M Renault; F Elkik; P Baguet; S Boutelant,"This study was designed to assess the compliance of hypertensive patients with a once-daily regimen of the angiotensin converting enzyme (ACE) inhibitor trandolapril and to evaluate the antihypertensive efficacy of the drug in relation to the time interval between taking the final dose and measuring the blood pressure (BP). After a 2-week wash-out period, hypertensive patients, recruited by cardiologists, received trandolapril 2 mg once daily in the morning for 4 weeks. In order to assess compliance, each patient's supply of trandolapril capsules was presented in a pillbox that incorporated in its lid a microprocessor that recorded the date and time of each occasion that it was opened. BP was measured using validated semi-automatic devices, at the end of both the wash-out and the treatment period. A total of 590 patients entered the study. Compliance data were evaluable for 501 patients. Overall compliance, defined as the ratio of the number of openings recorded to the number of doses prescribed was less than 80, 80-100, and more than 100% in 17, 63 and 20% of patients, respectively. The average number (+/- SD) of missed doses was 4.5 +/- 8 (median 2). The average interval between successive openings was 25 h 07 min mean +/- 13 h (median 24 h). The average number of delayed doses (a delayed dose being defined as the box being opened 25-36 h after the previous occasion) was 5.6 +/- 3 (median 6). Patients living in the Paris area had more forgotten and delayed doses than those living in the provinces (7.9 versus 3.8 forgotten; P<0.0001 and 6.3 versus 5.5 delayed; P<0.005). Doses were forgotten and delayed more often during weekends than on weekdays. The greatest number of delayed doses occurred in those patients under 60 years of age (6.0 versus 5.2; P<0.01). Decreases in systolic blood pressure (SBP and diastolic blood pressure (DBP) were 20.3/12.8 mmHg, for patients whose final drug was taken on the same day as the BP measurement, and 18.9/11.2 mmHg for patients whose final dose was taken on the previous day. Electronic compliance monitoring allows refined analysis of the behaviour of hypertensive patients. In this study doses were missed and delayed frequently during the first month of treatment, depending on the patient's lifestyle.",2002.0,0,0
969,12014552,Time to reverse that altruism bypass...,Alec Logan,,2002.0,0,0
970,12016544,Mechanisms of hepatic transport of drugs: implications for cholestatic drug reactions.,Alan Bohan; James L Boyer,"Hepatocellular and canalicular transport proteins are major determinants of the hepatic uptake and biliary excretion of xenobiotics and their metabolites. Recent advances in molecular cloning have resulted in the characterization of many of these transport systems. These advances have enabled the identification of a number of drugs that are substrates for the transporters, and it has facilitated studies of mechanisms of drug-induced cholestasis. This review summarizes the normal function of hepatobiliary transporters and their alteration by drugs or other foreign compounds. Although most of these investigations have been performed in animal models of drug-induced cholestasis, the application to human forms of drug-induced cholestasis is also discussed when possible. One important finding is that genetic polymorphisms can result in changes in drug transporter expression and function that could increase susceptibility to cholestatic drug reactions.",2002.0,0,0
971,12016625,Comment--Val-HeFT and angiotensin-receptor blockers in perspective: A tale of the blind man and the elephant.,Marvin A Konstam,"The role of angiotensin-receptor blockers (ARBs) in the therapy of chronic heart failure (CHF) has not been clarified. There are no large placebo-controlled trials with these agents. The second Evaluation of Losartan in the Elderly trial (ELITE-II) compared the ARB losartan with captopril in 3,152 patients >/=60 years old with New York Heart Association (NYHA) class II-IV and left ventricular ejection fraction </=40% and did not establish the efficacy of the ARB or its equivalent to angiotensin-converting enzyme inhibitor. The Valsartan Heart Failure Trial was designed to determine whether addition of valsartan improved the outcomes of patients receiving standard therapy for heart failure, which in most cases included an ACE inhibitor. A total of 5,010 patients with NYHA class II-IV CHF and ejection fraction <40% were assigned to receive 160 mg valsartan or placebo twice daily. The 2 coprimary end points were all-cause mortality and the composite of mortality and morbidity, defined as the incidence of hospitalization for heart failure, resuscitated sudden death, or receipt of intravenous inotropic or vasodilator therapy for at least 4 hours (with hospitalizations accounting for 94% of the nonfatal end points). Mortality was similar in the 2 groups, but the combined mortality and morbidity end point was 13.2% lower with valsartan (relative risk, 0.87; 95% confidence interval, 0.77-0.97; P.009), primarily because of a reduction in the number of patients hospitalized for CHF (13.8% v 18.2%). There were improvements in several secondary end points, including ejection fraction, signs and symptoms of CHF, and quality of life with valsartan. Of note is that analyses of subgroups defined according to background therapy at baseline showed highly significant interactions. For instance, the small subgroup of 366 patients (7%) who were not receiving ACE inhibitors had a 33% reduction in mortality and a 44% decrease in mortality and morbidity, whereas the morbidity and mortality benefit of valsartan observed in the overall trial was no longer significant in patients receiving background ACE inhibitor therapy (relative risk, 0.90; P.10). The larger subgroup of patients receiving both an ACE inhibitor and a beta-blocker at baseline had a statistically significant 42% increase in mortality with valsartan (P.009) and a trend toward an increase in the mortality and morbidity composite (P.10). When added to standard therapy, valsartan has no overall effect on mortality and produces a modest (13.2%) reduction in morbidity and mortality. However, this benefit is much larger in patients not receiving concomitant ACE inhibitor therapy and statistically not significant in those who are taking ACE inhibitors. Somewhat troublesome is the finding of significant increase in mortality with valsartan in patients receiving both ACE inhibitor and beta-blocker therapy.",2002.0,0,0
972,12018554,Study on early intervention with ACE inhibitor in myocardical infarction and short term outcome.,B R Hazra; B P Roy; S Guha; K Rakshit; M B Ghosh,"The present study was carried out on 100 patients with acute myocardial infarction (AMI) being treated with angiotensin converting enzyme (ACE) inhibitor and another 80 patients with conventional treatment but without ACE inhibitor during the period from May 1, 1995 to August 7, 1996 in Medical College, Calcutta. Clinical and other laboratory investigations including echocardiographic parameters were noted and recorded meticulously within 24-48 hours after AMI and repeated at 4th week. The present study based on non-invasive methods other than haemodynamic methods has shown that the echocardiographic assessment of left ventricular functional parameters after 4 weeks of ACE inhibitor therapy (n = 100) were better in treated group in comparison to control group without ACE inhibitor (n = 80) and the difference was statistically significant at 99% level of confidence. Overall mortality was 4% in ACE inhibitor group and 8.75% in the control group. This short term study with early intervention with ACE inhibitor within 48 hours of AMI has shown statistically significant evidence of beneficial effect of ACE inhibitor in improving the ventricular functional parameters and also reducing short term mortality from cardiac cause within 4 weeks compared to the group not receiving ACE inhibitors.",2002.0,0,1
973,12018672,Bullous skin disease: an unusual allergic reaction to vancomycin.,Bogdan I Neughebauer; Gerardo Negron; Stephen Pelton; Richard W Plunkett; Ernst H Beutner; Richard Magnussen,"Severe reactions due to vancomycin are uncommon. We describe a case of vancomycin-induced linear immunoglobulin A bullous disease and review the literature pertinent to this entity. This is a rare subepidermal blistering disorder, with a heterogenous clinical presentation. It is characterized by IgA deposition in a linear pattern along the basement membrane zone. It seems to be autoantibody-mediated and is not dose-dependent. Spontaneous and complete skin healing follows vancomycin withdrawal; rechallenge reproduces the disease with a more rapid and severe onset. Because vancomycin is almost never suspected to be the cause of such manifestations, awareness of this rare autoimmune reaction is crucial. Early diagnosis through direct immunofluorescence of the perilesional skin would avoid unnecessary laboratory investigations and therapeutic measures and would shorten significantly the pain and suffering of these patients.",2002.0,0,0
974,12018825,'Why don't you do as I tell you?' Compliance and antihypertensive regimens.,L Hansson,"Although hypertension is recognised as one of the major health hazards in the developed world, compliance with antihypertensive regimens is still undesirably low. This brings important costs, both to patients in increased morbidity and mortality, and to society in hospitalisations and lost productivity. This review surveys possible reasons for non-compliance with treatments generally and antihypertensive medications specifically. It also looks at how insights into reasons for non-compliance can help us design more effective treatments, and discusses current and emerging medications in the context of compliance. As one of the reasons for low compliance is thought to be the impact of a drug on the patient's lifestyle, recently developed agents such as angiotensin II-receptor blockers may be expected to have less effect on patients' daily lives than earlier treatments, which brings hope for increased compliance with these regimens.",2002.0,0,0
975,12019599,Current indications for ACE inhibitors and HOPE for the future.,Stephanie Burch; Narith Ou,"Angiotensin-converting enzyme (ACE) inhibitors are effective in several disease states such as congestive heart failure, myocardial infarction, and diabetes. This article reviews the evidence supporting the clinical use, efficacy, and cost effectiveness of ACE inhibitors in these various disease states. With the findings of the Heart Outcomes Prevention Evaluation trial, these agents may now have a positive impact on the primary prevention of coronary artery disease. New and ongoing trials will provide more information about the role of ACE inhibitors in coronary artery disease.",2002.0,0,0
976,12022252,The PROGRESS trial: questions about the effectiveness of angiotensin converting enzyme inhibitors. Perindopril pROtection aGainst REcurrent Stroke Study.,Bruce M Psaty; Noel S Weiss; Curt D Furberg,,2002.0,0,0
977,12022388,ACE inhibitors vs ARBs: is one class better for heart failure.,Mark E Dunlap; Ross C Peterson,"Although angiotensin-converting enzyme (ACE) inhibitors decrease mortality in heart failure, they incompletely suppress angiotensin II with long-term therapy. Since angiotensin receptor blockers (ARBs) block the biologic effects of angiotensin II more completely than ACE inhibitors, they could be beneficial in the treatment of heart failure.",2002.0,0,0
978,12022909,ACE inhibitor-induced bronchial reactivity in patients with respiratory dysfunction.,Kathleen A Packard; Richard L Wurdeman; Amy J Arouni,"Angiotensin-converting enzyme (ACE) inhibitors are often associated with an increased incidence of cough and bronchial responsiveness that may cause further deterioration of patients with impaired pulmonary function. To review the available literature on the incidence of cough and bronchial responsiveness associated with ACE-inhibitor therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). Literature was accessed through MEDLINE (1985-September 2001). Key search terms included cough, bronchospasm, asthma, congestive heart failure, chronic obstructive pulmonary disease, ACE inhibitors, and angiotensin II receptor blockers. The literature reports several cases of increased bronchial responsiveness associated with ACE inhibitors. Larger, controlled studies evaluating the increased risk in patients with pulmonary dysfunction are limited. Data from these trials are summarized in this article. The literature shows that patients with primary airway disease such as asthma and COPD are not at an increased risk of developing cough or bronchoconstriction as a result of ACE-inhibitor therapy. Despite the ability of ACE inhibitors to improve exercise tolerance, perfusion, and gas transfer, patients with CHF may be at higher risk of developing cough than the general population. Whether this cough is attributed to ACE inhibition or increased left-ventricular dysfunction remains uncertain. If increased bronchial responsiveness does occur, angiotensin II receptor antagonists are another reasonable option.",2003.0,0,0
979,12035833,Blood pressure management in acute stroke: comparison of current guidelines with prescribing patterns.,Salmann Kanji; Céline Corman; Andre G Douen,"Current recommendations for treating elevated blood pressure (BP) in the acute stroke are based largely on expert opinion and vary with regard to treatment thresholds and choice of antihypertensive agents. In this study we investigate the influence of these recommendations by comparing the management of hypertension in acute stroke at a tertiary care hospital with current guidelines. Retrospective chart review of patients admitted with acute stroke at The Ottawa Hospital-General Campus over six consecutive months. The use of antihypertensive medications (type, dose, routes of administration, BP recordings) in the first seven days after admission was noted. Transdermal nitroglycerin paste was the most commonly used antihypertensive agent. In contrast to the 15% reduction in BP over 24 hours recommended for lowering BP in hypertensive patients with ischemic stroke, nitroglycerin caused a >15% reduction of BP over the first 24 hours on 60% of the occasions used. Furthermore, despite concerns about sublingual nifedipine, this was the second most commonly prescribed agent. Surprisingly, the mean time to first BP measurement following initiation of antihypertensive therapy was 117 +/- 43 minutes in ischemic stroke and 88 +/- 89 minutes in hemorrhagic strokes. The current guidelines for management of acute poststroke hypertension appear to have little influence on prescribing patterns, leading to considerable variations in practice. Such variations, likely due to uncertainty caused by lack of evidence from randomised controlled trials, are intolerable as patients maybe submitted to nonstandardised, potentially harmful care such as inappropriate choice of antihypertensives and inadequate BP monitoring as observed in this study.",2002.0,0,0
980,12035873,"""Treating hypertension"" or ""lowering blood pressure""? Extending the concept.",John Chalmers,,2002.0,0,0
981,12042007,European comparison of costs and quality in the treatment of acute myocardial infarction (2000-2001).,A Gandjour; F Kleinschmit; K W Lauterbach; INTERCARE International Investigators. International Comparison of Costs and Quality in Health Care,"To compare the inpatient costs and process quality in the treatment of acute myocardial infarction in France, Germany, Italy, The Netherlands, Sweden, Switzerland, and the U.K. A total of 208 European hospitals assessed services for one hypothetical average patient with acute myocardial infarction (cost evaluation) and prospectively followed up one or two real acute myocardial infarction patients (quality evaluation) in 2000/2001. The following cost modules were evaluated: general medicine ward, critical care unit (both personnel costs only), and reperfusion therapy. The following process quality indicators were evaluated: reperfusion therapy; and prescription of aspirin, lidocaine, beta-blockers, and ACE inhibitors. Switzerland, Germany, and France had the highest reperfusion costs due to a relatively high percentage of patients receiving percutaneous transluminal coronary angioplasties, stents, and glycoprotein IIb/IIIa blockers. Personnel costs for general medicine wards and critical care units were highest in Italy and Germany due to relatively long hospital stays. Average quality ratings ranged from 89% in the U.K. and France to 96% in Germany. There was little variation in the process quality of care for treating acute myocardial infarction. Differences in resource use may result from differences in the types of reimbursement and in the rates of diffusion of new technology.",2002.0,0,0
982,12045365,Omapatrilat provides long-term control of hypertension: a randomized trial of treatment withdrawal.,R Guthrie; R A Reeves,"Omapatrilat simultaneously inhibits neutral endopeptidase and angiotensin-converting enzyme, increasing levels of vasodilatory peptides while decreasing production of angiotensin II. This study evaluated the clinical effects of withdrawal of omapatrilat after a patient's hypertension had been controlled (seated diastolic blood pressure <90 mm Hg) on omapatrilat for at least 6 months, with or without adjunctive antihypertensive medications. This double-blind study randomized 83 patients to receive either their established omapatrilat dose or placebo for 8 weeks; any concomitant antihypertensive medications were kept constant. Patients continuing on omapatrilat had no change in blood pressure. Patients whose chronic omapatrilat treatment was replaced by placebo had clinically important increases in both systolic (+16.5 mm Hg) and diastolic ((+9.6 mm Hg) blood pressures (both p<0.001). An increase in blood pressure was also seen in patients who were taking adjunctive antihypertensive medications prior to withdrawal of omapatrilat. This study demonstrates that when compared to withdrawal placebo, omapatrilat maintains clinically and statistically significant blood pressure reductions.",2002.0,0,0
983,12045387,Doxazosin and congestive heart failure.,Domenic A Sica,"Doxazosin remains a commonly used antihypertensive medication, although its use has been tainted by recent findings from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT was a large, simple trial, designed in a fashion to closely mimic clinical practice as it occurs in high-risk hypertensive patients aged 55 years or older. Its goals were to determine whether the incidence of the primary outcome--a composite of fatal coronary heart disease and nonfatal myocardial infarction--differed between treatment with a diuretic (chlorthalidone) (12.5-25.0 mg/day) and treatment with each of three other types of antihypertensive drugs-a calcium-channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and a peripheral alpha-adrenergic blocker (doxazosin) (2-8 mg/day). Doxazosin was recently withdrawn from this trial after an interim analysis showed the secondary end point of combined cardiovascular disease to be 25% greater in patients on doxazosin than in those assigned to treatment with chlorthalidone. This finding was largely driven by congestive heart failure. The practicing clinician should not abandon doxazosin completely because of the ALLHAT findings, although these findings are indisputably important. These results represent an interim analysis and their application to clinical practice needs to occur carefully. A valued member of our therapeutic armamentarium need not be laid entirely to rest; rather, doxazosin should now be viewed as a secondary or tertiary antihypertensive therapy pending a more complete review of the ALLHAT data.",2002.0,0,0
984,12055364,Blockade of the renin-angiotensin system.,B M Y Cheung,"The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit angiotensin-converting enzyme and have been shown to be effective in many cardiovascular diseases. They should be considered for the treatment of hypertension in patients with heart failure, previous myocardial infarction, diabetes, or proteinuria. There are a number of side-effects associated with angiotensin-converting enzyme inhibitors, especially persistent dry cough. Angiotensin II receptor antagonists (sartans) provide a more specific blockade of the renin-angiotensin-aldosterone system and are associated with fewer side-effects, including cough. Their long-term efficacy and tolerability in the treatment of patients with hypertension has, however, yet to be established. Periodic monitoring of renal function and electrolytes is required in patients treated with an angiotensin-converting enzyme inhibitor or a sartan.",2002.0,0,0
985,12055395,Diagnosis and management of lupus pleuritis.,Der-Yuan Wang,"Systemic lupus erythematosus is a chronic inflammatory autoimmune disorder that can affect any organ system. Predominant manifestations include arthralgia, rash, photosensitivity, pleuritis, renal and central nervous system involvement. Fortunately, pleuritis in systemic lupus erythematosus is not usually as life threatening as may be the renal or central nervous system complications. Nevertheless, pleuritis does occur in systemic lupus erythematosus and may be a significant cause of morbidity. In addition to primary pleuritis attributed to systemic lupus erythematosus, secondary pleural complications, especially infections, may occur as a consequence of systemic lupus erythematosus. Pleuritis in patients with systemic lupus erythematosus may therefore frequently challenge the diagnostic and therapeutic acumen of physicians.",2002.0,0,0
986,12062731,The liver and lovastatin.,Keith G Tolman,"The cholesterol-lowering agents, known as statins, have been in use for 15 years and are among the most commonly prescribed drugs. Animal studies and premarketing clinical trials have given signals of hepatotoxicity, primarily minor elevations in serum alanine aminotransferase enzyme (ALT) levels. For that reason, all of the cholesterol-lowering drugs have labeling that requires monitoring of liver enzymes. Postmarketing experience, however, suggests that hepatotoxicity is rare and thus it is timely to revisit the issue. The first of the statins, lovastatin, was approved in 1986 and has acquired 24 million patient-years of clinical experience. Minor elevations in liver enzymes, i.e., ALT 3 x the upper limit of normal (ULN) occur in 2.6% and 5.0% of patients on lovastatin doses of 20 and 80 mg/day, respectively. These elevations are reversible with continuing therapy, are dose related, and are probably related to cholesterol lowering per se. Rare cases of acute liver failure (ALF) have been reported with all of the cholesterol-lowering drugs. With lovastatin, the rate is approximately 1/1.14 million patient-treatment years, which is 9% of the background rate of all causes of ALF and approximately equal to the background rate of idiopathic ALF. Monitoring for hepatotoxicity has not been effective in preventing serious liver disease, largely because of its rarity and the poor predictive value of minor ALT elevations. In fact, it may increase patient risk because of needless discontinuation of cholesterol-lowering therapy for false-positive results in patients who are benefiting from treatment.",2002.0,0,0
987,12067927,Patients with acute coronary syndrome should start a statin while still in hospital.,C G Isles,,2002.0,0,0
988,12067934,Impact of availability and use of coronary interventions on the prescription of aspirin and lipid lowering treatment after acute coronary syndromes.,P G Steg; B Iung; L J Feldman; D Cokkinos; J Deckers; K A A Fox; U Keil; A P Maggioni,"It has been suggested that patients undergoing acute intervention for coronary syndromes may not receive adequate secondary prevention. To analyse the impact of availability and use of coronary interventions on the prescription of secondary prevention after acute coronary syndromes. Analysis of a prospective multicentre register of patients admitted to hospital for acute coronary syndromes. A 1999 pan-European survey in 390 hospitals. 3092 patients admitted to hospital with acute coronary syndromes (including 777 for ST elevation myocardial infarction within 12 hours of onset). Rates of prescription of aspirin and lipid lowering agents. Performance of coronary angiography and percutaneous coronary interventions (PCI) during the hospital stay were independent predictors of prescription of aspirin at discharge (odds ratio (OR) 1.29 and 1.89, p = 0.053 and p < 0.0001, respectively). Lipid lowering agents were prescribed more often on discharge in patients admitted to hospitals with catheterisation laboratories than without (for infarction with ST elevation, 45% v 40% (NS); for other acute coronary syndromes, 46% v 36%; p < 0.05). Prescription rates were higher among patients undergoing coronary angiography or PCI than in those treated conservatively (for infarction with ST elevation, 49%, 53%, and 39%, p < 0.05; for other acute coronary syndromes, 50%, 54%, and 34%, p < 0.05). Logistic regression analysis showed that PCI was an independent predictor of prescription of lipid lowering agents at discharge (OR 1.48, p < 0.0002). Contrary to expectations, invasive procedures for acute coronary syndromes are associated with higher rates of prescription of pharmacological secondary prevention.",2002.0,0,0
989,12070557,A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure.,Afaf A Mahgoub; Azza H El-Medany; Ahmed S Abdulatif,"To evaluate the effect of an arteriolar dilator (diltiazem hydrochloride) versus a venodilator (isosorbide dinitrate) on digoxin kinetics and to estimate the efficacy and tolerability of these vasodilators when combined with digoxin for 10 days therapy in patients with congestive heart failure secondary to ischemic heart disease. A double blind randomized cross over study was carried out to investigate the effect of an arteriolar dilator (diltiazem hydrochloride 180 mg/day orally) versus a venodilator (isosorbide dinitrate 30 mg/day orally) on digoxin kinetics (0.25 mg/day orally), after 10 days therapy in patients with heart failure due to ischemic heart disease. Also, the effect of these drugs on blood pressure, heart rate, renal functions and serum electrolytes, and their efficacy and tolerability in combination with digoxin were studied. This study was carried out in the Department of Medicine, Main Alexandria University Hospital, Alexandria, Egypt, during the period May 1999 through to May 2000. Diltiazem caused a significant increase in digoxin maximum serum concentration without significant change in time to reach maximum concentration and the apparent volume of distribution. The total digoxin clearance was significantly reduced and the elimination half life was prolonged. Subsequently the area under time-concentration curve and the steady-state digoxin level were increased, but were still within therapeutic margin. On the other hand isosorbide dinitrate significantly increased digoxin maximum serum concentration but without change in the other digoxin pharmacokinetic parameters. Isosorbide dinitrate, but not diltiazem, caused significant reduction in supine and standing blood pressure, while both drugs did not significantly alter pulse rate, renal functions, serum sodium potassium and electrocardiographic pattern. Patients who received diltiazem displayed a mean 51% increase in the area under the plasma concentration-time curve, 50% increase in mean steady state serum digoxin concentration, and 37% increase in peak serum digoxin concentration. While patients who received isosorbide dinitrate showed only a 15% increase in digoxin maximum serum concentration and no statistically significant change in mean steady state digoxin concentration or area under the plasma concentration-time curve. The elimination half life during the diltiazem phase was prolonged by 29% while there was no significant change with isosorbide dinitrate. Netiher diltiazem or isosorbide dinitrate significantly altered the time to reach maximum serum digoxin concentration. The addition of a vasodilator such as, diltiazem or isosorbid dinitrate to digoxin could significantly improve the symptoms and signs of heart failure compared to digoxin alone. They were well tolerated and without fear of electrolyte imbalance which potentiate digoxin toxicity.",2002.0,0,0
990,12074358,Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting.,Franz H Messerli; Matthew R Weir; Joel M Neutel,"Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.",2003.0,0,0
991,12074359,Effects of omapatrilat on the renin-angiotensin system in salt-sensitive hypertension.,Carlos M Ferrario; Ronald D Smith; Bridget Brosnihan; Mark C Chappell; Vito M Campese; Ole Vesterqvist; Wei-chi Liao; Michael C Ruddy; Clarence E Grim,"The contribution of angiotensin-(1-7) [Ang-(1-7)] to the antihypertensive actions of omapatrilat, a novel vasopeptidase inhibitor, was evaluated in 22 salt-sensitive, low renin, hypertensive subjects as a substudy of a multicenter randomized, double-blind, parallel study of 4 weeks duration. A total of 25 other subjects received lisinopril as the active control. Omapatrilat (40 mg) produced sustained control of blood pressure (BP) (as assessed by 24-h ambulatory BP measurements) that was significantly greater than that produced by 20 mg daily of lisinopril. The antihypertensive response to either drug was accompanied by similar sustained inhibition of angiotensin converting enzyme activity. Plasma levels of angiotensin I (Ang I), angiotensin II (Ang II) and Ang-(1-7) were not altered by treatment with either omapatrilat or lisinopril, even though both regimens produced a modest rise in plasma renin activity. In contrast, urinary excretion rates of Ang I and Ang-(1-7) but not Ang II increased significantly throughout the dosing period of subjects who were given omapatrilat, whereas the smaller antihypertensive response produced by lisinopril had a smaller and transient effect on increasing urinary excretion rates of Ang-(1-7). Omapatrilat, being a single molecule inhibiting neutral endopeptidase and converting enzyme simultaneously, controlled salt-sensitive hypertension by a mechanism that was associated with sustained increases in urinary Ang-(1-7) excretion. We suggest that Ang-(1-7) may be a component of the mechanisms by which omapatrilat induces an antihypertensive response in salt sensitive hypertension.",2003.0,0,0
992,12075271,Vasopeptidase inhibitor reduces inhospital costs for patients with congestive heart failure: results from the IMPRESS trial. Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure.,Eric L Eisenstein; Charlotte L Nelson; Teresa A Simon; Allison L Smitten; Pablo Lapuerta; Daniel B Mark,"The Inhibition of Metallo Protease by BMS-186716 in a Randomized Exercise and Symptoms Study in Subjects With Heart Failure (IMPRESS) clinical trial randomized patients with congestive heart failure to a daily regimen of either omapatrilat or lisinopril. At 24 weeks, patients randomized to omapatrilat had a significant reduction in the combined end point of death, hospitalization, or discontinuation of study drug for worsening heart failure when compared with patients randomized to lisinopril. They also had significantly fewer serious cardiac adverse events. This study sought to determine the economic consequences of the lower event rates of patients who were given omapatrilat. Economic outcomes (major hospitalizations and their associated medical costs) were compared between treatment groups and assessed by use of the societal perspective. Hospitalization information was obtained from the IMPRESS trial's standardized case report and serious adverse event forms. Hospital costs were evaluated by means of assigning each hospital admission a diagnosis-related group and an average cost for physician and hospital services. Emergency department visits were included only when they were made for worsening heart failure and were assigned costs equivalent to the average hospital and physician Medicare reimbursement for these visits in Duke University Medical Center's heart failure program. Drug costs were not assessed. Although the typical patient in both treatment groups was event-free, there was a trend toward a greater number of hospitalizations in the patients given lisinopril than in the patients given omapatrilat (P =.07). Differences in the distribution of cardiac hospitalizations between patients given lisinopril and patients given omapatrilat were significant (P =.03). There was a trend toward lower medical costs at 24 weeks in patients given omapatrilat versus patients given lisinopril ($1930 vs $2002, P =.09). Considering only cardiac medical costs, this trend toward reduced medical costs was significant ($1240 vs $1442, P =.03). At 24 weeks, patients with heart failure treated with omapatrilat had fewer hospitalizations and lower medical costs than patients treated with lisinopril. However, drug treatment costs were not available for this analysis.",2002.0,0,1
993,12080243,Angiotensin-converting enzyme inhibitors and diarrhea.,Cesare Tosetti,,2002.0,0,0
994,12081581,Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy.,Henrik Post Hansen; Ellis Tauber-Lassen; Berit R Jensen; Hans-Henrik Parving,"Recent data suggest that dietary protein restriction improves survival and delays the progression to end-stage renal disease (ESRD) in non-diabetic nephropathies. The purpose of our study was to determine the effect of dietary protein restriction on survival and progression to ESRD in diabetic nephropathy. A four-year prospective, controlled trial with concealed randomization was performed comparing the effects of a low-protein diet (0.6 g/kg/day) with a usual-protein diet. The study included 82 type 1 diabetic patients with progressive diabetic nephropathy [pre-study mean decline in glomerular filtration rate (GFR) 7.1 mL/min/year (95% CI, 5.8 to 8.5)]. The main outcome measures were decline in GFR and development of ESRD or death. During the follow-up period the usual-protein diet group consumed 1.02 g/kg/day (95% CI; 0.95 to 1.10) as compared with 0.89 (0.83 to 0.95) in the low-protein diet group (P = 0.005). The mean declines in GFR were 3.9 mL/min/year (2.7 to 5.2) in the usual-protein diet group and 3.8 (2.8 to 4.8) in the low-protein diet group. ESRD or death occurred in 27% of patients on a usual-protein diet as compared with 10% on a low-protein diet (log-rank test; P = 0.042). The relative risk of ESRD or death was 0.23 (0.07 to 0.72) for patients assigned to a low-protein diet, after an adjustment at baseline for the presence of cardiovascular disease (P = 0.01). Blood pressure and glycemic control were comparable in the two diet groups during the follow-up period. Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment.",2002.0,0,0
995,12081987,Omapatrilat reduces pulse pressure and proximal aortic stiffness in patients with systolic hypertension: results of the conduit hemodynamics of omapatrilat international research study.,Gary F Mitchell; Joseph L Izzo; Yves Lacourcière; Jean-Pascal Ouellet; Joel Neutel; Chunlin Qian; Linda J Kerwin; Alan J Block; Marc A Pfeffer,"Increased pulse pressure, an indicator of conduit vessel stiffness, is a strong independent predictor of cardiovascular events in hypertensive cohorts, which suggests that reduction of conduit vessel stiffness may be desirable in hypertension. We assessed changes in pulse pressure and conduit vessel stiffness in a 12-week double-blind, randomized clinical trial that compared monotherapy with the ACE inhibitor enalapril 40 mg daily (n=87) versus the vasopeptidase (dual ACE and neutral endopeptidase) inhibitor omapatrilat 80 mg daily (n=80) in patients with systolic hypertension. Patients were withdrawn from antihypertensive medications 1 to 2 weeks before enrollment, and systolic pressure was confirmed to be > or =160 mm Hg. With the use of calibrated tonometry and pulsed Doppler, pulsatile hemodynamics were assessed before randomization and at 12 weeks. Characteristic impedance (Z(c)), a direct measure of the stiffness of the central aorta, was calculated from the ratio of changes in carotid pressure and aortic flow in early systole. Omapatrilat compared with enalapril produced greater reductions in peripheral (-8.2+/-12.2 versus -4.0+/-12.2 mm Hg, P<0.05) and central (-10.2+/-16.2 versus -3.2+/-16.9 mm Hg, P<0.01) pulse pressures and Z(c) (237+/-83 to 208+/-70 versus 225+/-87 to 231+/-94 dyne x s/cm(5), P<0.001); the latter remained significant (P<0.05) after adjusting for change in mean pressure. Greater reductions in pulse pressure and Z(c) in hypertensive subjects treated with omapatrilat compared with enalapril suggest that aortic stiffness is maintained by specific, partially reversible mechanisms and underscore a potential role for pharmacological modulation of natriuretic peptides in the treatment of hypertension.",2002.0,0,0
996,12082487,Losartan and the meaning of LIFE.,G Y H Lip,,2002.0,0,0
997,12082488,The effect of antihypertensive drugs on the fetus.,T Rosenthal; S Oparil,"A critical review of the literature on the effects of antihypertensive drugs on the fetus in pregnant women is presented. The survey covers the alpha-adrenergic receptor agonists, beta-blockers including topical eye medications, alpha-beta blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. The lack of data on angiotensin II receptor blockers is noted although effects are considered to be similar to those reported with ACE inhibitors and therefore to be avoided. Analysis of the literature underscores that some antihypertensive drugs can be used safely at certain stages of pregnancy, while others are suspect and to be avoided at all costs. The lack of placebo-controlled studies on the treatment of severe hypertension in pregnancy due to ethical considerations is discussed against the background of the pressing need to treat these women despite the possible deleterious effects of antihypertensive drugs.",2002.0,0,0
998,12084604,Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay.,Angelo Auricchio; Christoph Stellbrink; Stefan Sack; Michael Block; Jürgen Vogt; Patricia Bakker; Christof Huth; Friedrich Schöndube; Ulrich Wolfhard; Dirk Böcker; Olaf Krahnefeld; Hans Kirkels; Pacing Therapies in Congestive Heart Failure (PATH-CHF) Study Group,"We sought to compare the short- and long-term clinical effects of atrial synchronous pre-excitation of one (univentricular) or both ventricles (biventricular), that provide cardiac resynchronization therapy (CRT). In patients with heart failure (HF) who have a ventricular conduction delay, CRT improves systolic hemodynamic function. The clinical benefit of CRT is still being investigated. Forty-one patients were randomized to four weeks of first treatment with biventricular or univentricular stimulation, followed by four weeks without treatment, and then four weeks of a second treatment with the opposite stimulation. The best CRT stimulation was continued for nine months. Cardiac resynchronization therapy was optimized by hemodynamic testing at implantation. The primary end points were exercise capacity measures. Data were analyzed by two-way repeated-measures analysis of variance. The left ventricle was selected for univentricular pacing in 36 patients. The clinical effects of univentricular and biventricular CRT were not significantly different. The results of each method were pooled to assess sequential treatment effects. Oxygen uptake during bicycle exercise increased from 9.48 to 10.4 ml/kg/min at the anaerobic threshold (p = 0.03) and from 12.5 to 14.3 ml/kg/min at peak exercise (p < 0.001) with the first treatment, and from 10.0 to 10.7 ml/kg/min at the anaerobic threshold (p = 0.2) and from 13.4 to 15.2 ml/kg/min at peak exercise (p = 0.002) with the second treatment. The 6-min walk distance increased from 342 m at baseline to 386 m after the first treatment (p < 0.001) and to 416 m after the second treatment (p = 0.03). All improvements persisted after 12 months of therapy. Cardiac resynchronization therapy produces a long-term improvement in the clinical symptoms of patients with HF who have a ventricular conduction delay. The differences between optimized biventricular and univentricular therapy appear to be small for short-term treatment.",2002.0,0,0
999,12085418,"[Effect of antihypertensive combinations on arterial pressure, albuminuria, and glycemic control in patients with type II diabetic nephropathy: a randomized study].",I Goicolea; R Fernández González; J Piniés; J Garrido; J M Martínez; S Armenteros; E Moreno Carretero,"Type II diabetic patients with albuminuria are at high risk for cardiovascular complications; the intense antihypertensive treatment required often involves using drug combinations. The aim of the present study was to compare the effect of two different, renin-angiotensin blocking combinations, on blood pressure (BP), albuminuria and glycemic control. Its design was prospective, randomised, controlled, of parallel branches, and performed in one Endocrinology Department, in Spain. 77 type-II diabetic patients, with stable albuminuria (30-1,000 mg/day) were included. After a pre-inclusion time of 2 weeks, patients were randomised to verapamil SR/trandolapril 180/2 (VT) or losartan/hydrochlorothiazide (LH) 20/12.5 mg/day. Duration of treatment was 1 year. The evaluated parameters were changes in blood pressure, urinary albumin excretion for 24 hours, glycated hemoglobin and plasmatic urea. Overall BP significantly decreased from 161.6 +/- 18.7/83.6 +/- 10.2 mmHg to 137.2 +/- 15.7/70.9 +/- 8.3 mmHg (p < 0.0005). Values, by treatment, were: For VT, 164.3 +/- 18.5/87.2 +/- 10.7 mmHg at baseline and 135.0 +/- 15.1/71.3 +/- 8.4 mmHg at conclusion. For LH, 158.8 +/- 17.4/80.1 +/- 8.4 mmHg at baseline and 139.3 +/- 16.1/70.5 +/- 8.2 mmHg at conclusion. Albuminuria significantly decreased from 308.2 +/- 544.7 mg/day to 198.0 +/- 285.3 mg/day. Both parameters showed no significant difference between treatments. Glycated hemoglobin decreased from 7.59 +/- 1.3% to 7.14 +/- 1.2% in the VT group, and from 7.96 +/- 1.29% to 7.84 +/- 1.62% in the LH group (ANOVA, p = 0.022). Changes adjusted from baseline values showed a trend to the difference between both treatments (p = 0.092). Plasmatic urea increased from 39.8 +/- 12.7 to 40.5 +/- 11.1 mg/dL in the TV group and from 43.4 +/- 12.0 mg/dL to 52.4 +/- 19.4 mg/dL in the LH group (ANOVA, p = 0.028). In conclusion, both treatments reduce blood pressure and albuminuria in a similar way in type II diabetic patients. The verapamil/trandolapril combination contributes to a better carbohydrate metabolism than losartan/hydroclorothiazide.",2002.0,0,0
1000,12086766,Aminopeptidase P in individuals with a history of angio-oedema on ACE inhibitors.,Albert Adam; Massimo Cugno; Giuseppe Molinaro; Melissa Perez; Yves Lepage; Angelo Agostoni,"Angio-oedema is a rare but potentially life threatening side-effect of angiotensin-converting-enzyme (ACE) inhibitor treatment. Identification of individuals at risk of this adverse effect is not possible. Angio-oedema is associated with raised concentrations of bradykinin, which is mainly inactivated by ACE. We assessed the plasma activity of two other enzymes that catabolise bradykinin (aminopeptidase P and carboxypeptidase N) in 39 hypertensive patients with a history of angio-oedema during ACE inhibitor treatment and in 39 hypertensive patients who had never had ACE inhibitor associated side-effects. Patients with previous angio-oedema had a lower plasma activity of aminopeptidase P than did those who never presented with angio-oedema (p=0 003). Our data suggest that low plasma concentrations of aminopeptidase P could be a predisposing factor for development of angio-oedema in patients treated with ACE inhibitors.",2002.0,0,0
1001,12088475,Guideline-discordant care in acute myocardial infarction: predictors and outcomes.,Ian A Scott; Catherine M Harper,"To determine (i) factors which predict whether patients hospitalised with acute myocardial infarction (AMI) receive care discordant with recommendations of clinical practice guidelines; and (ii) whether such discordant care results in worse outcomes compared with receiving guideline-concordant care. Retrospective cohort study. Two community general hospitals. 607 consecutive patients admitted with AMI between July 1997 and December 2000. Clinical predictors of discordant care; crude and risk-adjusted rates of inhospital mortality and reinfarction, and mean length of hospital stay. At least one treatment recommendation for AMI was applicable for 602 of the 607 patients. Of these patients, 411(68%) received concordant care, and 191 (32%) discordant care. Positive predictors at presentation of discordant care were age > 65 years (odds ratio [OR], 2.5; 95% CI, 1.7-3.6), silent infarction (OR, 2.7; 95% CI, 1.6-4.6), anterior infarction (OR, 2.5; 95% CI, 1.7-3.8), a history of heart failure (OR, 6.3; 95% CI, 3.7-10.7), chronic atrial fibrillation (OR, 3.2; 95% CI, 1.5-6.4); and heart rate >/= 100 beats/min (OR, 2.1; 95% CI, 1.4-3.1). Death occurred in 12.0% (23/191) of discordant-care patients versus 4.6% (19/411) of concordant-care patients (adjusted OR, 2.42; 95% CI, 1.22-4.82). Mortality was inversely related to the level of guideline concordance (P = 0.03). Reinfarction rates also tended to be higher in the discordant-care group (4.2% v 1.7%; adjusted OR, 2.5; 95% CI, 0.90-7.1). Certain clinical features at presentation predict a higher likelihood of guideline-discordant care in patients presenting with AMI. Such care appears to increase the risk of inhospital death.",2002.0,0,0
1002,12089368,Cardiac and renal effects of standard versus rigorous blood pressure control in autosomal-dominant polycystic kidney disease: results of a seven-year prospective randomized study.,Robert Schrier; Kimberly McFann; Ann Johnson; Arlene Chapman; Charles Edelstein; Godela Brosnahan; Tevfik Ecder; Lyn Tison,"This study sought to investigate the cardiac and renal effects of rigorous versus standard BP control on autosomal-dominant polycystic kidney disease (ADPKD). A prospective, randomized, 7-yr study was performed to examine the effect of rigorous (<120/80 mmHg) versus standard (135-140/85-90 mmHg) BP control on left ventricular mass index (LVMI) and kidney function in 75 hypertensive ADPKD patients with left ventricular hypertrophy. LVMI was measured by echocardiogram at baseline and at 1 and 7 yr. Renal function was assessed by measuring serum creatinine and 24-h creatinine clearance every 6 mo for 3 yr, then annually for an additional 4 yr. The baseline characteristics were comparable in the two groups. During the study, average mean arterial pressure was 90 +/- 5 mmHg for the rigorous group and 101 +/- 4 mmHg for the standard group (P < 0.0001). The LVMI decreased by 21% in the standard group and by 35% in the rigorous group. A mixed model longitudinal data analysis revealed that rigorous BP control was significantly more effective in decreasing LVMI (P < 0.01). There was no statistically significant difference in renal function between the two groups. In conclusion, left ventricular hypertrophy, a major cardiovascular risk factor, was decreased to a significantly greater extent by rigorous than standard BP control. This finding has particular clinical importance because cardiovascular complications are the most common cause of death in ADPKD patients.",2002.0,0,0
1003,12089891,[Captopril in the treatment of acute myocardial infarction. Hypotension as an important clinical problem].,Michał Wierzchowiecki; Katarzyna Szymanowska; Kajetan Poprawski; Tadeusz Krzyś; Andrzej Sieńko; Barbara Michałowicz; Marek Michalski; Anna Juszczak,"The aim of study was to analyze the effect of captopril (C) on blood pressure in patients with acute myocardial infarction (AMI) during 1 year treatment. Patients less then 70 years old with systolic blood pressure (sBP) > or = 100 mm Hg were qualified to the study. Administration of C was started during the first 4 days of AMI (mean 21 +/- 24 h). 50 pts treated with C and control group of 43 pts were finally analyzed. Doses of C were gradually increased from 3.125 t.i.d. on the first day till 25 mg t.i.d. on the 4th day. Significant decrease of sBP after administration of C was observed at 60 and 120 min after the 1st, 2nd and 3rd dose on the first day, and after 30-120 min after first C dose on the 4th day. dBP decreased only at 60-120 min after the 1st dose on first day and at 90 min after the first dose on 4th day. Hypotension after 1st and 2nd dose of C on the first day caused exclusion of 3 pts (6%) from the study. In conclusion, hypotension seems to be quite often encountered during captopril therapy of early phase of AMI. It appears not only after the first but also after the following doses. The initial dose of 3.125 mg seems to be safe and sufficient to assess its hypotensive action.",2002.0,0,0
1004,12092742,Comparative effects on dynamic renal potassium excretion of ACE inhibition versus angiotensin receptor blockade in hypertensive patients with type II diabetes mellitus.,Richard A Preston; Neyton M Baltodano; Alberto B Alonso; Murray Epstein,"Both ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) are renoprotective beyond their effects on blood pressure (BP), but their widespread use is limited by their tendency to provoke hyperkalemia. The comparative effects of ACEI and ARB on potassium handling have not been investigated. The objective of this study was to determine whether there are differences in dynamic renal potassium handling between ACEI and ARB in response to an oral potassium challenge. This was a randomized crossover study of candesartan versus lisinopril titrated to control BP followed by an inpatient study of renal potassium handling in 24 hypertensive patients with type II diabetes mellitus (DMII) and preserved renal function. Following an oral potassium challenge (0.75 mmol/kg), differences in hourly serum K (mmol/L), rate of urinary potassium excretion (UkV, micromol/min), and fractional excretion of potassium (FEK) were assessed by repeated-measures ANOVA. Hourly UkV(p = .45) and FEK (p = .19) were similar for candesartan and lisinopril, although FEK at 2 hours for candesartan tended to exceed that for lisinopril (.34 [.04] vs. .26 [.03]) and approached significance (p = .096). UkVfor candesartan at hour 2 was 177 (26) and 121 (21) for lisinopril and also approached significance (p = .10). Serial serum potassium did not differ (p = .70). No statistical differences were discovered in renal potassium handling between candesartan and lisinopril in patients with DMII and preserved renal function. Whether there are differences between the drug classes in renal impairment remains to be determined.",2003.0,0,0
1005,12097849,"Hydroxyethyl starch for hypervolemic hemodilution in patients with acute ischemic stroke: a randomized, placebo-controlled phase II safety study.",J Rudolf; HES in Acute Stroke Study Group,"Hypervolemic hemodilution (HH) with hydroxyethyl starch (HES) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window. The objective of this study was to investigate the safety of a 10% solution of HES 130/0.4 versus 0.9% saline solution in acute ischemic stroke by the incidence of adverse events (AEs). In a controlled, double-blind, randomized, multicenter, phase II, parallel-group study, 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a randomization ratio of 2:1 in favor of HES therapy. There were no significant differences between the groups with regard to the incidence of the specific AEs (cardiovascular events, bleeding complications, allergic reactions) assessed over days 1-30, or mortality over days 1-8. In addition, global tests of efficacy showed a trend towards a better functional outcome with HES therapy; however, the study was not designed to prove efficacy. High-dose HH with HES or NaCl was generally safe and well tolerated. Safety profiles were similar for the two treatment groups, and there was a nonsignificant trend towards a better functional outcome with HES therapy.",2003.0,0,0
1006,12105139,"Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).","Charles G C Spencer; David Gurney; Andrew D Blann; D Gareth Beevers; Gregory Y H Lip; ASCOT Steering Committee, Anglo-Scandinavian Cardiac Outcomes Trial","To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P=0.002,) and a greater proportion of smokers, 31% versus 16% (P=0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P<0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.",2002.0,0,0
1007,12106847,Frequency of postprandial lipemia after a first acute coronary event (unstable angina pectoris or non-ST-segment elevation acute myocardial infarction) and the effects of atenolol on the lipemia.,Fernando Boccalandro; Jennifer Farias; Cristina Boccalandro; Dan Vaisman,,2002.0,0,0
1008,12106850,Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pectoris or non-Q-wave acute myocardial infarction.,Luis C L Correia; Andrei C Spósito; Luiz C S Passos; José C Lima; Júlio C Braga; Mário S Rocha; J Péricles Esteves; Argemiro D'Oliveira,,2002.0,0,0
1009,12106937,Efficacy of angiotensin-converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients.,Daniel L Dries; Mark H Strong; Richard S Cooper; Mark H Drazner,"This study was undertaken to determine whether enalapril had comparable efficacy in black and white patients with asymptomatic left ventricular dysfunction (ALVD) in preventing the development of symptomatic heart failure (HF). Recent studies have suggested that black patients with HF due to systolic dysfunction may derive less benefit than white patients with HF when treated with the same medication. This is a post hoc analysis of the 4,054 black and white participants of the Studies of Left Ventricular Dysfunction Prevention Trial. Randomization to enalapril was associated with a comparable reduction in the relative risk of the development of symptomatic HF in black (relative risk [RR] 0.67, 95% confidence interval [CI] 0.49, 0.92, p = 0.01) and white patients (RR 0.61, 95% CI 0.53, 0.70, p < 0.001). Treatment with enalapril was also associated with a comparable reduction in the risk of the development of HF requiring medical therapy and the composite end point of death or development of HF in black and white patients. Black as compared with white patients with ALVD were at increased risk of the development of symptomatic HF (RR 1.81, 95% CI 1.51, 2.17, p < 0.001) despite adjustment for available measures of disease severity. Despite the increased absolute risk in black patients compared with white patients for the progression of ALVD, enalapril was equally efficacious in reducing the risk of progression of ALVD in these two ethnic groups.",2002.0,0,0
1010,12107420,The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy.,Finlay A McAlister; Kelly B Zarnke; Norman R C Campbell; Ross D Feldman; Mitchell Levine; Jeff Mahon; Steven A Grover; Richard Lewanczuk; Frans Leenen; Sheldon Tobe; Marcel Lebel; James Stone; Ernesto L Schiffrin; Simon W Rabkin; Richard I Ogilvie; Pierre Larochelle; Charlotte Jones; George Honos; George Fodor; Ellen Burgess; Pavel Hamet; Robert Herman; Jane Irvine; Bruce Culleton; James M Wright; Canadian Hypertension Recommendations Working Group,"To provide updated, evidence-based recommendations for the therapy of hypertension in adults. For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. A high value was placed on the avoidance of cardiovascular morbidity and mortality. Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.",2002.0,0,0
1011,12109041,From toxic precursors to safe drugs. Mechanisms and relevance of idiosyncratic drug reactions.,Karl-Uwe Petersen,"In adverse drug reactions, effects accounted for by the pharmacological profile of the drug may be distinguished from sometimes bizarre, unpredictable events (""idiosyncrasies""). In the majority of cases, the latter are due to reactive intermediates formed by members of the cytochrome P450 family of enzymes. These products are usually formed at very low quantities. However, genetic disposition (e.g. by enhanced expression of the catalyzing enzyme or failure of protective factors such as glutathione) or certain external conditions (for example comedication of inducers of drug metabolism) may lead to toxic intermediates being available at relevant quantities. Once generated, these metabolites will react with macromolecules and finally cause cell necrosis. Necrosis may result from direct damage to functions essential to the cell or be secondary to harmful immune reactions activated by recognition of the new structures as neoantigens. As the principal site of drug metabolism, the liver is most frequently affected by idiosyncratic reactions, which often enough are recognized only after large numbers of patients have been treated. The idiosyncratic potential of a drug relates to its chemical structure rather than its pharmacological mechanism. Risks are evident if biotransformation yields products with chemical substructures such as quinones, phenoles, acyl halides, aromatic and hydroxyl amines. There are numerous cases of precursor drugs with idiosyncratic potential that have been replaced or marginalized by agents with more favorable chemical properties. Examples include beta 1-preferential beta-adrenoceptor antagonists (toxic precursor: practolol) and the choline esterase inhibitors used in treatment of Alzheimer's disease. In the latter group, tacrine (CAS 321-64-2) gives rise to high liver enzyme levels in about 30% of the patients, an effect not shared with more recent, chemically different entities. A similar case can be made for the insulin sensitizer troglitazone (CAS 97322-87-7) (marketed, now withdrawn in the USA) and its successors rosiglitazone (CAS 122320-73-4) and pioglitazone (CAS 111025-46-8). Due to its different chemical structure, only troglitazone can be transformed into a reactive quinone metabolite, a process that may be accelerated by the drug inducing its own metabolism. In agreement with this view, there is no evidence of specific hepatic toxicity with the two successor drugs. Ongoing progress in molecular toxicology may aid in minimizing idiosyncratic hazards already at early stages of drug development.",2002.0,0,0
1012,12113598,Stopping smoking slows accelerated progression of renal failure in primary renal disease.,Helmut Schiffl; Susanne M Lang; Rainald Fischer,"Cigarette smoking accelerates the progression of renal failure in primary kidney diseases. It is not known, however, whether stopping smoking slows this accelerated loss of renal function. 45 patients with progressive primary nephropathies (glomerulonephritis or tubulointerstitial nephritis) and moderate renal failure were encouraged to stop heavy cigarette smoking (1-2 packs per day); 26 patients refused to change their smoking habits (current smokers), and 16 successfully stopped (ex-smokers) during the 24 month study period. Carboxyhemoglobin and creatinine clearance were measured every six months. The primary end-point of the study was end-stage renal disease requiring renal replacement therapy. There were no significant differences between the two patient groups in demographic, renal and treatment characteristics at the start of the study. Current and ex-smokers had similar rates of decline of creatinine clearance during the 24 months before the investigations. Compared to ex-smokers or matched non-smoking renal patients, permanent smokers had a significantly faster decline in creatinine clearance during the two-year study period. Renal replacement therapy had to be started in six smokers, but only in one ex-smoker and none of the non-smokers during the study period. Giving up smoking slowed the rapid progression of renal failure, but did not reverse the loss of renal function induced by smoking. We recommend that increased efforts should be made to encourage renal patients to give up smoking in order to prolong dialysis-free kidney survival.",2003.0,0,0
1013,12117852,Effects of combined treatment with enalapril and losartan on myocardial function in heart failure.,G Cocco; S Kohn; P Jerie,,2002.0,0,0
1014,12118904,"Angiotensin converting enzyme inhibition and angiotensin II AT1-receptor blockade reduce the levels of asymmetrical N(G), N(G)-dimethylarginine in human essential hypertension.",Christian Delles; Markus P Schneider; Stefan John; Michael Gekle; Roland E Schmieder,"Asymmetrical N(G), N(G)-dimethylarginine (ADMA) is associated with impaired endothelium-dependent vasodilation in humans. Twenty young, male, mildly hypertensive subjects were included in a randomized, double-blind, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or a combination of both drugs (10 and 300 mg/day, respectively) each over 1 week, followed by a 2-week wash-out phase. After each treatment phase, ADMA concentration was measured. ADMA concentration was 1.69+/-0.59 micromol/L in the placebo phase, and was significantly lower in the enalapril, eprosartan, and combination phases (1.41+/-0.29, 1.42+/-0.43, and 1.38+/-0.30 micromol/L, respectively; all P < 0.05 v placebo). Changes in ADMA levels were independent of the drugs' action on blood pressure (BP). Levels of ADMA were reduced with enalapril and eprosartan therapy. Our results suggest a specific action of these drugs on ADMA levels that is independent of BP.",2003.0,0,0
1015,12123409,Successful blood pressure control in the African American Study of Kidney Disease and Hypertension.,Jackson T Wright; Lawrence Agodoa; Gabriel Contreras; Tom Greene; Janice G Douglas; James Lash; Otelio Randall; Nancy Rogers; Michael C Smith; Shaul Massry; African American Study of Kidney Disease and Hypertension Study Group,"The African American Study of Kidney Disease and Hypertension (AASK) is an ongoing trial to evaluate the effect of blood pressure and choice of antihypertensive drug on the rate of decline of renal function. To present the success of the AASK in achieving the trial's rigorous blood pressure goals in an extremely challenging patient population. The AASK participants included African American patients with hypertension (n = 1094), aged 18 to 70 years, with glomerular filtration rates between 20 and 65 mL/min per 1.73 m(2) and no other identified causes of renal insufficiency. Participants were randomized to a goal mean arterial blood pressure (MAP) of either 102 to 107 mm Hg (usual MAP goal) or 92 mm Hg or less (low MAP goal). Participants in each of these groups were also randomized (double-blind) to a regimen containing metoprolol succinate, ramipril, or amlodipine besylate. Additional agents were added, if required, in the following recommended order: furosemide, doxazosin mesylate, clonidine hydrochloride, or hydralazine hydrochloride (or minoxidil, if needed). In participants randomized to the low MAP goal, the percentage of participants who achieved a blood pressure of less than 140/90 mm Hg increased from a baseline of 20.0% to 78.9% by 14 months after randomization. For usual MAP goal participants, the corresponding percentages increased from 21.5% to 41.8%. The difference in median levels of MAP between the 2 MAP goal groups increased and remained at approximately 12 mm Hg. Blood pressure reduction was similar regardless of age, sex, body mass index, education, insurance or employment status, income, or marital status. The blood pressure goals set and achieved in AASK participants clearly demonstrate that adequate blood pressure control can be achieved even in hypertensive populations whose blood pressure is the most difficult to control.",2002.0,0,0
1016,12125952,Cold urticaria and angiotensin converting enzyme inhibitor.,Birger Kränke; Sigrid Mayr-Kanhäuser,,2002.0,0,0
1017,12126263,Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild to moderate essential hypertension.,Brian N C Prichard; Bodo A Jäger; Joachim H Luszick; Leslie J Küster; Caes N Verboom; Peter R Hughes; Wilhelm Sauermann; Hartmut E Küppers,"To compare the antihypertensive efficacy and tolerability of the imidazoline I1-receptor agonist moxonidine, administered as a single daily dose of 0.6 mg, with the angiotensin-converting enzyme inhibitor enalapril (20 mg o.d.) in patients with mild to moderate essential hypertension. A total of 154 patients were enrolled and randomized to placebo (n = 50), moxonidine (0.2 mg o.d.; n = 51) or enalapril (5 mg o.d.; n = 53) for 2 weeks. Dosages were then increased to moxonidine 0.6 mg o.d. or enalapril 20 mg o.d. for a further 6 weeks. Blood pressure responses to therapy were measured using conventional office techniques and by 24-h ambulatory blood pressure monitoring. The average reduction in sitting blood pressure with moxonidine was similar to that achieved with enalapril (24.9 +/- 20.7/13.2 +/- 8.4 mmHg vs 21.9 +/- 17.1/11.9 +/- 7.5 mmHg, respectively) and significantly superior to that seen with placebo (1.2 +/- 14.4/2.3 +/- 7.0 mmHg; p < 0.001). Reductions in blood pressure after 8 weeks of treatment were as follows: moxonidine, from 166.2 +/- 15.5/101.3 +/- 4.0 to 141.2 +/- 15.7/88.1 +/- 7.7mmHg; enalapril, from 165.4 +/- 14.3/101.1 +/- 4.4 to 143.5 +/- 12.7/89.2 +/- 7.4 mmHg; and placebo, from 162.5 +/- 14.4/99.9 +/- 3.9 to 161.3 +/- 17.9/97.6 +/- 6.6 mmHg. Both moxonidine and enalapril produced sustained reductions in blood pressure during 24-h recording (p < 0.01 for overall effect of either drug vs placebo). Average 24-h blood pressure was reduced from 149.8 +/- 14.3/92.2 +/- 7.0 to 134.0 +/- 13.1/82.3 +/- 8.9 mmHg with moxonidine and from 146.5 +/- 13.0/ 92.5 +/- 7.2 to 131.1 +/- 11.0/82.1 +/- 8.8 mmHg with enalapril; the change with placebo was small (from 147.3 +/- 13.3/90.0 +/- 6.2 to 144.8 +/- 12.9/89.5 +/- 8.0 mmHg). Both drugs were generally well tolerated. No patients withdrew from the study because of drug-attributed adverse events. Moxonidine 0.6 mg o.d. and enalapril 20 mg o.d. have similar antihypertensive efficacy.",2003.0,0,0
1018,12126264,Long-term exposure to telmisartan as monotherapy or combination therapy: efficacy and safety.,Frank Freytag; Nicolaas J Holwerda; Bengt E Karlberg; Thomas W Meinicke; Helmut Schumacher,"This multicentre, open-label extension study to four controlled trials involved 888 patients with mild-to-moderate primary hypertension. Patients received telmisartan 40-80 mg once daily with add-on hydrochlorothiazide (HCTZ; 12.5-25 mg) if necessary and/or other antihypertensives to achieve diastolic blood pressure (DBP) control (<90 mmHg). Treatment continued for up to 4 years. At treatment end, 578 (65.1%) patients were on telmisartan monotherapy, 106 (11.9%) were on telmisartan + HCTZ 12.5 mg, 101 (11.4%) were on telmisartan + HCTZ 25 mg, and 103 (11.6%) were on telmisartan + another antihypertensive + HCTZ. Overall, 84.4% (746/884) patients achieved DBP control. The highest proportion of responders was in the telmisartan monotherapy (40 or 80 mg) treatment category (89.0% 1,511/574 patients]). The mean change in systolic blood pressure (SBP)/DBP from the previous trial baseline to last available trough was -21.2/-17.3 mmHg with telmisartan alone, -24.6/-16.7 mmHg with telmisartan + HCTZ, and - 18.7/-14.9 mmHg with telmisartan + another antihypertensive +/- HCTZ. Most adverse events were of mild-to-moderate intensity and unrelated to treatment. The proportions of patients discontinuing the study due to adverse events, by treatment at onset, were 7.3% (65/888) with telmisartan monotherapy, 6.6% (20/304) with telmisartan + HCTZ and 2.9% (3/103) with telmisartan + another antihypertensive +/- HCTZ. There were 15 deaths during the study, but none was considered drug related. Thus, telmisartan alone or in combination with other antihypertensives achieved and maintained clinically relevant reductions in DBP and SBP. This long-term analysis supports the favourable efficacy and safety profile of telmisartan both as monotherapy and in combination with other antihypertensive drugs.",2003.0,0,0
1019,12135934,Beta-blockers in the post-myocardial infarction patient.,Mihai Gheorghiade; Sidney Goldstein,,2002.0,0,0
1020,12136395,Effects on heart rate variability of metoprolol supplementary to ongoing ACE-inhibitor treatment in Type I diabetic patients with abnormal albuminuria.,E Ebbehøj; P L Poulsen; K W Hansen; S T Knudsen; H Mølgaard; C E Mogensen,"Diabetic nephropathy is associated with a high risk of cardiac mortality including sudden death. This is presumably related to an imbalance between sympathetic and parasympathetic tone resulting in a decreased heart rate variability (HRV). In non-diabetic patients a decreased HRV is known to be a strong predictor of cardiovascular death. Studies in non-diabetic patients have shown that beta-blockers improve HRV parameters known to reflect parasympathetic function. The aim of our study was to investigate effects of additional beta-blocker treatment on: cardiac autonomic function, blood pressure, and urine albumin excretion in ACE-inhibitor treated Type I (insulin-dependent) diabetes mellitus patients with abnormal albuminuria. We studied the effects of 6 weeks treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in 20 patients participating in a randomised, placebo controlled, double blind, crossover trial. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording, and 24-h fractionated urine collections. Heart rate variability was assessed by four different methods; ambulatory HRV analysis was carried out by spectral and time domain analysis, and on days of investigation short-term spectral analysis and bed-side tests were carried out. Metoprolol treatment improved in vagal tone assessed by short-term spectral analysis. The 24-h ambulatory HRV analysis showed improvement in some parameters reflecting vagal function. A minor decrease in daytime diastolic blood pressure was shown, no alterations in diurnal variation of blood pressure or urine albumin excretion were observed. These preliminary findings indicate that beta-blocker treatment could improve autonomic function in Type I diabetic patients with abnormal albuminuria and an associated high risk of cardiovascular disease.",2003.0,0,0
1021,12140805,The prognostic importance of different definitions of worsening renal function in congestive heart failure.,Stephen S Gottlieb; William Abraham; Javed Butler; Daniel E Forman; Evan Loh; Barry M Massie; Christopher M O'connor; Michael W Rich; Lynne Warner Stevenson; James Young; Harlan M Krumholz,"Worsening renal function in patients hospitalized for heart failure portends a poor prognosis. However, criteria used to define worsening renal function are arbitrary, and the implications of different definitions remain unclear. We therefore compared the prognostic importance of various definitions of worsening renal function in 1,002 patients hospitalized for congestive heart failure (CHF). The patient population was 49% female, aged 67 +/- 15 years. Twenty-three percent had a prior history of renal failure, 73% had known depressed ejection fraction, and 63% had known CHF. On admission to the hospital, 47% were receiving ACE inhibitors, 22% beta-blockers, 70% diuretics and 6% NAID's. 72% developed increased serum creatinine during the hospitalization, with 20% developing an increase of > or = 0.5 mg/dL. Worsening renal function predicted both in-hospital mortality and length of stay > 10 days. Even an increased creatinine of 0.1 mg/dL was associated with worse outcome. Sensitivity for death decreased from 92% to 65% as the threshold for increased creatinine was raised from 0.1 to 0.5 mg/dL, with specificity increasing from 28% to 81%. At a threshold of a 0.3 mg/dL increase, sensitivity was 81% and specificity was 62% for death and 64% and 65% for length of stay >10 days. Adding a requirement of final creatinine of > or = 1.5 mg/dL improved specificity. This analysis demonstrates that any detectable decrease in renal function is associated with increased mortality and prolonged hospital stay. This suggests that therapeutic interventions which improve renal function might be beneficial.",2002.0,0,0
1022,12141320,Do the investigative sites that take part in a positive clinical trial translate that evidence into practice?,Sumit R Majumdar; Wei-Ching Chang; Paul W Armstrong,"The earliest awareness of new evidence should beat the trial sites that first generated the evidence. We hypothesized that sites that had taken part in the Survival and Ventricular Enlargement (SAVE) trial, which demonstrated that angiotensin-converting enzyme (ACE) inhibitors were beneficial following myocardial infarction, would be more likely to adopt their use in this group of patients. We performed a cross-sectional analysis of data collected for the 25,886 North American patients with myocardial infarction enrolled in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) study from 1990 to 1993. Patients were treated at 659 hospitals, 22 of which had also taken part in SAVE. One third of patients were enrolled after SAVE was published in 1992. The primary outcome was use of an ACE inhibitor at discharge. We analyzed the data using hierarchical models and multivariate regression. Patients treated at sites that had taken part in SAVE were not more likely to receive an ACE inhibitor at discharge than were patients treated at non-SAVE sites (226/1415 [16%] vs. 3671/24,471 [15%]; odds ratio [OR] = 1.1; 95% confidence interval [CI]: 0.8 to 1.4; P = 0.67). Although patients with heart failure were more likely to receive ACE inhibitors than were those without heart failure, there was no difference between SAVE and non-SAVE sites (90/297 [30%] vs. 1322/4405 [30%]; P = 0.75). Use of ACE inhibitors increased following the publication of the SAVE trial, but again there was no significant difference in adoption of the drug between SAVE and non-SAVE sites. Sites that had taken part in SAVE were no more likely to adopt ACE inhibitors for patients with myocardial infarction than were sites that had not taken part. If those who generated the evidence are slow to translate it into practice, it is unlikely that passive forms of dissemination can improve the quality of care. To accelerate adoption of new evidence, we need to understand factors other than knowledge and awareness that influence practice.",2002.0,0,0
1023,12147929,"Essential hypertension of Caribbean Hispanics: sodium, renin, and response to therapy.",Cheryl L Laffer; Fernando Elijovich,"Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest-growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double-blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3-4 weeks on placebo. Blood pressure responses to angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8-12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low-renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and beta blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low-renin type. Responses to therapy are consistent with those observed in other populations with the low-renin phenotype and suggest salt-sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics.",2002.0,0,0
1024,12149103,Effects of enalapril and losartan on circulating adhesion molecules and monocyte chemotactic protein-1.,B Jilma; F L Li-Saw-Hee; O F Wagner; D G Beevers; G Y H Lip,"At least four independent studies in different clinical settings showed that angiotensin-converting enzyme inhibitors (ACE-Is) such as enalapril effectively decrease plasma levels of circulating adhesion molecules (cAMs). To examine whether this effect may be mediated by the decreased action of angiotensin, we compared the effects of enalapril with the direct angiotensin-II antagonist, losartan, on plasma levels of cAMs, and monocyte chemotactic protein-1 (MCP-1). In a randomized trial, we recruited 32 untreated patients (19 male, aged 59+/-13 years) with hypertension, who received either enalapril (mean dose 17 mg/day) or losartan (mean dose 77 mg/day) at equipotent doses. Enalapril decreased plasma levels of all cAMs after 8 weeks of treatment: cE-selectin levels decreased by 13% (P=0.007), intercellular adhesion molecule-1 (cICAM-1) by 15% (P=0.002) and vascular cell adhesion molecule-1 (cVCAM-1) by 19% (P=0.003). Similarly, enalapril decreased plasma levels of MCP-1 by 13% (P<0.001). Losartan did not significantly change cAM or MCP-1 plasma concentrations after 8 weeks of treatment: cE-selectin levels decreased by 3%, cICAM-1 by 5%, cVCAM-1 by 8%, whereas MCP-1 increased by 2% (all P=NS; not significant). The enalapril effect on percentage changes of cVCAM-1 was significantly different from losartan (P=0.0429). Eight weeks of antihypertensive treatment with enalapril but not losartan, significantly decreased plasma levels of cAMs and MCP-1 in hypertensive patients. The beneficial effects of ACE-Is on cAMs may have implications for atherogenesis and the reduction of cardiovascular events, which cannot be fully explained by their antihypertensive effects alone.",2002.0,0,0
1025,12149106,Long-term angiotensin-converting enzyme inhibition with ramipril reduces thrombin generation in human hypertension.,Mikael Ekholm; N Håkan Wallén; Hans Johnsson; Keith Eliasson; Thomas Kahan,"Antihypertensive treatment reduces the risk of thromboembolic events in hypertension. The aim of this study was to examine the influence of angiotensin-converting enzyme inhibition on blood coagulation in subjects with mild-to-moderate essential hypertension. Fibrinogen, thrombin-antithrombin complex (TAT) and Factor VII were determined in plasma at rest and after a mental stress test following placebo for 6 weeks, or ramipril for 6 weeks or 6 months. Ramipril reduced resting TAT, and tended to reduce fibrinogen; Factor VII remained unchanged. Mental stress increased fibrinogen, but did not alter TAT or Factor VII activity. The reduced thrombin generation in patients taking ramipril may explain in part why angiotensin-converting enzyme inhibitors reduce thromboembolic complications in patients with cardiovascular disease.",2002.0,0,0
1026,12149661,"Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.",Z Hlubocká; V Umnerová; S Heller; J Peleska; A Jindra; M Jáchymová; J Kvasnicka; K Horký; M Aschermann,"The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Willebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.",2002.0,0,0
1027,12149663,A population-based European cohort study of persistence in newly diagnosed hypertensive patients.,J Hasford; A Mimran; W R Simons,"This study assessed the percentage of patients after 1 year who persisted on initially prescribed antihypertensive therapy. Medical records of 2416 patients with newly diagnosed hypertension who were prescribed initial antihypertensive monotherapy by general practitioners in Germany, France, and the United Kingdom were evaluated. Comparisons were made among the angiotensin II receptor antagonist (AIIRA) irbesartan, all other antihypertensive classes (including AIIRAs other than irbesartan), and the AIIRA losartan. Patients initiated on the AIIRA irbesartan scored highest with a persistence rate of 60.8%, followed by patients who received all other AIIRA agents with a persistence rate of 51.3%. Angiotensin-converting enzyme inhibitors, calcium channel blockers, beta-blockers, and losartan were associated with comparable persistence rates, between 42.0% and 49.7%. Patients who received diuretics scored lowest with a persistence rate of 34.4%. Persistence has emerged as an essential factor for blood pressure control. Prescribing an antihypertensive agent that provides a favourable efficacy and tolerability profile may provide greater persistence with therapy and hence a higher level of blood pressure control.",2002.0,0,0
1028,12149667,Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.,F Franchi; C Lazzeri; M Foschi; C Tosti-Guerra; G Barletta,"Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.",2002.0,0,0
1029,12152252,[The effect of aspirin on rheological properties of erythrocytes in essential hypertension].,Renata A Korbut; Teresa Adamek-Guzik,"Essential hypertension is one of the most important risk factors for cardiovascular diseases. Its pathophysiological mechanism is unknown. Recent data suggests that deformability and aggregation of red blood cells may play an important role in the regulation of blood rheology in hypertension. Simultaneously there are reports suggesting that antihypertensive effects of angiotensin converting enzyme inhibitors (ACEI) could be counteracted by high doses of aspirin. We postulate that these effects could be related to the changes in blood rheology. Accordingly we designed a study to evaluate the effect of low or high dose of aspirin on deformability and aggregability of red blood cells from patients with essential hypertension. Deformability and aggregability of red blood cells were measured by laser diffractometer (Rheodyn SSD, Myrenne GmbH) and computerized automatic aggregometer (MA1 Myrenne GmbH, Germany), respectively. The effects of aspirin on deformability and aggregation of red blood cells were studied ex vivo in whole blood from three groups of patients with essential hypertension (group I: 10 patients receiving placebo, group II: 23 patients receiving 75 mg/day p.o. aspirin for 3 days, and group III: 23 patients receiving 300 mg/day p.o. aspirin for 3 days). Subjects in all groups received the same combination of antihypertensive agents consisting of: one of ACEI (enalapril or perindopril), one of beta-antagonists (metoprolol or bisoprolol), and diuretic agent (indapamid). In patients receiving high dose of aspirin (300 mg/day) we observed that erythrocyte aggregability was 25% higher than in the placebo group (MEA = 25.8 +/- 6 SD, vs MEA = 20.6 +/- 3 SD, p < 0.05). Aspirin had no effects on deformability of erythrocytes or on arterial blood pressure. High doses of aspirin or possibly also other nonsteroidal anti-inflammatory drugs (NSAID) in patients receiving antihypertensive therapy can directly affect rheological properties of the blood due to the activation of red blood cell aggregation. Increased aggregation of red blood cells during antihypertensive therapy may be an important indicator of the worsening of organ perfusion.",2002.0,0,0
1030,12153550,Amadori-albumin correlates with microvascular complications and precedes nephropathy in type 1 diabetic patients.,C G Schalkwijk; N Chaturvedi; H Twaafhoven; V W M van Hinsbergh; C D A Stehouwer; EUCLID Study Group,"Amadori-albumin, a major glycated protein, is involved in experimental hyperglycaemia-induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori-albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low-degree inflammation therein. Amadori-albumin, the Amadori product of haemoglobin (HbA1c), C-reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2-year randomised, double-blind, placebo-controlled trial of lisinopril in 447 Type I diabetic patients. Retinal photographs were taken in 341 patients at baseline and 294 at follow up. Amadori-albumin was positively associated with albumin the excretion rate and retinopathy status (P = 0.0001 and P = 0.02 for trend, respectively) and with the progression from normoalbuminuria to (micro)albuminuria (38.6 U mL(-1) in nonprogressors, 44.3 U mL-1 in progressors; P = 0.02), but not with the development or progression of retinopathy during a 2-year follow up. Amadori-albumin levels at baseline were associated with C-reactive protein and fibrinogen (P = 0.0007 and P = 0.0001, respectively). C-reactive protein and fibrinogen were also associated with albumin excretion rates (P = 0.03 and P = 0.01, respectively) and retinopathy status (P = 0.02 and P = 0.0006, respectively). Adjustment for these inflammatory markers did not markedly attenuate the association between Amadori-albumin and the albumin excretion rate, while adjustment for fibrinogen, but not C-reactive protein, abolished the association between Amadori-albumin and retinopathy. Lisinopril had no impact on the association between the levels of Amadori-albumin and albumin excretion rates or retinopathy. Amadori-albumin was associated with early nephropathy and with retinopathy in Type I diabetic patients and preceded an increase in albumin excretion rate, but not retinopathy. A chronic low-degree inflammation does not appear to be involved in Amadori-albumin-associated microvascular complications in Type I diabetes.",2003.0,0,0
1031,12154100,Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients.,Henry Krum; Hector Nolly; Diane Workman; Weizhong He; Barbara Roniker; Scott Krause; Kaffa Fakouhi,"The efficacy and tolerability of eplerenone, a selective aldosterone blocker, was assessed when added to existing antihypertensive therapy with an ACE inhibitor or an angiotensin II receptor blocker (ARB). Hypertensive patients (n=341) whose blood pressure (BP) was not controlled despite ACE inhibitor or ARB were randomized (double-blind) to receive 50 mg eplerenone (increasing to 100 mg if required) once daily or placebo for 8 weeks. Diastolic and systolic BP and adverse events were recorded. By study end (week 8), mean seated diastolic BP was significantly reduced from week 0 among patients receiving eplerenone/ARB (-12.7+/-0.81 mm Hg) compared with those receiving placebo/ARB (-9.3+/-0.83 mm Hg). The change in mean seated diastolic BP was -9.9+/-0.88 mm Hg in eplerenone/ACE inhibitor patients and -8.0+/-0.86 mm Hg in placebo/ACE inhibitor patients (P=NS). Systolic BP levels were also significantly lower at week 8 for eplerenone/ACE inhibitor (-13.4+/-1.35 mm Hg) and eplerenone/ARB (-16.0+/-1.37 mm Hg) patients, respectively, compared with placebo/ACE inhibitor (-7.5+/-1.31 mm Hg) and placebo/ARB patients (-9.2+/-1.41 mm Hg). Adverse events were generally nonsevere and not significantly different between eplerenone and placebo. This study demonstrated that in patients whose BP was not controlled with an ACE inhibitor or ARB, the addition of eplerenone over an 8-week period significantly lowered systolic BP in both groups and diastolic BP in ARB patients. Selective aldosterone blockade with eplerenone, therefore, may be useful add-on therapy in hypertensive patients inadequately controlled on ACE inhibitor or ARB alone.",2002.0,0,0
1032,12160198,Skeletal muscle magnesium content is correlated with plasma glucose concentration in patients with essential hypertension treated with lisinopril or bendrofluazide.,Arvo Haenni; Rikard Reneland; Per-Erik Andersson; Lars Lind; Hans Lithell,"The association between change in glucose metabolism and change in skeletal muscle magnesium (Mg) concentration induced by antihypertensive treatment was evaluated in 37 patients with essential hypertension randomly treated with either lisinopril or bendrofluazide. Before and after 6 months of treatment, skeletal muscle biopsies were performed, glucose tolerance was determined by oral (OGTT) and intravenous glucose tolerance tests (IVGTT), and insulin sensitivity was assessed by the hyperinsulinemic euglycemic clamp technique. An inverse relationship was found between the treatment-induced change in fasting plasma glucose concentration and change in skeletal muscle Mg concentration (r = -0.39, P < .05). However, there was no significant correlation between skeletal muscle Mg content and either insulin sensitivity measured by the hyperinsulinemic euglycemic clamp test or glucose tolerance evaluated by IVGTT and OGTT. In conclusion, an increased circulating glucose concentration was correlated with a decreased Mg concentration in skeletal muscle during antihypertensive treatment. However, the Mg concentration in skeletal muscle did not significantly predict the insulin sensitivity or glucose tolerance.",2003.0,0,0
1033,12162469,"A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension.",Thomas Wells; Virginia Frame; Beth Soffer; Wayne Shaw; Zhongxin Zhang; Pamela Herrera; Shahnaz Shahinfar; Enalapril Pediatric Hypertension Collaborative Study Group,"Despite widespread use to treat childhood hypertension, enalapril has never been studied systematically to determine effectiveness, dose response, and safety in a pediatric population. This study was conducted prospectively in 110 hypertensive children ages 6 to 16 years in two sequential phases. The primary outcome variable for both phases of the study was trough (24-h postdose) sitting diastolic blood pressure. The primary objective of the first phase of the study was to determine whether enalapril lowered blood pressure in children in a dose-dependent manner. During a 2-week, double-blind, randomized, dose-response period, patients were stratified by weight (< 50 kg or > or = 50 kg), then assigned to one of three dosing groups: low(0.625 or 1.25 mg), middle (2.5 or 5 mg), or high dose (20 or 40 mg). Reduction in blood pressure was examined as a function of dose ratio (1:4:32) and on a weight-adjusted basis. On completion of the dose-response phase of the study, patients entered a 2-week, double-blind, randomized withdrawal to either enalapril or placebo. Antihypertensive effectiveness, defined as the difference in sitting diastolic blood pressure between the placebo and enalapril groups, was determined. Adverse events were carefully recorded throughout the study. The dose-response relationship for enalapril had a negative slope and was linear over the chosen dosing range, suggesting that larger doses of enalapril were associated with a greater reduction in blood pressure. Randomized withdrawal to active drug orplacebo confirmed the antihypertensive effectiveness of enalapril in the middle- and high-dose groups. The antihypertensive effect of enalapril was maintained across age, gender, race, and Tanner stage. Enalapril appears to be an effective and generally well-tolerated antihypertensive agent in children ages 6 to 16 years. An initial dose of 2.5 mg in children weighing < 50 kg and 5 mg in children weighing > 50 kg (mean = 0.08 mg/kg) administered once daily effectively lowered blood pressure within 2 weeks in most patients. Blood pressure was reduced in a dose-dependent fashion, with larger doses resulting in a greater reduction.",2003.0,0,1
1034,12164885,Effect of high dose ramipril with or without indomethacin on glomerular selectivity.,Roberto Pisoni; Piero Ruggenenti; Fabio Sangalli; Maria Serena Lepre; Andrea Remuzzi; Giuseppe Remuzzi,"Despite the accumulating evidence of their efficacy, angiotensin-converting enzyme inhibitors (ACEi) still provide imperfect renoprotection. Up-titration above conventional doses and combined therapy with other antiproteinuric agents may serve to achieve renoprotection in patients at risk of rapid disease progression. The effect of maximum tolerated ACEi doses (ramipril 15 mg/day, range 5 to 20) alone or combined with indomethacin (75 mg x 2/day) on urinary protein excretion (UPE) and glomerular barrier size-selective function was evaluated in 19 patients with chronic non-diabetic nephropathies and persistent proteinuria. Maximum ramipril doses decreased UPE more effectively than non-ACEi therapy. Proteinuria reduction was associated with significant reduction (>50%) of the non-selective glomerular membrane shunt, but did not correlate with concomitant changes in arterial pressure and renal hemodynamics, nor was it influenced by treatment duration. The reduction in UPE and sieving coefficient of the largest neutral dextrans exceeded by twofold the reduction achieved by conventional ACEi doses in historical controls with similar renal dysfunction and proteinuria, previously studied under identical experimental conditions. Indomethacin did not influence renal effects of maximum ramipril doses and was prematurely withdrawn in six patients because of reversible side effects. Serum potassium significantly increased only in combination with indomethacin and never required treatment withdrawal. Up-titration to maximally tolerated doses safely increases ACEi antiproteinuric effect and may serve to achieve maximum renoprotection in the long-term. Combination with indomethacin is poorly tolerated and ineffective. Innovative approaches are needed to use ACEi more effectively.",2003.0,0,0
1035,12165118,"Clinical and experimental studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analogue, in heart failure.",Eugene Morkin; Gregory D Pennock; Peter H Spooner; Joseph J Bahl; Steven Goldman,"Thyroid hormone has unique actions that make it a novel and possibly useful agent for treatment of heart failure. Because of potential adverse effects of thyroid hormone, however, there has been interest in developing analogues with fewer undesirable side effects. Screening of compounds structurally related to levothyroxine identified 3,5-diiodothyropropionic acid (DITPA) as an analogue with inotropic selectivity and low metabolic activity in hypothyroid rats. When DITPA was administered alone or in combination with captopril in rat and rabbit postinfarction models of heart failure, cardiac output was increased and left ventricular end-diastolic pressure (LV EDP) was decreased without increasing heart rate. A pilot clinical study was undertaken to evaluate the safety and efficacy of DITPA. In a dose-ranging study in 7 normal volunteers the drug was well tolerated. A double-blind comparison then was made of DITPA versus placebo in a group of 19 patients with moderately severe heart failure. Patients were randomly assigned to receive either 1.875 mg/kg of DITPA or placebo daily. After 2 weeks the drug was increased to 3.75 mg/kg daily for an additional 2 weeks. In heart failure patients receiving the drug for 4 weeks, cardiac index was increased (p = 0.04) and systemic vascular resistance index was decreased (p = 0.02). Total serum cholesterol (p = 0.013) and triglycerides (p = 0.005) also were decreased significantly. These results indicate that DITPA is well tolerated and could represent a useful new agent for treatment of congestive heart failure.",2003.0,0,0
1036,12165170,Combination antihypertensive therapy in the treatment of diabetic nephropathy.,Geoffrey Boner; Zemin Cao; Mark E Cooper,"Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.",2003.0,0,0
1037,12169073,Sertraline treatment of major depression in patients with acute MI or unstable angina.,Alexander H Glassman; Christopher M O'Connor; Robert M Califf; Karl Swedberg; Peter Schwartz; J Thomas Bigger; K Ranga Rama Krishnan; Louis T van Zyl; J Robert Swenson; Mitchell S Finkel; Charles Landau; Peter A Shapiro; Carl J Pepine; Jack Mardekian; Wilma M Harrison; David Barton; Michael Mclvor; Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group,"Major depressive disorder (MDD) occurs in 15% to 23% of patients with acute coronary syndromes and constitutes an independent risk factor for morbidity and mortality. However, no published evidence exists that antidepressant drugs are safe or efficacious in patients with unstable ischemic heart disease. To evaluate the safety and efficacy of sertraline treatment of MDD in patients hospitalized for acute myocardial infarction (MI) or unstable angina and free of other life-threatening medical conditions. Randomized, double-blind, placebo-controlled trial conducted in 40 outpatient cardiology centers and psychiatry clinics in the United States, Europe, Canada, and Australia. Enrollment began in April 1997 and follow-up ended in April 2001. A total of 369 patients with MDD (64% male; mean age, 57.1 years; mean 17-item Hamilton Depression [HAM-D] score, 19.6; MI, 74%; unstable angina, 26%). After a 2-week single-blind placebo run-in, patients were randomly assigned to receive sertraline in flexible dosages of 50 to 200 mg/d (n = 186) or placebo (n = 183) for 24 weeks. The primary (safety) outcome measure was change from baseline in left ventricular ejection fraction (LVEF); secondary measures included surrogate cardiac measures and cardiovascular adverse events, as well as scores on the HAM-D scale and Clinical Global Impression Improvement scale (CGI-I) in the total randomized sample, in a group with any prior history of MDD, and in a more severe MDD subgroup defined a priori by a HAM-D score of at least 18 and history of 2 or more prior episodes of MDD. Sertraline had no significant effect on mean (SD) LVEF (sertraline: baseline, 54% [10%]; week 16, 54% [11%]; placebo: baseline, 52% [13%]; week 16, 53% [13%]), treatment-emergent increase in ventricular premature complex (VPC) runs (sertraline: 13.1%; placebo: 12.9%), QTc interval greater than 450 milliseconds at end point (sertraline: 12%; placebo: 13%), or other cardiac measures. All comparisons were statistically nonsignificant (P> or = .05). The incidence of severe cardiovascular adverse events was 14.5% with sertraline and 22.4% with placebo. In the total randomized sample, the CGI-I (P =.049), but not the HAM-D (P =.14), favored sertraline. The CGI-I responder rates for sertraline were significantly higher than for placebo in the total sample (67% vs 53%; P =.01), in the group with at least 1 prior episode of depression (72% vs 51%; P =.003), and in the more severe MDD group (78% vs 45%; P =.001). In the latter 2 groups, both CGI-I and HAM-D measures were significantly better in those assigned to sertraline. Our results suggest that sertraline is a safe and effective treatment for recurrent depression in patients with recent MI or unstable angina and without other life-threatening medical conditions.",2002.0,0,0
1038,12169868,Renoprotective effect of small doses of losartan and enalapril in patients with primary glomerulonephritis. Short-term observation.,Leszek Tylicki; Przemyslaw Rutkowski; Marcin Renke; Boleslaw Rutkowski,"The renin-angiotensin system is thought to be involved in progression of chronic renal diseases of both diabetic and nondiabetic origin. It is confirmed that angiotensin-converting enzyme inhibitors reduce urinary protein excretion (UPE) and attenuate the development of renal injury. The angiotensin II receptor blockers are an alternative class of drugs inhibiting the renin-angiotensin system activity with preliminarily confirmed renoprotective activity. However, there is lack of data concerning renoprotective action of very small doses of these drugs. Prospective, randomized, 3-month study of the effects of losartan 25 mg (n = 17) vs. enalapril 10 mg (n = 17) vs. combination of losartan 25 mg and enalapril 10 mg (n = 15) on proteinuria, kidney function and metabolic profile in 51 patients with biopsy proven chronic glomerulonephritis with normal or slightly declined kidney function [creatinine clearance (CRCL) between 36 and 93 ml/min] was performed. Clinical evaluation and laboratory tests were estimated before treatment (basal), during the first week and after 3 months of therapy. Both, monotherpy with losartan and enalapril significantly reduced proteinuria by 25.35 and 45.07%, respectively. There was no significant difference between groups. Combined therapy induced a more remarkable reduction of proteinuria (65.96%) than either of the drugs administered alone. This antiproteinuric effect was significantly more pronounced only in comparison with the losartan group (p = 0.009). Decreasing of blood pressure was most pronounced in the combined group. In all groups, no correlation between fall of UPE and reducing the systolic or diastolic blood pressure was found. Significant decline in CRCL was observed with enalapril treatment just after 1 week of therapy (p = 0.039) and at the end of observation (p = 0.043). CRCL remained stable in losartan-treated subjects. No changes in serum creatinine level, metabolic profile and sodium excretion were observed during therapy in studied groups. These results indicated that even very small doses of losartan and enalapril reduce proteinuria in patients with primary glomerulonephritis. Combination of these drugs could cause significantly greater antiproteinuric effect than either of the agents in monotherapy. It is likely that the treatment with losartan, compared to enalapril, is associated with less risk of acute fall of glomerular filtration at the beginning of therapy.",2002.0,0,0
1039,12172327,Effects of six anti-hypertensive medications on cognitive performance.,Matthew F Muldoon; Shari R Waldstein; Christopher M Ryan; John Richard Jennings; Joanna M Polefrone; Alvin P Shapiro; Stephen B Manuck,"To describe and compare the effects of six different antihypertensive medications on cognitive performance. Prospective, randomized, and double-blind with treatment cross-over. University hypertension clinic and neuropsychology laboratory. Ninety-eight Caucasian men between 25 and 55 years of age with mild-to-moderate essential hypertension (88 of whom completed the study), and 32 normotensive men with similar socio-demographic characteristics. Six-week treatment periods with atenolol, metoprolol, hydrochlorothiazide, methyldopa, enalapril and verapamil, and 2-week placebo baseline and wash-out periods. In-depth neuropsychological assessments and several mood questionnaires were completed during placebo (baseline) periods and active treatment periods. Practice effects due to repeated neuropsychological testing were estimated from data collected concurrently in the normotensive participants. The antihypertensive treatments lowered blood pressure comparably and did not affect mood or anxiety. Small treatment effects were noted in four of seven domains of cognitive performance. Irrespective of medication type, treatment reduced the simple motor speed (P < 0.001), and slowed completion of two tests measuring perceptuo-motor speed and mental flexibility (P </= 0.05). Manual dexterity declined somewhat with metoprolol and methyldopa (P = 0.01). In contrast, all antihypertensive agents favorably affected performance on several tests that require working memory (P < 0.01). Performance on other tests assessing grip strength, learning and memory, attention and executive function was not affected. Short-term treatment with standard antihypertensive medications was associated with some small decrements in psychomotor performance and small improvements in working memory, without notable drug-class differences. Long-term effects await further study.",2003.0,0,0
1040,12172328,Gender influence on the dose-ranging of a low-dose perindopril-indapamide combination in hypertension: effect on systolic and pulse pressure.,Michel E Safar; Martin G Myers; Frans Leenen; Roland Asmar,"Dose-ranging of antihypertensive agents have been done to optimize diastolic blood pressure (DBP) reduction, but with little information on systolic (SBP), mean (MBP), or pulse (PP) pressures. A low-dose combination of perindopril (Per) and indapamide (Ind) has been shown to reduce more SBP than atenolol for the same DBP reduction. However, the possible influence of gender on this finding has never been tested. A database of five randomized, double-blind, dose-ranging studies was established to determine the optimal dose of the Per/Ind combination in hypertensive men and women. A total of 2907 patients were treated by either placebo or various combinations associating Per (2, 4, 8 mg) and Ind (0.625, 1.25, 2.5 mg). In the overall population, there was a significant dose-response relationship (P < 0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in SBP, DBP, MBP. When men and women were analyzed by dose, SBP, DBP and MBP (but not PP) decreased significantly more in women than in men until the Per 4/Ind 1.25 dosage was reached. Thereafter, with higher dosages, generating a slight but significant hypokalemia, the finding was reversed, resulting in a gender interaction in the overall population. In hypertensive subjects, the low-dose combinations Per 2/Ind 0.625 and Per 4/Ind 1.25 are the most effective in reducing blood pressure and avoiding hypokalemia. This effect is more pronounced in women, in which increased SBP and PP are predominant hemodynamic features.",2003.0,0,0
1041,12176567,"Impact of ACE polymorphism on renal allograft function, blood pressure, and proteinuria under ACE inhibition.",Barbara Suwelack; M Kempkes-Koch; V Kobelt; U Hillebrand; F Matzkies; U Gerhardt; H Hohage,,2003.0,0,0
1042,12181216,Clinical characteristics and prognosis of hospitalised inpatients with heart failure and preserved or reduced left ventricular ejection fraction.,A Varela-Roman; J R Gonzalez-Juanatey; P Basante; R Trillo; J Garcia-Seara; J L Martinez-Sande; F Gude,"To determine the clinical and prognostic differences between patients with heart failure who had preserved or deteriorated systolic function, defined as a left ventricular ejection fraction of > 50% or < 50%, respectively, within two weeks of admission to hospital. The records of 229 patients with congestive heart failure were studied. There were 95 women and 134 men, mean (SD) age 66.7 (11.7) years, who had been admitted to a cardiology department for congestive heart failure in the period 1991 to 1994, and whose left ventricular systolic function had been evaluated echocardiographically within two weeks of admission. Data were collected on the main clinical findings, supplementary investigations, treatment, and duration of hospital admission. Follow up information was obtained in the spring of 1998 by searching the general archives of the hospital and by a telephone survey. Left ventricular systolic function was preserved in 29% of the patients. The preserved and deteriorated groups differed significantly in the sex ratio (more women in the preserved group) and in the presence of a third heart sound, cardiomegaly, alveolar oedema, ischaemic cardiomyopathy, and treatment with angiotensin converting enzyme (ACE) inhibitors (all more in the deteriorated group). There were no significant differences in age, New York Heart Association functional class, rhythm disturbances, left ventricular hypertrophy, treatment with drugs other than ACE inhibitors, or survival. In the group as a whole, the survival rates after three months, one year, and five years were 92.6%, 80%, and 48.4%, respectively. In view of the unexpectedly poor prognosis of patients with congestive heart failure and preserved left ventricular systolic function, controlled clinical trials should be carried out to optimise their treatment.",2002.0,0,0
1043,12186794,Comparison of omapatrilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE).,Milton Packer; Robert M Califf; Marvin A Konstam; Henry Krum; John J McMurray; Jean-Lucien Rouleau; Karl Swedberg,"Combined inhibition of the angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) may produce greater benefits in heart failure than ACE inhibition alone. We randomly assigned 5770 patients with New York Heart Association class II to IV heart failure to double-blind treatment with either the ACE inhibitor enalapril (10 mg BID, n=2884) or to the ACE-NEP inhibitor omapatrilat (40 mg once daily, n=2886) for a mean of 14.5 months. The primary end point-the combined risk of death or hospitalization for heart failure requiring intravenous treatment--was used prospectively to test both a superiority and noninferiority hypothesis (based on the effect of enalapril in the Studies of Left Ventricular Dysfunction [SOLVD] Treatment Trial). A primary end point was achieved in 973 patients in the enalapril group and in 914 patients in the omapatrilat group (hazard ratio 0.94; 95% CI: 0.86 to 1.03, P=0.187)--a result that fulfilled prespecified criteria for noninferiority but not for superiority. The omapatrilat group also had a 9% lower risk of cardiovascular death or hospitalization (P=0.024) and a 6% lower risk of death (P=0.339). Post hoc analysis of the primary end point with the definition used in the SOLVD Treatment Trial (which included all hospitalizations for heart failure) showed an 11% lower risk in patients treated with omapatrilat (nominal P=0.012). Omapatrilat reduces the risk of death and hospitalization in chronic heart failure but was not more effective than ACE inhibition alone in reducing the risk of a primary clinical event. Between-group differences in favor of omapatrilat observed in secondary and post hoc analyses warrant further study.",2002.0,0,1
1044,12191747,A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients.,G A Cooke; S G Williams; P Marshall; J K Al-Timman; J Shelbourne; D J Wright; L-B Tan,"Angiotensin converting enzyme inhibitors at high doses have been shown to improve prognosis of heart failure patients. Their beneficial effects on exercise capacity have been less convincing in large parallel group studies. The objective of this investigation was to explore the mechanisms involved in dose-related functional effects and to test the hypothesis that a trial recommended high dose of lisinopril would improve aerobic exercise capacity and cardiovascular function more than with a low dose. Twelve patients with symptomatic heart failure completed a randomized double-blind crossover trial of lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12 weeks. The primary end-point was aerobic exercise capacity, and the secondary end-points were cardiac performance at peak exercise and dobutamine stimulation. The aerobic exercise capacity (primary end-point) was significantly higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(-1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(-1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of patients showed greater peak oxygen consumption and peak cardiac power output with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms of cardiac performance, although the results were not statistically significant, there was a consistent pattern showing the same directional changes in favour of the lower dose in peak exercise cardiac power output and cardiac power output at maximal dobutamine. There were no significant differences in the resting values. A total of 24 adverse reactions were reported during the 5 mg phase compared to 38 during the 20 mg phase. Contrary to expectation, the aerobic exercise capacity of patients was found to be greater with the lower dose of lisinopril, suggesting that therapy with ACE inhibitors for heart failure may require tailoring the doses to the individual to optimize functional benefits in relation to the assumed prognostic benefits.",2002.0,0,0
1045,12192262,Oral and intra-articular remedies: Review of papers published from March 2001 to February 2002.,Ronald W Jubb,"There have been considerable advances in the drug treatments used to treat osteoarthritis. The development of selective cyclo-oxygenase inhibitors (COX-II) and confirmation of their efficacy and gastrointestinal safety will reduce treatment morbidity in the elderly. Guidelines for safe and appropriate use of COX-II drugs are now available. The role of anti-inflammatory drugs in precipitating cardiorenal events has been highlighted but remains to be fully evaluated. Glucosamine, diacerein, and hyaluronan may all be disease-modifying drugs for osteoarthritis but confirmatory studies are still needed.",2003.0,0,0
1046,12195132,Risk of new-onset diabetes in the Losartan Intervention For Endpoint reduction in hypertension study.,Lars H Lindholm; Hans Ibsen; Knut Borch-Johnsen; Michael Hecht Olsen; Kristian Wachtell; Björn Dahlöf; Richard B Devereux; Gareth Beevers; Ulf de Faire; Frej Fyhrquist; Stevo Julius; Sverre E Kjeldsen; Krister Kristianson; Ole Lederballe-Pedersen; Markku S Nieminen; Per Omvik; Suzanne Oparil; Hans Wedel; Peter Aurup; Jonathan M Edelman; Steven Snapinn; LIFE study group,"There has been uncertainty about the risk of new-onset diabetes in hypertensive individuals treated with different blood pressure-decreasing drugs. To study this risk in hypertensive individuals who were at risk of developing diabetes mellitus in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. In the LIFE study, with a double-masked, randomized, parallel-group design, 9193 patients (46% men) with hypertension (mean age 67 years, average pressure 174/98 mmHg after placebo run-in) and electrocardiogram-documented left ventricular hypertrophy were randomly assigned to once-daily losartan- or atenolol-based antihypertensive treatment and followed for at least 4 years (mean 4.8 years). At baseline, 7998 patients did not have diabetes mellitus and were thus at risk of developing this condition during the study. To demonstrate ability to predict new-onset diabetes, we developed a prediction score using the significant variables from multivariate analyses (serum glucose, body mass index, serum high-density lipoprotein cholesterol, systolic blood pressure and history of prior use of antihypertensive drugs). There was a steadily increasing risk of diabetes with increasing level-of-risk score; patients in the highest quartile were at considerably greater risk than those in the three lower ones. Treatment with losartan was associated with lower risk of development of diabetes within each of the four quartiles of the risk score. As previously reported, new-onset diabetes mellitus occurred in 242 patients receiving losartan (13.0 per 1000 person-years) and 320 receiving atenolol (17.5 per 1000 person-years); relative risk 0.75 (95% confidence interval 0.63 to 0.88; P<0.001). New-onset diabetes could be strongly predicted by a newly developed risk score using baseline serum glucose concentration (non-fasting), body mass index, serum high-density lipoprotein cholesterol concentration, systolic blood pressure and history of prior use of antihypertensive drugs. Independently of these risk factors, fewer hypertensive patients with left ventricular hypertrophy developed diabetes mellitus if they were treated with losartan than if they were treated with atenolol.",2003.0,0,0
1047,12196335,"Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction.",Edimar Alcides Bocchi; Guilherme Guimarães; Amilcar Mocelin; Fernando Bacal; Giovanni Bellotti; José Franchini Ramires,"Erectile dysfunction (ED) is common in patients with congestive heart failure (CHF). ED reduces quality of life, and it may affect compliance, thereby impairing the success of CHF treatment. In the first phase (fixed-dose double-blind, randomized, placebo-controlled, two-way crossover study), we studied in 23 men with CHF the effects of 50 mg sildenafil on exercise and neurohormonal activation. Patients underwent a treadmill 6-minute cardiopulmonary walking (6'WT) test followed by a maximal cardiopulmonary exercise test (ET). In the second phase, patients received sildenafil, taken as required for ED. Sildenafil reduced the heart rate (HR) (bpm) before the 6'WT (from 75+/-15 to 71+/-14, P=0.02) and ET (from 75+/-15 to 71+/-15, P=0.02); the systolic blood pressure (mm Hg) before the 6'WT (from 116+/-18 to 108+/-18, P=0.004) and ET (from 116+/-15 to 108+/-17, P=0.001); the diastolic blood pressure before the 6'WT (from 69+/-9 to 63+/-11, P=0.01) and ET (from 70+/-8 to 65+/-10, P=0.004); and the Ve/VCO2 slope during the 6'WT (from 32+/-7 to 31+/-6, P=0.04) and ET (from 33+/-8 to 31+/-5, P=0.03). Sildenafil attenuated the HR increment during the 6'WT (P=0.003) and ET (P=0.000). Sildenafil increased the peak *O2 from 16.6+/-3.4 to 17.7+/-3.4 mL/kg per min (P=0.025) and the exercise time from 12.3+/-3.4 to 13.7+/-3.2 minutes (P=0.003). Sildenafil improved most scores of International Index of Erectile Function. Sildenafil was tolerated and effective for ED treatment in CHF, and improved the exercise capacity. The reduction of HR during exercise with sildenafil could theoretically decrease the myocardial oxygen consumption during sexual activity.",2002.0,0,0
1048,12200795,Antiproteinuric versus antihypertensive effects of high-dose ACE inhibitor therapy.,Martin Haas; Zdenka Leko-Mohr; Christoph Erler; Gert Mayer,"Angiotensin-converting enzyme (ACE) inhibitors effectively reduce proteinuria; however, the optimal antiproteinuric dose is still unknown. We conducted this study to determine whether an increase in ACE-inhibitor dose above the maximal antihypertensive effect has additional antiproteinuric potential. Twenty-three proteinuric patients were administered the ACE inhibitor spirapril at a starting dose of 3 to 6 mg/d. The dose was increased every 6 weeks until the maximal antihypertensive effect, assessed by 24-hour ambulatory blood pressure (ABP) monitoring, was achieved (spir(max)), then increased to a supramaximal dose (spir(supramax)). Renal parameters, urinary protein excretion, and systemic activity of the renin-angiotensin system were compared between baseline, spir(max), and spir(supramax). Glomerular filtration rate and renal plasma flow were determined before the administration of spirapril and after administration of the supramaximal dose. Median ABP and proteinuria decreased significantly between baseline and spir(max) (median, 102 mm Hg; range, 82 to 122 mm Hg versus 97 mm Hg; range, 82 to 113 mm Hg; median protein, 2.56 g/d; range, 1.05 to 22.1 g/d versus 1.73 g/d; range, 0.42 to 4.7 g/d). Both creatinine level and creatinine clearance remained unchanged. Suppression of angiotensin II formation led to a significant increase in renin and angiotensin I concentrations and a nonsignificant decrease in aldosterone levels. The increase in spirapril to a supramaximal dose had no further effect on serum renin or angiotensin I levels or proteinuria. There was an additional slight decrease in aldosterone levels and, subsequently, a significantly lower level than at baseline. Our results show that the antiproteinuric effect of spirapril is associated with its antihypertensive effect. Although high-dose ACE-inhibitor therapy has no additional influence on proteinuria, a possible beneficial long-term effect cannot be ruled out.",2002.0,0,0
1049,12201354,Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.,G Cremonesi; L Cavalieri; I Cikes; J Dobovisek; S Bacchelli; D Degli Esposti; F V Costa; C Borghi; E Ambrosioni,"This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP < or =90 mm Hg) and responder (sitting DBP reduction of 10 mm Hg or DBP < or =90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.",2002.0,0,0
1050,12201967,Five-year mortality for stable angina in a medical practice study and a randomized trial.,Edvardas Varnauskas; Torkel Aberg; Bengt Brorsson; Thomas Karlsson; Bertil Olsson; Lars Werkö,"Evolution of revascularization and medical therapy has increased the probability of improved survival in patients with stable angina. The present investigation tests the hypothesis that medical practice will generate lower mortality than randomly assigned bypass surgery in the European Coronary Surgery Study (ECSS) two decades earlier. Using eligibility criteria of ECSS, a clinical decision strategy (CDS) cohort of 362 patients was selected from a nationwide study of medical practice in Sweden. Access to the individual data allowed common protocol design to compare 5-year mortality between CDS and surgical strategy of ECSS. CDS advised bypass surgery (BS) or percutaneous transluminal coronary angioplasty (PTCA) in 93% and medical treatment alone in 7%, while 94% of 394 patients randomized to surgery (Euro-S) in ECSS obtained BS. Operative mortality was 3.2% for Euro-S while no operative deaths occurred in CDS reflecting medical progress during two decades. However, the 5-year mortality for CDS decreased first when the risk ratio was adjusted for age, diabetes mellitus and hypertension (RR = 0.49 with 95% CI 0.26-0.93) p = 0.03 suggesting a need for improved comprehensive medical care.",2003.0,0,0
1051,12204014,Relationship of antihypertensive treatment regimens and change in blood pressure to risk for heart failure in hypertensive patients randomly assigned to doxazosin or chlorthalidone: further analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial.,Barry R Davis; Jeffrey A Cutler; Curt D Furberg; Jackson T Wright; Michael A Farber; James V Felicetta; John D Stokes; ALLHAT Collaborative Research Group,"The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial reported that treatment initiated with doxazosin compared with chlorthalidone doubled the risk for heart failure in high-risk hypertensive patients (relative risk, 2.04 [95% CI, 1.79 to 2.32]). Patients assigned to doxazosin therapy had a mean in-trial systolic/diastolic blood pressure 3/0 mm Hg higher than that in patients assigned to chlorthalidone. Sixty-eight percent (6167 of 9061) of the former patients and 59% (9081 of 15 256) of the latter patients were given additional medications to achieve a target blood pressure of less than 140/90 mm Hg. To ascertain the influence of open-label antihypertensive drugs and subsequent blood pressure on relative risk for heart failure. Randomized, double-blind, active-controlled clinical trial. 623 sites in the United States and Canada. Hypertensive patients 55 years of age or older with at least one additional risk factor for cardiovascular disease. Chlorthalidone (12.5 to 25 mg/d) or doxazosin (2 to 8 mg/d) for a planned follow-up of 4 to 8 years. Data on blood pressure, medication, and incident heart failure (treated outside hospital, hospitalized, or fatal) from February 1994 through December 1999. After the treatment groups were categorized as having no exposure to open-label medications (monotherapy) or exposure to open-label therapy, the relative risk for heart failure with doxazosin versus chlorthalidone was 3.10 (CI, 2.51 to 3.82) and 1.42 (CI, 1.20 to 1.69), respectively. After adjustment for follow-up systolic/diastolic blood pressure, the overall relative risk was 2.00 (CI, 1.72 to 2.32). In high-risk patients with hypertension, the higher risk for heart failure while taking doxazosin compared with chlorthalidone is attenuated but not eliminated by adding other antihypertensive drugs. The small observed difference in systolic blood pressure does not explain this increased risk.",2002.0,0,0
1052,12204495,Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).,Andreas W Bonz; Björn Lengenfelder; Jörg Strotmann; Stefanie Held; Oliver Turschner; Kerstin Harre; Christian Wacker; Christiane Waller; Nikolaus Kochsiek; Malte Meesmann; Ludwig Neyses; Peter Schanzenbächer; Georg Ertl; Wolfram Voelker,"The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.",2002.0,0,0
1053,12204499,Effect of long-term therapy with ramipril in high-risk women.,Eva Lonn; Rosa Roccaforte; Qilong Yi; Gilles Dagenais; Peter Sleight; Jackie Bosch; Pamela Suhan; Mary Micks; Jeffrey Probstfield; Victoria Bernstein; Salim Yusuf; HOPE Investigators. Heart Outcomes Prevention Evaluation,"We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes in high-risk women. The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of ramipril in women in the HOPE study. The study randomized 2,480 women aged >or=55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. Treatment with ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of ramipril was similar in women and men. Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.",2002.0,0,1
1054,12204500,Augmentation of myocardial blood flow in hypertensive heart disease by angiotensin antagonists: a comparison of lisinopril and losartan.,Olakunle O Akinboboye; Ru-Ling Chou; Steven R Bergmann,"The goal of this study was to compare myocardial perfusion reserve (MPR) before and after long-term treatment with lisinopril and losartan in patients with hypertension and left ventricular hypertrophy (LVH). Studies have suggested that treatment with angiotensin-converting enzyme inhibitors (ACEIs) improves MPR in patients with hypertension by potentiating endogenous bradykinins. Because angiotensin receptor blockers (ARBs) lack a direct effect on bradykinins, we hypothesized that they may not improve MPR. We measured pre- and post-treatment myocardial blood flow (MBF) by positron emission tomography in 17 patients (lisinopril: 9 patients, losartan: 8 patients) with hypertension and LVH at baseline and after coronary vasodilation with intravenous dipyridamole. In addition, we measured rest and hyperemic blood flow in eight normotensive controls. Post-treatment maximal coronary blood flow and MPR in the lisinopril group increased significantly compared with pretreatment values (3.5 +/- 1.2 vs. 2.6 +/- 1.1 ml/min/g, p = 0.02; 3.7 +/- 1.1 vs. 2.4 +/- 1 ml/min/g, respectively, p = 0.002, respectively). Post-treatment hyperemic flow in the patients treated with lisinopril was not significantly different from corresponding measurements in controls (3.5 +/- 1.2 vs. 3.9 +/- 1 ml/min/g, respectively, p = NS). In the patients treated with losartan, there was no difference between pre- and post-treatment MBF values and MPR. Myocardial perfusion reserve and maximal coronary flow improved in asymptomatic patients with hypertension-induced LVH after long-term treatment with lisinopril but not with losartan. Thus, ACEIs, but not ARBs, might be effective in repairing the coronary microangiopathy associated with hypertension-induced LVH.",2002.0,0,0
1055,12208409,Comparison of the effects of omapatrilat and lisinopril on circulating neurohormones and cytokines in patients with chronic heart failure.,Tej Sheth; Tom Parker; Alan Block; Christian Hall; Albert Adam; Mark A Pfeffer; Duncan J Stewart; Chunlin Qian; Jean L Rouleau; IMPRESS Investigators,"Angiotensin-converting enzyme (ACE) inhibitors exert their effects by modulating the neurohumoral milieu. Vasopeptidase inhibitors (VPI) are ACE and neutral endopeptidase inhibitors and may increase natriuretic peptides, bradykinin, and perhaps endothelin-1 in patients with congestive heart failure. Patients (n = 107) with ischemic or dilated cardiomyopathy, New York Heart Association functional class II to III, with left ventricular ejection fraction <40%, and on ACE inhibitor therapy were randomized to either the VPI omapatrilat 40 mg/day or the ACE inhibitor lisinopril 20 mg/day. Trough levels of neurohormones (24 hours after dosing) were assessed at baseline, and at 12 and 24 weeks of follow-up. C-terminal atrial natriuretic peptide (C-ANP) levels decreased with lisinopril (p = 0.035), but not with omapatrilat. In contrast, N-terminal ANP levels did not change, and brain natriuretic peptide (BNP) levels tended to decrease similarly in both groups. Endothelin-1 levels increased in both groups, the increase reaching statistical significance with omapatrilat (p = 0.008). Levels of the proinflammatory cytokine interleukin-6 tended to decrease, and the anti-inflammatory cytokine interleukin-10 increased in both groups, with statistical significance only for interleukin-10 with omapatrilat therapy. Neither agent changed catecholamines or angiotensin II. Thus, even at trough levels, omapatrilat potentiates C-ANP more than lisinopril. Potentially important effects of omapatrilat on endothelin-1 and anti-inflammatory cytokines were identified, providing potential explanations for differences in clinical outcome.",2002.0,0,0
1056,12208593,Safety and efficacy of valsartan versus enalapril in heart failure patients.,Ronnie Willenheimer; Claes Helmers; Emil Pantev; Erik Rydberg; Per Löfdahl; Allan Gordon; Heart Failure Valsartan Exercise Capacity Evaluation Study Group,"Although a cornerstone in the treatment of heart failure, angiotensin-converting enzyme inhibitors are under-used, partly due to side effects. If proven at least similarly efficacious to angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers may replace them due to their superior tolerability. We aimed to compare the efficacy and safety of valsartan and enalapril in heart failure patients stabilised on an angiotensin-converting enzyme inhibitor. We randomised 141 patients (mean 68 years, 74% males) with stable mild/moderate heart failure and left ventricular ejection fraction 0.45 or less, to valsartan 160 mg q.d. (n=70) or enalapril 10 mg b.i.d. (n=71) for 12 weeks. Changes in 6-min-walk test (primary efficacy variable), patients' wellbeing and left ventricular size and function did not differ significantly between the treatment groups. Valsartan was significantly non-inferior to enalapril in walk test distance change: least-square means treatment difference +1.12 m (95% confidence interval -21.9 to 24.1), non-inferiority P<0.001. Left ventricular size (P<0.001) and function (P=0.048) improved significantly only in the valsartan group. Fewer patients experienced adverse events in the valsartan group (50%) than in the enalapril group (63%), although statistically non-significant. Valsartan is similarly efficacious and safe to enalapril in patients with stable, mild/moderate heart failure, previously stabilised on an angiotensin-converting enzyme inhibitor and directly switched to study medication.",2002.0,0,0
1057,12214166,Patterns of ACE inhibitor use in elderly medicaid patients with heart failure.,Patricia A Howard; Theresa I Shireman; Ashish Dhingra; Edward F Ellerbeck; Jack E Fincham,"The authors identified 321 elderly Kansas Medicaid patients with congestive heart failure and examined angiotensin-converting enzyme (ACE) inhibitor use. Using retrospective claims data, ACE inhibitor use was quantified and daily doses compared to a target enalapril-equivalent dose of 20 mg. The cohort patients averaged 80 years of age, 84% were female, and 70% resided primarily in a nursing home. Only 37.8% received an ACE inhibitor. Users were younger than nonusers (t=2.00; p=0.046), but there was no gender difference (odds ratio [OR], 1.4; 95% confidence interval [CI], 0.73, 2.6). ACE inhibitor users averaged eight prescriptions annually, providing approximately 257 medication days (70% of the study period). The average enalapril-equivalent daily dose was 10.6 mg, and only 22% received the target dose. Nursing home residents were less likely to receive an ACE inhibitor than ambulatory patients (OR, 0.55; 95% CI, 0.34, 0.89) but equally likely to receive target doses (OR, 1.3; 95% CI, 0.34, 4.9). ACE inhibitor use in the Kansas Medicaid congestive heart failure population is not consistent with practice guidelines, particularly among older and/or nursing home patients.",2002.0,0,0
1058,12214263,Efficacy of very low dose perindopril 2 mg/indapamide 0.625 mg combination on left ventricular hypertrophy in hypertensive patients: the P.I.C.X.E.L. study rationale and design.,P Gosse; O Dubourg; P Guéret; G De Simone; R Schmieder; P W De Leeuw; J-P Degaute; J García Puig; Y Karpov; D Magometschnigg; L Matos; P Amouyel; R Asmar; J-Y Le Heuzey; M Nieminen; B Dahlöf,"The PICXEL study is designed to evaluate the effects of long-term administration of very low-dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) vs enalapril in reducing left ventricular hypertrophy (LVH) in hypertensive patients. This multicentre, controlled, randomised, double-blind, parallel group study is carried-out to assess the variation of left ventricular mass index (LVMI) after treatment, using a centralised control of M-mode echocardiography determinations, and a dedicated software for semi-automatic measurement. Following a 4-week placebo run-in period, hypertensive outpatients aged >/=18 years, with LVH (LVMI >120 and 100 g/m(2) for men and women, respectively), are randomised to receive once daily, over 52 weeks, either Per/Ind or enalapril. According to blood pressure levels, the dose may be adjusted. In addition to clinical examinations, ECG, blood pressure, heart rate and laboratory assessments echocardiographic determinations are performed for selection, at baseline, after 24 weeks and at the end of the study. The main outcome criteria is the change from baseline in LVMI which is considered the primary efficacy criterion; changes in blood pressure and echo-Doppler parameters constitute secondary criteria. Two-sided Student's t-test for independent samples will be used to differentiate the effects of the treatment between groups with alpha = 5%, and the inter-group difference of LVMI variation will be analysed with a power of 90%. A sample size of 500 patients is required making it necessary to randomise at least 550 patients, based on a 10% proportion of potentially non-assessable patients. The results of this study, obtained after applying strict methodological procedures and requirements, are expected to provide valuable and reliable information on the effects of long-term administration of Per/Ind on LVH, and on its potential superiority over enalapril.",2003.0,0,0
1059,12219878,Additive effect of drospirenone/17-beta-estradiol in hypertensive postmenopausal women receiving enalapril.,Richard A Preston; Alberto Alonso; Darlene Panzitta; Paul Zhang; Adel H Karara,"Aldosterone has been implicated in the pathogenesis of progressive cardiovascular disease. Drospirenone (DRSP) is a novel progestin with aldosterone receptor antagonist activity developed for hormone replacement therapy (HRT) as DRSP/17beta-estradiol (DRSP/ E2). We investigated the additive effect of DRSP/E2 versus placebo on 24-h ambulatory blood pressure (BP) in postmenopausal women with hypertension treated with enalapril maleate (ENA). This was a double-blind, randomized, two-parallel group trial. Twenty-four nonsmoking postmenopausal women receiving 10 mg of ENA twice a day before study were randomized to DRSP/E2 + ENA (n = 12) or placebo (P) + ENA (n = 12) for 14 days. Twenty-four-hour ambulatory BP, plasma renin activity, and serum aldosterone were determined at baseline and on day 14. Compared to placebo, 24-h mean [SD] BP in the DRSP/E2 + ENA group decreased significantly from baseline (139/80 mm Hg), systolic (-9 [51 mm Hg, P = .014) and diastolic (-5 [4] mm Hg, P = .007). Essentially no change from baseline (139/83 mm Hg) in systolic or diastolic 24-h ambulatory BP were observed in the P + ENA group. Aldosterone (mean [SD]) increased from baseline by 2.6 [4.5] ng/dL in the DRSP/E2 + ENA group, and decreased by 0.3 [5.5] ng/dL in the P + ENA group (P = .08) consistent with an antimineralocorticoid effect. Our results suggest a significant additive BP-lowering effect of DRSP/E2 on both systolic and diastolic BP in hypertensive postmenopausal women receiving ENA, consistent with an antimineralocorticoid effect. DRSP/E2, a HRT with antimineralocorticoid effects, could offer a novel potential mechanism for reducing cardiovascular end points in postmenopausal women.",2003.0,0,0
1060,12224677,Heart failure in primary care: measuring the quality of care.,P A James; T M Cowan; R P Graham; C R Jaén; B A Majeroni; J S Schwartz,"Concerns exist about the quality of care provided to heart failure patients by primary care physicians. Using an evidence-based clinical guideline, we evaluated the care given to patients with systolic heart failure. We retrospectively reviewed the medical records of 420 patients from 25 primary care practices in upstate New York who had received a diagnosis of heart failure. Chart documentation confirmed the diagnosis (n = 395). We excluded patients with noncardiogenic volume overload or correctable valvular disease (n = 338). Performance profiles measured use of diagnostic tests, left ventricular ejection fraction (LVEF) measurement, patient education, and prescription of angiotensin-converting enzyme (ACE) inhibitors. For treatment recommendations, patients were classified according to LVEF status. Only 82% of the patients studied had an LVEF test result documented in their charts. Of these, 49% had an LVEF < or = 40%. ACE inhibitor use was greater among patients with low LVEF (91%) than among those with a normal LVEF (62%). Among patients with systolic heart failure taking ACE inhibitors, 87% were at target doses. Adherence measures were low for laboratory evaluation and patient-education criteria. Heart failure with normal LVEF was as prevalent as systolic heart failure in these primary care practices. Performance profiles for the physicians' prescriptions of ACE inhibitors exceeded those published in the literature. Patients who did not have a documented measure of LVEF, however, received lower quality of care as measured by this disease-specific guideline. This underscores the importance of measuring LVEF.",2002.0,0,0
1061,12224817,Angiotensin-converting enzyme activity is involved in the mechanism of increased endogenous nitric oxide synthase inhibitor in patients with type 2 diabetes mellitus.,Akira Ito; Kensuke Egashira; Takahiro Narishige; Kouhei Muramatsu; Akira Takeshita,"The renin-angiotensin system plays an important role in the elevation of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, in hypertensive patients, so the present study was designed to examine whether angiotensin-converting enzyme (ACE) activity is also involved in the mechanism of ADMA elevation in type 2 diabetes mellitus (NIDDM). A crossover study was performed to determine if ACE inhibition with perindopril (4 mg/day) for 4 weeks decreases serum ADMA concentration and plasma von Willebrand factor (vWF) level (a marker of endothelial injury) in 11 patients with NIDDM. None of the patients was treated with insulin or oral hypoglycemic drugs, and none had major diabetic complications. Before the protocol began, serum ADMA and plasma vWF were significantly higher in the 11 NIDDM patients, when compared with 8 control subjects without diabetes. Perindopril did not affect blood pressure or glucose metabolism, but did significantly decrease serum ADMA and plasma vWF. These results suggest that endothelial injury associated with ADMA elevation may be present even in patients with non-complicated NIDDM, and that increased activity of ACE may be involved in such endothelial dysfunction.",2003.0,0,0
1062,12225709,"Late intervention after anterior myocardial infarction: effects on left ventricular size, function, quality of life, and exercise tolerance: results of the Open Artery Trial (TOAT Study).",Zaheer R Yousef; Simon R Redwood; Clifford A Bucknall; Alfred N Sulke; Michael S Marber,"We sought to conduct a randomized trial comparing late revascularization with conservative therapy in symptom-free patients after acute myocardial infarction (AMI). In the absence of ischemia, the benefits of reperfusion late after AMI remain controversial. However, the possibility exists that an open infarct related artery benefits healing post AMI. Of 223 patients enrolled with Q-wave anterior AMI, 66 with isolated persistent occlusion of the left anterior descending coronary artery (LAD) were randomized to the following treatments: 1) medical therapy (closed artery group; n = 34) or 2) late intervention and stent to the LAD + medical therapy (open artery group; n = 32). The study was powered to compare left ventricular (LV) end-systolic volume between the two groups 12 months post AMI. Late intervention 26 +/- 18 days post AMI resulted in significantly greater LV end-systolic and end-diastolic volumes at 12 months than medical therapy alone (106.6 +/- 37.5 ml vs. 79.7 +/- 34.4 ml, p < 0.01 and 162.0 +/- 51.4 ml vs. 130.1 +/- 46.1 ml, p < 0.01, respectively). Exercise duration and peak workload significantly increased in both groups from 6 weeks to 12 months post AMI, although absolute values were greater in the open artery group. Quality of life scores tended to deteriorate during this time interval in the closed artery patients but remained unchanged in the open artery patients. Coronary angiography at 1 year documented a low incidence of intergroup cross-over (spontaneous recanalization in 19% and closure in 11%). In the present study, recanalization of occluded infarct-related arteries in symptom-free patients approximately 1 month post AMI had an adverse effect on remodeling but tended to increase exercise tolerance and improve quality of life.",2002.0,0,0
1063,12225725,Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study.,Maylene Wong; Lidia Staszewsky; Roberto Latini; Simona Barlera; Alberto Volpi; Yann-Tong Chiang; Raymond L Benza; Sidney O Gottlieb; Thomas D Kleemann; Franco Rosconi; Pieter M Vandervoort; Jay N Cohn; Val-HeFT Heart Failure Trial Investigators,"The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy. The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling. At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF. Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups. The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling.",2002.0,0,0
1064,12228852,Comparison of the effects of antihypertensive treatment with angiotensin II blockade and beta-blockade on carotid wall structure and haemodynamics: protocol and baseline demographics.,Ben Ariff; Alice Stanton; Dean Barratt; Alex Augst; Fadi Glor; Neil Poulter; Peter Sever; Yun Xu; Alun Hughes; Simon A Mc G Thom,"Several systemic factors have been shown to contribute to the acceleration of large vessel atheroma. Correction of these factors leads to a reduction in the progression of plaque formation and associated arterial wall thickness. Atheroma remains, however, a focal disease, developing at characteristic sites within the arterial tree. These sites are typically at areas of vessel branching or marked curvature, and correspond to regions of high tensile stress and low sheer stress, leading to the hypothesis that local haemodynamic factors and vessel wall mechanics potentiate the focal development of atheroma. Current assessment of vascular haemodynamics suffers from an inability to handle complex flow, and does not allow accurate determination of locally varying flow, and shear stress patterns. The application of computational fluid dynamic (CFD) flow simulation techniques to ultrasound and local pressure data, however, allows a comprehensive, non-invasive appraisal of haemodynamic flow parameters to be performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint Trial (CACHET) study compares the effects of two antihypertensive regimens, one b-blocker-based, the other angiotensin receptor blocker based, on carotid intima-media thickness. The collection of ultrasound and pressure data on each subject provides a unique opportunity to apply these data to the CFD model to study the effects of these antihypertensive regimens on local fluid dynamics. This will lead to a greater understanding of the relationship of these factors to atheroma formation and regression.",2003.0,0,0
1065,12231083,Effects of furosemide versus captopril on postprandial and orthostatic blood pressure and on cerebral oxygenation in patients > or = 70 years of age with heart failure.,D Jannet Mehagnoul-Schipper; Willy N J M Colier; Willibrord H L Hoefnagels; Freek W A Verheugt; René W M M Jansen,"Elderly patients with heart failure are at risk of postprandial hypotension (PPH), orthostatic hypotension (OH), and concomitant cerebral oxygenation changes because of altered cardiovascular balance and the use of cardiovascular medications, such as furosemide and captopril. In 24 patients with heart failure (New York Heart Association class II to III, in stable condition, and receiving cardiovascular medication [aged 70 to 83 years]), blood pressure (BP) was measured by Finapres, and cortical concentrations of oxyhemoglobin and deoxyhemoglobin were measured using near-infrared spectroscopy during standing and after a 292-kcal carbohydrate meal. Tests were performed before and during therapy with furosemide 40 mg once daily (n = 11) or captopril 6.25 and 12.5 mg twice daily (n = 13) in a double-blind randomized trial. Before treatment, 13 of 24 patients had PPH, and 2 of 24 patients had OH. The first dose of furosemide significantly decreased postprandial systolic BP (p <0.05) and postprandial frontal cortical oxygenation (p <0.05), whereas the first dose of captopril did not. Furosemide and captopril did not significantly affect postprandial or orthostatic BP or cortical oxygenation after 2 weeks of treatment. Thus, PPH is a common phenomenon in elderly patients with heart failure, whereas OH is not. The first dose of furosemide 40 mg decreased postprandial systolic BP and frontal cortical oxygenation, in contrast with the first dose of captopril 6.25 mg and 2-week treatment with furosemide 40 mg once daily or captopril 12.5 mg twice daily. These findings indicate that initiating furosemide treatment worsens PPH, and furosemide is less safe in elderly patients with heart failure.",2002.0,0,0
1066,12241832,Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan.,Kenneth Dickstein; John Kjekshus; OPTIMAAL Steering Committee of the OPTIMAAL Study Group,"ACE inhibitors attenuate the detrimental effects of angiotensin II, and improve survival and reduce morbidity in patients with acute myocardial infarction and evidence of heart failure or left-ventricular dysfunction. Selective antagonism of the angiotensin type 1 receptor represents an alternative approach to inhibition of the renin-angiotensin system. We did a multicentre, randomised trial to test the hypothesis that the angiotensin II antagonist losartan would be superior or non-inferior to the ACE inhibitor captopril in decreasing all-cause mortality in high-risk patients after acute myocardial infarction. 5477 patients 50 years of age or older (mean age 67.4 years [SD 9.8]), with confirmed acute myocardial infarction and heart failure during the acute phase or a new Q-wave anterior infarction or reinfarction, were recruited from 329 centres in seven European countries. Patients were randomly assigned and titrated to a target dose of losartan (50 mg once daily) or captopril (50 mg three times daily) as tolerated. The primary endpoint was all-cause mortality. Analysis was by intention to treat. There were 946 deaths during a mean follow-up of 2.7 (0.9) years: 499 (18%) in the losartan group and 447 (16%) in the captopril group (relative risk 1.13 [95% CI 0.99-1.28], p=0.07). The results for the secondary and tertiary endpoints were as follows: sudden cardiac death or resuscitated cardiac arrest 239 (9%) versus 203 (7%), 1.19 (0.98-1.43), p=0.07, and fatal or non-fatal reinfarction 384 (14%) versus 379 (14%), 1.03 (0.89-1.18), p=0.72. The all-cause hospital admission rates were 1806 (66%) versus 1774 (65%), 1.03 (0.97-1.10), p=0.37. Losartan was significantly better tolerated than captopril, with fewer patients discontinuing study medication (458 [17%] vs 624 [23%], 0.70 [0.62-0.79], p<0.0001). Since we saw a non-significant difference in total mortality in favour of captopril, ACE inhibitors should remain first-choice treatment in patients after complicated acute myocardial infarction. Losartan cannot be generally recommended in this population. However, it was better tolerated than captopril, and was associated with significantly fewer discontinuations. Although the role of losartan in patients intolerant of ACE inhibition is not clearly defined, it can be considered in such patients.",2002.0,0,0
1067,12298188,[The effect of enalapril and captopril on emotional processes in hypertensive patients].,Wiesława Karwowska-Polecka; Dorota Halicka; Piotr Jakubów; Jan J Braszko,"This study was aimed at the estimation of influence of enalapril and captopril on emotional processes in hypertensive patients. Hypertensive subjects evaluated before introducing drug treatment and normotensive persons comprised the control groups. All groups were examined with the psychological methods (BDI, HSC, Raven's Matric test). In BDI, there were no significant differences between the groups in the total score and particular factors as well. In HSC, there were significant differences in the total ratings between untreated hypertensive subjects and the normotensive group (p < 0.05). The depression/anxiety profile was the main contributing factor being itself significantly different (p < 0.05) in those groups. Enalapril and captopril reversed the negative behavioural changes caused by hypertension only moderately with no statistical significance. There were no alterations in intellectual abilities tested by the Raven's Matric test in any group examined. In conclusion, significant negative emotional effects of high blood pressure are only partly reversed by the antihypertensive doses of enalapril and captopril.",2002.0,0,0
1068,12351451,Podocyte number in normotensive type 1 diabetic patients with albuminuria.,Kathryn E White; Rudolf W Bilous; Sally M Marshall; Meguid El Nahas; Giuseppe Remuzzi; Giampiero Piras; Salvatore De Cosmo; GianCarlo Viberti,"We estimated glomerular cell number in 50 normotensive type 1 diabetic patients with raised albumin excretion rate (AER) and investigated any change after 3 years in a subgroup of 16 placebo-treated patients. Biopsies from 10 normal kidney donors were used as controls. Mesangial and endothelial cell number was increased in the 50 diabetic patients at the start of the study compared with control subjects. There was no difference in podocyte number. Glomerular volume was increased in diabetic patients, but surface area of glomerular basement membrane (GBM) underlying the podocytes did not differ between groups. AER correlated positively with mesangial cell number in microalbuminuric patients (r = 0.44, P = 0.012) and negatively with podocyte number in proteinuric patients (r = -0.48, P = 0.040). In the 16 placebo-treated patients, glomerular volume increased after 3 years owing to matrix accumulation and increased GBM surface area. Although overall cell number did not differ significantly from baseline, the decrease in podocyte number during follow-up correlated with AER at follow-up (r = -0.72, P = 0.002). In conclusion, cross-sectional analysis of podocyte number in type 1 diabetic patients with raised AER but normal blood pressure shows no significant reduction compared with nondiabetic control subjects. Longitudinal data provide evidence for an association between podocyte loss and AER, but whether cellular changes are a response to, a cause of, or concomitant with the progression of nephropathy remains uncertain.",2002.0,0,0
1069,12353420,The effect of the year angiotensin-converting enzyme inhibitors (ACE I) intake on circadian heart rate variability in patients with primary hypertension.,T Banach; W Kolasińska-Kloch; A Furgała; J Laskiewicz,"The autonomic nervous system (ANS) disturbances have been considered as one of the important factors in development of essential hypertension. However information about the effect of antyhypertensive treatment (angiotensin-converting enzyme inhibitors--ACEI) on cardiac ANS activity is ccscarce. The purpose of the study was to evaluate the HRV circadian changes in patients with essential hypertension, treated with ACEI throughout the period of one year. Ten patients with essential hypertension, aged 26 to 64 years (mean 54.3 +/- 12.3) and 10 healthy volunteers, matched for age and gender were qualified for the investigation. Twenty four-hour arterial blood pressure measurements with simultaneous ECG monitoring were conducted in both mentioned groups. The hypertensive patients were examined before and after 1 year of ACE inhibitor (enalapril) intake. HRV analysis was carried out by the fast Fourier transformation (FFT). The time and spectral parameters were compared in 8 examined subjects characteristic for dippers, in time periods of day (6 a.m.-10 p.m.) and night (10 p.m.-6 a.m.). The results obtained before the treatment, likewise in control group, presented night's increases of RMSSD (p < 0.05), pNN50 (NS, p > 0.05), VLF, LF (p < 0.05) and HF (NS) mean values with a decrease of LF/HF ratio (p < 0.05). Similar tendencies in the cardiac ANS activity were observed after 1 year of the enalapril intake. A comparison of day's HRV before and after one year of the ACE inhibition presented the increase in values of the parasympathetic system reflecting parameters: RMSSD, pNN50 (p = 0.01) and HF (NS) with a decrease of LF/HF ratio (p < 0.01). The evaluation of the night's HRV parameters presented the increase of HF mean value (p < 0.05), without any other significant changes between the trials. After 1-year of ACE inhibitor administration the only improvement of the day's parasympathetic activity was observed. The night's vagal activity suggested as one of the essential factor in development of hypertension remained unchanged in patients qualified into ""dippers"" hypertension group.",2002.0,0,0
1070,12357261,Ventricular arrhythmia: role of the implantable cardioverter defibrillator and radiofrequency ablation in addition to drugs.,Avi Fischer; Rajiv Verma; Joseph A Gomes; Davendra Mehta,"The control of life-threatening arrhythmias in the prevention of sudden cardiac death has been a long-standing challenge to clinicians. Large-scale, randomized, controlled trials have contributed immensely to our understanding of the management of life-threatening arrhythmias. There are many causes of life-threatening ventricular arrhythmias, which they occur mostly in the setting of healed myocardial infarction. Available treatments for the management of ventricular arrhythmias include antiarrhythmic drugs, implantable cardioverter defibrillators and catheter ablation. Each therapy provides unique advantages for selected patients with life-threatening arrhythmias. Because the goal of arrhythmia management is not only to provide the single best therapy but to provide the greatest assurance of symptomatic arrhythmia control, the use of combined therapy has become a standard treatment strategy for patients with sustained ventricular arrhythmias. This review will discuss the different modes of treatment available for the treatment of life-threatening ventricular arrhythmias, and their potential risks and benefits. The rationale for using hybrid or combination therapy will be presented. Finally, some of the better-known primary and secondary prevention trials for treatment of ventricular tachycardias will be reviewed.",2002.0,0,0
1071,12359987,Quality of life on randomized treatment for isolated systolic hypertension: results from the Syst-Eur Trial.,Astrid E Fletcher; Christopher J Bulpitt; Lutgarde Thijs; Jaakko Tuomilehto; Riitta Antikainen; Alfredo Bossini; John Browne; Joseph Duggan; Kalina Kawecka-Jaszcz; Paula Kivinen; Cinzia Sarti; Laura Terzoli; Jan A Staessen; Syst-Eur Trial Investigators,"To compare quality of life in elderly patients with isolated systolic hypertension allocated randomly to groups to receive placebo or active treatment in the Systolic Hypertension in the Elderly Trial. Double-blind randomized controlled trial. Patients aged 60 years were allocated randomly to groups to receive first-line treatment with nitrendipine (with second- and third-line enalapril and hydrochlorothiazide) or placebo. Trained interviewers administered trail-making tests (Trail A and B), Brief Assessment Index (a measure of depressed mood) and four subscales from the Sickness Impact Profile (Ambulation, Social Interaction, Sleep and Rest, and Home work). Six hundred and ten patients completed a baseline and at least one follow-up questionnaire. Trail-making scores were slower in actively treated patients, especially in the first 6 months of follow-up when the between-group effect sizes were 0.25 [95% confidence interval (CI) 0.07 to 0.43] for Trail-making A and 0.13 (95% CI -0.05 to 0.31) for Trail-making B. Across the 4 years of follow-up, patients receiving active treatment were more likely to report problems on the Social Interaction scale than were placebo-treated patients (odds ratio 1.32, 95% CI 1.02 to 1.69), equivalent to a 7% difference. There were no significant differences between active and placebo treatment in the other Sickness Impact Profile dimensions or in the measure of depression. Active treatment in the Systolic Hypertension in Europe trial was associated with some small adverse impacts on quality of life.",2003.0,0,0
1072,12360162,"Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising.",William B White; Domenic A Sica; David Calhoun; George A Mansoor; Robert J Anders,"Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period, a time when both morbid and mortal cardiovascular events are increased compared with other times of the day. We studied the effects of a chronotherapeutic delivery system of verapamil (controlled-onset extended release [COER]-24 system) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure (BP), heart rate, and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled, forced-titration trial. There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP > or =85 mm Hg. Patients were randomized to either COER-verapamil hydrochloride each evening (240 mg titrated to 360 mg), enalapril each morning (10 mg titrated to 20 mg), losartan each morning (50 mg titrated to 100 mg), or placebo. Early morning assessments of BP, heart rate, and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks (low dose) and 8 weeks (high dose) of therapy. Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8. After 8 weeks of treatment, reductions in early morning BP by COER-verapamil were significantly greater (-15/-10 mm Hg) than enalapril (-9/-7 mm Hg, P <.01) and losartan (-8/-5 mm Hg, P <.001). COER-verapamil also led to greater reductions in morning heart rate, the rate-pressure product, and the rate-of-rise of BP compared with the other 2 active treatment groups. Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan, and similar to reductions in patients treated with enalapril. Bedtime administration of an agent designed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning.",2002.0,0,0
1073,12361192,N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients.,Vivencio Barrios; Alberto Calderón; Josefa Navarro-Cid; Vicente Lahera; Luis M Ruilope,"Sulfhydryl group donors, such as N-acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 +/- 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients (n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group (n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01). DtBP: 149.7 +/- 5.6 vs 141 +/- 3.7 and 92.1 +/- 4 vs 86 +/- 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.",2003.0,0,0
1074,12365090,[Evaluation of blood pressure self-monitoring of the residual efficacy of telmisartan compared to perindopril. The EVERESTE study].,S Ragot; A Meunier; M Poterre; R Bourkaïb; D Herpin,"The aim of this multicentre, prospective, randomised, open study was to compare the trough effect of telmisartan (T) and perindopril (P) on diastolic blood pressure (DBP) after a 12-week treatment, using self blood pressure measurement (SBPM). To enter the study, patients had to be 18 years of age or older and were required to suffer from mild to moderate hypertension (90 < or = PAD < 110 mmHg and/or PAS < 180 mmHg). At the end of a 3-week run-in placebo period, patients were allocated to receive either T (40 mg) or P (4 mg) once daily for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the sixth week, were given a double dose regimen. SBPM was performed over 7 consecutive days at 3 different times: at the end of the washout period (W0), at week 6 (W6) and week 12 (W12). A clinic determination of blood pressure (BP) was also performed at each visit, using the same automatic device as that used for SBPM. 671 patients were selected and 441 were randomised (age: 55 +/- 12 years: 240 men and 201 women). Study populations were the following: the safety population (n = 441, T = 220; P = 221), the intent-to-treat (ITT) population (n = 435, T = 217 and P = 218), and the per protocol population (n = 368, T = 188; P = 180). ITT analysis showed a greater diminution of trough DBP from W0 to W12 with T than with P (T: -6.6 +/- 6.7 mmHg and P: -5.1 +/- 7.0 mmHg; p = 0.018 according to ANOVA for repeated measures). Regarding clinic BP, the same results were observed. Likewise, the per-protocol analysis provided similar findings. Doubling dose was significantly less frequent with T (41%; n = 85) than with P (55%; n = 115; p = 0.005). The overall frequency of adverse events was similar in both treatment groups: T = 34% (n = 74) vs p = 32% (n = 70). Most of them were of mild to moderate intensity and transient. As expected, the occurrence of cough was more frequent with P [5% (n = 12), T < 1% (n = 2), p = 0.007]. The trough effect on DBP was statistically higher with T (40 mg) than with P (4 mg), using SBPM as well as automatic clinic BP measurement.",2002.0,0,0
1075,12366619,Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications.,Ali Ahmed; Catarina I Kiefe; Richard M Allman; Richard V Sims; James F DeLong,"To determine the association between angiotensin-converting enzyme (ACE) inhibitor therapy and survival of older heart failure patients with conditions perceived by physicians as contraindications to ACE inhibitors. Hospital. Retrospective follow-up study. Hospitalized older heart failure patients with systolic blood pressure of 90 mmHg or less, serum creatinine of 2.5 mg/dL or more, serum potassium of 5.5 mmol/L or more, or severe aortic stenosis. One-year postdischarge mortality (with and without adjustment for various patient and care characteristics). Logistic regression analyses were used to estimate the effect of the perceived contraindications on subsequent use of ACE inhibitors. Using Cox proportional hazards models, crude and adjusted hazard ratios (HRs) of 1-year mortality with 95% confidence intervals (CIs) were estimated for patients discharged on ACE inhibitors and compared with those without. HRs were estimated for all patients and were repeated after stratifying patients based on the presence of perceived contraindications to ACE inhibitor use. Of the 295 subjects, 52 (18%) had conditions perceived as contraindications, 186 (63%) received ACE inhibitors, and 107 (40%) died within 1 year of discharge. Presence of a perceived contraindication was independently associated with underutilization of ACE inhibitors on discharge (adjusted OR = 0.35, 95% CI = 0.17-0.71). ACE inhibitor prescription at discharge was associated with lower 1-year mortality overall (HR = 0.58, 95% CI = 0.40-0.85) and for the groups of patients with (HR = 0.34, 95% CI = 0.14-0.81) and without (HR = 0.66, 95% CI = 0.42-1.02) perceived contraindications. ACE inhibitor use was associated with a significant survival benefit in this cohort of hospitalized older heart failure patients with perceived contraindications.",2002.0,0,0
1076,12368933,Cold temperature impairs maximal exercise performance in patients with heart failure: attenuation by acute ACE inhibitor therapy.,Martin Juneau; Lucie Larivée; Michel White,"Cold exposure decreases ischemic threshold in patients with coronary artery disease and preserved left ventricle (LV) function. The impact of cold exposure and the effect of acute angiotensin-converting enzyme (ACE) inhibitor therapy on maximal exercise capacity have not been studied in patients with symptomatic congestive heart failure. Eleven patients with New York Heart Association class II and III congestive heart failure, aged 61 6 years (mean  SD), with LV ejection fraction 25 6%, completed four symptoms-limited maximal exercise tests at 20 C and -8 C in a cold chamber. The exercise tests were performed while the patients were treated with lisinopril for three days, or a placebo. Cold exposure significantly decreased exercise duration in patients treated with a placebo (506 156 s [20 C] versus 419 182 s [-8 C], P<0.01). Rate-pressure products measured at 4 min during the test and at peak performance were significantly increased at -8 C. Patients treated with lisinopril exhibited a significant attenuation of the decrease in exercise time in the cold (-17% for placebo versus -6.6% for lisinopril, P<0.05). Cold temperature increases cardiac demand in response to exercise and significantly reduces maximal exercise capacity in patients with symptomatic heart failure. Acute treatment with lisinopril attenuates the impact of cold on exercise capacity.",2002.0,0,0
1077,12372669,Ambulatory pulse pressure as predictor of outcome in older patients with systolic hypertension.,Jan A Staessen; Lutgarde Thijs; Eoin T O'Brien; Christopher J Bulpitt; Peter W de Leeuw; Robert H Fagard; Choudomir Nachev; Paolo Palatini; Gianfranco Parati; Jaakko Tuomilehto; John Webster; Michel E Safar; Syst-Eur Trial Investigators,"We enrolled 808 older patients with isolated systolic hypertension (160 to 219/71 <95 mm Hg) to investigate whether ambulatory measurement of pulse pressure and mean pressure can refine risk stratification. The patients (> or =60 years) were randomized to nitrendipine (10 to 40 mg/day) with the possible addition of enalapril (5 to 20 mg/day) or hydrochlorothiazide (12.5 to 25 mg/day) or to matching placebos. At baseline, pulse pressure and mean pressure were determined from six conventional blood pressure (BP) readings and from 24-h ambulatory recordings. With adjustment for significant covariables, we computed mutually adjusted relative hazard rates associated with 10 mm Hg increases in pulse pressure or mean pressure. In the placebo group, the 24-h and nighttime pulse pressures consistently predicted total and cardiovascular mortality, all cardiovascular events, stroke, and cardiac events. Daytime pulse pressure predicted cardiovascular mortality, all cardiovascular end points, and stroke. The hazard rates for 10 mm Hg increases in pulse pressure ranged from 1.25 to 1.68. Conventionally measured pulse pressure predicted only cardiovascular mortality with a hazard rate of 1.35. In the active treatment group compared with the placebo patients, the relation between outcome and ambulatory pulse pressure was attenuated to a nonsignificant level. Mean pressure determined from ambulatory or conventional BP measurements was not associated with poorer prognosis. In conclusion, in older patients with isolated systolic hypertension higher pulse pressure estimated by 24-h ambulatory monitoring was a better predictor of adverse outcomes than conventional pulse pressure, whereas conventional and ambulatory mean pressures were not correlated with a worse outcome.",2003.0,0,0
1078,12372680,Antihypertensive effects of angiotensin converting enzyme inhibition by lisinopril in post-transplant patients.,Lionel H Opie; Matthias Haus; Patrick J Commerford; Basil Levetan; Karen Moore; Johan Brink,"It is not known whether strict control of blood pressure (BP) in mild post-transplant hypertension gives any benefit. Our primary objective was to test the antihypertensive effects of lisinopril added to standard therapy on ambulatory BP (ABP) of post-transplant patients. The secondary objective was to monitor echocardiographic and hemodynamic end points. Post-transplant patients with an abnormality of the 24-h ABP recording were recruited to this double-blind randomized prospective study that started 2 to 3 months after transplantation. Patients were then evaluated at 6, 12, 18, and 24 months after transplantation. Lisinopril decreased the clinic BP and ABP, the latter from 134/85 to 126/82 mm Hg at 6 months (P =.01 v placebo) and 121/79 mm Hg after 2 years (P =.03 v placebo). Fewer patients in the lisinopril group required added amlodipine to control the BP (P =.01). Data on left ventricular (LV) mass are difficult to interpret because by coincidence in this small study, the lisinopril group had lower initial values than placebo. However, in the lisinopril group mean LV mass decreased by 10% (P =.02) and mass index by 13% (P =.01), whereas placebo LV mass and index did not change. The LV end-diastolic diameter increased only in the placebo group (P =.008). There were no significant changes in any of the other secondary outcomes, including the cardiac index and systemic vascular resistance. Thus, in these post-transplant patients, stricter BP control to normal levels by the addition of lisinopril to existing therapy, reduced BP and modestly decreased LV mass without altering cardiac hemodynamic function.",2003.0,0,0
1079,12374512,The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study.,Françoise Forette; Marie-Laure Seux; Jan A Staessen; Lutgarde Thijs; Marija-Ruta Babarskiene; Speranta Babeanu; Alfredo Bossini; Robert Fagard; Blas Gil-Extremera; Tovio Laks; Zhanna Kobalava; Cinzia Sarti; Jaakko Tuomilehto; Hannu Vanhanen; John Webster; Yair Yodfat; Willem H Birkenhäger; Systolic Hypertension in Europe Investigators,"After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation. To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs. Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33). The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.",2002.0,0,0
1080,12391928,Impact of Levovist ultrasonographic contrast agent on the diagnosis and management of hypertensive patients with suspected renal artery stenosis: a Canadian multicentre pilot study.,Yves Lacourcière; Jacques Lévesque; John M Onrot; Stephanie R Wilson; Esther Szaky; Micheline Thibodeau; Murray L Vasilevsky; Sidney M Dashefsky; Donald R Allan; Michel Lafortune; Benoît Vendeville; Witold M Zaleski; Denis E Pagé; Franco D'Onofrio,"To compare the diagnoses obtained with unenhanced ultrasonography (US), contrast-enhanced US and captopril-enhanced renal scintigraphy and to determine whether use of a contrast agent improves ability to assess the renal arteries with duplex Doppler US. The study was an open-label controlled trial involving 78 patients with hypertension suspected to have a renovascular cause. The patients underwent captopril-enhanced scintigraphy or routine unenhanced US (the usual diagnostic methods at the centres where the study was conducted) and contrast-enhanced US (with Levovist, Berlex Canada, Lachine, Que.). The patients were followed for 3 months after the diagnostic tests were performed. Enhanced US yielded a diagnosis for a significantly greater proportion of patients than did unenhanced US (77 [99%] v. 64 [82%] of 78 patients; p = 0.002) or captopril-enhanced scintigraphy (71 [99%] v. 58 [81%] of 72 patients; p = 0.002). Diagnosis was possible with both enhanced and unenhanced duplex Doppler US in only 64 (82%) of the 78 patients, and the diagnosis was the same with both methods for 63 (98%) of these 64 patients. In contrast, diagnosis was possible for only 58 (81%) of the 72 patients who underwent both enhanced US and captopril-enhanced scintigraphy; the same diagnosis was reported in 53 (91%) of these 58 cases. During follow-up, 11 patients (21 kidneys) underwent angiography. Significant stenosis was detected in 6 (55%) of the patients (8 [38%] of the kidneys). Both the enhanced and unenhanced US results agreed more often with angiography than did captopril-enhanced scintigraphy (9 [82%] v. 8 [73%] of the 11 patients). The proportion of patients in whom the left and right renal artery could be assessed by duplex Doppler US increased significantly (by 58% and 43%, respectively) with use of the contrast agent. Enhanced US had a higher rate of successful diagnosis than unenhanced US and captopril-enhanced renal scintigraphy. Enhanced US might therefore be suitable as a screening method for hypertensive patients with suspected renal artery stenosis.",2002.0,0,0
1081,12397697,[Angiotensin II type 1 antagonist suppress left ventricular hypertrophy and myocardial fibrosis in patient with end stage renal disease (ESRD)].,Yasunobu Shibasaki; Takashi Nishiue; Hiroya Masaki; Hiroaki Matsubara; Toshiji Iwasaka,"Fibrosis of left ventricle commonly occurs in end stage renal disease(ESRD) patients and is an independent risk factor of cardiovascular events. Angiotensin II type 1 receptor antagonist may be able to reverse fibrosis of left ventricle in ESRD patients. Ultrasonography-integrated backscatter(IBS) of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. In this study, 30 chronically hemodialyzed patients with hypertension were randomly allocated to receive antihypertensive therapy with either angiotensin II type 1 receptor(AT1-R) antagonist losartan(n = 10), angiotensin-converting enzyme(ACE) inhibitor enalapril(n = 10) or calcium antagonist amlodipine(n = 10). IBS of posterior wall of left ventricule were measured by IBS before and after 6 months treatment. Baseline demographic and clinical characteristics did not differ in three subgroups. Although losartan(34.2 +/- 1.8 to 30.2 +/- 2.4 dB: p = 0.0094) treatment demonstrated significant reduce of IBS values, enalapril(30.3 +/- 1.5 to 31.7 +/- 1.4 dB: p = 0.3268) and amlodipine (31.6 +/- 1.6 to 33.1 +/- 1.9 dB: p = 0.4632) did not changed it significantly before and after 6 months treatment. All three groups reduced left ventricular mass index(Losartan 154.5 +/- 9.9 to 114.6 +/- 5.8 g/m2: p = 0.0002) (enalapril 155.6 +/- 14.3 to 135.3 +/- 10.4 g/m2: p = 0.0275) (amlodipine 156.6 +/- 7.3 to 137.2 +/- 4.1 g/m2: p = 0.0589). Three groups manifested a similar significant decrease in the mean blood pressure. Plasma angiotensin II concentration was markedly increased by 5.0-fold relative to the control levels before treatment in Losartan treatment, in contrast unchanged in enalapril and only 2.0-fold increased in amlodipine treatment. This study indicates that losartan reduce of fibrosis of left ventricule and this effect may be via an anti-AT1-R effect.",2002.0,0,0
1082,12401122,Influence of drugs and gender on the arterial pulse wave and natriuretic peptide secretion in untreated patients with essential hypertension.,Alison J Deary; Anne L Schumann; Helen Murfet; Stephen Haydock; Roger S Foo; Morris J Brown,"Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infarction and stroke, and differences among the major drugs in their efficacy at preventing these individual endpoints. We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same. We studied 30 untreated hypertensive patients, aged 28-55 years, who were rotated through six 6-week periods of daily treatment with amlodipine 5 mg, doxazosin 4 mg, lisinopril 10 mg, bisoprolol 5 mg, bendrofluazide 2.5 mg or placebo. The best drug was repeated at the end of the rotation. Blood pressure readings and radial pulse tonometry (by Sphygmocor) were performed at each visit, and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide (BNP). The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave (T(R)) and the augmentation index (AI), which is the proportional increase in systolic pressure due to the reflected wave. There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis. Bisoprolol caused the greatest falls in blood pressure and T(R), but was the only drug to increase AI. This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels. There was a smaller elevation of BNP in women compared with men, as described previously, and this elevation also was associated with significantly higher values of AI. Other drugs reduced AI, and this was associated with a significant decrease in BNP by amlodipine. In conclusion, antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart, regarded as a sensitive measure of strain on cardiomyocytes. These differences may help to explain cause-specific differences in outcome in recent trials.",2002.0,0,0
1083,12401733,Effects of vitamin E on cardiovascular and microvascular outcomes in high-risk patients with diabetes: results of the HOPE study and MICRO-HOPE substudy.,Eva Lonn; Salim Yusuf; Byrcon Hoogwerf; Janice Pogue; Qilong Yi; Bernard Zinman; Jackie Bosch; Gilles Dagenais; Johannes F E Mann; Hertzel C Gerstein; HOPE Study; MICRO-HOPE Study,"Experimental and observational studies suggest that vitamin E may reduce the risk of cardiovascular (CV) events and of microvascular complications in people with diabetes. However, data from randomized clinical trials are limited. Therefore, we evaluated the effects of vitamin E supplementation on major CV outcomes and on the development of nephropathy in people with diabetes. The Heart Outcomes Prevention Evaluation (HOPE) trial is a randomized clinical trial with a 2 x 2 factorial design, which evaluated the effects of vitamin E and of ramipril in patients at high risk for CV events. Patients were eligible for the study if they were 55 years or older and if they had CV disease or diabetes with at least one additional coronary risk factor. The study was designed to recruit a large number of people with diabetes, and the analyses of the effects of vitamin E in this group were preplanned. Patients were randomly allocated to daily treatment with 400 IU vitamin E and with 10 mg ramipril or their respective placebos and were followed for an average of 4.5 years. The primary study outcome was the composite of myocardial infarction, stroke, or CV death. Secondary outcomes included total mortality, hospitalizations for heart failure, hospitalizations for unstable angina, revascularizations, and overt nephropathy. There were 3,654 people with diabetes. Vitamin E had a neutral effect on the primary study outcome (relative risk = 1.03, 95% CI 0.88-1.21; P = 0.70), on each component of the composite primary outcome, and on all predefined secondary outcomes. The daily administration of 400 IU vitamin E for an average of 4.5 years to middle-aged and elderly people with diabetes and CV disease and/or additional coronary risk factor(s) has no effect on CV outcomes or nephropathy.",2003.0,0,0
1084,12409969,Comparative effects of candesartan and enalapril on left ventricular hypertrophy in patients with essential hypertension: the candesartan assessment in the treatment of cardiac hypertrophy (CATCH) study.,Cesare Cuspidi; M Lorenza Muiesan; Laura Valagussa; Massimo Salvetti; Carlo Di Biagio; Enrico Agabiti-Rosei; Bruno Magnani; Alberto Zanchetti; CATCH investigators,"A limited number of studies have evaluated the effect of angiotensin II receptor antagonists (AIIAs) on left ventricular hypertrophy (LVH) in comparison with other antihypertensive drugs, and no large study has compared AIIAs with angiotensin-converting enzyme inhibitors (ACEIs). The CATCH (Candesartan Assessment in the Treatment of Cardiac Hypertrophy) study was a multicenter prospective randomized double-blind trial comparing the effects of candesartan cilexetil (8-16 mg once daily) and enalapril (10-20 mg once daily) with possible addition of hydrochlorothiazide (12.5-25 mg once daily) on echocardiographic left ventricular mass index (LVMI), in 239 hypertensives with LVH (LVMI 120 g/m2 in men and 100 g/m2 in women). Two-dimensionally guided M-mode echocardiograms were carried out at screening (recruiting scan), randomization (baseline scan) and after 24 and 48 weeks of treatment. Baseline and treatment echocardiograms were read at two central labs without knowledge of the scan time sequence. In intention-to-treat (ITT) analyses (196 patients), systolic and diastolic blood pressures (SBP, DBP) were significantly and equally reduced by the two treatments. Candesartan and enalapril reduced LVMI to the same extent, i.e. by 15.0 and 13.1 g/m2 (-10.9 and -8.4%; P<0.001 for both). The proportion of patients achieving normalization of LVMI was non-significantly higher with candesartan (36.3 versus 28.6%). Similar results were obtained in per-protocol (PP) analyses. Cough incidence was lower with candesartan ( P<0.03). CATCH is the first large study comparing the effects of an AIIA and an ACEI on LVMI. Candesartan cilexetil was found to be equally effective as enalapril in reducing SBP, DBP and LVMI in hypertensives with LVH, according to both ITT and PP analyses.",2003.0,0,0
1085,12420198,"Assessment of drug effects on blood pressure and pulse pressure using clinic, home and ambulatory measurements.",G S Stergiou; S P Efstathiou; I I Skeva; N M Baibas; C B Kalkana; T D Mountokalakis,"This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor (ACEI) compared with an angiotensin receptor blocker (ARB) on blood pressure (BP) and pulse pressure (PP) measured in the clinic (CBP and CPP, respectively), at home (HBP, HPP) and with ambulatory monitoring (ABP, APP). Twenty-seven hypertensive patients were randomised to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of CBP, 24-h ABP and 5-days HBP were performed before randomisation and at the end of each treatment period. All measurement methods showed that lisinopril was more effective than losartan in reducing BP. However, the difference between the two drugs was demonstrated with greater precision using HBP (P<0.001) than 24-h ABP (P<0.01), whereas the poorest precision for demonstrating this difference was provided by CBP (P<0.05). Lisinopril was also found more effective than losartan in reducing HPP (P=0.01) and 24-h APP (P=0.03) whereas no such a difference was detected using measurements of CPP. It was concluded that the antihypertensive drugs may differ in their effects not only on BP, but also on PP. HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP. Clinic measurements seem to be the least reliable method, particularly in the detection of differences in PP.",2003.0,0,0
1086,12423701,Impact of ramipril versus other angiotensin-converting enzyme inhibitors on outcome of unselected patients with ST-elevation acute myocardial infarction.,Harm Wienbergen; Rudolf Schiele; Anselm Kai Gitt; Claus Juenger; Tobias Heer; Christina Meisenzahl; Helmut Landgraf; Claus Bossaller; Jochen Senges; MITRA PLUS Study Group,"We examined the impact of treatment with ramipril versus other angiotensin-converting enzyme (ACE) inhibitors on clinical outcome in unselected patients of the prospective multicenter registry Maximal Individual Therapy of Acute Myocardial Infarction PLUS registry (MITRA PLUS). Of 14,608 consecutive patients with ST-elevation acute myocardial infarction, 4.7% received acute therapy with ramipril, 39.0% received other ACE inhibitor therapy, and 56.3% received no ACE inhibitor therapy. In a multivariate analysis, the treatment with ramipril compared with the treatment without ACE inhibitors was associated with a significantly lower hospital mortality and a lower rate of nonfatal major adverse coronary and cerebrovascular events. Compared with other generic ACE inhibitors, ramipril therapy was independently associated with a significantly lower hospital mortality (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.32 to 0.90) and a lower rate of nonfatal major adverse coronary and cerebrovascular events (OR 0.65, 95% CI 0.46 to 0.93), but not with a lower rate of heart failure at discharge (OR 0.79, 95% CI 0.50 to 1.27).",2002.0,0,1
1087,12435255,Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.,Jackson T Wright; George Bakris; Tom Greene; Larry Y Agodoa; Lawrence J Appel; Jeanne Charleston; DeAnna Cheek; Janice G Douglas-Baltimore; Jennifer Gassman; Richard Glassock; Lee Hebert; Kenneth Jamerson; Julia Lewis; Robert A Phillips; Robert D Toto; John P Middleton; Stephen G Rostand; African American Study of Kidney Disease and Hypertension Study Group,"Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998. A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups. No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline.",2002.0,0,0
1088,12441211,Tolerability of long-term treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives.,Gastone Leonetti; Bruno Magnani; Achille Cesare Pessina; Alessandro Rappelli; Bruno Trimarco; Alberto Zanchetti; COHORT Study Group,"Irrespective of their clinical relevance, side effects cannot be considered a negligible problem in antihypertensive therapy. The aim of this trial was to evaluate the tolerability profile of lercanidipine with that of two other calcium antagonists (amlodipine and lacidipine) in elderly hypertensives. In a multicenter, double-blind, parallel study 828 elderly (aged > or =60 years) hypertensives were randomized to lercanidipine 10 mg/day (n = 420), amlodipine 5 mg/day (n = 200), or lacidipine 2 mg/day (n = 208) (ratio 2:1:1). If blood pressure (BP) control was unsatisfactory (systolic BP/diastolic BP > or =140/90 mm Hg), the dose of the double-blind medication was doubled and, as a further step, enalapril or atenolol (plus diuretic, if needed) was added. Patients were treated for an average of 12 months. Amlodipine patients had significantly (P <.001) higher rates of edema (19%) and of early study discontinuations due to edema (8.5%) compared with lercanidipine (9% and 2.1%) and lacidipine patients (4% and 1.4%). Similarly, edema-related symptoms (lower limb swelling and heaviness) occurred significantly (P <.01) more often with amlodipine (50% and 45%, respectively) than with lercanidipine (35% and 33%) and lacidipine (34% and 31%). Most edema cases occurred in the first 6 months, a between-treatment difference being evident since beginning of treatment. Other drug-related adverse events did not differ between treatments. Blood pressure was equally and effectively reduced in the three groups. The two lipophilic dihydropyridine calcium antagonists, lercanidipine and lacidipine, have an antihypertensive effect comparable to that of amlodipine, but a better tolerability profile.",2003.0,0,0
1089,12441222,Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor.,Tomoyuki Okuguchi; Tomohiro Osanai; Naoto Fujiwara; Takeshi Kato; Norifumi Metoki; Yoshiyuki Konta; Ken Okumura,"Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% +/- 5.9% v 2.5% +/- 6.9%, diastolic BP: 6.4% +/- 6.5% v 3.3% +/- 7.8%, both P <.05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% +/- 9.7% v 42.8% +/- 17.2%, P <.05). Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.",2003.0,0,0
1090,12451325,Metabolic effects of combined antihypertensive treatment in patients with essential hypertension.,Alfredo Quiñones-Galvan; Antonio Pucciarelli; Demetrio Ciociaro; Antonio Masoni; Ferdinando Franzoni; Andrea Natali; Ele Ferrannini,"Single-drug treatment of essential hypertension (HT) is often insufficient to normalize blood pressure (BP), and high doses of antihypertensive agents can have adverse effects on glucose tolerance (GT) and insulin sensitivity. This study tested whether aggressive BP lowering with combination treatment had any influence on GT or insulin action. In all, 29 nonobese (body mass index [BMI], <30 kg/m ), normolipidemic patients with established HT (159 +/- 3/99 +/- 1 mm Hg) but normal GT were recruited. Eleven normotensive (125 +/- 3/85 +/- 1 mm Hg) subjects were matched to the patients for both anthropometric and metabolic variables. Following baseline studies (serum lipid profile, oral GT, insulin release, and insulin sensitivity assessed by the insulin clamp technique), patients were randomized in a double-blind fashion to two combination regimens (verapamil 180 mg/day + trandolapril 2 mg/day or atenolol 50 mg/day + nifedipine 20 mg/day) and restudied 3 months later. Blood pressure was normalized in both groups (with decrements of 25 +/- 5/17 +/- 2 and 29 +/- 3/15 +/- 2 mm Hg, respectively). Lipid profile, GT, insulin release, and insulin sensitivity of both glucose uptake and lipolysis were unchanged following both treatments. The authors conclude that in nonobese, normolipidemic, glucose-tolerant hypertensive patients, BP normalization with combination therapy is feasible at no cost in terms of undesired effects on glucose and lipid metabolism and insulin sensitivity.",2003.0,0,0
1091,12460699,Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients.,Roberto Fogari; Paola Preti; Annalisa Zoppi; Andrea Rinaldi; Luca Corradi; Carlo Pasotti; Luigi Poletti; GianLuigi Marasi; Giuseppe Derosa; Amedeo Mugellini; Carlo Voglini; Pierangelo Lazzari,"The aim of this study is to compare the long-term effect of amlodipine and fosinopril in monotherapy or in combination on urinary albumin excretion (UAE) in hypertensive diabetic patients. We selected 453 hypertensive patients with type 2 diabetes and microalbuminuria and randomized them to amlodipine (5 to 15 mg/day), fosinopril (10 to 30 mg/day), or amlodipine plus fosinopril (5/10 to 15/30 mg/day) for a 3-month titration period. The nonresponder patients or those complaining of side effects during the titration period were discontinued (n = 144); the remaining 309 patients were enrolled in the trial and treated with the same therapy for 4 years. Every 6 months, blood pressure (BP), heart rate (HR), UAE, creatinine clearance, and glycosylated hemoglobin (HbA1c) were evaluated. The combination therapy was more effective in reducing BP than either drug alone at any time of the study without affecting glucose homeostasis. All three treatments provided a significant decrease in UAE during the 48-month study period. However, this effect was more pronounced and became evident earlier with fosinopril than with amlodipine monotherapy (after 3 v 18 months of therapy). In addition, the combination therapy provided a greater antialbuminuric effect than the single drugs. This could be due to the greater antihypertensive effects, although other drug-specific effects cannot be excluded. The cardiovascular outcomes were similar in the amlodipine and in the fosinopril group, but they were lower in the combination group. These results strengthen the rationale to use a calcium-antagonist/angiotensin converting enzyme inhibitor combination in the treatment of hypertensive patients with type 2 diabetes.",2003.0,0,0
1092,12461301,Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT).,William C Cushman; Charles E Ford; Jeffrey A Cutler; Karen L Margolis; Barry R Davis; Richard H Grimm; Henry R Black; Bruce P Hamilton; Joanne Holland; Chuke Nwachuku; Vasilios Papademetriou; Jeffery Probstfield; Jackson T Wright; Michael H Alderman; Robert J Weiss; Linda Piller; Judy Bettencourt; Sandra M Walsh; ALLHAT Collaborative Research Group,"Blood pressure control (<140/90 mm Hg) rates for hypertension fall far short of the US national goal of 50% or more. Achievable control rates in varied practice settings and geographic regions and factors that predict improved blood pressure control are not well identified. To determine the success and predictors of blood pressure control in a large hypertension trial involving a multiethnic population in diverse practice settings. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial is a randomized, double-blind, active-controlled clinical trial with a mean follow-up of 4.9 years. Participant enrollment began in February 1994 and follow-up was completed in March 2002. A total of 623 centers in the United States, Canada, and the Caribbean. A total of 33,357 participants (aged > or =55 years) with hypertension and at least one other coronary heart disease risk factor. Participants were randomly assigned to receive (double-blind) chlorthalidone, 12.5-25 mg/d (n=15,255), amlodipine 2.5-10 mg/d (n=9048), or lisinopril 10-40 mg/d (n=9054) after other medication was discontinued. Doses were increased within these ranges and additional drugs from other classes were added as needed to achieve blood pressure control (<140/90 mm Hg). The outcome measures for this report are systolic and diastolic blood pressure, the proportion of participants achieving blood pressure control (<140/90 mm Hg), and the number of drugs required to achieve control in all three groups combined. Mean age was 67 years, 47% were women, 35% black, 36% diabetic; 90% were on antihypertensive drug treatment at entry. At the first of two pre-randomization visits, blood pressure was <140/90 mm Hg in only 27.4% of participants. After 5 years of follow-up, the percent controlled improved to 66%. Systolic blood pressure was <140 mm Hg in 67% of participants, diastolic blood pressure was <90 mm Hg in 92%, the mean number of drugs prescribed was 2.0+/-1.0, and the percent on > or =2 drugs was 63%. Blood pressure control varied by geographic regions, practice settings, and demographic and clinical characteristics of participants. These data demonstrate that blood pressure may be controlled in two thirds of a multiethnic hypertensive population in diverse practice settings. Systolic blood pressure is more difficult to control than diastolic blood pressure, and at least two antihypertensive medications are required for most patients to achieve blood pressure control. It is likely that the majority of people with hypertension could achieve a blood pressure <140/90 mm Hg with the antihypertensive medications available today.",2003.0,0,0
1093,12461307,Sexual dysfunction in patients with hypertension: implications for therapy.,Carlos M Ferrario; Pavel Levy,"Sexual dysfunction associated with hypertension or antihypertensive therapies may impact the ability of patients to stay on therapy and lead to deterioration in patients' quality of life. Therefore, it is important for practitioners to become familiar with the wide variation in sexual side effects produced by antihypertensive agents and to discuss the potential occurrence of these side effects with their patients. In many cases, a change in the patient's drug regimen may help patients overcome specific sexual side effects experienced with certain treatments. Practitioners should consider selecting an antihypertensive therapy that is highly effective in lowering blood pressure but preserves patients quality of life. The effect of medications on sexual function remains controversial. Some blinded trials report little difference between placebo and specific medications, whereas other studies indicate that antihypertensive medications increase sexual dysfunction, which has an impact on quality of life. Recent evidence suggests that losartan, an angiotensin II antagonist, is not typically associated with development of sexual dysfunction and may actually positively impact several indices of sexual function (erectile function, sexual satisfaction, and frequency of sexual activity) as well as perceived quality of life. Thus, angiotensin II antagonists may offer a therapeutic option to prevent or correct erectile dysfunction in patients with hypertension. The favorable effects of these agents on sexual function may be related, in part, to their ability to block angiotensin II, which has recently become recognized as an important mediator of detumescence and possibly erectile dysfunction.",2003.0,0,0
1094,12468570,ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time.,Nancy J Brown; Sandeep Kumar; Corrie A Painter; Douglas E Vaughan,"ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.",2003.0,0,0
1095,12479763,Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial,"Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.",2002.0,0,0
1096,12482789,Mode of death in heart failure: findings from the ATLAS trial.,P A Poole-Wilson; B F Uretsky; K Thygesen; J G F Cleland; B M Massie; L Rydén; Atlas Study Group. Assessment of treatment with lisinopril and survival,"To investigate markers that predict modes of death in patients with chronic heart failure. Randomised, double blind, three period, comparative, parallel group study (ATLAS, assessment of treatment with lisinopril and survival). 3164 patients with mild, moderate, or severe chronic heart failure (New York Heart Association functional class II-IV). High dose (32.5 or 35 mg) or low dose (2.5 or 5 mg) lisinopril once daily for a median of 46 months. All cause mortality, cardiovascular mortality, sudden death, and chronic heart failure death related to prognostic factors using competing risks analysis. Mode of death was classified by trialists and by an independent end point committee. Age, male sex, pre-existing ischaemic heart disease, increasing heart rate, creatinine concentration, and certain drugs taken at randomisation were markers of increased risk of all cause mortality and cardiovascular death. There were risk markers for sudden death that were different from the risk markers for death from chronic heart failure. Low systolic blood pressure at baseline, raised creatinine, reduced serum sodium or haemoglobin, and increased heart rate were associated with chronic heart failure death. Use of beta blockers or antiarrhythmic agents (mainly amiodarone) was associated with a reduced risk of sudden death, whereas long acting nitrates and previous use of angiotensin converting enzyme inhibitors were markers for increased risk. The use of competing risks analysis on the data from the ATLAS study has identified variables associated with certain modes of death in heart failure patients. This approach to analysing outcomes may make it possible to predict which patients might benefit most from particular therapeutic interventions.",2003.0,0,0
1097,12486426,Risks and benefits of early treatment of acute myocardial infarction with an angiotensin-converting enzyme inhibitor in patients with a history of arterial hypertension: analysis of the GISSI-3 database.,Fausto Avanzini; Gabriele Ferrario; Luigi Santoro; Paolo Peci; Paolo Giani; Eugenio Santoro; Maria Grazia Franzosi; Gianni Tognoni; Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico-3 Investigators,"Many trials have proved the benefits of early systematic treatment with angiotensin-converting enzyme inhibitors in patients with acute myocardial infarction (AMI). Pathophysiological studies, however, suggest potential harm in excessive reduction of blood pressure (BP) in hypertensive patients with ischemic heart disease. We analyzed data from the GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico) trial to assess the effects of early treatment with angiotensin-converting enzyme inhibitors during AMI in patients with a history of hypertension compared with normotensive patients. The trial randomly assigned 19,394 patients to 6 weeks of lisinopril treatment or control, starting treatment within 24 hours of AMI onset. In the 10,661 normotensive patients, lisinopril significantly reduced lethal events, but in the 7362 hypertensive patients, a higher rate of lethal events was reported the first day of treatment, and the benefits only appeared subsequently. These results may be attributable to the subgroup of 1165 hypertensive patients with low baseline systolic BP (lower quintile, BP <120 mm Hg), in whom critical hypotension was more prone to develop after lisinopril treatment. In fact, these patients showed a higher mortality rate as the result of an excess of cardiogenic shock during the first day of lisinopril treatment (odds ratio 3.07, 95% CI 1.39-6.77) and a persistent, unfavorable death trend after 6 weeks. These data suggest that caution should be exercised when using lisinopril in the acute phase of a myocardial infarction in patients with a history of hypertension but low systolic BP at presentation.",2003.0,1,1
1098,12487393,Strategy for the treatment of noncompliant hypertensive hemodialysis patients.,E A Ross; T B Pittman; L C Koo,"Hypertensive hemodialysis patients noncompliant for their medications do not benefit from pharmacologic advances in the treatment of high blood pressure, and increase their already high risk of cardiovascular complications. The medical staff often becomes frustrated by severe hypertension in those who refuse to take medicines at home, drink excessive fluids, miss multiple dialysis sessions and sign-off dialysis early. In addition to addressing the psychosocial, financial, educational and substance abuse problems which contribute to noncompliance, we have developed a medication strategy to serve as an at least interim means of lowering blood pressure. Antihypertensive agents which have long half-lives in renal failure (lisinopril) and/or are intrinsically long acting (transdermal clonidine and amlodipine) were administered on dialysis days by the unit personnel to those patients who did not or would not take that or any dose on their own. The lisinopril and amlodipine were assured to have been taken on at least the dialysis days (thrice weekly), and the clonidine patch replaced weekly. Sixteen patients were thus treated when they failed to reliably self-administer medications. They had a significant decline in the predialysis systolic pressure of 15 mm Hg (175 +/- 6 to 160 +/- 5 mm Hg), diastolic of 12 mm Hg (103 +/- 3 to 91 +/- 3 mm Hg), and mean pressure of 13 mm Hg (127 +/- 4 to 114 +/- 4 mm Hg). There was an improvement in post-dialysis bood pressures, with the mean pressure declining 13 mm Hg from 110 +/- 4 to 97 +/- 4 mm Hg. Many individuals had erratic blood pressure control, having intermittently missed dialysis and hence unit-administered medicine, as well as continued fluid or drug abuse. The patients had uniformly excellent acceptance of this regimen, even spontaneously requesting it, and had no appreciable adverse effects. In summary while noncompliance is being addressed by the entire medical team, dialysis unit administration of long-acting medicines helps many hypertensive dialysis patients who would otherwise be at increased risk for severe cardiovascular complications.",2003.0,0,0
1099,12493427,Effects of angiotensin converting enzyme inhibitor and angiotensin II receptor antagonist therapy in hypertensive renal transplant recipients.,W Kim; S Lee; S K Kang; H C Yu; B H Cho; S K Park,,2003.0,0,0
1100,12502669,Intrarenal hemodynamic changes after captopril test in patients with type 2 diabetes: a duplex Doppler sonography study.,Hiromichi Taniwaki; Eiji Ishimura; Takahiko Kawagishi; Naoki Matsumoto; Masayuki Hosoi; Masanori Emoto; Tetsuo Shoji; Shigeichi Shoji; Tatsuya Nakatani; Masaaki Inaba; Yoshiki Nishizawa,"ACE inhibitors are known to be effective in preventing the progression of diabetic nephropathy. Activation of the renin-angiotensin system (RAS) is reported to contribute to intrarenal hemodynamic abnormality in diabetic patients. We examined whether RAS blockade by captopril induces intrarenal hemodynamic changes in normotensive patients with type 2 diabetes. The patients ranged in age from 40 to 65 years (20 men and 20 women). A total of 15 age- and sex-matched healthy individuals served as control subjects. Resistive index (RI) of interlobar arteries was examined by duplex Doppler sonography before and after the oral captopril (25 mg) test. At baseline, no significant differences in RI values or plasma renin activity (PRA) were seen between the patients and healthy subjects. In healthy subjects, the RI values after the captopril test were significantly higher than baseline values (P < 0.01). However, in patients with type 2 diabetes, both with normoalbuminuria and microalbuminuria, RI values after the test were significantly lower than baseline values (P < 0.001). There were significant negative correlations between DeltaRI value and HbA1c (r = -0.458, P < 0.005) and between DeltaRI value and baseline PRA in diabetic patients (r = -0.339, P < 0.05). Multiple regression analysis showed that HbA1c and baseline PRA significantly and independently affected the magnitude of decrease in RI values after captopril administration in diabetic patients (R2 = 0.391, P < 0.0001). These results indicate that the intrarenal RAS may be activated in diabetic patients, that such activation may be affected by poor glycemic control, and that blockade of RAS activation by ACE inhibitor reduces intrarenal vascular resistance in diabetic patients. The results emphasize the beneficial effects of ACE inhibition in improving intrarenal hemodynamics in diabetic patients.",2003.0,0,0
1101,12507406,Are cholesterol-lowering medications and antihypertensive agents preventing stroke in ways other than by controlling the risk factor?,Sean Ruland; Philip B Gorelick,"Statins and angiotensin-converting enzyme (ACE) inhibitors are an important component of our armamentarium for stroke prevention. Both of these classes of agents have a primary mechanism of action of reducing the level of the respective risk factor. They also have mechanisms of action that may confer benefits beyond what is believed to be the primary action of the agent. This has led to speculation that statins reduce stroke risk by means beyond cholesterol lowering, and ACE inhibitors reduce stroke risk by means beyond blood pressure lowering. We review the mounting evidence that suggests that statins and ACE inhibitors have so-called pleiotropic effects that may lead to stroke prevention.",2003.0,0,0
1102,12514646,Prehospital management of acute ST-elevation myocardial infarction: a time for reappraisal in North America.,Robert C Welsh; Joseph Ornato; Paul W Armstrong,"Although the medical and technologic revolution in the last 3 decades has improved clinical outcome in patients sustaining acute ST-elevation myocardial infarction (STEMI), residual morbidity and mortality remain major health concerns. The critical roles of temporal delay and optimal sustained patency as modulators of successful reperfusion have been repeatedly demonstrated, and investigation into the ideal interface between pharmacologic and mechanical reperfusion continues. Despite physician awareness and patient education programs, time from symptom onset to treatment in STEMI remains stalled at approximately 3 hours for pharmacologic reperfusion, as documented in major clinical trials. Multifaceted improvements with advanced paramedic training, transmittable 12-lead electrocardiograms, and bolus fibrinolytics facilitate potential prehospital diagnosis and treatment. Thus, as we proceed into the 21st century, it is essential to reexamine strategies for addressing these and other issues relating to the process of delivering optimal care to most patients with STEMI. Especially notable are the opportunities provided through prehospital management with initiation of therapy, triage to appropriate hospitals, or both as major potential avenues to further enhance patient outcomes. We review past research in prehospital therapy for STEMI and practical impediments to implementation to establish a framework for interpretation of future developments.",2003.0,0,0
1103,12514658,Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study.,Claudio Borghi; Ettore Ambrosioni; Survival of Myocardial Infarction Long-term Evaluation-2 Working Party,"Angiotensin-converting enzyme (ACE) inhibitors have been reported to be effective in placebo-controlled trials in various subsets of patients with acute myocardial infarction (MI). However, no direct comparisons have been performed between different ACE inhibitors in the same patient population. This phase III, double-blind, parallel-group, multicenter study compared the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed patients with acute MI. Patients, aged 18 to 75 years, were randomized to receive oral zofenopril (30-60 mg/day) or lisinopril (5-10 mg/day), starting within 12 hours of completion of thrombolytic therapy and continuing for 42 days. The primary study end point was the incidence of severe hypotension (systolic blood pressure <90 mm Hg), either cumulative or drug-related. Secondary end points included additional safety and efficacy parameters. The overall incidence of severe hypotension was slightly 5 more reduced with zofenopril (10.9%) than with lisinopril (11.7%, P =.38). The incidence of drug-related severe hypotension was slightly but significantly lower with zofenopril than with lisinopril (6.7 vs 9.8%, 2-tailed P =.048). The 6-week mortality rate was 3.2% in the zofenopril group and 4.0% in the lisinopril group (P =.38), and no significant differences were observed in the incidence of major cardiovascular complications or any safety variables between the 2 ACE inhibitors. The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and associated with a rather low rate of severe hypotension when given in accordance with a dose-titrated scheme to thrombolyzed patients with acute MI. These findings could have a positive clinical impact and increase the proportion of patients with acute MI who can be safely treated with ACE inhibitors.",2003.0,0,1
1104,12517682,Different drug classes have variable effects on blood pressure depending on the time of day.,Trefor O Morgan; Adrianne Anderson,"Blood pressure (BP) is controlled by a variety of systems, the activities of which vary throughout the day. As drugs are developed that selectively block these systems, the fall in BP may not be consistent over 24 h. A total of 24 patients (aged >65 years) with systolic BP (SBP; >150 mm Hg) that had not been treated entered a substudy of a larger study performed in 74 patients. In a double blind, crossover study with a balanced design, they received placebo, atenolol 50 mg, perindopril 8 mg, felodipine 10 mg, or hydrochlorothiazide 50 mg. The study periods were 2 months. Ambulatory BP monitoring was performed at the end of each period, and was divided into awake periods (9:00 AM to 10:00 PM), sleep periods (12:00 AM to 6:00 AM), and morning periods (6:00 AM to 9:00 AM). Medication was taken at 9:00 AM. The four drug classes lowered 24-h mean SBP (P <.05), but the fall with atenolol was less than with the other drugs. The fall in awake BP with perindopril was less than with felodipine or hydrochlorothiazide. Atenolol caused no significant fall in sleep or morning SBP, and the falls with the other three drugs were significant and were greater than the fall with atenolol. The fall in sleep BP with perindopril was greater than with the other drug classes. The awake-sleep difference in SBP increased with perindopril, stayed the same with felodipine and hydrochlorothiazide, and was reduced by atenolol. In this study, the response to the different drug classes differed. The response to drugs that work relatively nonspecifically (diuretics, calcium blockers) was relatively consistent over 24 h. The response to beta blockers and to angiotensin converting enzyme inhibitors reflected the activity of control systems. This finding supports the concept of multiple drug therapy that may need to be tailored to the time of day.",2003.0,0,0
1105,12518180,"Differential effects of once-daily antihypertensive drugs on blood pressure, left ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER versus enalapril.",Frans H H Leenen; Martin G Myers; Campbell D Joyner; Corey B Toal,"Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular (LV) mass for comparable decreases in blood pressure (BP). However, some dihydropyridines, such as felodipine-extended release (ER), still increase sympathetic activity and may, therefore, be less effective in decreasing LV mass. To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control (assessed by 24 h ambulatory BP monitoring) and sympathetic activity (assessed by plasma catecholamine concentrations). Enalapril was started at 10 mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively, if the office BP remained 160/90 mmHg or greater at the end of the dosing interval. Evaluable echocardiograms were obtained for 116 patients at the end of the study (30 weeks of treatment). On 24 h ambulatory BP monitoring, nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval, whereas felodipine-ER caused a more marked fall in BP during the day, and enalapril's effects diminished during the night and had disappeared by the morning. Only felodipine-ER significantly increased supine and standing plasma noradrenaline by more than 50% similarly after six, 18, and 30 weeks of treatment. In BP responders (decrease in systolic BP 10 mmHg or greater), enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2, whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus enalapril). Once-daily dihydropyridines should not be regarded as one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits a better profile regarding 24 h BP control, sympathetic activation and regression of LV mass.",2003.0,0,0
1106,12522468,Comparison of trough effect of telmisartan vs perindopril using self blood pressure measurement: EVERESTE study.,S Ragot; A Ezzaher; A Meunier; M Poterre; R Bourkaib; D Herpin,"This multicentre study was aimed at comparing the trough effect of telmisartan and perindopril on diastolic blood pressure (DBP), using self blood pressure measurement (SBPM). A second objective was to compare the data obtained from SBPM with those provided by automatic office BP measurement. A total of 441 mild-to-moderate hypertensive patients were randomised to receive either telmisartan 40 mg or perindopril 4 mg for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the 6th week (W6) were given a double-dose regimen. Office BP and SBPM were performed at baseline (W0), at W6 and at week 12 (W12), both with the same automatic device. A greater diminution of trough DBP was obtained with telmisartan (-6.6+/-6.7 mmHg) than with perindopril (-5.1+/-7.0 mmHg; P=0.018). Regarding clinic BP, the same results were observed. Doubling dose was significantly less frequent with telmisartan (41%; n=85) than with perindopril (55%; n=115, P=0.005). Mean values of SBPM were lower than office BP values, with a difference of a greater importance at W0 than at W12: 6.6 vs 4.7 mmHg for systolic blood pressure (P<0.005) and 3.2 vs 1.4 mmHg for DBP (P<0.0001). At W12, isolated office hypertension was found in 9% of the patients (n=37), while there were 14% of the patients (n=55) with isolated home hypertension. In conclusion, the trough effect on DBP was statistically higher with telmisartan than with perindopril. SBPM values were lower than office BP values, with greater differences before than after treatment. About a quarter of the patients were found to be controlled with a method but not with the other one.",2003.0,0,0
1107,12522893,[Comparison of the antihypertensive activity of fosinopril and irbesartan].,E Angulo; N R Robles; J Grois; A Barquero; M Pérez Miranda,"To compare the antihypertensive effect of two daily single dose drugs acting on the renin-angiotensin axis by two different ways. Thirty patients were randomized to receive either irbesartan (150 mg once daily) (n = 15, mean age 65.2 +/- 8.7 years, 9 men and 6 women) or fosinopril (20 mg once daily) (n = 15, mean age 57.4 +/- 11.5 years, 4 men and 11 women, difference are not significant) during 12 weeks. When needed, hydroclorothiazide (12.5 mg) was added to treatment to improve hypotensive response. A reduction of SBP and DBP was observed in both treatment groups throughout the study. In order to obtain further BP reduction, hydrochlorothiazide was added to 6 patients with inadequate BP response at the 4th week (3 patients in the irbesartan group) and 8th week (2 patients in irbesartan group and 1 patient in fosinopril group). SBP was reduced in irbesartan group from 157.7 +/- 11.2 to 131.0 +/- 8.7 mmHg (12th week, p < 0.001). DBP decreases from 94.1 +/- 5.6 to 82.7 +/- 4.2 mmHg (p < 0.001). In fosinopril group SBP was reduced from 147.9 +/- 11.7 to 132.2 +/- 12.4 mmHg (p < 0.001) and DBP decreases from 92.3 +/- 6.3 to 84.0 +/- 5.4 mmHg (p < 0.001). Final between group differences in BP are not significant. Final BP reduction in irbesartan group (26.7 +/- 11.6 mmHg) was bigger than that obtained in fosinopril group (15.6 +/- 11.6 mmHg, p = 0.011). BP reduction was significant in fosinopril group from the first month (SBP 140.7 +/- 12.2, p = 0.021; DBP 87.2 +/- 6.2, p = 0.003). In irbesartan group BP reduction was not significant until the second month (SBP 135.5 +/- 10.4, p < 0.001; DBP 85.3 +/- 4.3, p < 0.001). Fosinopril and irbesartan seems to be equally effective to reduce DBP. Irbesartan might have higher effectiveness on systolic blood pressure. Irbesartan act more gradually than fosinopril and this may be useful to prevent from acute blood pressure falls.",2003.0,0,0
1108,12523675,The angiotensin-receptor blockers: from antihypertensives to cardiovascular all-round medications in 10 years?,Aldo P Maggioni; Roberto Latini,"Angiotensin-receptor blockers have been part of the antihypertensive treatment armamentarium since the mid-1990s. During this period, the number of agents has increased greatly, as has the number of indications for which these drugs are being tested in randomized controlled clinical trials. Beginning as efficacious and very well tolerated antihypertensives, angiotensin-receptor blockers have been shown to have benefits in patients with diabetes and heart failure that are not only attributable to the reduced blood pressure, as supported by recently concluded trials. The expanding treatment areas with these agents widen the interest in their applicability across the entire cardiovascular continuum. A number of large-scale studies set to report within the next few years will further determine the effects of angiotensin-receptor blockers in a range of cardiovascular indications beyond hypertension.",2003.0,0,0
1109,12526280,ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension.,J Amerena; S Pappas; J P Ouellet; L Williams; D O'Shaughnessy,"In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40-80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of -2.02 mmHg (P < 0.01). A significantly greater proportion of patients achieved a seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05), also measured with the same ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.",2003.0,0,0
1110,12530929,Best bang for the buck?,Alan B Weder,,2003.0,0,0
1111,12530940,The L-arginine-nitric oxide pathway in hypertension.,Malte Kelm,"Nitric oxide is involved in the regulation of resting vascular tone, adaptation of blood flow to metabolic demand of tissue, and adaptation of vessel diameter to volume of inflow, ie, flow-mediated dilation. Arterial hypertension is associated with an increased vascular tone of resistance vessels, a reduced compliance of conduit arteries, along with a thickening of the intima-media leading to vascular remodeling. Dysfunctional endothelium triggers such maladaptive processes. A reduced bioavailability of nitric oxide has been shown in hypertensive individuals dependent on the duration and severity of arterial hypertension. Angiotensin-converting enzyme inhibitors reverse endothelial dysfunction, whereas a concomitant reduction in significant cardiac events due to improved bioavailability has yet to be established. Long-term follow-up studies in individuals with manifest endothelial dysfunction and in offspring from hypertensive patients underscore the prognostic and genetic significance of a reduced nitric oxide bioavailability for the pathophysiology of arterial hypertension.",2003.0,0,0
1112,12531578,Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.,Naoyuki Nakao; Ashio Yoshimura; Hiroyuki Morita; Masyuki Takada; Tsuguo Kayano; Terukuni Ideura,"Present angiotensin-converting-enzyme inhibitor treatment fails to prevent progression of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker, and monotherapy of each drug at its maximum dose, in patients with non-diabetic renal disease. 336 patients with non-diabetic renal disease were enrolled from one renal outpatient department in Japan. After screening and an 18-week run-in period, 263 patients were randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent doses. Survival analysis was done to compare the effects of each regimen on the combined primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease. Analysis was by intention to treat. Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.018) and 20 (23%) of 86 on losartan alone (0.40, 0.17-0.69, p=0.016). Covariates affecting renal survival were combination treatment (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.011), age (1.30, 1.03-2.29, p=0.009), baseline renal function (1.80, 1.02-2.99, p=0.021), change in daily urinary protein excretion rate (0.58, 0.24-0.88, p=0.022), use of diuretics (0.80, 0.30-0.94, p=0.043), and antiproteinuric response to trandolapril (0.81, 0.21-0.91, p=0.039). Frequency of side-effects with combination treatment was the same as with trandolapril alone. Combination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive non-diabetic renal disease need to be researched.",2003.0,0,0
1113,12538743,Enalapril and losartan reduce sympathetic hyperactivity in patients with chronic renal failure.,Inge H H T Klein; Gerry Ligtenberg; P Liam Oey; Hein A Koomans; Peter J Blankestijn,"The aim of this study was to compare the effects on BP and sympathetic activity of chronic treatment with an angiotensin (Ang)-converting enzyme (ACE) inhibitor and an AngII receptor blocker in hypertensive patients with chronic renal failure (CRF). In ten stable hypertensive CRF patients (creatinine clearance, 46 +/- 17 ml/min per 1.73 m(2)), muscle sympathetic nerve activity (MSNA), plasma renin activity (PRA), baroreceptor sensitivity, and 24-h ambulatory BP were measured in the absence of antihypertensive drugs (except diuretics) after 6 wk of enalapril (10 mg orally) and after 6 wk of losartan (100 mg orally). The order of the three phases was randomized. Normovolemia was controlled with diuretics and confirmed with extracellular fluid volume measurements throughout the study. Both enalapril and losartan reduced MSNA (from 33 +/- 10 to 27 +/- 13 and 27 +/- 13 bursts/min, respectively; P < 0.05) and average 24-h BP (from 141 +/- 8/93 +/- 8 to 124 +/- 9/79 +/- 8 and 127 +/- 8/81 +/- 9 mmHg; P < 0.01). PRA was not different during the treatments. The change in BP and the change in MSNA during the treatments were correlated (r = 0.70 and r = 0.63, respectively; both P < 0.05). Baroreceptor sensitivity was not affected by the treatments. This is the first study to compare the effects of ACE inhibition and AngII blockade on MSNA. In hypertensive CRF patients, enalapril and losartan equally reduced BP and MSNA. Differences in modes of action of the two drugs did not result in differences in effects on MSNA, supporting the view that AngII-mediated mechanisms contribute importantly in the pathogenesis of sympathetic hyperactivity in these patients.",2003.0,0,0
1114,12544432,Renal dopamine receptors and hypertension.,Albert Ferro,,2003.0,0,0
1115,12544861,The role of blood pressure lowering before and after stroke.,Geoffrey A Donnan; Stephen M Davis; Amanda Thrift,"Elevated blood pressure is one of the most potent risk factors for first ever and recurrent stroke as well as influencing early outcome after acute stroke. There have been a number of significant randomized controlled trials which may influence management in each of these three categories. For primary prevention, the recent information from the Heart Outcomes Prevention Evaluation, Losartan Intervention for Endpoint Reduction to Hypertension, Study on Cognition and Prognosis in the Elderly and Australian National Blood Pressure Study support the view that blood pressure lowering protects against stroke regardless of baseline blood pressure level. There is some evidence that blockade of the angiotensin system may give additional protection. For secondary prevention, evidence from the Perindopril Protection against Recurrent Stroke Study shows that blood pressure lowering with perindopril based therapy reduces fatal or non-fatal stroke events, again in hypertensive or normotensive individuals. There is uncertainty about blood pressure lowering in acute stroke, although presentation of the recent Acute Candesartan Cilexetil Evaluation in Stroke Survivors trial in which there was significant protection against vascular events using candesartan suggests that further studies should be undertaken. Blood pressure lowering for primary prevention of stroke should be undertaken using a variety of therapeutic agents. For secondary stroke prevention perindopril based therapy should be used based on current evidence. Uncertainty still exists as to whether blood pressure lowering in the acute stroke setting is safe or improves outcomes.",2003.0,0,0
1116,12556541,Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.,Peter Gaede; Pernille Vedel; Nicolai Larsen; Gunnar V H Jensen; Hans-Henrik Parving; Oluf Pedersen,"Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.",2003.0,0,0
1117,12559222,Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure: an analysis based on the international LIDO trial.,J G F Cleland; A Takala; M Apajasalo; N Zethraeus; G Kobelt,"Levosimendan, a novel calcium sensitiser, improves cardiac performance and symptoms without increasing oxygen consumption, and decreases the mortality of patients with low-output heart failure. To estimate the cost-effectiveness of intravenous treatment with levosimendan compared with dobutamine in patients with severe low-output heart failure. This economic evaluation was based on a European clinical trial (LIDO), in which 203 patients with severe heart failure randomly received a 24 h infusion with either levosimendan or dobutamine. Survival and resource utilisation data were collected for 6 months; survival was extrapolated assuming a mean additional lifetime of 3 years based on data from the Cooperative North Scandinavian Enalapril Survival Study trial. Costs were based on study drug usage and hospitalisation in the 6-month follow-up. A sensitivity analysis on dosage of drug and duration of survival was performed. The mean survival over 6 months was 157+/-52 days in the levosimendan group and 139+/-64 days in the dobutamine group (P<0.01). When extrapolated up to 3 years, the gain in life expectancy was estimated at 0.35 years (discounted at 3%). Levosimendan increased the mean cost per patient by 1108, which was entirely due to the cost of the study drug. The incremental cost per life-year saved (LYS) was 3205 at the European level; in the individual countries the cost per LYS ranged between 3091 and 3331. The result was robust in the sensitivity analysis. Although the patients in the levosimendan group were alive for more days and thus at risk of hospitalisation for longer, there was no increase in hospitalisation or hospitalisation costs with levosimendan treatment. The cost per LYS using levosimendan compares favourably with other cost-effectiveness analyses in cardiology.",2003.0,0,0
1118,12566371,Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies.,Piero Ruggenenti; Naobumi Mise; Roberto Pisoni; Federica Arnoldi; Anna Pezzotta; Annalisa Perna; Dario Cattaneo; Giuseppe Remuzzi,"Dyslipidemia frequently complicates chronic nephropathies and increases the risk of renal and cardiovascular events. This might be ameliorated by drugs, such as angiotensin-converting enzyme inhibitors, which effectively reduce proteinuria. In this longitudinal study, we evaluated the extent to which uptitration of the ACE inhibitor lisinopril to maximum tolerated doses (median [range]: 30 [10 to 40] mg/d) ameliorated proteinuria and dyslipidemia in 28 patients with nondiabetic chronic nephropathies. Maximum lisinopril doses significantly and safely reduced proteinuria, serum total, LDL cholesterol, and triglycerides without substantially affecting serum HDL and renal hemodynamics. Proteinuria already decreased at 10 mg/d. Serum lipids progressively and dose-dependently decreased during uptitration to maximum doses. Reduction in total and LDL cholesterol correlated with increases in serum albumin/total protein concentration and oncotic pressure, peaked at lisinopril maximum doses, and persisted after treatment withdrawal. Despite less proteinuria reduction, hypercholesterolemia decreased more (and reflected the increase in serum albumin) in hypoalbuminemic than in normoalbuminemic patients who, despite more proteinuria reduction, had less decrease in cholesterol and no changes in serum albumin. Changes in serum triglycerides were independent of changes in serum proteins, were strongly correlated with lisinopril doses (r=-0.89, P=0.003) and recovered promptly after treatment withdrawal. Lisinopril was well tolerated, did not affect renal hemodynamics, and caused symptomatic, reversible hypotension in only two patients. In chronic nephropathies, angiotensin converting enzyme inhibitor uptitration to maximum tolerated doses safely ameliorated hypertriglyceridemia by a direct, dose-dependent effect, and hypercholesterolemia through amelioration of the nephrotic syndrome, particularly in patients with more severe hypoalbuminemia.",2003.0,0,0
1119,12568205,An open comparative clinical trial to assess the efficacy and safety of losartan versus enalapril in mild to moderate hypertension.,K N Chowta; M N Chowta; P Bhat; P M R Adhikari,"To compare the efficacy and safety of losartan with enalapril, in mild to moderate hypertension. An open, enalapril controlled study was conducted in 30 patients with mild to moderate hypertension. Losartan 50 mg was administered to patients for eights weeks. Throughout the study blood pressure was measured every two weeks. Routine laboratory investigations were performed before entering the trial, fourth week and at the end of the study. Adverse effects were recorded. After eight weeks losartan was stopped and enalapril 10 mg daily was administered to the same patients after two weeks washout period. The same methodology that was followed for losartan trial was repeated for enalapril trial also. Losartan treatment resulted in a highly significant reduction in the mean sitting diastolic blood pressure. Comparison with enalapril showed that both drugs are equally efficacious in reducing blood pressure in mild to moderate hypertension. The percentage of responders was slightly more with losartan than enalapril (86.7% vs 76.7%). Adverse events reported with losartan were mild. Enalapril also was well tolerated like losartan but there was high incidence of dry cough, which was reported in nine patients (30%). Losartan is an effective antihypertensive drug with an excellent safety and tolerability profile. It shows similar blood pressure lowering efficacy to that of enalapril. In contrast to enalapril, losartan does not cause dry cough.",2003.0,0,0
1120,12568207,Effects of angiotensin converting enzyme inhibitor on renal function in patients of membranoproliferative glomerulonephritis with mild to moderate renal insufficiency.,S Giri; S K Mahajan; R Sen; A Sharma,"To determine the effect of enalapril, angiotensin-converting-enzyme inhibitor (ACE-I) on progression of renal insufficiency in primary membranoproliferative glomerulonephritis with mild to moderate renal insufficiency. Thirty patients with histopathologically proved MPGN having hypertension (grade I and II of JNC-VI criteria of hypertension) and mild to moderate impairment of renal function (creatinine clearance varying from 30-80 ml/min, significant albuminuria and serum creatinine 1.2-3.0 mg/dl) were initially treated with diuretics and 3-blockers to bring down BP < 140/90 mm Hg. These patients were then randomly divided into three groups of 10 each, group I--Control; group II--Nifedipine and group III--Enalapril. In group II and III Nifidepine 30 mg/day and in group III Enalapril 10 mg/day respectively were added in addition and treatment was continued for nine months. These patients were followed up monthly for drug efficacy, side effects and any adverse drug reaction. Out of 30, 28 patients completed the study. At the end of nine months of treatment the patients of control group revealed significant increase in serum creatinine (1.65 +/- 0.38 to 2.17 +/- 0.31 mg/dl), blood urea (34.0 +/- 3.9 to 40.0 +/- 3.1 mg/dl), and 24 hours albuminuria (3.6 +/- 0.6 to 4.2 +/- 0.6 gm) and decrease in creatinine clearance (60.3 +/- 13.3 to 37.5 +/- 11.8 m/min); however, in enalapril group there was decrease in serum creatinine (1.72 +/- 0.45 to 1.24 +/- 0.58 mg/dl), blood urea (34.6 +/- 4.7 to 28.1 +/- 6.7 mg/dl) and 24 hours albuminuria (3.3 +/- 1.0 to 1.6 +/- 1.1 gm) and increase in creatinine clearance (56A +/- 15.8 to 77.1 +/- 23.5 ml/min). The patients on nifedipine showed statistically nonsignificant changes in creatinine clearance, blood urea and serum creatinine; while albuminuria increased from 3.0 +/- 1.3 to 3.9 +/- 0.4 gm/24 hours (p < 0.01). The blood pressure was well controlled in all patients. None of the patient had side effects leading to withdrawal of drugs. No adverse drug reaction was noted. ACE-I (enalapril) provided protection against the progression of renal insufficiency in patients of MPGN having hypertension with mild to moderate renal impairment. The renoprotective effects of ACE inhibitor (enalapril) is associated with substantial decrease in albuminuria.",2003.0,0,1
1121,12573197,Aggressive medical management of coronary artery disease versus mechanical revascularization.,Elaine Chiquette; Robert Chilton,"The treatment of patients with stable angina has three goals: 1) minimize or eliminate ischemia (silent or symptomatic), 2) reduce morbidity, and 3) decrease mortality. Surgical and now angiographic revascularization procedures are increasingly popular approaches to the management of these patients. The results of randomized, controlled trials suggest that revascularization may not improve survival, but is useful to improve symptoms and exercise capacity. However, these trials are of limited value because they do not reflect current state of the art revascularization techniques or optimal medical management. Because many of these studies were conducted more than a decade ago, patients were recruited before the survival benefits of antiplatelet therapy, b-blockers, angiotensin-converting enzyme inhibitors, and aggressive lipid lowering were accepted. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial should help us determine the best approach in these patients. It is a multicenter, randomized trial comparing aggressive medical therapy with aggressive medical therapy with current state of the art percutaneous coronary intervention (PCI) for patients with stable coronary disease. The COURAGE protocol targets global risk reduction emphasizing 1) lifestyle modification, 2) maximal use of drugs to lower blood pressure to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) VI goals, 3) maximal use of drugs to lower cholesterol to below National Cholesterol Education Program Adult Treatment Panel III goals for secondary prevention, and 4) maximal use of drug to alleviate anginal symptoms with or without the best interventional devices to conduct PCI.",2003.0,0,0
1122,12573198,The renin-angiotensin-aldosterone system as a target in coronary disease.,James H O'Keefe; Jared T Lurk; Ravindra C Kahatapitiya; Janet A Haskin,"The renin-angiotensin-aldosterone system (RAAS) plays a fundamental role in the development of atherosclerosis and adverse cardiovascular events. Traditionally, the pathologic effects of the RAAS were assumed to result from vasoconstriction induced by angiotensin II, and salt and water retention due to aldosterone. However, these hormones also have powerful trophic effects, stimulating increased mass in both the arterial wall and left ventricle. In addition, angiotensin II and aldosterone predispose to vascular inflammation, thrombosis, oxidative stress, and sudden cardiac death. Therapy directed at RAAS overactivity is essential for normalizing the prognosis of most patients with atherosclerosis. An angiotensin-converting enzyme (ACE) inhibitor improves the prognosis of patients with atherosclerosis and/or diabetes even in the setting of normal baseline blood pressure. Angiotensin receptor blocking agents also improve cardiovascular structure and prognosis. Although these agents are better tolerated than ACE inhibitors, they do not appear to be as effective in reducing event rates. Aldosterone receptor blocking agents also improve cardiovascular structure, function, and prognosis. Aldosterone receptor blockers appear to provide additive benefit when used in conjunction with either an ACE inhibitor or an angiotensin receptor blocker.",2003.0,0,0
1123,12574098,Effects of isosorbide mononitrate and AII inhibition on pulse wave reflection in hypertension.,Gordon S Stokes; Edward S Barin; Kerry L Gilfillan,"The aortic pulse wave contour in isolated systolic hypertension often shows a prominent reflection peak, which combines with the incident wave arising from cardiac ejection so as to widen pulse pressure. We investigated the effects of an extended-release nitrate preparation and of 2 angiotensin II (AII) inhibitors (an AII receptor antagonist and an ACE inhibitor) on the aortic pulse wave contour and systemic blood pressure in hypertensive subjects with high augmentation index caused by exaggerated pulse wave reflection. Two double-blind, randomized, placebo-controlled crossover studies were carried out in a total of 16 elderly patients with systolic hypertension resistant to conventional antihypertensive therapy. In 1 study, pharmacodynamic responses to single doses of placebo, isosorbide mononitrate, eprosartan, and captopril were determined; in the other, single-dose isosorbide mononitrate and placebo were compared in subjects treated with AII inhibitors at baseline. Blood pressure was measured by sphygmomanometry and pulse wave components by applanation tonometry at the radial artery. All 3 agents were shown to decrease brachial systolic blood pressure, aortic systolic blood pressure, and aortic pulse pressure. Qualitative effects on the aortic pulse wave contour differed: augmentation index was not significantly altered by either captopril or eprosartan but was decreased (P<0.0001) by approximately 50% of the placebo value with isosorbide mononitrate in both study groups. We propose that isosorbide mononitrate corrected the magnified wave reflection in systolic hypertension of these elderly patients by an effect that was distinct from that exercised by either acute or chronic AII inhibition.",2003.0,0,0
1124,12574793,"Evaluation of the efficacy and tolerability of the combination delapril plus indapamide in the treatment of mild to moderate essential hypertension: a randomised, multicentre, controlled study.",E A Rosei; D Rizzoni; DIMS II (Delapril-Indapamide Multicenter Study II),"The aim of the study was to evaluate efficacy and tolerability of two different fixed combinations of an angiotensin-converting enzyme inhibitor and a diuretic: delapril+indapamide (D+I) and captopril+hydrochlorothiazide (C+H) administered for 6 months to patients with mild to moderate essential hypertension. In all, 96 centres participated in this randomised, parallel groups, controlled study. A total of 829 patients with uncomplicated mild to moderate hypertension were randomised, and 790 were eligible for the analysis of efficacy (intention to treat). Patients of both sexes, aged 18-75 years, newly diagnosed or untreated during the last month were included in the study if their diastolic blood pressure (DBP) was > or =95 and < or =114 mmHg. The starting doses of the drugs were delapril 30 mg+indapamide 1.25 mg tablets o.d. or captopril 50 mg+hydrolchlorothiazide 15 mg tablets o.d. After a 1-month treatment period, nonresponders (DBP >90 mmHg, or decrease in DBP <10 mmHg) had the daily dose increased to either delapril 30 mg+indapamide 2.5 mg or captopril 50 mg+hydrochlorothiazide 25 mg tablets for a further 5 months. The primary assessment of antihypertensive efficacy was the percentage of patients who responded after a 6-month drug treatment. The responder rates were 72.6% with D+I and 62.9% with C+H (P=0.004 between treatments) after 60 days of treatment, and 92.6% in the D+I and 85.2% in the C+H (P<0.001 between treatments) at the end of the treatment period. The final value of systolic blood pressure was 134.5+/-13.1 mmHg with D+I and 138.3+/-14.0 mmHg with C+H (P<0.001 between treatments). At the final visit, DBP was 84.57+/-7.0 mmHg in the D+I group and 85.57+/-8.0 mmHg in the control group (P=0.017 between treatments). In all, 11 patients in the D+I group and 19 patients in the C+H group were withdrawn from the study because of adverse events. In all, 30 patients (7.6%) with D+I and 32 patients (8.1%) with C+H experienced adverse events. In conclusion, D+I was more effective than C+H in terms of overall reduction in blood pressure and response rate. Greater efficacy was obtained without any increase in adverse effects, since both treatments were equally well tolerated.",2003.0,0,0
1125,12575970,High-dose angiotensin-converting enzyme inhibition restores body fluid homeostasis in heart-transplant recipients.,Randy W Braith; Roger M Mills; Christopher S Wilcox; Gary L Davis; James A Hill; Charles E Wood,"We tested the hypothesis that salt and fluid retention in heart-transplant recipients (HTRs) is caused by a failure to reflexively suppress the renin-angiotensin-aldosterone system (RAAS). It is known that extracellular fluid volume is expanded (12% to 15%) in HTRs who develop hypertension. Responses to volume expansion were measured in eight HTRs (ages 57 +/- 6 years) and six liver-transplant recipients (LTRs) (ages 52 +/- 2 years) both before and after treatment with captopril (225 mg/day). After three days of a standardized diet, 0.154 mol/l saline was infused at 8 ml/kg/h for 4 h. Blood pressure, hormones, and renal function were monitored for 48 h. After four months, the same subjects received captopril (225 mg/day), and the protocol was repeated. Before captopril, saline infusion suppressed the RAAS in LTRs but not in HTRs, resulting in elimination of 86 +/- 12% versus 50 +/- 11% of the sodium load by 48-h postinfusion. Blood pressure increased only in the HTRs (+16 +/- 5/9 +/- 3 mm Hg) and remained elevated for 48 h (p < or = 0.05). After captopril, sodium elimination was comparable in the liver (87 +/- 13%) and heart groups (86 +/- 12%) and blood pressure did not change in either group. CONCLUSIONS; Heart transplant recipients have blunted diuretic and natriuretic responses to volume expansion that is mediated by their inability to suppress the RAAS. Pharmacologic suppression of the RAAS normalized defects in blood pressure and fluid homeostasis. These findings indicate that hypertension in HTRs is caused, in part, by a failure to reflexively suppress the RAAS when these patients become hypervolemic.",2003.0,0,0
1126,12578880,Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes.,Philip S Mehler; Joseph R Coll; Raymond Estacio; Anne Esler; Robert W Schrier; William R Hiatt,"Peripheral arterial disease (PAD) and diabetes are both associated with a high risk of ischemic events, but the role of intensive blood pressure control in PAD has not been established. The Appropriate Blood Pressure Control in Diabetes study followed 950 subjects with type 2 diabetes for 5 years; 480 of the subjects were normotensive (baseline diastolic blood pressure of 80 to 89 mm Hg). Patients randomized to placebo (moderate blood pressure control) had a mean blood pressure of 137+/-0.7/81+/-0.3 mm Hg over the last 4 years of treatment. In contrast, patients randomized to intensive treatment with enalapril or nisoldipine had a mean 4-year blood pressure of 128+/-0.8/75+/-0.3 mm Hg (P<0.0001 compared with moderate control). PAD, which is defined as an ankle-brachial index <0.90 at the baseline visit, was diagnosed in 53 patients. In patients with PAD, there were 3 cardiovascular events (13.6%) on intensive treatment compared with 12 events (38.7%) on moderate treatment (P=0.046). After adjustment for multiple cardiovascular risk factors, an inverse relationship between ankle-brachial index and cardiovascular events was observed with moderate treatment (P=0.009), but not with intensive treatment (P=0.91). Thus, with intensive blood pressure control, the risk of an event was not increased, even at the lowest ankle-brachial index values, and was the same as in a patient without PAD. In PAD patients with diabetes, intensive blood pressure lowering to a mean of 128/75 mm Hg resulted in a marked reduction in cardiovascular events.",2003.0,0,1
1127,12580985,Blood pressure response to conventional and low-dose enalapril in chronic renal failure.,Thomas Elung-Jensen; Jens Heisterberg; Anne-Lise Kamper; Jesper Sonne; Svend Strandgaard,"In chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat. As part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data were analysed in all patients completing 3 months of follow-up. The patients were allocated to two trough plasma concentrations of enalaprilat, either above 50 ng ml(-1) (high) (n = 17) or below 10 ng ml(-1) (low) (n = 18), and the daily dose of enalapril titrated accordingly. Median (range) glomerular filtration rate (GFR) at baseline was 18 (7.9) in the high enalaprilat concentration group and 17 (7.3) ml min(-1) 1.73 m(2) in the low concentration group (NS). Nine patients in each group were on treatment with enalapril at baseline with a median daily dose of 5 mg in both the high (5-10) and low (2.5-20) concentration group. At 3 months' follow-up, the dose was 10 (2.5-30) and 1.9 (1.25-5) mg (P < 0.0001), respectively. After 3 months median trough concentrations of enalaprilat were 82.5 (22-244) ng ml(-1) and 9.1 (2.5-74.8) ng ml(-1) (P < 0.002). At baseline the median systolic blood pressures in the two groups were 140 (110-200) and 133 (110-165), in the high and low enalaprilat concentration groups, respectively, and after 3 months they were 135 (105-170) and 130 (105-170) mmHg (NS). Median diastolic blood pressure was 80 mmHg in each group both at baseline (65-100) and at follow-up (60-95) (NS). There was no difference between the groups in concomitant antihypertensive treatment (number of patients treated, mean daily dose) during the observation period. Proteinuria remained stable during the study period in both groups; patients in the high concentration group had higher plasma potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR. In moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective of concomitant antihypertensive treatment.",2003.0,0,0
1128,12584366,A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly.,Lindon M H Wing; Christopher M Reid; Philip Ryan; Lawrence J Beilin; Mark A Brown; Garry L R Jennings; Colin I Johnston; John J McNeil; Graham J Macdonald; John E Marley; Trefor O Morgan; Malcolm J West; Second Australian National Blood Pressure Study Group,"Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.",2003.0,0,0
1129,12584670,ACE-I and ARBs in early diabetic nephropathy.,Michael Mauer; Bernard Zinman; Robert Gardiner; Keith N Drummond; Samy Suissa; Sandra M Donnelly; Trudy D Strand; Michael S Kramer; Ronald Klein; Alan R Sinaiko,"Antihypertensive treatment of patients with clinical manifestations of diabetic nephropathy, and especially, renin-angiotensin system (RAS) inhibition, slows, but may not fully arrest progression towards end-stage renal disease. Studies using hard endpoints such as doubling of serum creatinine, dialysis, or death that are initiated before emergence of any renal functional abnormalities in diabetes, would be of impractical length and size. We therefore undertook a primary prevention study (The Renin-Angiotensin System Study or RASS) to determine if inhibition of the RAS could slow the development of a key diabetic glomerulopathy structural endpoint, increase in mesangial fractional volume (Vv[Mes/glom]). This is a parallel group, double-blind, placebo-controlled trial with 285 patients with Type 1 diabetes mellitus (95 per group) randomised to receive the angiotensin-converting enzyme inhibitor, enalapril, the angiotensin II receptor blocker, losartan, or placebo. All patients are normotensive, normoalbuminuric and have normal or increased glomerular filtration rates at study entry. The study is based on primary endpoint of change in Vv(Mes/glom) from baseline to the five-year renal biopsy, with baseline and interval measures of albumin excretion rate, glomerular filtration rate, blood pressure, and glycaemia. Baseline, mid-point, and five-year retinal fundus photography are also performed. One thousand and sixty-five patients were interviewed, 707 refused participation and 73 were excluded. The target of 285 subjects were randomised and their clinical and demographic characteristics are described. Biopsy complications occurred in 17 (6%), only one of which required hospitalisation. There were no permanent biopsy-related sequelae. Renal structural variables are reasonable surrogate endpoints for studies of progression of early diabetic nephropathy. Although requiring substantial recruitment effort, diabetic nephropathy primary prevention trials based on change in renal structure are feasible.",2003.0,0,0
1130,12595499,Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study.,Johannes F E Mann; Hertzel C Gerstein; Qi-Long Yi; Eva M Lonn; Byron J Hoogwerf; Andrew Rashkow; Salim Yusuf,"In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril's effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 microM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria.",2003.0,0,0
1131,12600907,Cost implications of the use of ramipril in high-risk patients based on the Heart Outcomes Prevention Evaluation (HOPE) study.,Andre Lamy; Salim Yusuf; Janice Pogue; Amiram Gafni; Heart Outcomes Prevention Evaluation Investigators,"The HOPE study has demonstrated that ramipril is beneficial (ie, prevents cardiovascular death, myocardial infarction, and stroke) for a broad range of patients without evidence of left ventricular dysfunction or heart failure who are at high risk for cardiovascular event. In this study, we report the cost implications, in both the United States and Canada, of the use of ramipril after the HOPE study. A third-party perspective was chosen (Medicare for the United States and Ministry of Health for Canada). We calculated the costs of the management strategies of ramipril and placebo. An annual discount rate of 3% was used over the 4.5 years of follow-up. Sensitivity analyses were performed. Costs are reported in United States dollars and in Canadian dollars, respectively. The total costs per patient (including acquisition costs of ramipril) were not different between the groups in both countries (United States, $13 520 versus $13 631; Canada, $8702 versus $8588). From the distribution of cases in the bootstrap analysis, we found that 90% of cases fall either into a cost-neutral or cost-saving situation (64% in United States and 27% in Canada) or into a cost-effectiveness situation with an incremental cost-effectiveness ratio <$10 000 (in respective currency) per primary event saved. On the basis of these results, we suggest that the use of ramipril is likely to represent an efficient use of resources in both countries. These findings support the use of ramipril in populations included in the HOPE study.",2003.0,0,0
1132,12602460,FOSIDIAL: a randomised placebo controlled trial of the effects of fosinopril on cardiovascular morbidity and mortality in haemodialysis patients. Study design and patients' baseline characteristics.,Faiez Zannad; Michèle Kessler; Jean Pierre Grünfeld; Christian Thuilliez; FOSInopril in DIALysis Investigators,"The prevalence of end stage renal disease (ESRD) is growing in western countries. Patients with ESRD are more frequently elderly and diabetic and are exposed to very high cardiovascular morbidity and mortality. The main aim of the FOSIDIAL study is to assess the efficacy and safety of fosinopril, an angiotensin converting enzyme (ACE) inhibitor, in reducing the mortality and cardiovascular events in haemodialysis patients presenting with left ventricular hypertrophy. A total number of 397 patients are included in the study. They are aged 50-80 years (average 66.7 years) and have been undergoing haemodialysis for 4.8 years. All have left ventricular hypertrophy with cardiac mass index > 100 g/m2 in women and > 130 g/m2 in men, measured within 3 months prior to inclusion. Baseline cardiac mass index is 174 g/m2. After a 2 week placebo period, the patients are randomised into two groups receiving either fosinopril 5-20 mg/day, or a placebo for a duration of 24 months. The target dose is reached at the sixth, seventh or eighth week of treatment. Depending on tolerance, 300 patients reached the maximum recommended dose. Patients are subsequently assessed clinically every 3 months until the end of the study. The primary outcome is a composite endpoint of fatal and nonfatal major cardiovascular events. Secondary endpoints are individual cardiovascular events, event-free survival, overall mortality and all-cause hospitalisations. The trial began in October 1998. All patients were included by December 2000 and follow-up is ongoing. The last visit for the last patient is scheduled for 30 December 2002. We report here on the study design and the baseline characteristics of the study population.",2003.0,0,0
1133,12610049,"Development of congestive heart failure in type 2 diabetic patients with microalbuminuria or proteinuria: observations from the DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study.","Laurent Vaur; Pascal Gueret; Michel Lievre; Sylvie Chabaud; Philippe Passa; DIABHYCAR Study Group (type 2 DIABetes, Hypertension, CARdiovascular Events and Ramipril) study","The DIABHYCAR (type 2 DIABetes, Hypertension, CArdiovascular Events and Ramipril) study allowed investigators to analyze factors leading to the development of congestive heart failure (CHF) in type 2 diabetic patients with abnormal urinary albumin concentration. Type 2 diabetic subjects of both sexes aged >or=50 years who had a urinary albumin concentration >or=20 mg/l were randomly allocated to 1.25 mg/day ramipril or placebo in addition to their usual treatment and treated for 3-6 years in a double-blind fashion. Major outcomes including hospitalization for CHF were recorded during the follow-up. Of the 4912 included patients, 187 developed CHF during the study. There was no significant difference in the incidence of CHF between the two treatment groups. Using a multivariate analysis, independent risk factors for the occurrence of CHF were age, history of cardiovascular disease, baseline urinary albumin concentration, baseline HbA(1c), and smoking habits. A total of 68 of the 187 patients (36.4%) died during the 12 +/- 11-month period after the first hospitalization for CHF, whereas the annual mortality rate of the population who did not develop CHF was 3.2%. Presence of atherosclerotic disease, baseline urinary albumin concentration, and HbA(1c) level were indicators for further development of CHF. Occurrence of CHF is a major prognostic turn in a diabetic patient's life.",2003.0,0,0
1134,12611125,Improving practice patterns in heart failure through a national cardiological network: the case of ACE-inhibitors.,Maurizio Porcu; Cristina Opasich; Marino Scherillo; Donata Lucci; Renata De Maria; Giuseppe Di Tano; Aldo P Maggioni; Italian Network on Congestive Heart Failure (IN-CHF) Investigators,"Despite the well-established benefits of ACE-inhibitors in chronic heart failure (CHF), current treatment rates and prescribed doses are lower than those proven to improve survival. We evaluated whether participation in a specialist network and the use of a common database would impact on the compliance with CHF guidelines. We analyzed the rate and determinants of ACE-inhibitor use and prescribed doses among 8102 patients with CHF enrolled at 133 cardiology centers participating in a national network. 6625 patients (82%) took ACE-inhibitors, most commonly enalapril (41%, mean dose 16 +/- 9 mg), captopril (25%, mean dose 74 +/- 44 mg) and lisinopril (14%, mean dose 13 +/- 8 mg). The predictors of the non-prescription of ACE-inhibitors were: female gender (odds ratio--OR 1.46, 95% confidence interval-CI 1.28-1.67), older age (OR 1.01, 95% CI 1.01-1.02), valvular etiology (OR 1.87, 95% CI 1.60-2.20), NYHA class III-IV (OR 1.25, 95% CI 1.09-1.42) and creatinine levels > 2.5 mg/dl (OR 5.19, 95% CI 3.36-8.02). Conversely a left ventricular ejection fraction < 30% (OR 0.78, 95% CI 0.65-0.94) and a hypertensive (OR 0.69, 95% CI 0.55-0.86) or idiopathic (OR 0.67, 95% CI 0.57-0.78) etiology increased the rate of ACE-inhibitor prescription. Low ACE-inhibitor doses were prescribed to 26.4% of cases. The IN-CHF database, an educational and organizational effort led by a national cardiology society, demonstrates that high rates of ACE-inhibitor treatment may be achieved in routine clinical practice in a cardiology setting.",2003.0,0,0
1135,12614193,ACE inhibitors or AT-1 antagonists - which is OPTIMAAL after acute myocardial infarction?,Sheila A Doggrell,"OPTIMAAL (Optimal Trial in Myocardial Infarction with the Angiotensin II Antagonist Losartan) is the first major study to compare an angiotensin II Type 1 antagonist losartan (Cozaar trade mark, Merck) with an ACE inhibitor captonpril (Capoten trade mark, Elan) after myocardial infarction in patients with left ventricular dysfunction. Patients were assigned to a target dose of losartan 50 mg/day and captopril 50 mg t.i.d., as tolerated. The primary end point was all-cause mortality and there were 499 (18%) and 447 (16%) deaths in the losartan and captopril group, respectively (p = 0.07). However, there were significantly more cardiovascular deaths with losartan (420, 15%) than with captopril (363, 13%; p = 0.03). Losartan was better tolerated than captopril with fewer patients discontinuing medication (17 versus 23% for losartan and captopril, respectively). In conclusion, if tolerated, captopril should remain the preferred treatment for patients after complicated acute myocardial infarction.",2003.0,0,0
1136,12624612,Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients.,R Fogari; G D Malamani; A Zoppi; A Mugellini; A Rinaldi; A Vanasia; P Preti,"The aim of this study was to evaluate the effect of benazepril addition to amlodipine antihypertensive treatment on ankle-foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. A total of 32 mild to moderate essential hypertensives (DBP>90 and <110 mmHg), aged 30-70 years were studied. After a 4-week placebo period, they were randomized to amlodipine 5 mg o.d. or benazepril 10 mg o.d. or amlodipine 5 mg plus benazepril 10 mg o.d. for 4 weeks, according to a crossover design. At the end of the placebo period and of each active treatment period, blood pressure,AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed using a system, the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and benazepril monotherapy significantly reduced SBP (-18.2+/-4 and -17.8+/-4 mmHg, respectively, P<0.01 vs baseline) and DBP (-12.1+/-3 and -11.7+/-3 mmHg, respectively, P<0.01); the reduction was increased by the combination (-24.2+/-5 mmHg for SBP, P<0.001 and -16.8+/-4 mmHg for DBP, P<0.001). Amlodipine monotherapy significantly increased both AFV (+17.1%, P<0.001 vs baseline) and PSTP (+56.6%, P<0.001 vs baseline). As compared to amlodipine alone, the combination produced a less pronounced increase in AFV (+5.5%, P<0.05 vs baseline and P<0.01 vs amlodipine) and PSTP (+20.5%, P<0.05 vs baseline and P<0.01 vs amlodipine). Ankle oedema was clinically evident in 11 patients with amlodipine monotherapy and in three patients with the combination. These results suggest that ACE-inhibitors partially counteract the microcirculatory changes responsible for Ca-antagonists-induced oedema formation.",2003.0,0,0
1137,12628079,Heart failure in women.,David H Silber,"Congestive heart failure represents a growing health issue with significant morbidity, expense, and mortality. Unfortunately, despite heart failure affecting men and women equally, women historically have represented a minority in heart failure trials. Despite this disparity, treatment decisions rely heavily on these trials. Women with heart failure often have different clinical features than men, such as age of onset and comorbidities. Compared with men, women also demonstrate differences in remodeling and the response to injury, such as volume or pressure overload and myocardial infarction. We are only beginning to understand the clinical implications of these gender differences and their impact on pharmacologic treatments. After discussing these differences, a review of the agents useful in systolic failure is made, including angiotensin-converting enzyme inhibitors, b-blockers, digoxin, and aldosterone inhibition. Treatment of diastolic heart failure with empiric guidelines follows.",2003.0,0,0
1138,12628949,Prevention of Heart Failure in Patients in the Heart Outcomes Prevention Evaluation (HOPE) Study.,J Malcolm O Arnold; Salim Yusuf; James Young; James Mathew; David Johnstone; Alvaro Avezum; Eva Lonn; Janice Pogue; Jackie Bosch; HOPE Investigators,"Previous trials in the prevention of heart failure have been restricted to patients with low ejection fraction or hypertension. We assessed an angiotensin-converting enzyme (ACE) inhibitor, ramipril, to prevent the development of heart failure in high-risk patients without known low ejection fraction or heart failure. We randomly assigned 9297 patients to receive double-blind ramipril (10 mg daily) or matching placebo for 4.5 years. Death attributable to heart failure, hospitalization for heart failure, initiation of open-label ACE inhibitor for heart failure, or development of typical signs or symptoms of heart failure developed in 951 patients and was associated with a 4.01-fold increase in the risk of death (P<0.0001). The rate of developing heart failure was significantly increased with coronary disease (risk ratio, 2.17), microalbuminuria (1.82), left ventricular hypertrophy (1.47), increasing age (by decade, 1.37), and diabetes (1.36). Ramipril reduced new-onset heart failure rate from 11.5% to 9.0% (relative risk, 0.77; 95% CI, 0.68 to 0.87; P<0.0001). Ramipril consistently reduced heart failure rate both in those with (relative risk, 0.87) and those without an interim myocardial infarction (relative risk, 0.78). Ramipril also reduced the heart failure rate more in patients with baseline systolic pressure above the median (139 mm Hg) (relative risk, 0.67) compared with those below the median (relative risk, 0.91; P=0.024 for interaction of group by treatment). Ramipril significantly reduces the rate of development of heart failure in patients at high risk of cardiovascular events.",2003.0,0,1
1139,12628950,Enalapril reduces the incidence of diabetes in patients with chronic heart failure: insight from the Studies Of Left Ventricular Dysfunction (SOLVD).,Emmanuelle Vermes; Anique Ducharme; Martial G Bourassa; Myriam Lessard; Michel White; Jean-Claude Tardif; Studies Of Left Ventricular Dysfunction,"Diabetes mellitus is a predictor of morbidity and mortality in patients with heart failure. The effect of angiotensin-converting enzyme (ACE) inhibitors on the prevention of diabetes in patients with left ventricular dysfunction is unknown. The aim of this retrospective study was to assess the effect of the ACE inhibitor enalapril on the incidence of diabetes in the group of patients from the Montreal Heart Institute enrolled in the Studies of Left Ventricular Dysfunction (SOLVD). Clinical charts were evaluated for fasting plasma glucose (FPG) levels by blinded reviewers. A diagnosis of diabetes was made when a FPG > or =126 mg/dL (7 mmol/L) was found at 2 visits (follow-up, 2.9+/-1.0 years). Of the 391 patients enrolled at the Montreal Heart Institute, 291 were not diabetic (FPG <126 mg/dL without a history of diabetes), 153 of these were on enalapril and 138 were on placebo. Baseline characteristics were similar in the 2 groups. Forty patients developed diabetes during follow-up, 9 (5.9%) in the enalapril group and 31 (22.4%) in the placebo group (P<0.0001). By multivariate analysis, enalapril remained the most powerful predictor for risk reduction of developing diabetes (hazard ratio, 0.22; 95% confidence intervals, 0.10 to 0.46; P<0.0001). The effect of enalapril was striking in the subgroup of patients with impaired FPG (110 mg/dL [6.1 mmol/L] < or =FPG <126 mg/dL) at baseline: 1 patient (3.3%) in the enalapril group versus 12 (48.0%) in the placebo group developed diabetes (P<0.0001). Enalapril significantly reduces the incidence of diabetes in patients with left ventricular dysfunction, especially those with impaired FPG.",2003.0,1,1
1140,12633543,Accelerated decline and prognostic impact of renal function after myocardial infarction and the benefits of ACE inhibition: the CATS randomized trial.,H L Hillege; W H van Gilst; D J van Veldhuisen; G Navis; D E Grobbee; P A de Graeff; D de Zeeuw; CATS Randomized Trial,"Information regarding the cardiorenal axis in patients after a myocardial infarction (MI) is limited. We examined the change in renal function after a first MI, the protective effect of angiotensin converting enzyme (ACE) inhibition and the prognostic value of baseline renal function. The study population consisted of 298 patients with a first anterior wall MI who were randomized to the ACE inhibitor captopril or placebo after completion of streptokinase infusion. Renal function, by means of glomerular filtration rate (GFR), was calculated using the Cockroft-Gault equation (GFR(c)). In the placebo group, renal function (GFR(c)) declined by 5.5 min(-1)within 1 year, vs only 0.5 ml min(-1)in the ACE inhibitor group (P<0.05). This beneficial effect of captopril was most pronounced in patients with the most compromised renal function at baseline. The incidence of chronic heart failure (CHF) within 1 year increased significantly with decreasing GFR(c)(divided into tertiles: 24.0, 28.9, and 41.2%; P<0.01). The risk-ratio for GFR(c)<81 ml min(-1)vs >103 mL min(-1)was 1.86 (95% CI 1.11-3.13; P=0.019). Renal function markedly deteriorates after a first MI, but is significantly preserved by ACE inhibition. Furthermore, an impaired baseline renal function adds to the prognostic risk of developing CHF in patients after a first anterior MI.",2003.0,1,1
1141,12633548,Effects of a perindopril-based blood pressure lowering regimen on cardiac outcomes among patients with cerebrovascular disease.,PROGRESS Collaborative Group,"To determine the effects of a perindopril-based blood pressure lowering regimen on major cardiac events among hypertensive and non-hypertensive patients with a history of cerebrovascular disease. A total of 6105 individuals with a history of stroke or transient ischaemic attack were randomly assigned active treatment (n=3051) or placebo (n=3054). Active treatment comprised the angiotensin-converting-enzyme inhibitor perindopril (4 mg daily), with the addition of the diuretic indapamide at the discretion of treating physicians. Over a mean of 3.9 years of follow-up, active treatment reduced blood pressure by 9/4 mm Hg compared with placebo and reduced the primary outcome, stroke, by 28%. Major coronary events occurred in 269 participants (active 3.8%, placebo 5.0%) and heart failure was diagnosed in 264 participants (active 3.7%, placebo 4.9%). Active treatment reduced the risk of major coronary events by 26% (95% CI: 6-42%; p=0.02) and the risk of congestive heart failure by 26% (5-42%; p=0.02). For each of these outcomes, there was no clear evidence of differences between the treatment effects in participants classified as hypertensive or non-hypertensive, and those with or without a history of coronary heart disease. Among individuals with cerebrovascular disease, blood pressure lowering with a regimen involving perindopril and indapamide not only reduced the risk of stroke, but also substantially reduced the risks of cardiac outcomes.",2003.0,0,0
1142,12640507,Exercise testing in hypertensive patients taking different angiotensin-converting enzyme inhibitors.,Maria Angela M Q Carreira; Leandro R Tavares; Rafaela F Leite; Jamila C Ribeiro; Antônio C Santos; Karla G Pereira; Guilhermo C Velarde; Antonio Claudio L Nóbrega,"To compare blood pressure response to dynamic exercise in hypertensive patients taking trandolapril or captopril. We carried out a prospective, randomized, blinded study with 40 patients with primary hypertension and no other associated disease. The patients were divided into 2 groups (n=20), paired by age, sex, race, and body mass index, and underwent 2 symptom-limited exercise tests on a treadmill before and after 30 days of treatment with captopril (75 to 150 mg/day) or trandolapril (2 to 4 mg/day). The groups were similar prior to treatment (p<0.05), and both drugs reduced blood pressure at rest (p<0.001). During treatment, trandolapril caused a greater increase in functional capacity (+31%) than captopril (+17%; p=0.01) did, and provided better blood pressure control during exercise, observed as a reduction in the variation of systolic blood pressure/MET (trandolapril: 10.7 1.9 mmHg/U vs 7.4 1.2 mmHg/U, p=0.02; captopril: 9.1 1.4 mmHg/U vs 11.4 2.5 mmHg/U, p=0.35), a reduction in peak diastolic blood pressure (trandolapril: 116.8 3.1 mmHg vs 108.1 2.5 mmHg, p=0.003; captopril: 118.2 3.1 mmHg vs 115.8 3.3 mmHg, p=0.35), and a reduction in the interruption of the tests due to excessive elevation in blood pressure (trandolapril: 50% vs 15%, p=0.009; captopril: 50% vs 45%, p=0.32). Monotherapy with trandolapril is more effective than that with captopril to control blood pressure during exercise in hypertensive patients.",2003.0,0,0
1143,12641480,The Perindopril Protection Against Recurrent Stroke Study (PROGRESS): clinical implications for older patients with cerebrovascular disease.,Yogini Ratnasabapathy; Carlene M M Lawes; Craig S Anderson,"Blood pressure levels are strongly predictive of the risks of first-ever and recurrent stroke. The benefits of blood pressure-lowering therapy for the prevention of fatal and non-fatal stroke in middle-aged individuals are well established. However, until recently, there has been uncertainty about the consistency of such benefits across different patient groups and in particular, for older people and in those with a history of stroke. This paper discusses the evidence surrounding the effectiveness of blood pressure-lowering therapy, specifically in older patients with a history of stroke, with particular attention paid to the results from the Perindopril Protection Against Recurrent Stroke Study (PROGRESS). PROGRESS was a randomised, double-blind, placebo-controlled trial of 6105 individuals with a history of cerebrovascular disease recruited from 172 hospital outpatient clinics in ten countries. Participants (mean age 64 years; range 26-91 years) were randomly assigned to receive active treatment with an ACE inhibitor-based blood pressure-lowering regimen (perindopril) with or without addition of the diuretic indapamide, or matched placebo. At the end of follow up (mean of 4 years), active treatment reduced the incidence of total stroke by 28% (95% CI 17-38%) and the rate of major vascular events by 26% (95% CI 16-34%). Importantly, benefits of treatment were consistent across key patient subgroups, including those with and without hypertension, patients who were Asian and non-Asian, and for both ischaemic and haemorrhagic strokes subtypes. Current evidence is now strong for clinicians to consider blood pressure-lowering therapy as pivotal in the prevention of stroke, especially in patients with a known history of cerebrovascular disease (and vascular disease, in general), irrespective of blood pressure levels, as soon as patients are clinically stable after an acute stroke or other vascular event. Additional age-specific analyses of the PROGRESS data, together with those from other completed trials, will provide more reliable information about the size of the benefits of blood pressure-lowering therapy, specifically for different age groups, and particularly in the oldest old (those aged >80 years). In the meantime though, an ACE inhibitor plus diuretic treatment regimen that maximises the degree of blood pressure reduction has a good safety profile and is an effective treatment that should be considered in all patients with stroke, including the elderly.",2003.0,0,0
1144,12642014,Role of endothelin-1 in hypertension.,Marc Iglarz; Ernesto L Schiffrin,"Endothelin-1 (ET-1) was first characterized as a potent vasoconstrictor and is overexpressed in the vasculature in different models of hypertension, such as deoxycorticosterone acetate-salt rats, Dahl salt-sensitive rats, and stroke-prone spontaneously hypertensive rats. Moreover, patients with moderate to severe hypertension present increased vascular levels of prepro-ET-1 mRNA. In addition to their blood pressure-lowering effects, ET receptor antagonists are able to reduce vascular growth. Recent data suggest the involvement of an inflammatory response in the effects of ET-1, which contributes to vascular remodeling and endothelial dysfunction. Increasing evidence underscores the potential therapeutic benefit of ET receptor antagonists in different hypertension-related complications, not only in essential hypertension, but also in patients with type 2 diabetes.",2003.0,0,0
1145,12642018,Angiotensin II and the glomerulus: focus on diabetic kidney disease.,James W Scholey,"The renin-angiotensin system plays a key role in the progression of kidney disease, in addition to its well-described role in the maintenance of extracellular fluid volume and blood pressure. Recent studies have shown that blockade of the renin-angiotensin system at the level of the angiotensin II type 1 receptor can have important effects on proteinuria and the rate of progression of kidney disease in patients with type 2 diabetes mellitus. This review first discusses recent experimental studies relating angiotensin II to kidney function in diabetes mellitus and changes in glomerular permselectivity, and then focuses on recent clinical trials with angiotensin II receptor blockers in patients with type 2 diabetes mellitus.",2003.0,0,0
1146,12643149,Epidemiology of the insulin resistance syndrome.,James B Meigs,"The insulin resistance syndrome consists of the co-occurrence of metabolic risk factors for type 2 diabetes and cardiovascular disease, including overall obesity, central obesity, dyslipidemia (characterized by elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol), hyperglycemia, and hypertension. Using criteria proposed by the National Cholesterol Education Program Adult Treatment Panel III, national survey data suggest the insulin resistance syndrome is very common, affecting about 24% of US adults aged greater than 20 years. The syndrome is more common in older people and in Mexican Americans, and will increase in prevalence as populations age and become more obese. Identification of the syndrome warrants aggressive interventions known to prevent type 2 diabetes and cardiovascular disease, including weight reduction, increased physical activity, and control of hypertension and dyslipidemia.",2003.0,0,0
1147,12643339,How do minor changes in the definition of blood pressure control affect the reported success of hypertension treatment?,Beverly B Green; Robert C Kaplan; Bruce M Psaty,"In 1999, the first reporting year of the Health Plan Employer Data and Information Set, our organization noted a significant difference in the proportion of patients with controlled blood pressure (BP) when the target was changed from < 140/90 mm Hg to < or = 140/90 mm Hg. We compared these data with a second larger dataset to determine if these findings were an isolated or common phenomenon and to determine what factors influenced this difference. Subjects were drug-treated hypertensive patients. Blood pressure measurements were taken from outpatient medical records. The percent of hypertensive patients with controlled BP levels was significantly greater (P <.001) when the cutoff of < or = 140/90 mm Hg was used rather than <140/90 mm Hg. When a single BP measurement was used to estimate control, the percent of patients with controlled hypertension increased 12.7% simply by changing the definition to include the level of systolic BP = 140 mm Hg or diastolic BP = 90. When multiple BP readings were used to estimate control, the difference was much less pronounced (2.7%). When evaluating the success of hypertension treatment, defining BP control as a BP of < or = 140 mm Hg systolic and < or = 90 diastolic mm Hg will result in significantly more people having controlled BP than when <140 mm Hg systolic and <90 mm Hg diastolic are used. This difference is most likely the result of end-digit preference. The use of multiple measures reduces this effect. Policy makers and guideline authors should consider these aspects when setting BP goals.",2003.0,0,0
1148,12654706,Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER.,Carl Erik Mogensen; Giancarlo Viberti; Serge Halimi; Eberhard Ritz; Luis Ruilope; György Jermendy; Jiri Widimsky; Pinchas Sareli; Jan Taton; Juan Rull; Gürbüz Erdogan; Pieter W De Leeuw; Arthur Ribeiro; Ramiro Sanchez; Rachid Mechmeche; John Nolan; Jana Sirotiakova; Ahmed Hamani; André Scheen; Bernhard Hess; Anton Luger; Stephen M Thomas; Preterax in Albuminuria Regression (PREMIER) Study Group,"Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.",2003.0,0,0
1149,12658059,Combination of lisinopril and nifedipine GITS increases blood pressure control compared with single drugs in essential hypertensive patients.,Stefano Taddei; Stefano Omboni; Lorenzo Ghiadoni; Alberto Caiazza; Roberto Fogari; Pierfranco Innocenti; Carlo Porcellati; Roberto Giovannetti; Luca Corradi; Giuseppe Mancia; Antonio Salvetti,"The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 +/- 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.",2003.0,0,0
1150,12658252,Severely increased blood pressure in the emergency department.,Philip H Shayne; Stephen R Pitts,"Patients with severely increased blood pressure often present to the emergency department. Emergency physicians evaluate and treat hypertension in various contexts, ranging from the compliant patient with well-controlled blood pressure to the asymptomatic patient with increased blood pressure to the critically ill patient with increased blood pressure and acute target-organ deterioration. Despite extensive study and national guidelines for the assessment and treatment of chronically increased blood pressure, there is no clear consensus on the acute management of patients with severely increased blood pressure. In this article, we examine the broad spectrum of disease, from the asymptomatic to critically ill patient, and the dilemma it creates for the emergency physician in deciding how and when in the process to intervene.",2003.0,0,0
1151,12660333,Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy.,Peter Jacobsen; Steen Andersen; Berit R Jensen; Hans-Henrik Parving,"Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m(2). Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.",2003.0,0,0
1152,12667031,The evidence base for tight blood pressure control in the management of type 2 diabetes mellitus.,Vincenza Snow; Kevin B Weiss; Christel Mottur-Pilson; Clinical Efficacy Assessment Subcommittee of the American College of Physicians,,2003.0,0,0
1153,12667032,"Treatment of hypertension in type 2 diabetes mellitus: blood pressure goals, choice of agents, and setting priorities in diabetes care.",Sandeep Vijan; Rodney A Hayward,"Hypertension in patients with type 2 diabetes mellitus is a prevalent condition that leads to substantial morbidity and mortality. To evaluate the goals and optimal agents for treatment of hypertension in type 2 diabetes. Review of the medical literature Randomized trials that evaluated the pharmacologic treatment of hypertension in patients with diabetes and reported microvascular and macrovascular outcomes. Studies were identified by using the Cochrane Library, MEDLINE, meta-analyses, review articles, and expert recommendation. The searches of the Cochrane Library and MEDLINE were performed in May 2000 and updated in April 2002. Data were abstracted to standardized forms by a single reviewer and were confirmed by a second reviewer. Treatment of hypertension in type 2 diabetes provides dramatic benefit. Target diastolic blood pressures of less than 80 mm Hg appear optimal; systolic targets have not been as rigorously evaluated, but targets of 135 mm Hg or less are reasonable. Studies that compare drug classes do not suggest obviously superior agents. However, it is reasonable to conclude that thiazide diuretics, angiotensin-II receptor blockers, and perhaps angiotensin-converting enzyme (ACE) inhibitors may be the preferred first-line agents for treatment of hypertension in diabetes. beta-Blockers and calcium-channel blockers are more effective than placebo, but they may not be as effective as diuretics, angiotensin-II receptor blockers, or ACE inhibitors; however, study results are inconsistent in this regard. Treatment of hypertension in type 2 diabetes, with blood pressure goals of 135/80 mm Hg, provides dramatic benefits. Thiazide diuretics, angiotensin II receptor blockers, and ACE inhibitors may be the best first-line treatments, although other agents are usually necessary and goals may not be achieved even with three or four agents. Aggressive blood pressure control may be the most important factor in preventing adverse outcomes in patients with type 2 diabetes.",2003.0,0,1
1154,12671322,Treatment of hypertension in African Americans and Latinos: the effect of JNC VI on urban prescribing practices.,Sean O Henderson; Philip Bretsky; Vincent DeQuattro; Brian E Henderson,"In 1997, national recommendations for the treatment of hypertension were made in the form of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). African American hypertensives are considered a special population with a higher prevalence of hypertension, and therefore, unique treatment needs. The study objective was to review medication use among an African American and Latino urban population in relation to the JNC recommendations. The study population was drawn from a preexisting cohort of African Americans and Latinos. Records were reviewed for self-description of hypertension and the use of any antihypertensive medication in individuals less than 60 years of age. A small subgroup of individuals was separately reviewed for specific medications used to treat hypertension. There were 34,118 individuals in the cohort greater than 45 years of age and less than 60 years of age that qualified for review; 40% were African American and 60% were Latino. Of the 13,593 African Americans, 6387 (47%) were hypertensive. Of the 20,525 Latinos, 29% were hypertensive. Only 56% of all hypertensives were on some blood pressure medication (61% of the African Americans and 48% of the Latinos). Within the subgroup of 550 individuals with detailed medication information (223 African Americans and 327 Latinos), calcium channel blockers and diuretics were the most frequently used medication among the African Americans and angiotensin-converting enzyme inhibitors were the most frequently used medication among the Latinos. Beta blockers were used only 13% of the time. The authors concluded that in this cohort of hypertensive urban Latinos and African Americans, more than 40% of individuals were not being treated for hypertension and, despite the guidelines suggested in JNC VI, few individuals were being treated for their hypertension with diuretic monotherapy or beta blockers as first-choice drugs. Instead there was extensive use of calcium channel blockers and angiotensin-converting enzyme inhibitors.",2003.0,0,0
1155,12672310,Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study.,Stefan D Anker; Abdissa Negassa; Andrew J S Coats; Rizwan Afzal; Philip A Poole-Wilson; Jay N Cohn; Salim Yusuf,"Weight loss in chronic heart failure is linked to impaired survival. We aimed to assess the frequency of weight loss in patients with this disease, whether the degree of weight loss predicts mortality, and whether weight loss can be prevented by angiotensin-converting-enzyme (ACE) inhibitors. We investigated weight changes in 1929 patients from the SOLVD trial who had chronic heart failure, were free of oedema at baseline, and survived for at least 4 months after trial entry. Meanfollow-up was 35 months (SD 13). We analysed the effect of weight loss at cutpoints of 5%, 7.5%, 10%, 15% (a priori), and 6% (post hoc) to identify which one best predicted outcome. To validate results, we analysed data for 619 patients in the V-HeFT II trial. 817 (42%) patients in the SOLVD trial had weight loss from baseline of 5% or more. At 8 months follow-up, all cutpoints for weight loss were significantly associated with impaired survival after adjustment for age, sex, New York Heart Association class, left ventricular ejection fraction, and treatment allocation. Weight loss of 6% or more at any time during follow-up was the strongest predictor of impaired survival (adjusted hazard ratio 2.10, 95% CI 1.77-2.49; p<0.0001). Patients on the ACE inhibitor enalapril had a lower hazard of 6% or more weight loss than did those not taking the drug (adjusted reduction 19%, p=0.0054). Results from analyses of V-HeFT II data lent support to our findings. Weight loss occurs frequently in patients with chronic heart disease, its reversal is rare, and when present, it is independently linked to impaired survival. Weight loss of more than 6% should be used to define the presence of cachexia in patients with chronic heart failure. In chronic heart failure, treatment with an ACE inhibitor reduces the risk of weight loss.",2003.0,0,0
1156,12675866,Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy.,Peter Jacobsen; Steen Andersen; Kasper Rossing; Berit R Jensen; Hans-Henrik Parving,"Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. We tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor blocker (ARB) is superior to maximal recommended dose of ACE inhibitor in type 1 diabetic patients with diabetic nephropathy (DN). We performed a randomized, double-blind, crossover trial with 8 weeks treatment with placebo and irbesartan 300 mg (once daily), added on top of enalapril 40 mg (once daily). We included 24 type 1 patients with DN. At the end of each treatment period, albuminuria, 24-hour blood pressure, and glomerular filtration rate (GFR) were measured. Values on ACE inhibitors + placebo were: albuminuria [mean (95% CI)], 519 (342 to 789) mg/24 hours; blood pressure [mean (SEM)], 131 (3)/74 (1) mm Hg, and GFR [mean (SEM)], 65 (5) mL/min/1.73 m2. Dual blockade of the RAS induced a reduction in albuminuria [mean (95% CI)] of 25% (15, 34) (P < 0.001), a reduction in systolic blood pressure of 8 mm Hg (4, 12) (P = 0.002), and a reduction of 4 mm Hg (2, 7) (P = 0.003) in diastolic blood pressure. GFR and plasma potassium remained unchanged during both treatment regimes. Dual blockade was safe and well tolerated. Dual blockade of the RAS is superior to maximal recommended dose of ACE inhibitors with regard to lowering of albuminuria and blood pressure in type 1 patients with DN. Long-term trials are needed to further establish the role of dual blockade of the RAS in renal and cardiovascular protection.",2003.0,0,0
1157,12678218,The ALLHAT Trial. Diuretics are still the preferred initial drugs for high blood pressure.,Donald G Vidt,"The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) compared four antihypertensive agents in patients 55 years and older: chlorthalidone, doxazosin, amlodipine, and lisinopril. The doxazosin arm was terminated early because of an excess of congestive heart failure. Chlorthalidone was at least equivalent to amlodipine and lisinopril in all of the outcomes measured, and was better in some, notably heart failure.",2003.0,0,0
1158,12680979,Quality of care of patients hospitalized with congestive heart failure.,I A Scott; C P Denaro; J L Flores; C J Bennett; A C Hickey; A M Mudge; J Atherton; Brisbane Cardiac Consortium Leader Group,"Congestive heart failure (CHF) is an increasingly prevalent poor-prognosis condition for which effective interventions are available. It is -therefore important to determine the extent to which patients with CHF receive appropriate care in Australian hospitals and identify ways for improving suboptimal care, if it exists. To evaluate the quality of in-hospital acute care of patients with CHF using explicit quality indicators based on published guidelines. A retrospective case note review was -performed, involving 216 patients admitted to three teaching hospitals in Brisbane, Queensland, Australia, between October 2000 and April 2001. Outcome measures were process-of-care quality -indicators calculated as proportions of all, or strongly -eligible (ideal), patients who received -specific interventions. Assessment of underlying causes and acute precipitating factors was undertaken in 86% and 76% of patients, respectively, and objective evaluation of left ventricular function was performed in 62% of patients. Prophylaxis for deep venous thrombosis (DVT) was used in only 29% of ideal patients. Proportions of ideal patients receiving pharmacological treatments at discharge were: (i) angiotensin--converting enzyme inhibitors (ACEi) (82%), (ii) target doses of ACEi (61%), (iii) alternative vasodilators in patients ineligible for ACEi (20%), (iv) beta-blockers (40%) and (v) warfarin (46%). Opportunities exist for improving quality of in-hospital care of patients with CHF, -particularly for optimal prescribing of: (i) DVT prophylaxis, (ii) ACEi, (iii) second-line vasodilators, (iv) beta-blockers and (v) warfarin. More research is needed to identify methods for improving quality of in-hospital care.",2003.0,0,0
1159,12681079,How effective are diuretics for high-risk hypertension?,Julie Nielsen Lindsey; Warren Newton,,2003.0,0,0
1160,12684727,Drug use for non-hepatic associated conditions in patients with liver cirrhosis.,M Isabel Lucena; Raúl J Andrade; Gianni Tognoni; Ramón Hidalgo; Felipe Sanchez de la Cuesta; Spanish Collaborative Study Group on Therapeutic Management of Liver Diseases,"To study the prescribing patterns of practising physicians for the most frequent non-hepatic associated conditions in patients with liver cirrhosis. A multi-centre prospective observational study carried out in 25 Spanish hospitals. Inpatients admitted to gastrointestinal and liver units with a diagnosis of liver cirrhosis were included in five centrally assigned index days, between February and June 1999. Information was collected about pharmacological treatments used on admission and recommended at discharge. Five hundred and sixty-eight in-patients with a diagnosis of liver cirrhosis (44% alcoholic cirrhosis) and an average number of 2.5 co-morbid conditions were studied: diabetes mellitus (30%), infectious disorders (24%), cardiovascular disease (20%) and active alcoholism (15%)--the most common associated conditions. Chlormethiazole, amoxicillin-clavulanic acid, paracetamol, gliblenclamide, lorazepam, captopril and tiapride were the drugs used most prevalently. The average prescribed daily dose was <1 defined daily dose per day for most medication classes hepatically handled except for calcium channel blockers. The present study expands current knowledge of prescribing patterns for associated conditions in patients with underlying liver cirrhosis. Drug dosing was affected in general by the influence of age and hepatic disease on the disposition of drugs, but knowledge on drug selection needs further attention.",2003.0,0,0
1161,12685514,"Time-effect profile of antihypertensive agents assessed with trough/peak ratio, smoothness index and dose omission: an ambulatory blood pressure monitoring study with trandolapril vs. quinapril.",Anca Radauceanu; Jean-Marc Virion; Jean-Marc Boivin; Faiez Zannad,"The duration of action of antihypertensive drugs may be assessed by several methods using ambulatory blood pressure monitoring (ABPM). The aim of this double-blind, randomized study was to compare the time-effect profile of once daily Trandolapril (Tra) 2 mg vs. Quinapril (Qui) 20 mg in 92 patients with mild-to-moderate hypertension. All patients received placebo during a 30-day run-in period followed by 2 months of active therapy and 1-day medication omission. ABPM was conducted on each period. 24 h antihypertensive coverage was assessed by trough:peak ratio (T/P) and smoothness index (SI) methods. Residual lowering of blood pressure after single-blind, 1 day medication omission was investigated as the SBP/DBP 48-h trough effect. There were no statistically significant differences between treatment groups in the mean SBP/DBP peak or trough effect. Individual T/P were not normally distributed and had very large variations explained by BP random- and activity-related fluctuations. Group T/P were 0.85 for Tra and 0.62 for Qui. The SI values were normally distributed and not statistically different between the two treatment groups. After dose omission, Qui was ineffective at 48-h trough while Tra retained a significant effect (SBP/DBP = -3.4/-4.3 mmHg) and this difference was even greater in ABPM-responders. Comparison of the trough:peak ratios and smoothness indexes of Tra and Qui failed to show any statistically significant difference on 24-h antihypertensive coverage. Nevertheless, residual lowering of blood pressure at 48-h trough suggests that Tra had a longer duration of action than Qui.",2003.0,0,0
1162,12691635,Sex differences in the causes and natural history of heart failure.,Bobbi L Hoppe; Denise D Hermann,"Heart failure is a clinical syndrome of increasing prevalence in the United States, with significant morbidity and mortality. Although men have a higher annual mortality rate, more women than men die from heart failure each year. Optimal disease management is critical in limiting the impact of heart failure on life quality, quantity, and health care expenditures. Women have a unique risk-factor profile and different clinical manifestations of heart failure than men. Understanding inherent sex differences in heart failure epidemiology, pathophysiology, and natural history is imperative in determining whether the optimal therapy for this prevalent and important syndrome is affected by sex.",2003.0,0,0
1163,12691637,The prognostic significance of renal dysfunction in patients with chronic systolic heart failure.,S Raja Laskar; Daniel L Dries,"Renal insufficiency is an independent powerful predictor of morbidity and mortality in a number of cardiovascular disorders. A number of retrospective analyses of large heart failure trials have shown that even mild renal insufficiency has powerful negative predictive power in patients with both mild and severe heart failure. We discuss the available data on the prognostic value of mild renal insufficiency in heart failure, as well as possible mechanisms of this phenomenon. Future research should focus on its possible pathophysiology.",2003.0,0,0
1164,12692572,Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease.,H Matsuda; K Hayashi; T Saruta,"Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NO(x)) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine < 265 (range, 44-265) micromol/l or creatinine clearance > 30 (range, 30-121) ml/min). Patients with mild (<1 g/day; range, 0.4-1.0) and moderate proteinuria (>1 g/day; range, 1.1-6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44 +/- 6% reduction in proteinuria (from 2.7 +/- 0.5 to 1.5 +/- 0.4 g/day, n = 14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2 +/- 0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23 +/- 8%, n = 13), but a 41 +/- 6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NO(x) excretion were observed with ACE-I (from 257 +/- 70 to 1111 +/- 160 micromol/day) and ARB (from 280 +/- 82 to 723 +/- 86 micromol/day), the ARB-induced increase in NO(x) excretion was smaller than that by ACE-I (P < 0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NO(x) excretion. Conversely, ARB decreased proteinuria and increased urinary NO(x) excretion gradually. These time course-dependent changes in proteinuria and urinary NO(x) may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.",2003.0,0,0
1165,12692753,Combination is better than monotherapy with ACE inhibitor or angiotensin receptor antagonist at recommended doses.,Juliá Segura; Manuel Praga; Carlos Campo; José L Rodicio; Luis M Ruilope,"The combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonist (ARB) could provide a higher degree of blockade of the renin-angiotensin system(RAS) than either agent alone. The primary aim of this study was to look at the effect of three therapeutic regimens (titrated ACE inhibitor (ACE-I) versus titrated ARB versus the combination of an ACE-I and an ARB) on the attainment of adequate blood pressure (BP) control and antiproteinuric effect. Both ACE-I and ARB were titrated as monotherapy up to the maximal recommended dose. A pilot randomised, parallel group open-label study was conducted in 36 patients with primary renal disease, proteinuria above 1.5 g/day and BP >140/90 mmHg while on therapy with an ACE-I. Patients were randomly assigned to (1) benazepril, n=12; (2) valsartan, n=12; or (3) benazepril plus valsartan, n=12. Other antihypertensive therapies could also be added to attain goal BP (<140/90 mmHg). The primary endpoint was the change in proteinuria during six months of follow-up. In the presence of similar BP decreases and stable creatinine clearance values, mean proteinuria decreases were 0.5+1.7, 1.2+2.0 and 2.5+1.8 g/day in groups 1, 2 and 3, respectively. When compared with baseline values, only the fall induced by the combination of ARB and ACE-I attained statistical significance (p<0.05). The antiproteinuric capacity of monotherapy at recommended doses with either an ACE-I or an ARB is lower than that obtained with the combination of the two drugs.",2003.0,0,0
1166,12699135,Evaluation of the effect of the sublingually administered nifedipine and captopril via transcranial doppler ultrasonography during hypertensive crisis.,Kani Gemici; Ibrahim Baran; Mustafa Bakar; Celalettin Demircan; Bülent Ozdemir; Jale Cordan,"This study was designed to show the effects of sublingually administered nifedipine and captopril on middle cerebral arterial blood flow during hypertensive crisis in the emergency department. Transcranial Doppler ultrasonography (TCD) was performed on the patients fulfilling the criteria (15 patients given captopril, 13 patients given nifedipine, mean (+/-SD) age 56 +/- 11 and 54 +/- 10 years, respectively). Then, patients were randomized into sublingually administered captopril or nifedipine groups and after the drug administration, TCD was repeated. Initial systolic and diastolic blood pressures were 200 +/- 21/125 +/- 21 mmHg in the captopril group and 199 +/- 17/ 123 +/- 20 mmHg in the nifedipine group. There was no significant difference between antihypertensive effects of the drugs after initiation of treatment. Before the treatment with captopril, middle cerebral artery (MCA) flow velocities (Vm) and pulsatility index (PI) were 76.74 +/- 6.38 cm/s and 1.18 +/- 0.09, respectively. The values after the treatment with captopril were 78.21 +/- 5.24cm/s (p < 0.05) and 0.92 +/- 0.08 (p < 0.001), respectively. Before the treatment with nifedipine, Vm and PIs were 64.73 +/- 5.11 cm/s and 1.14 +/- 0.18, respectively. After the treatment with nifedipine, Vm was 60.04 +/- 5.36 cm/s (p < 0.01) and PI was 1.21 +/- 0.09 (p < 0.01). After treatment with captopril, PIs were decreased to normal limits but in the group treated with nifedipine, PIs increased to more pathological values. These results showed that we should reconsider the use of nifedipine in the emergency departments as an antihypertensive agent in hypertensive attack treatment.",2003.0,0,0
1167,12701984,Initial findings of the AASK: African Americans with hypertensive kidney disease benefit from an ACE inhibitor.,Mahboob Rahman,"Experts have long thought that African Americans were less responsive to ACE inhibitors than other racial or ethnic groups. The African American Study of Kidney Disease and Hypertension (AASK) provides the first evidence of a beneficial effect of ACE inhibition on renal function in African American patients, in addition to excellent blood pressure control.",2003.0,0,0
1168,12706934,Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients.,Tetsuya Matsumoto; Kazuo Minai; Hajime Horie; Naoto Ohira; Hiroyuki Takashima; Yasuhiro Tarutani; Yo Yasuda; Tomoya Ozawa; Shinro Matsuo; Masahiko Kinoshita; Minoru Horie,"We compared the effects of perindopril and losartan on endothelium-dependent coronary vasomotor and fibrinolytic function. The renin-angiotensin system regulates the vascular fibrinolytic balance. However, the effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on coronary fibrinolytic function have not been compared in hypertensive patients. Forty-five patients with hypertension were randomly assigned to three groups: 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group). Graded doses of bradykinin (BK) (0.2, 0.6, and 2.0 microg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Bradykinin induced dose-dependent increases in CBF in all groups. The increases in CBF induced by BK in the perindopril and losartan groups were significantly greater than those in the control group. Net coronary tissue-type plasminogen activator (t-PA) release was enhanced by BK in all groups, and the increase in the perindopril group was greater than that in the losartan and control groups. Bradykinin did not alter plasminogen activator inhibitor type 1 levels in any of the groups. Perindopril and losartan similarly augment BK-induced coronary vasodilation. Perindopril may have a greater potential to enhance the BK-induced coronary release of t-PA than losartan.",2003.0,0,0
1169,12708881,"[ADVANCE study: objectives, design and current status].",John Chalmers,"Patients with type 2 diabetes mellitus have markedly increased risks of developing vascular diseases. These risks are reduced by lowering blood pressure in hypertensive individuals. However, the association between blood pressure and vascular risk appears continuous, with no clearly defined blood pressure level below which the risks fail to further decline. Intensive glucose lowering in these patients has also been shown to reduce microvascular disease, but effects on macrovascular disease remain uncertain. ADVANCE (Action in Diabetes and Vascular disease; preterAx and diamicroN-MR Controlled Evaluation) will examine the hypotheses that intensive blood pressure lowering (with an angiotensin-converting enzyme [ACE] inhibitor-diuretic combination) and glucose control in high-risk hypertensive or non-hypertensive individuals with type 2 diabetes reduce the incidence of vascular diseases. The study will also provide an opportunity to examine the effects of blood pressure lowering against a background of ACE inhibition among such patients. This 2 x 2 factorial randomised controlled trial will recruit 10 000 adults with type 2 diabetes at elevated risk of vascular disease, from approximately 200 clinical centres in 20 countries worldwide. Eligible patients are randomised to, first, the fixed combination of perindopril 2mg/indapamide 0.625 mg then perindopril 4 mg/indapamide 1.25mg or matching placebo, and, second, to an intensive sulphonylurea-based glucose control regimen (target glycosylated haemoglobin [HbA(1c)] </= 6.5%), or usual guidelines-based therapy. Any participant in whom ACE inhibition is thought to be indicated is provided with background perindopril therapy. The scheduled period of treatment and follow-up is 4.5 years. Primary outcomes are a composite of macrovascular and a composite of microvascular events. By mid-September 2002, more than 8000 patients had been recruited from 17 countries, with registrations expected to be completed by December 2002. Approximately half the participants recruited will be from Asia or from Eastern Europe. Final results are expected early in 2007. (Author's note: registration closed on January 24, 2003, with sufficient participants to exceed the target of 10 000 randomised subjects.)",2003.0,0,0
1170,12714127,Lack of improvement in the treatment of hyperlipidemia among patients with type 2 diabetes.,Philip S Mehler; Anne Esler; Raymond O Estacio; Thomas D MacKenzie; William R Hiatt; Robert W Schrier,"We investigated the adequacy of treatment of hyperlipidemia in patients with type 2 diabetes, and assessed the temporal trends in adherence to published guidelines. We performed a post hoc analysis of 501 patients enrolled in the Appropriate Blood Pressure Control in Diabetes trial. All patients had fasting lipid profiles at baseline and during the 5 years (1993 to 1998) of the trial. Achieving the National Cholesterol Education Panel's goals for hyperlipidemia management was the primary outcome. The percentage of patients with a low-density lipoprotein (LDL) cholesterol level less than 130 mg/dL was 53% (n = 266) at baseline and 54% (n = 270) at the end of 5 years (P = 0.75). Almost 14% (n = 69) of these patients continued to have an LDL cholesterol level greater than 160 mg/dL at the completion of the study. Only 19% (n = 25) of the 133 patients with known coronary artery disease had an LDL cholesterol level less than 100 mg/dL at baseline, and only 16% (n = 21) achieved this level at the completion of the study (P = 0.37). Although prevention of cardiovascular disease in patients with diabetes is a public health priority, our results suggest that hyperlipidemia is being treated suboptimally.",2003.0,0,0
1171,12717482,Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT).,Jeffrey R Burton; Koon K Teo; Christopher E Buller; Sylvain Plante; Diane Catellier; Wayne Tymchak; Dylan Taylor; Vladimir Dzavik; Terrence J Montague; SCAT investigators,"This study examined the effects of long term cholesterol lowering therapy with simvastatin on progression and regression of coronary atherosclerosis, as determined by quantitative angiographic end points, in subgroups of patients with known coronary risk factors. In this randomized, placebo controlled clinical trial, the effect of simvastatin on coronary atherosclerosis was compared with that of placebo in 394 patients who had paired coronary angiograms taken an average of four years apart. The effects of treatment on the following prespecified subgroups were examined: sex, age (less than 65 years versus at least 65 years), smoking status (current or previous/never), history of diabetes mellitus or hypertension, and severity of coronary artery lesions (diameter at least 50% versus less than 50%). There were significantly smaller decreases in the average minimum diameters, between closeout and baseline angiograms, in all simvastatin-treated subgroups, compared with placebo. Trends toward or significantly smaller decreases in the average of the mean diameters, and similar smaller increases in percentage diameter stenosis were also seen in all subgroups. The slowing of angiographically demonstrable coronary atherosclerotic narrowing supports the contention that this treatment effect is causally related to the reduction of coronary events repeatedly seen in large outcome clinical trials of lipid lowering therapy. Also, this treatment effect occurs in the presence or absence of the traditional coronary risk factors.",2003.0,0,0
1172,12719441,Different effect of antihypertensive drugs on conduit artery endothelial function.,Lorenzo Ghiadoni; Armando Magagna; Daniele Versari; Isabella Kardasz; Yale Huang; Stefano Taddei; Antonio Salvetti,"To compare the effect of antihypertensive drugs on endothelium-dependent vasodilation in the peripheral conduit arteries of patients with essential hypertension, in a prospective, randomized, parallel group study, endothelial function was assessed in 168 hypertensive patients before and after 6-month treatment with randomly assigned nifedipine GITS (30 to 60 mg, n=28), amlodipine (5 to 10 mg, n=28), atenolol (50 to 100 mg, n=29), nebivolol (5 to 10 mg, n=28), telmisartan (80 to 160 mg, n=29), and perindopril (2 to 4 mg, n=28). If necessary, hydrochlorothiazide (25 mg) was added to each compound. We evaluated brachial artery flow-mediated, endothelium-dependent dilation (high-resolution ultrasound) compared with endothelium-independent response to glyceryl trinitrate (25 microg/s). Brachial artery diameter was measured by automatic computerized analysis. Forty healthy subjects were evaluated as a control group. Oxidative stress production was evaluated by measuring plasma malondialdehyde and plasma lipoperoxides; plasma antioxidant capacity was assessed as ferric-reducing antioxidant power. Hypertensive patients showed a significantly (P<0.01) lower flow-mediated dilation (5.2+/-1.9%) as compared with healthy control subjects (7.1+/-2.6%). Response to glyceryl trinitrate was similar in control subjects and patients. At baseline, blood pressure, diameter, flow-mediated dilation, and response to glyceryl trinitrate were similar in the different treatment groups. All treatments similarly reduced blood pressure, but only perindopril increased flow mediated dilation (from 5.1+/-2 to 6.4+/-2.4%; P<0.01) without modifying the response to glyceryl trinitrate. Perindopril but also telmisartan nifedipine and amlodipine reduced oxidative stress and increased plasma antioxidant capacity. In patients with essential hypertension, ACE inhibitors appear to be the only compounds able to improve conduit artery endothelium-dependent vasodilation.",2003.0,0,0
1173,12723015,Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity.,Adesuyi A Leslie Ajayi; Gbenga G Sofowora; Adegboyega Q Adigun; Bola Asiyanbola,"Congestive heart failure (CHF) is characterized by an initial compensatory, but subsequently deleterious, activation of both the renin-angiotensin (RAS) and the sympathetic nervous system (SNS). Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF. Carvedilol, a mixed alpha and beta-blocker with antioxidant properties, and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF. However, beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma. The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings. The aims of the present study were to examine and compare the cardiovascular, autonomic, and clinical effects of additional alpha-1, or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF. Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics, were randomized to 3 groups of similar demographics according to a single blind, parallel group design. The patients were aged 53 +/- 6 years, and comprised 14 men and 14 women, with a mean cardiothoracic ratio of 0.66 +/- 0.03, and ejection fraction of 0.38 +/- 0.10, 60% hypertensive etiology. Group 1 patients received 5 mg enalapril alone, group 2 received 5 mg enalapril + 1 mg prazosin, and group 3 received 5 mg enalapril + 50 mg atenolol. All medication was taken daily for 4 weeks. Blood pressure, heart rate, pressure rate product, 6-minute walk test, NYHA class, and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment. Two-way repeated measures ANOVA, and a one-way ANOVA were used in data analysis. The 3 treatments caused significant (P<.001 ANOVA) and similar improvements for the NYHA class (-1.0 to -1.6), and increased the 6-minute distance covered (+130 m to +205 m). Although no treatment differences were observed, a trend suggesting a greater improvement with enalapril + atenolol became apparent. By the fourth week, the sympathoplegic treatments, enalapril + atenolol, and enalapril + prazosin, caused significant reductions in the pressure rate product (-3726 +/- 1885 mm Hg x beats/min; -3498 +/- 396 mm Hg beats/min, respectively), (compared to enalapril alone (-1349 +/- 894 mm Hg x beats/min) (P<.001 ANOVA). During the Valsalva maneuver, the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol (944 +/- 66 msec) or with enalapril + prazosin (825 +/- 48 msec), compared to enalapril alone (760 +/- 45 msec) (P<.001 ANOVA). The phase II Valsalva tachycardia were similar between treatments. The respiratory sinus arrhythmia ratio increased significantly (P<.005 ANOVA) and equally on all treatments. However, the pressor and chronotropic responses to forearm isometric handgrip increased significantly on the enalapril + prazosin combination (P<.02), compared to the other treatments. Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF, but also the resultant improvement in exercise tolerance and NYHA class. Compared to using ACE inhibition alone, the combined therapies caused a marked reduction in the pressure rate product, an index of myocardial oxygen consumption, and a greater enhancement of cardiac parasympathetic activity. Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade. Conversely, the pressor and chronotropic abnormalities during forearm isometric handgrip in CHF, were normalized by alpha-1, but not beta-1, blockade. Thus, the combined reflex cardiac vagal augmentation following selective beta-1 blockade, and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition, may be of major therapeutic and prognostic benefit in Blacks with non-ischemic (hypertensive) CHF stabilized on digoxin and diuretics.",2003.0,0,0
1174,12724050,Optimizing target-organ protection in patients with diabetes mellitus: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers?,Wei X Lu; Jay Lakkis; Matthew R Weir,"High blood pressure in the setting of type 1 and type 2 diabetes is commonly associated with the earlier development of target-organ damage, including cardiovascular and cerebrovascular disease and progressive renal insufficiency. The major goal of treating high blood pressure in this population is to prevent or reduce the likelihood of target-organ damage. The treatment goal for high blood pressure, therefore, has to be defined based on optimal means of preventing cardiovascular and renal events. The reduction of high blood pressure with pharmacologic therapy is associated with reduction of cardiovascular events, renal disease, and associated mortality. However, many questions remain. Some of the basic and important questions include the following: What should be the goal of treated blood pressure in the diabetic, and are there preferred agents that should be used in the hypertensive diabetic population? How do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers fit in? Are there advantages of one class over the other? The goal of this review is to summarize the recent clinical trial findings and try to provide recommendations based on the evidence of these trials to help the clinician better choose blood pressure goals and treatment strategies in the diabetic population.",2003.0,0,0
1175,12724056,Are low target blood pressure goals justified in persons with diabetes mellitus?,Errol D Crook; Latha Velusamy,"Hypertension is common in patients with diabetes and is a major risk factor for development and progression of the macro- and microvascular complications seen in diabetes. The Joint National Committee VI recommendation for goal blood pressure is less than 130/85 mm Hg in diabetics--a more aggressive target than in nondiabetic patients. Data over the past decade support these aggressive goals, especially for cardiovascular and renal outcomes and overall mortality. In addition, in diabetics, blood pressure appears to be a continuous risk factor for these outcomes without evidence of a J-point effect. While these goals are rarely obtained in diabetic patients, studies demonstrate that they are achievable with attention to detail and use of multiple antihypertensive agents.",2003.0,0,0
1176,12727575,Third heart sound and elevated jugular venous pressure as markers of the subsequent development of heart failure in patients with asymptomatic left ventricular dysfunction.,Mark H Drazner; J Eduardo Rame; Daniel L Dries,"To determine the independent prognostic value of a third heart sound (S(3)) and elevated jugular venous pressure in patients with asymptomatic left ventricular dysfunction. We performed a post hoc analysis of 4102 participants from the Studies of Left Ventricular Dysfunction (SOLVD) prevention trial. In that trial, participants with asymptomatic or minimally symptomatic left ventricular dysfunction (New York Association class I or II, left ventricular ejection fraction < or =0.35, no treatment for heart failure) were allocated randomly to enalapril or placebo and followed for a mean (+/- SD) of 34 +/- 14 months. The presence of an S(3) and elevated jugular venous pressure was ascertained by physical examination at study enrollment. We used multivariate proportional hazards models to determine whether these physical examination findings were associated with the development of heart failure, a prespecified endpoint of the SOLVD prevention trial. At baseline, 209 subjects (5.1%) had an S(3) and 70 (1.7%) had elevated jugular venous pressure. Heart failure developed in 1044 subjects (25.5%). After adjusting for other markers of disease severity, an S(3) was associated with an increased risk of heart failure (relative risk [RR] = 1.38; 95% confidence interval [CI]: 1.09 to 1.73; P = 0.007) and the composite endpoint of death or development of heart failure (RR = 1.34; 95% CI: 1.09 to 1.64; P = 0.005). Elevated jugular venous pressure was also associated with these outcomes in multivariate models. The physical examination provides prognostic information among patients with asymptomatic or minimally symptomatic left ventricular dysfunction.",2003.0,0,0
1177,12732606,Left ventricular remodeling and ventricular arrhythmias after myocardial infarction.,Martin St John Sutton; Douglas Lee; Jean Lucien Rouleau; Steven Goldman; Ted Plappert; Eugene Braunwald; Marc A Pfeffer,"The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction. Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 years were significantly related to LV size, LVMA, and function. Furthermore, changes in LV size and function from baseline to 2 years predicted both VT and PVCs >10/h. The study was underpowered to detect treatment effect of ACE inhibitors and beta-adrenergic receptor blockers but did not alter the relations between ventricular arrhythmias, LV size, and function. Quantitative echocardiographic assessment of LV size, LVMA, and function and changes in these measurements over time predict ventricular arrhythmias after infarction. Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias.",2003.0,0,0
1178,12742294,"Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials.",Paul G Shekelle; Michael W Rich; Sally C Morton; Col Sid W Atkinson; Wenli Tu; Margaret Maglione; Shannon Rhodes; Michael Barrett; Gregg C Fonarow; Barry Greenberg; Paul A Heidenreich; Tom Knabel; Marvin A Konstam; Anthony Steimle; Lynne Warner Stevenson,"This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes. Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established. The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups. Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality. Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.",2003.0,0,0
1179,12742805,Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.,Christophe Tzourio; Craig Anderson; Neil Chapman; Mark Woodward; Bruce Neal; Stephen MacMahon; John Chalmers; PROGRESS Collaborative Group,"High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score). During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke. Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.",2003.0,0,0
1180,12745200,Antihypertensive therapy with verapamil SR plus trandolapril versus atenolol plus chlorthalidone on glycemic control.,Heinrich Holzgreve; Roumen Nakov; Katrin Beck; Hans Uwe Janka,"There is evidence that diuretics and beta blockers impair glucose tolerance, whereas calcium channel blockers and angiotensin converting enzyme blockers lack this metabolic effect. We compared the effect of a combination therapy with a nondihydropyridine calcium channel blocker plus an angiotensin converting enzyme inhibitor and a beta blocker plus a diuretic on hemoglobin A(1c) (Hb A(1c)) in patients with type 2 diabetes and mild-to- moderate hypertension. A total of 463 hypertensive outpatients with non-insulin treated type 2 diabetes on stable antidiabetic therapy for at least 3 months and with HbA(1c) between 6.5% and 10% were recruited. In a randomized, double blind trial patients were treated for 20 weeks with fixed combinations of verapamil sustained release (SR) plus trandolapril and of atenolol plus chlorthalidone following a 2-week placebo run-in period. The main outcome measures were HbA(1c), fasting plasma glucose, and fructosamine levels as well as systolic and diastolic blood pressure. HbA(1c) remained stable at 7.9% after administration of verapamil SR plus trandolapril and increased from 7.8% to 8.6% with atenolol plus chlorthalidone; the differences between treatment groups were significant at 4, 12, and 20 weeks of treatment and at last visit (P <.0001). Mean blood pressure fell from 169/96 to 150/85 and from 168/95 to 145/83 mm Hg after administration of verapamil SR plus trandolapril and atenolol plus chlorthalidone, respectively. Both combinations were well tolerated. HbA(1c) and other parameters of short- and long-term glycemic control were in a more favorable range after antihypertensive treatment with verapamil SR plus trandolapril as compared with atenolol plus chlorthalidone.",2003.0,0,0
1181,12748199,"The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.","Aram V Chobanian; George L Bakris; Henry R Black; William C Cushman; Lee A Green; Joseph L Izzo; Daniel W Jones; Barry J Materson; Suzanne Oparil; Jackson T Wright; Edward J Roccella; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee","""The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure"" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.",2003.0,0,0
1182,12751133,Regression of left ventricular hypertrophy after treatment of hypertension: comparison of directed M-echocardiography with magnetic resonance imaging in quantification of serial mass changes.,Hung-Fat Tse; Bernard M Y Cheung; William Ng; John K F Chan; Richard B Devereux; Chu-Pak Lau,"This study sought to validate the reliability of serial echocardiographic measurements in detecting left ventricular (LV) hypertrophy regression by using magnetic resonance imaging (MRI) as a reference standard. We studied a small population (n = 20) of patients enrolled in the Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) trial for evaluating LV hypertrophy regression. LV mass was measured by both echocardiography and MRI at baseline and after 1 year. As compared with baseline, systolic and diastolic blood pressures were significantly decreased after 1 year (all P <.05). Echocardiographic technique showed an overestimation of LV mass by 27.6 g at baseline (P =.005) and by 37.1 g after 1 year (P <.001), and there were wide 95% limits of agreement (+/-36.0 g at baseline; and +/-27.6 g after 1 year) when compared with MRI measurement. Significant changes of LV mass from baseline of -20 +/- 22 g (P<.01) and -29 +/- 19 g (P <.01) were detected by using echocardiography and MRI after 1 year, respectively (P =.02), and there were similarly wide limits of agreement for change in LV mass (+/-24.2 g). Despite the use of careful methodology, echocardiographic measurement of LV mass at a single time point or for serial studies resulted in significant variation in LV mass estimates from measurement using MRI.",2003.0,0,0
1183,12751915,The cost effectiveness of ACE inhibitors as first-line antihypertensive therapy.,Alain J Nordmann; Murray Krahn; Alexander G Logan; Gary Naglie; Allan S Detsky,"Current hypertension guidelines differ in their recommendations for first-line antihypertensive therapy. To evaluate the cost effectiveness of ACE inhibitor therapy as antihypertensive first-line therapy as compared with conventional antihypertensive therapy with beta-adrenoceptor antagonists or diuretics. Cost-effectiveness analysis based on data from randomised trials and observational studies comparing the effectiveness of ACE inhibitor and conventional antihypertensive therapy, we constructed a Markov model to compare four strategies in the management of uncomplicated hypertension: (i) prescribing ACE inhibitor therapy to all patients; (ii) prescribing conventional therapy to all patients; (iii) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on electrocardiography (ECG); or (iv) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on echocardiography. Cost data were derived from the medical literature and focus groups, and utility values were derived from patients on antihypertensive monotherapy. All costs were calculated in 1999 Canadian dollars, but are reported in US dollars according to the 1999 purchasing power parity rate for medical and healthcare. The effectiveness of ACE inhibitor therapy in the presence of left ventricular hypertrophy was derived from observational studies. The time horizon was over a lifetime. Third-party payer. A cohort of men aged 40 years without cardiovascular comorbidity requiring antihypertensive drug therapy. In the baseline analysis, all four strategies resulted in expected discounted QALYs that differed from each other only at the third decimal point (i.e. less than 0.003). Given the uncertainties in the variable estimates and the small size of the differences, these differences are extremely small and unlikely to represent real differences. Even accepting the small gains as real, the resulting cost-effectiveness ratios are unattractively high: $US 200,000 per QALY gained for the echocardiography strategy (compared with ECG), and $US 700,000 for the ""ACE inhibitor for all"" strategy (compared with ECG). The incremental cost effectiveness of prescribing ACE inhibitor therapy to everybody was never less than $US 100,000/QALY in the sensitivity analysis. Prescribing ACE inhibitors as antihypertensive first-line therapy in patients without cardiovascular morbidity cannot be recommended at the present time unless the acquisition costs of ACE inhibitors become substantially more attractive.",2003.0,0,0
1184,12759323,"Race, quality of care, and outcomes of elderly patients hospitalized with heart failure.",Saif S Rathore; JoAnne M Foody; Yongfei Wang; Grace L Smith; Jeph Herrin; Frederick A Masoudi; Pamela Wolfe; Edward P Havranek; Diana L Ordin; Harlan M Krumholz,"Black patients hospitalized with heart failure reportedly receive poorer quality of care and have worse outcomes than white patients. Because previous studies have been based on selected patient populations treated more than a decade ago, it is unclear if racial differences in quality of care and outcomes currently exist in the United States. To evaluate differences in quality of care and patient outcomes between black and white Medicare beneficiaries hospitalized with heart failure. Retrospective analysis of medical record data systematically collected for the National Heart Failure Project. Nationwide US sample of 29 732 fee-for-service Medicare beneficiaries hospitalized with heart failure in 1998 and 1999. Prescription of angiotensin-converting enzyme (ACE) inhibitors, measurement of left ventricular ejection fraction (LVEF), readmission within 1 year of discharge, and mortality within 30 days and 1 year of admission. Black patients and white patients had similar crude rates of LVEF assessment (67.8% black vs 66.6% white; P =.29). Among patients classified as ideal for ACE inhibitor use, black patients had higher crude rates of ACE inhibitor use than white patients (81.0% vs 73.8% white; P<.001) but had similar rates of ACE inhibitor or angiotensin receptor blocker (ARB) use (85.7% black vs 82.5% white; P =.08). After multivariable adjustment, black patients had comparable rates of LVEF assessment (risk ratio [RR], 0.99; 95% confidence interval [CI], 0.95-1.03). Black patients remained more likely to be prescribed ACE inhibitors (RR, 1.22; 95% CI, 1.14-1.28) than were white patients in an adjusted analysis, but there were no significant racial differences in the prescription of ACE inhibitors or ARBs (black vs white, RR, 1.03; 95% CI, 0.97-1.07). Black patients had higher rates of readmission within 1 year of discharge (68.2% vs 63.0%; P<.001) but had lower crude 30-day (6.3% vs 10.7%; P<.001) and 1-year (31.5% vs 40.1%; P<.001) mortality rates than white patients. After multivariable adjustment, black patients had a slightly higher rate of readmission than white patients (RR, 1.09; 95% CI, 1.06-1.13) but remained at lower risk of 30-day mortality (RR, 0.78; 95% CI, 0.68-0.91) and 1-year mortality (RR, 0.93; 95% CI, 0.88-0.98). Black Medicare patients hospitalized with heart failure received comparable quality of care and had slightly higher rates of readmission but had lower mortality rates up to 1 year after hospitalization than did white patients.",2003.0,0,0
1185,12759325,Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.,Bruce M Psaty; Thomas Lumley; Curt D Furberg; Gina Schellenbaum; Marco Pahor; Michael H Alderman; Noel S Weiss,"Establishing relative benefit or harm from specific antihypertensive agents is limited by the complex array of studies that compare treatments. Network meta-analysis combines direct and indirect evidence to better define risk or benefit. To summarize the available clinical trial evidence concerning the safety and efficacy of various antihypertensive therapies used as first-line agents and evaluated in terms of major cardiovascular disease end points and all-cause mortality. We used previous meta-analyses, MEDLINE searches, and journal reviews from January 1995 through December 2002. We identified long-term randomized controlled trials that assessed major cardiovascular disease end points as an outcome. Eligible studies included both those with placebo-treated or untreated controls and those with actively treated controls. Network meta-analysis was used to combine direct within-trial between-drug comparisons with indirect evidence from the other trials. The indirect comparisons, which preserve the within-trial randomized findings, were constructed from trials that had one treatment in common. Data were combined from 42 clinical trials that included 192 478 patients randomized to 7 major treatment strategies, including placebo. For all outcomes, low-dose diuretics were superior to placebo: coronary heart disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81); cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR, 0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies-beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), alpha-blockers, and angiotensin receptor blockers-was significantly better than low-dose diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00) and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96), cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR, 0.86; 0.77-0.97). Compared with beta-blockers, low-dose diuretics were associated with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98). Compared with alpha-blockers, low-dose diuretics were associated with reduced risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events (RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between comparison treatments. Low-dose diuretics are the most effective first-line treatment for preventing the occurrence of cardiovascular disease morbidity and mortality. Clinical practice and treatment guidelines should reflect this evidence, and future trials should use low-dose diuretics as the standard for clinically useful comparisons.",2003.0,0,0
1186,12761258,Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial.,Manuel Praga; Eduardo Gutiérrez; Ester González; Enrique Morales; Eduardo Hernández,"Some retrospective studies have suggested a beneficial influence of angiotensin-converting enzyme (ACE) inhibitors on the progression of IgA nephropathy (IgAN), but prospective and controlled studies demonstrating this effect are lacking. Forty-four patients with biopsy-proven IgAN, proteinuria > or = 0.5 g/d, and serum creatinine (SCr) < or = 1.5 mg/dl were randomly assigned either to receive enalapril (n = 23) or to a control group (n = 21) in whom BP was controlled with antihypertensives other than ACE inhibitors. Primary outcome was renal survival estimated by a 50% increase in baseline SCr. Secondary outcomes were the presence of a SCr > 1.5 mg/dl at the last visit and the evolution of proteinuria. Baseline clinical findings were similar at baseline between enalapril-treated and control group, and there were no differences in BP control during follow-up. Mean follow-up was 78 +/- 37 mo in the enalapril group and 74 +/- 36 mo in the control group. Three patients (13%) in the enalapril group and 12 (57%) in the control group reached the primary end point (P < 0.05). Kaplan-Meier renal survival was significantly better in enalapril group than in control group: 100% versus 70% after 4 yr and 92% versus 55% after 7 yr (P < 0.05). Three patients in the enalapril group (13%) and 11 (52%) in the control group showed SCr > 1.5 mg/dl at the last visit (P < 0.05). Proteinuria significantly decreased in the enalapril group, whereas it tended to increase in the control group (P < 0.001 between groups). In conclusion, ACE inhibitors significantly improve renal survival in proteinuric IgAN with normal or moderately reduced renal function.",2003.0,0,0
1187,12762972,Prevention of type 2 diabetes.,Samy I McFarlane; John J Shin; Tanja Rundek; J Thomas Bigger,"Diabetes is a major public health problem that is approaching epidemic proportions in our society and worldwide. Cardiovascular disease is the major cause of morbidity and mortality in people with diabetes. Control of cardiovascular disease risk factors is achieved only in a minority of patients. Given the magnitude of the problem and the seriousness of diabetes complications, prevention appears to be a logical approach to curb the rising prevalence of the disease. Interventions such as lifestyle modifications and the use of metformin and acarbose have been shown in randomized prospective trials to prevent diabetes in high-risk patients. Other interventions are currently being examined in large prospective studies. It is likely that one or a combination of these approaches will make diabetes prevention a reality in the near future.",2003.0,0,0
1188,12771010,Enalapril decreases the incidence of atrial fibrillation in patients with left ventricular dysfunction: insight from the Studies Of Left Ventricular Dysfunction (SOLVD) trials.,Emmanuelle Vermes; Jean-Claude Tardif; Martial G Bourassa; Normand Racine; Sylvie Levesque; Michel White; Peter G Guerra; Anique Ducharme,"Atrial fibrillation (AF) is frequently encountered in patients with heart failure (HF) and is also a predictor of morbidity and mortality in this population. Recent experimental studies have shown electrical and structural atrial remodeling with increased fibrosis in animals with HF and have suggested a preventive effect of ACE inhibitors (ACEi) on the development of AF. To verify the hypothesis that ACEi prevent the development of AF in patients with HF, we conducted a retrospective analysis of the patients from the Montreal Heart Institute (MHI) included in the Studies Of Left Ventricular Dysfunction (SOLVD). Clinical charts were reviewed and serial ECGs interpreted by a single cardiologist blinded to drug allocation. Patients with AF or flutter on the baseline ECG were excluded. Baseline characteristics were obtained from the SOLVD databases. The mean follow-up was 2.9+/-1.0 years. Of the 391 patients randomly assigned at MHI, 374 were in sinus rhythm at the time of random assignment, with 186 taking enalapril and 188 taking placebo. Baseline characteristics were similar in the two groups except for a higher incidence of previous myocardial infarction in the enalapril group. Fifty-five patients had AF during the follow-up: 10 (5.4%) in the enalapril group and 45 (24%) in the placebo group (P<0.0001). By Cox multivariate analysis, enalapril was the most powerful predictor for risk reduction of AF (hazard ratio, 0.22; 95% CI, 0.11 to 0.44; P<0.0001). Treatment with the ACEi enalapril markedly reduces the risk of development of atrial fibrillation in patients with left ventricular dysfunction.",2003.0,0,0
1189,12779302,Pharmacotherapy for heart failure in patients with renal insufficiency.,Michael G Shlipak,"Clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and spironolactone improve survival in patients with heart failure. Because patients with heart failure and renal insufficiency have been underrepresented in these trials, little evidence is available to guide clinicians in the optimal management of patients with both conditions. Approximately one third to one half of patients with heart failure have renal insufficiency (estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m2), and renal insufficiency is among the strongest predictors of mortality in patients with heart failure. Evidence supports the use of ACE inhibitors to improve survival in patients with moderate renal insufficiency (GFR, 30 to 60 mL/min per 1.73 m2), but there is little evidence with which to weigh the risks and benefits in patients with more advanced renal dysfunction. beta-Blockers improve survival in patients with heart failure, and their beneficial effect is unlikely to differ according to renal function. Spironolactone improves outcomes in patients with advanced heart failure, but renal insufficiency appears to increase risk for hyperkalemia and limits the use of the drug in patients with severe renal insufficiency. Future clinical trials in heart failure should include a representative number of patients with renal insufficiency to improve the evidence base and outcomes in this vulnerable population.",2003.0,0,0
1190,12796754,Differential effects of antihypertensive agents on electrocardiographic voltage: results from the Appropriate Blood Pressure Control in Diabetes (ABCD) trial.,Edward P Havranek; Anne Esler; Raymond O Estacio; Philip S Mehler; Robert W Schrier; Appropriate Blood Pressure Control in Diabetes Trial,"Serial decline in electrocardiographic voltage in patients with increased left ventricular mass has been associated with a lower risk of cardiovascular events. We studied 468 patients with diabetes mellitus and hypertension in the Appropriate Blood Pressure Control in Diabetes (ABCD) trial. Patients were randomized in a stratified design to receive initial treatment with either enalapril or nisoldipine and to either intensive or moderate treatment goals. We measured an electrocardiographic index for increased left ventricular mass, the adjusted Cornell voltage, serially by treatment group. The association between changes in electrocardiographic voltage and cardiovascular events was defined with Cox proportional hazards analysis. In 5 years of follow-up, the decline in adjusted Cornell voltage was significantly greater for patients treated with enalapril than for patients treated with nisoldipine (repeated measures analysis of variance P =.002). In the Cox proportional hazards model, treatment assignment (enalapril vs nisoldipine) was the strongest predictor of cardiovascular events, but the presence of coronary disease at baseline, the duration of diabetes mellitus, and change in voltage were also independent predictors of cardiovascular events. In the ABCD study, enalapril treatment was associated with a lower risk of myocardial infarction. The reduction in left ventricular mass as reflected by diminished electrocardiographic voltage may explain some, but not all, of the effect of enalapril in this study.",2003.0,0,0
1191,12798838,Is multidisciplinary care of heart failure cost-beneficial when combined with optimal medical care?,Mark Ledwidge; Michael Barry; John Cahill; Enda Ryan; Brian Maurer; Mary Ryder; Bronagh Travers; Lorna Timmons; Ken McDonald,"Multidisciplinary care (MDC) of heart failure (HF) can significantly reduce rates of unplanned hospitalisation, the major cost component of HF care. This prospective, randomised, controlled study examines the cost-benefits of MDC of HF in the setting of optimal medical care. 98 NYHA class IV HF patients (mean age 70.8+/-10.5 years) were randomised to MDC (n=51) or routine care (RC; n=47) of HF. A direct intervention cost was calculated from contact time (scheduled and unscheduled) spent by the MDC team. Unplanned hospitalisation costs for HF were calculated at a daily rate of 242. Outcomes were determined in monetary terms, i.e. the cost of the service per hospitalisation prevented and net costs/savings at 3 months. The direct intervention cost of the MDC team was 5860, with an average cost per patient of 113 (95% Cl: 97-128). At 3 months, there were a total of 12 unplanned HF readmissions in the RC group (25.5% rate, 195 days) compared to 2 in the MDC group (3.9% rate, 17 days). The number needed to treat to prevent one hospitalisation for HF was 6 over 3 months. The cost of the service per hospitalisation prevented was 586. The intervention produced a net cost saving of 37,216 for 51 patients treated over 3 months. Sensitivity analyses using 50% variation in costs and lower relative risk reductions confirmed the cost-benefits of the intervention. MDC of HF remains cost-beneficial when combined with optimal, medical care. The significant clinical and cost-benefits suggest that this intensive approach to MDC and medical management should become the standard of care for HF.",2003.0,0,0
1192,12803510,Combination of pentoxifylline with angiotensin converting enzyme inhibitors produces an additional reduction in microalbuminuria in hypertensive type 2 diabetic patients.,Ozlem Harmankaya; Selcuk Seber; Mürvet Yilmaz,"To investigate the anti proteinuric effect of pentoxifylline in diabetic patients, we prospectively studied in 25 hypertensive type 2 diabetic patients with persistent microalbuminuria and normal renal function the impact of combining pentoxifylline with an angiotensin converting enzyme inhibitor, lisinopril, on urinary albumin excretion and compared the results with those obtained in a control group of 25 type 2 diabetic patients treated with lisinopril only. Fifty hypertensive type 2 diabetic patients with persistent microalbuminuria (31 males and 19 females, aged between 47-73 years) were randomly assigned to two groups. Group A received lisinopril 10 mg/day, while group B was given lisinopril 10 mg/day and pentoxifylline 600 mg/day for nine months. There were no significant differences between serum creatinine, HbA1c, blood pressure and urinary albumin excretion in both groups (p > 0.05). Serum creatinine, creatinine clearance, blood pressure, HbA1c levels did not change significantly during the study. Urinary albumin excretion decreased from 228 +/- 28 to 148 +/- 15 mg/day in group A (p < 0.05). In group B urinary albumin excretion decreased from 219 +/- 26 to 128 +/- 12 mg/day (p < 0.05). Pentoxifylline and lisinopril combination caused a significant additional reduction in urinary albumin excretion when compared to lisinopril regimen (p < 0.05). Our findings suggest that the combination of pentoxifylline with an angiotensin converting enzyme inhibitor in hypertensive type 2 diabetic patients with persistent microalbuminuria causes a significant reduction in urinary albumin excretion and this effect seems independent from blood pressure and glycemic control.",2003.0,0,0
1193,12806591,Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients with diabetes mellitus: rationale and design.,Niels H Andersen; Søren T Knudsen; Per L Poulsen; Steen H Poulsen; Kjeld Helleberg; Hans Eiskjaer; Klaus W Hansen; Toke Bek; Carl E Mogensen,"Blood pressure (BP) reduction is the key to risk reduction of cardiovascular disease or renal failure in hypertensive patients with diabetes mellitus. Inhibition of the renin-angiotensin system by an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) provides efficient BP reduction and renal protection in hypertensive diabetes patients. But, despite this, the recommended BP levels can be difficult to achieve and dual blockade therapy might be a possible way of obtaining efficient BP reduction in hypertensive patients with diabetes. Dual blockade treatment is based on a principle of obtaining the broadest and most efficient blockade of angiotensin II, by using the combination of an ACE-inhibitor and an ARB. The Candesartan And Lisinopril Microalbuminuria (CALM II) study is a one centre, one observer, double-blind, randomised, active-controlled, parallel-group study, investigating the efficacy and tolerability of candesartan cilexetil in combination with lisinopril, compared with the maximum recommended dose of lisinopril in hypertensive patients with diabetes mellitus. The study design consists of two treatment arms with either 16 mg candesartan cilexetil or 20 mg lisinopril added to concomitant treatment with 20 mg lisinopril. It comprises 80 patients with a minimum of 35 patients in each group and statistical power of 90% to detect a difference in systolic BP reduction of 6.5 mmHg. The CALM II study aims to investigate the effects of dual blockade on systolic BP, albuminuria, left ventricular mass and function, and retinopathy in hypertensive patients with diabetes mellitus.",2003.0,0,0
1194,12806595,Effect of angiotensin-converting enzyme inhibition on endothelial function and insulin sensitivity in hypertensive patients.,Hakan Tezcan; Dilek Yavuz; Ahmet Toprak; Ihsan Akpinar; Mehmet Koç; Oguzhan Deyneli; Sema Akalin,"Evidence suggests an association between insulin resistance, hypertension and impaired endothelial function. Studies have shown that insulin resistance precedes the development of hypertension. By improving insulin sensitivity, it may be possible to improve hypertension and the subsequent damage to vessel walls. Some data indicates beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on insulin sensitivity and endothelial function. We aimed to investigate these effects of ACE inhibition in the same group of patients with essential hypertension. Nine non-smoking, untreated hypertensive patients (38.3+9 years, 4/5 male/female) and 12 age-matched healthy subjects (35.2+6.7 years, 5/7 male/female) were included in the study. Hypertensive patients were given enalapril maleate (5 40 mg/day) for six months. The following parameters were studied at baseline and at the end of treatment period. Whole body insulin sensitivity was measured by a formula derived from an oral glucose tolerance test and named as the insulin sensitivity index (ISI). Insulin was measured by chemiluminescence and glucose by a glucose oxidase method. Endothelial function was evaluated as flow-mediated dilatation (FMD) of the brachial artery by ultrasonography and expressed as a percentage change relative to baseline diameter. Endothelial- independent vasodilatation was measured after sublingual nitroglycerine. FMD was impaired in the hypertensive group compared with healthy subjects (7.3+3.1% vs. 15.3+4.8%, p<0.0005), and ISI values were 1.18+0.6 vs. 4.4+0.9 (p<0.0001) respectively. Both insulin sensitivity and FMD improved after the treatment period compared with baseline values, FMD increased from 7.3+3.1% to 16.0+2.9% (p<0.0005) and ISI from 1.18+0.6 to 4.2+1.0 (p<0.0001). FMD and ISI showed a significant positive correlation (r=0.67, p<0.001) in the hypertensive group. Patients with essential hypertension have impaired endothelial function and decreased whole body insulin sensitivity compared with healthy subjects. Treatment for six months with enalapril maleate seems to improve both FMD and ISI. This study confirms the beneficial effects of ACE inhibition on both endothelial function and insulin sensitivity tested in the same group of essential hypertensive patients. The mechanism of these favourable effects of ACE inhibition needs to be clarified.",2003.0,0,0
1195,12816171,High- versus low-dose angiotensin converting enzyme inhibitor therapy in the treatment of heart failure: an economic analysis of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial.,J Sanford Schwartz; Y Richard Wang; John G F Cleland; Longlong Gao; Mark Weiner; Philip A Poole-Wilson; ATLAS Study Group,"Angiotensin-converting enzyme (ACE) inhibitors reduce heart failure death and hospitalization. Prescribed doses often are lower than randomized clinical trial (RCT) targets and practice guideline recommendations. To assess the cost-effectiveness of high- versus low-dose ACE inhibitor therapy in the ATLAS trial. A 19-nation RCT of high-dose (32.5-35.0 mg/day) versus low-dose (2.5-5.0 mg/day) lisinopril in 3164 patients with class II-IV heart failure and left ventricular ejection fraction < or = 30%. Data on clinical outcomes and major cost events (hospitalizations and drug utilization) were collected prospectively. Hospital costs were estimated using Medicare and representative managed care diagnosis-related group reimbursement rates. ACE inhibitor drug costs were estimated using US average wholesale prices. Costs were discounted at 3% annually. Patients in the high-dose lisinopril group had fewer hospitalizations (1.98 vs 2.22, P = .014) and hospital days (18.28 vs 22.22, P = .002), especially heart failure hospitalizations (0.64 vs 0.80, P = .006) and heart failure hospital days (6.02 vs 7.45, P = .028) compared with the low-dose group. The high-dose lisinopril group also had lower heart failure hospital costs (dollars 5114 vs dollars 6361, P = .006) but higher ACE inhibitor drug costs (dollars 1368 vs dollars 855, P = .0001). Total hospital and drug costs were similar between high- and low-dose lisinopril groups (mean difference dollars -875, 95% CI dollars -2613 to dollars 884). Sensitivity analyses confirmed these findings. Cost savings from fewer heart failure hospitalizations offset higher ACE inhibitor costs in the high-dose group. The improved clinical outcomes were achieved without increased treatment costs.",2003.0,0,0
1196,12823686,Are thiazide diuretics preferred as first-line therapy for hypertension? An appraisal of The Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,I Scott; M Stowasser,,2003.0,0,0
1197,12826782,Response to six classes of antihypertensive medications by body mass index in a randomized controlled trial.,Barry J Materson; David W Williams; Domenic J Reda; William C Cushman; Veterans Affairs Cooperative Study Group on Antihypertensive Agents,"Blood pressure increases with increasing body mass index (BMI) and BMI is linearly related to blood pressure in population studies. Obesity has been said to cause resistance to antihypertensive medications. We compared short-term and 1-year blood pressure response by BMI category and weight change with hydrochlorothiazide, atenolol, diltiazem-SR, captopril, clonidine, prazosin, or placebo in 1292 male veterans. Drug doses were titrated to achieve goal diastolic blood pressure <90 mm Hg over 4-8 weeks. Patients who achieved goal blood pressure were maintained for 1 year. BMI did not predict change in systolic, diastolic or pulse pressures during titration for any drug. At 1 year obese patients (BMI >30) were 2.5 times more likely to have diastolic blood pressure controlled by atenolol than normal weight (BMI <27) patients (p=0.01). Only prazosin patients gained weight: 1.7 lb (end-titration, p<0.0001; 1-year, p=0.02). Obesity does not appear to cause resistance to antihypertensive medications.",2003.0,0,0
1198,12826783,Achieving goal blood pressure in patients with type 2 diabetes: conventional versus fixed-dose combination approaches.,George L Bakris; Matthew R Weir; Study of Hypertension and the Efficacy of Lotrel in Diabetes (SHIELD) Investigators,"Data from the Third National Health and Nutrition Examination Survey (NHANES III) demonstrate that only 11% of people with diabetes who are treated for high blood pressure achieve the blood pressure goal of <130/85 mm Hg recommended in the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The current study tests the hypothesis that initial therapy with a fixed-dose combination will achieve the recommended blood pressure goal in patients with type 2 diabetes faster than conventional monotherapy. This randomized, double-blind, placebo-controlled study had as a primary end point achievement of blood pressure <130/85 mm Hg. Participants (N=214) with hypertension and type 2 diabetes received either amlodipine/benazepril 5/10 mg (combination) or enalapril 10 mg (conventional) once daily for 4 weeks, titrated to 5/20 mg/day or 20 mg/day, respectively at this time, if target blood pressure was not achieved. Hydrochlorothiazide (HCTZ) 12.5 mg/day was added for the final 4 weeks, if target blood pressure was still not reached. Time from baseline to achieve blood pressure <130/85 mm Hg was shorter in the combination group (5.3+/-3.1 weeks combination vs. 6.4+/-3.8 weeks conventional; p=0.001). At 3 months, more participants in the combination group achieved treatment goal (63% combination vs. 37% conventional; p=0.002). Data analysis at 3 months comparing blood pressure control rates between the fixed-dose combination group (without HCTZ) to the conventional group (receiving HCTZ) showed an even greater disparity in blood pressure goal achievement (87% combination without HCTZ vs. 37% conventional group with HCTZ; p=0.0001). We conclude that initial therapy with a fixed-dose combination may be more efficacious than conventional monotherapy approaches for achieving blood pressure goals in the diabetic patient. A fixed-dose combination approach appears as safe as the current conventional approaches.",2003.0,0,0
1199,12827019,Role of I1-imidazoline receptors within the caudal ventrolateral medulla in cardiovascular responses to clonidine in rats.,Wei-Zhong Wang; Wen-Jun Yuan; An-Jing Ren; Yan-Xia Pan; Chao-Shu Tang; Ding-Feng Su,"Although it is recognized that imidazoline receptors play an important role in the central regulation of cardiovascular activities, little is known about their role in the caudal ventrolateral medulla. In male Sprague-Dawley rats anesthetized with urethane, we used antagonists of I1-imidazoline receptor or alpha2-adrenoceptor to assess the function of these receptors in the caudal ventrolateral medulla in controlling the cardiovascular effects of clonidine. Unilateral microinjection of clonidine (6 nmol/50 nl) into the caudal ventrolateral medulla significantly (P<0.01) increased blood pressure and the discharge of the rostral ventrolateral medulla presympathetic neurons, while heart rate remained unchanged. Microinjection of yohimbine (a selective alpha2-adrenoceptor antagonist, 500 pmol/50 nl) into the caudal ventrolateral medulla did not modify blood pressure, heart rate, or the discharge of the rostral ventrolateral medulla presympathetic neurons, and failed to attenuate the local caudal ventrolateral medulla clonidine-induced blood pressure elevation. However, unilateral microinjection of idazoxan (a mixed antagonist of imidazoline receptor and alpha2-adrenoceptor, 2 nmol/50 nl) into the caudal ventrolateral medulla significantly (P<0.01) decreased mean arterial pressure, heart rate, and the discharge of the rostral ventrolateral medulla presympathetic neurons, and completely abolished the pressor effect of clonidine. In addition, bilateral microinjection of idazoxan (4 nmol in 100 nl for each side) into the caudal ventrolateral medulla effectively (P<0.01) blocked the depressor effects of clonidine administered intravenously (5 and 50 microg/kg). These results confirm that I1-imidazoline receptors within the caudal ventrolateral medulla are involved in maintaining the tonic cardiovascular activities and in the pressor effect of clonidine in the caudal ventrolateral medulla. In addition, it seems that the caudal ventrolateral medulla plays an important role in the antihypertensive effects of systemically administered clonidine in rats.",2003.0,0,0
1200,12827024,Inhibition of the renin-angiotensin system: no effect on circulating macrophage colony-stimulating factor levels in acute myocardial infarction.,Kenji Kurosaki; Uichi Ikeda; Yoshiaki Murakami; Masafumi Takahashi; Kazuyuki Shimada,"Macrophage colony-stimulating factor, which induces proliferation and differentiation, and activation of monocytes and macrophages, plays an important role in the vulnerability of atheromatous plaques as well as the formation of atherosclerotic lesions. We measured serum concentrations of macrophage colony-stimulating factor in patients with acute myocardial infarction and also investigated the effects of early administration of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker on circulating macrophage colony-stimulating factor levels in these patients. The patients were divided randomly into 3 therapeutic groups; perindopril, candesartan, and control (without perindopril and candesartan) groups, and the drugs were administered within 24 to 36 hours after the onset of acute myocardial infarction. Serum macrophage colony-stimulating factor concentrations in acute myocardial infarction patients at the time of admission were significantly higher than those in healthy control subjects. The macrophage colony-stimulating factor levels in the patients decreased gradually after admission, but remained significantly higher than those in control subjects for 14 days. There were no significant differences in serum macrophage colony-stimulating factor levels among the 3 therapeutic groups during this study period. In conclusion, circulating macrophage colony-stimulating factor levels are elevated during the course of acute myocardial infarction, and inhibition of the renin-angiotensin system by angiotensin-converting enzyme inhibitor or angiotensin receptor blocker does not affect these levels.",2003.0,0,0
1201,12832683,Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study.,H Kanazawa; K Hirata; J Yoshikawa,"We have previously shown that angiotensin converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). A pilot study was designed to examine the effects of captopril on these exercise related variables in COPD patients categorised according to ACE gene polymorphisms. Thirty six patients with COPD (II=13, ID=11, DD=12) received oral captopril (25 mg) or placebo in a randomised, double blind, crossover manner and underwent right heart catheterisation with exercise. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), and lactate concentration after exercise with both placebo and captopril were higher in patients with the DD genotype than in those with the II or ID genotypes. In contrast, mixed venous oxygen tension (PvO(2)) was lower in patients with the DD genotype than in those with the other genotypes. Moreover, mPAP, PVR, and lactate concentration after exercise were lower in the captopril group than in the placebo group in patients with the II or ID genotype, but not in those with the DD genotype. PvO(2) after exercise was higher with captopril than with placebo in patients with the II genotype, but not in those with the other genotypes. These findings suggest that pulmonary haemodynamic variables and state of tissue oxygenation during exercise are dependent on ACE genotypes, and that captopril administration effectively influences these exercise related variables. Although the sample size in this pilot study was limited, it is likely that the improvement in exercise related variables in COPD patients with the II genotype is relatively sensitive to captopril.",2003.0,0,0
1202,12833584,Additive antiproteinuric effect of combination therapy with ACE inhibitor and angiotensin II receptor antagonist: differential short-term response between IgA nephropathy and diabetic nephropathy.,Moon Jae Kim; Joon Ho Song; Ju Hyun Suh; Seoung Woo Lee; Gyoung A Kim,"In previous studies, the synergistic antiproteinuric effect of the combination therapy of ACE inhibitors and angiotensin II receptor antagonists (ATRAs) has been inconsistent in relation to underlying renal diseases. The influence from the blood pressure (BP) - reducing effect in some studies might also contribute to this inconclusiveness. To examine the possibility of the benefit being different according to underlying renal diseases, we undertook a crossover therapeutic trial of the combination therapy in two selected homogenous groups of patients with diabetic and non-diabetic renal diseases. The BP-reducing effect was excluded during the study. Nineteen biopsy-proven IgA nephropathy, as examples of non-diabetic renal diseases, and 24 type 2 diabetic nephropathy patients were selected as the study subjects. The subjects had to meet the follow criteria: a creatinine clearance (Ccr) between 25 - 90 ml/min/1.73 m2, 24-hr urinary protein excretion rate over 1.0 g/day and a BP maintained at less than 130/80 mmHg, with more than six-month therapy of ramipril, (5.7 +/- 0.4 mg/day, 13 +/- 2 month). The baseline data between the two groups showed no significantly differences. After a 12-week stabilization period (control period), 4 mg, once daily, dose of candesartan (combination period) followed by a placebo (placebo period), or vice versa, were administered in addition to the ramipril, for 12 weeks. The combination, with candesartan, did not change the Ccr, BP, serum and urinary electrolytes or the urea. The 24 hour urinary protein excretion rate was significantly reduced by the combination therapy in the patients with IgA nephropathy (3.1 +/- 0.3 g/day in combination, 4.2 +/- 0.3 in control, and 4.3 +/- 0.2 in placebo; p < 0.05). However, the patients with diabetic nephropathy showed no reduction in their proteinuria with the combination therapy (3.8 +/- 0.2 g/day in combination, 3.9 +/- 0.3 in control, and 4.1 +/- 0.3 in placebo; p=NS). The changes in proteinuria showed no relationship with the changes in the BP in IgA nephropathy. In conclusions, the benefit of combination therapy of its antiproteinuric effect was different between IgA and diabetic nephropathy over the 12-week trial. The difference in the pathophysiological role, and the importance of the renin- angiotensin system, between the two diseases might contribute to the discrepancy in the result. We suggest the discrimination of the underlying renal diseases in the study subjects is an important prerequisite for future studies on this issue.",2003.0,0,0
1203,12844462,Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitors or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).,Helmy M Siragy,,2003.0,0,0
1204,12844463,Has the role of calcium channel blockers in treating hypertension finally been defined?,George S Chrysant; Steven G Chrysant,"Several large, prospective, randomized, clinical outcome trials have shown that calcium channel blockers are effective and safe antihypertensive drugs compared with placebo and reduce the cardiovascular morbidity and mortality of treated patients. In other studies, when compared with conventional antihypertensive drugs, they demonstrated similar blood pressure-lowering effects and similar reductions in cardiovascular morbidity and mortality, with the exception of a higher incidence of heart failure and fatal myocardial infarction in some studies. However, considering all the evidence available today, these drugs should be considered safe for the treatment of the uncomplicated hypertensive patient in combination with other drugs. They can also be used as first-line therapy for older, stroke-prone hypertensive patients. In addition, when a calcium channel blocker is indicated for better blood pressure control, its use should not be withheld for safety concerns.",2003.0,0,0
1205,12844464,Regression of left ventricular hypertrophy is a key goal of hypertension management.,Rubin Zhang; Judy Crump; Efrain Reisin,"Left ventricular hypertrophy (LVH) in patients with hypertension is associated with an increased risk for many cardiovascular events and predicts a higher mortality rate. The pathogenesis of LVH is complicated. In addition to the hemodynamic burden (pressure or volume overload) and demographic factors, several trophic humoral factors, such as angiotensin II, aldosterone, endothelin, leptin, and catecholamines, may also contribute to the development and progression of LVH. Effective antihypertensive therapy can reverse LVH as well as prevent its development. Regression of LVH decreases subsequent cardiovascular morbidity and mortality. The commonly used drugs have various effects on LVH. Angiotensin receptor blockers and angiotensin-converting enzyme inhibitors seem most effective. Several new agents, including direct antifibrotic drugs, aldosterone blockade, vasopeptidase inhibitors, and endothelin receptor antagonists that more specifically target the underlying pathogenesis of LVH may provide us with innovative approaches to treat LVH.",2003.0,0,0
1206,12844465,Management of diabetic and hypertensive cardiovascular disease.,Edward D Frohlich; James R Sowers,"The simultaneous occurrence of essential hypertension and diabetes mellitus is exceedingly common. In recent years the treatment of the cardiovascular and renal complications has not only become more specific but more effective. The evidence-based medicine data have been provided through many large multicenter studies and strongly support the promise not only of effective treatment in retarding the progression of target-organ involvement, but also the potential of reversal. These dramatic therapeutic improvements have been made possible by wedding the involved pathophysiologic disease mechanisms with the actions of pharmacologic agents. Inherent in this concept is the promise of retarding the development of the cardiovascular and renal morbid events and also reducing their associated mortal endpoints.",2003.0,0,0
1207,12844467,Lessons from trials in hypertensive type 2 diabetic patients.,Luis M Ruilope,"There is incontrovertible evidence that association of type 2 diabetes with hypertension markedly increases the risk of cardiovascular events, death, and nephropathy. In type 2 diabetes, even blood pressure values usually considered below the threshold for hypertension (ie, 140/90 mm Hg) in nondiabetic subjects represent an additional risk of clinical relevance. Evidence that more intensive blood pressure lowering is beneficial in type 2 diabetes over less intensive lowering is also overwhelming. However, most published trials show the need for combination therapy in the great majority of patients, and even with combination therapy it is difficult to attain the expected goal blood pressure, in particular goal systolic blood pressure. It should be recognized that the systolic blood pressure goal of less than 130 mm Hg is a very difficult one to achieve in diabetics. Evidence of the superiority or inferiority of different drug classes is vague and contradictory. Recent evidence concerning angiotensin II receptor antagonists has shown a significant reduction of cardiovascular events, cardiovascular death, and total mortality when losartan was compared with atenolol, but not when irbesartan was compared with amlodipine. If renal endpoints are considered, evidence of the benefit of angiotensin II receptor antagonists in type 2 diabetes is more robust than that available with angiotensin-converting enzyme inhibitors. Primary prevention of development of microalbuminuria seems to be greatly facilitated by strict blood pressure control. However, by attaining normal blood pressure levels (< 130/80 mm Hg), better preservation of glomerular filtration rate does not seem to be insured.",2003.0,0,0
1208,12844470,Ongoing trials: what should we expect after ALLHAT?,Ji-Guang Wang; Jan A Staessen; Anthony M Heagerty,"The publication of the Antihypertensive and Lipid-lowering Treatment to Prevent Heart Attack Trial (ALLHAT) results, when used in conjunction with a new meta-analysis, provides hypertension research with a watershed. Data demonstrate clearly that lowering blood pressure is the most important aspect of hypertension management, and that all agents are similarly effective. There is little sustainable evidence for pressure-independent advantages for any class of drug at this time. Therefore, by combining these findings with additional information on target levels of blood pressure and safety, plus the use of aspirin and statins, we can formulate health care policies that attack hypertension in a holistic risk-based way. The future will focus on gaining extra benefit for patients by testing the efficacy and superiority of drug combinations using novel agents that favorably influence intermediate markers such as arterial stiffness, and arresting the ever-increasing burden of cognitive impairment and dementia.",2003.0,0,0
1209,12844471,Recent clinical trials with omapatrilat: new developments.,Anne Zanchi; Marc Maillard; Michel Burnier,"Omapatrilat belongs to the vasopeptidase inhibitors, ie, drugs that possess the ability to inhibit simultaneously the membrane-bound zinc metalloproteases, angiotensin-converting enzyme (ACE), and the neutral endopeptidase EC 3.4.24.11 (NEP). Omapatrilat was targeted to treat patients with hypertension and congestive heart failure. The preclinical and early clinical studies conducted with omapatrilat were very promising. Indeed, omapatrilat appeared to be a very potent antihypertensive agent with very favorable effects on cardiac function in heart failure patients. In contrast to these early studies, the large clinical trials were more disappointing. The results of the OCTAVE trial confirmed the antihypertensive efficacy of omapatrilat, but at the price of an angioedema rate more than threefold higher than that of an ACE inhibitor in the overall population (2.17% vs 0.68%), and close to fourfold higher in the black population. In OVERTURE, a large randomized control trial in heart failure, angioedema was also more common with omapatrilat, but the incidence was much lower (0.8% with omapatrilat vs 0.5% with enalapril). However, omapatrilat was not convincingly superior to the ACE inhibitor. Because angioedema is probably a class side effect of vasopeptidase inhibitors, the higher incidence of this potentially life-threatening complication with omapatrilat has likely stopped the development of this new class of agents. The future of vasopeptidase inhibitors will depend on the ability to improve the risk/benefit ratio either by developing agents that produce less angioedema, or by defining more precisely a high-risk population that could take advantage of dual ACE/NEP inhibition.",2003.0,0,0
1210,12848875,Influence of perindopril on left ventricular global performance during the early phase of inferior acute myocardial infarction: assessment by Tei index.,Nearchos S Nearchou; Alexandros K Tsakiris; Maria D Lolaka; Ilias Zarcos; Dimitrios P Skoufas; Panagiotis D Skoufas,"The beneficial effect of angiotensin-converting enzyme inhibitors (ACE inhibitors) on left ventricular (LV) function in patients with acute myocardial infarction (AMI) is widely known. However, controversy exists about their efficacy on patients with small infarcts and preserved LV systolic function. The aim of the present study was to detect the influence of the ACE-I perindopril on the global LV performance in patients with pure inferior AMI (AMI-I) using a Doppler-derived index (DI) that combines systolic and diastolic time intervals (Tei index). Our study included 40 patients with first AMI-I, mean age 60 years +/- 9.06 years (SD) and 24 age- and gender-matched normal patients who constituted the control group (COG). Patients were randomized into two groups to receive the conventional treatment of AMI-I (GCT) or the above therapy plus P (GP). Complete Doppler echocardiography (systolic and diastolic parameters), DI, and systolic blood pressure (SBP) were measured on the 8.07 +/- 1.16(SD) post-infarct day. The same examination was performed to COG. The DI was significantly lower in healthy patients(0.45 +/- 0.23)compared with the value in patients of either GP(0.56 +/- 0.03; P = 0.023)or GCT(0.78 +/- 0.05; P = 0.000). Moreover DI was higher in patients of GCT compared with that of GP(P = 0.000). In addition, perindopril administration decreased isovolumic relaxation time(IRT; 120.00 +/- 4.23 vs. 139.00 +/- 6.74; P = 0.006)and increased significantly ejection time (ET;274.25 +/- 7.35 vs. 253.50 +/- 7.68; P = 0.042). SBP in patients of GP was similar to that of GCT(120.5 +/- 2.85 mmHg vs. 112.5 +/- 3.49 mmHg; P = NS). Global LV function (DI) is impaired in patients with AMI-I. Administration of perindopril has a favorable impact on LV performance in patients with AMI-I, achieved through improvement of the diastolic function (IRT), which indirectly improves LV systolic function (ET, DI). This beneficial influence of perindopril is the result of the direct tissue effect of the drug and not its hemodynamic action.",2003.0,0,0
1211,12851621,Beneficial effects of angiotensin-converting enzyme inhibitor and nitrate association on left ventricular remodeling in patients with large acute myocardial infarction: the Delapril Remodeling after Acute Myocardial Infarction (DRAMI) trial.,Roberto Latini; Lidia Staszewsky; Aldo P Maggioni; Paolo Marino; Francisco Hernandez-Bernal; Gianni Tognoni; Violeta Labarta; Silvana Gramenzi; Federico Bianchi; Giuseppe Sarcina; Giovanni Cremonesi; Gian Luigi Nicolosi; Enrico Geraci; Delapril Remodeling after Acute Myocardial Infarction Collaborative Group,"In the large-scale trial, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-3 (GISSI-3), patients receiving the combination of lisinopril and glyceryl trinitrate benefited most from experimental therapy. Therefore, a multicenter, randomized, double-blind study, Delapril Remodeling After Acute Myocardial Infarction (DRAMI), was designed to assess (1) the possible additive beneficial effect on left ventricular remodeling of nitrates when combined with an angiotensin-converting enzyme inhibitor (ACEI), and (2) the tolerability of a new ACEI, delapril, in respect to lisinopril in patients with large myocardial infarction (MI). A total of 177 patients were randomized to receive delapril plus isosorbide-5-mononitrate (IS5MN) placebo, delapril plus IS5MN, lisinopril plus IS5MN placebo, or lisinopril plus IS5MN starting within the first 36 hours after the onset of symptoms and continuing for 3 months. More than 80% of the patients showed extensive ST-segment changes and 36.7% had signs or symptoms of heart failure during the first 36 hours. Over 3 months, IS5MN reduced, by 76%, the increase in LVEDV (17.4 +/- 5.0 mL placebo vs 4.2 +/- 4.4 mL IS5MN, P =.0439), reversed the increase in LVESV (7.5 +/- 3.9 mL placebo vs -5.5 +/- 2.9 mL IS5MN, P =.0052), and increased the recovery of LVEF (1.9% +/- 1.3% placebo vs 6.7% +/- 1.2% IS5MN, P =.0119). Overall, 3-month mortality was 10.2%; the most frequent clinical events were new episodes of severe heart failure (18.1%), persistent hypotension (10.7%), and post-MI angina (18.1%), with no differences between treatment groups. Administration for 3 months of IS5MN combined with an ACEI, both started within 36 hours from the onset of symptoms, was safe and effective in reducing LV dilation and dysfunction after MI. The 2 ACEIs, delapril and lisinopril, appeared to be equally well tolerated.",2003.0,0,0
1212,12859160,"Effects of an angiotensin-converting enzyme inhibitor on residual renal function in patients receiving peritoneal dialysis. A randomized, controlled study.",Philip Kam-Tao Li; Kai-Ming Chow; Teresa Yuk-Hwa Wong; Chi-Bon Leung; Cheuk-Chun Szeto,"Residual renal function is an important determinant of mortality and morbidity in patients receiving peritoneal dialysis. However, few studies have evaluated therapeutic approaches for preserving residual renal function after the initiation of dialysis. To test the hypothesis that the angiotensin-converting enzyme (ACE) inhibitor ramipril slows the decline in residual renal function in patients with end-stage renal failure treated with peritoneal dialysis. Randomized, open-label, controlled trial. Single-center study in the dialysis unit of a university teaching hospital. 60 patients receiving peritoneal dialysis. Patients were randomly assigned to ramipril (5 mg daily) or no treatment. The target blood pressure was 135/85 mm Hg or less. Rate of decline in residual glomerular filtration rate (GFR) and development of complete anuria were compared among groups. Over 12 months, average residual GFR declined by 2.07 mL/min per 1.73 m2 in the ramipril group versus 3.00 mL/min per 1.73 m2 in the control group (P = 0.03). The difference between the average changes in residual GFR in the ramipril and control groups from baseline to 12 months was 0.93 mL/min per 1.73 m2 (95% CI, 0.09 to 1.78 mL/min per 1.73 m2). At 12 months, 14 patients in the ramipril group and 22 in the control group developed anuria. With intention-to-treat multivariable analysis using the Cox model, it was estimated that at 3, 6, and 9 months, patients assigned to ramipril had a higher adjusted hazard of complete anuria than did patients assigned to no treatment. Of the 25 patients who still did not have complete anuria at 12 months, those assigned to ramipril had a better prognosis than did those assigned to no treatment (adjusted hazard ratio, 0.58 [CI, 0.36 to 0.94]). The rates of death from any cause, duration of hospitalization, and cardiovascular events did not differ significantly between groups. Although the trial was small and had a limited ability to exclude effects of potential confounding factors, the angiotensin-converting enzyme inhibitor ramipril may reduce the rate of decline of residual renal function in patients with end-stage renal failure treated with peritoneal dialysis.",2003.0,0,0
1213,12860503,"Results of a pilot pharmacotherapy quality improvement program using fixed-dose, combination amlodipine/benazepril antihypertensive therapy in a long-term care setting.",Salvatore Sapienza; Patricia Sacco; Kristine Floyd; Joseph DiCesare; QuynhChau Diem Doan,"Hypertension is common in older adults (aged > or =65 years). Treatment frequently requires multiple medications and can be expensive. This study measured the impact of substituting low-dose, fixed-combination therapy using the calcium channel blocker (CCB) amlodipine and the angiotensin-converting enzyme (ACE) inhibitor benazepril for high-dose CCB monotherapy or dual therapy with a CCB and an ACE inhibitor on antihypertensive drug costs, the incidence of adverse events, and blood-pressure control. A multicenter, pilot pharmacotherapy quality improvement program was undertaken in a long-term care facility setting. Consultant pharmacists reviewed pharmacy records and medical charts from long-term care facilities, identifying older patients with a diagnosis of hypertension who either took CCB concomitantly with an ACE inhibitor or experienced adverse events on high-dose CCB therapy. Eligible patients were identified and their physicians contacted regarding switching them to fixed-dose combination therapy. A total of 51 patients at 17 facilities were switched to fixed-dose amlodipine/benazepril combination therapy; 94.1% were women and 5.9% were men (mean age, 85.1 years; range, 64-99 years). The mean number of comorbidities was 1.6. During the subsequent 2 months, mean blood pressure remained at levels similar to those at baseline. The number of patients reporting at least 1 drug-related adverse event decreased by 81.8% (P < 0.05), and the incidence of edema decreased by 75.0%. The mean per-patient cost of antihypertensive drugs decreased by 33.1% (P < 0.001), a mean per-patient savings of 19.21 US dollars per month. In patients aged > or =65 years with hypertension in long-term care facilities, a change from high-dose CCB monotherapy or CCB/ACE-inhibitor dual therapy to fixed-dose combination amlodipine/benazepril therapy significantly reduced drug costs and the incidence of adverse events and maintained blood-pressure control.",2003.0,0,0
1214,12865039,The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT): design and baseline characteristics.,BENEDICT Group,"Microalbuminuria is an early marker of diabetic nephropathy and its prevention is considered key for the primary prevention of diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and nondihydropyridine calcium channel blockers (CCBs) have specific renoprotective properties in diabetes, and preliminary evidence is available that they are more effective in combination than either of the two agents alone in limiting albuminuria either in micro- or macroalbuminuric type 2 diabetic patients. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) is a prospective, randomized, double-blind parallel-group study primarily aimed at evaluating the possibility of preventing the progression to microalbuminuria (urinary albumin excretion [UAE] rate 20-200 microg/min, i.e., incipient nephropathy) in 1209 hypertensive, type 2 diabetic patients with a normal UAE rate (<20 microg/min). During phase A of the study, patients are randomized to a 3-year treatment with one of the following: (1) a nondihydropyridine CCB (verapamil SR 240 mg/day); (2) an ACE inhibitor (trandolapril 2 mg/day); (3) the combination of the above study drugs (verapamil SR 180 mg/day plus trandolapril 2 mg/day); or (4) placebo. Phase B of the study evaluates the progression to macroalbuminuria (UAE> or =200 microg/min) in patients who progress to microalbuminuria in phase A or are found with microalbuminuria during the screening phase; these patients are randomized to a 2-year treatment with either trandolapril (2 mg/day) alone or verapamil SR (180 mg/day) plus trandolapril (2 mg/day). BENEDICT final results are expected to be available by the end of 2003 for phase A and 2 years later for phase B. The BENEDICT study, in addition to exploring whether primary prevention of diabetic nephropathy is an achievable goal, will also offer an opportunity to study prospectively risk factors of nephropathy and other chronic complications of type 2 diabetes. Here we provide an overview of the protocol and summarize the main baseline demographic, biochemical, and clinical characteristics of randomized participants.",2003.0,0,0
1215,12879551,Myalgia and arthralgia associated with enalapril and ramipril.,M P Peppers,,2003.0,0,0
1216,12882847,Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial.,Kasper Rossing; Peter Jacobsen; Lotte Pietraszek; Hans-Henrik Parving,"We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy. A total of 20 patients (17 men and 3 women) with type 2 diabetes along with hypertension and nephropathy were enrolled in this double-blind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the (51)Cr-EDTA plasma-clearance technique. During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349-1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 +/- 3/72 +/- 2 mmHg (mean +/- SE); and GFR was 77 +/- 6 ml x min(-1) x 1.73 m(-2) (mean +/- SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17-38) compared with ACEI alone (P < 0.001). There was a modest reduction in systolic/diastolic 24-h ABP of 3/2 mmHg (-2 to 8 systolic, -2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (-1 to 9) ml x min(-1) x 1.73 m(-2). Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy.",2003.0,0,0
1217,12911191,Acute renal infarction as a cause of low-back pain.,Fernando de la Iglesia; Pablo Asensio; Alejandro Díaz; Mercedes Darriba; Ricardo Nicolás; Fernando Diz-Lois,Detection of acute renal infarction is often delayed or missed because of both the rarity of the disease and its nonspecific clinical presentation. Abrupt onset of low-back pain in a patient at high risk for a thromboembolic event may be the first indication of renal infarction. We report a case of acute renal infarction and review its diagnosis and management.,2003.0,0,0
1218,12911844,Microalbuminuria and diabetic cardiovascular disease.,Richard J MacIsaac; Mark E Cooper,,2003.0,0,0
1219,12915925,"The OPTIMAAL study, not so optimal: the lessons of LIFE, RENAAL and IDNT.",Nathalie Lapointe; Ali Pourdjabbar; Jean L Rouleau,,2003.0,0,0
1220,12921816,VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context.,Eric J Velazquez; Marc A Pfeffer; John V McMurray; Aldo P Maggioni; Jean Lucien Rouleau; Frans Van de Werf; Lars Kober; Harvey D White; Karl Swedberg; Jeffrey D Leimberger; Paul Gallo; Mary Ann Sellers; Susan Edwards; Marc Henis; Robert M Califf; VALIANT Investigators,"The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin-converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin-receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) after myocardial infarction (MI). a goal of this active-control trial was to simulate conditions that would lead current practitioners to use ACEIs. Thus, we compared characteristics of VALIANT patients with those of patients in placebo-controlled trials that established ACEIs as standard treatment. We collected demographic, clinical, medication and imaging information from 14703 patients in 24 countries. This high-risk population was a median 65.8 years old, and 31.1% were female. Most (51.8%) showed imaging evidence of LVSD at enrollment. Most (72%) had Killip class>/=II HF. Patients received evidence-based therapies at rates similar to those of contemporary MI trials and at an improved rate compared with prior placebo-controlled ACEI trials. VALIANT represents the largest globally representative cohort enrolled with HF and/or LVSD after MI. Patients were similar to those in placebo-controlled ACEI trials while reflecting improvements in evidence-based care. With enrollment complete, VALIANT is poised to define the optimal strategy for renin-angiotensin system blockade after MI to improve cardiovascular outcomes.",2003.0,0,0
1221,12925048,Comparative metabolic effects of hydrochlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy.,H Krum; M Skiba; R E Gilbert,"ACE inhibitors, when used as monotherapy, are frequently unable to adequately control blood pressure in diabetic patients. A diuretic may be added; however, thiazide diuretics, but not indapamide, have been associated with adverse metabolic effects. Whether these effects also apply to thiazides when administered in the currently used lower doses, and whether they differ from indapamide in their metabolic effects, particularly when used in combination with an ACE inhibitor in diabetic patients, has not been previously studied. We conducted a prospective, randomized, open-label, blinded endpoint crossover study comparing the metabolic responses to the addition of either hydrochlorothiazide (HCTZ) or indapamide, in 18 diabetic hypertensive patients receiving ACE inhibitor monotherapy for hypertension. Patients stabilized on fosinopril 20 mg/day were randomized to receive either HCTZ 12.5 mg od or indapamide 2.5 mg od for 8 weeks, then crossed over to the alternate therapy for a further 8-week period. Blood pressure, heart rate and metabolic assessments were performed at the end of each 8-week treatment period. Seated and standing systolic and diastolic blood pressures were not different between HCTZ or indapamide when added to fosinopril, nor was the fasting lipid profile or urinary albumin : creatinine ratio. Plasma potassium was lower with indapamide compared with HCTZ treatment (indapamide 4.3+/-0.1 mmol/l; HCTZ 4.5+/-0.1 mmol/l, P<0.01) and HbA1c was higher with indapamide than with HCTZ therapy (indapamide 7.8+/-0.4%; HCTZ 7.2+/-0.3%, P<0.01). Hydrochlorothiazide 12.5 mg/day, when added to background ACE inhibitor therapy with fosinopril in hypertensive diabetic patients, resulted in a metabolic profile that was similar, if not superior on certain parameters, in comparison with indapamide 2.5 mg/day.",2003.0,0,0
1222,12925049,The albuminuric action of atrial natriuretic peptide is not modified by ACE-inhibition with perindopril in Type 2 diabetes.,K B Moore; K McKenna; W P Tormey; D McDonald; C J Thompson,"Atrial natriuretic peptide (ANP) increases urine albumin excretion (UAER) in humans with Type 1 diabetes. The aim of this study was to establish if ANP increases UAER in microalbuminuric subjects with Type 2 diabetes and to examine whether the albuminuric action of ANP was inhibited by pre-treatment with the ACE-inhibitor perindopril. Seven microalbuminuric, normotensive males with Type 2 diabetes were entered into a randomised, double-blind, three-armed study of (i) intravenous infusion of ANP (0.25 microg/kg/min in 0.9% NaCl) after 3 weeks' pre-treatment with placebo, (ii) intravenous infusion of vehicle (0.9% NaCl only) after 3 weeks' pre-treatment with placebo, or (3) intravenous infusion of ANP (0.25 microg/kg/min in 0.9% NaCl) after 3 weeks' pre-treatment with perindopril, 4 mg daily. Baseline parameters were similar on all three study days. During the placebo/vehicle arm there was no change in urine flow rate (UFR, P=0.61), urine cyclic guanosine monophosphate (UcGMP P=0.48) or UAER (P=0.99). During the placebo/ANP arm there was a rise in UFR [13.7+/-2.8 (mean+/-sd) to 25.7+/-7.7 mL/min, P<0.001], UcGMP (60.0+/-36.6 to 160.8+/-118.5 micromol/mmolCr, P=0.045) and UAER [5.13 [2.4-11.6][median (range)] to 71.6 [21.6-175.1] mg/mmolCr, P<0.001]. Pre-treatment with perindopril did not alter the changes in UFR (P=0.63), UcGMP (P=0.46) or UAER (P=0.99) to infusion of ANP, compared with the placebo/ANP arm. ANP increases UAER in microalbuminuric patients with Type 2 diabetes and the albuminuric action of ANP is not inhibited by pre-treatment with the ACE inhibitor perindopril.",2003.0,0,0
1223,12943892,Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension.,Kazuo Eguchi; Kazuomi Kario; Kazuyuki Shimada,"We performed a prospective crossover study in 73 essential hypertensives to compare the effects of candesartan and lisinopril on ambulatory blood pressure (BP) and early-morning BP. Twenty-four-hour ambulatory BP monitoring was performed at baseline and for each active treatment. Small doses of thiazide diuretic were added as needed. The effects of both drugs on 24-hour BP were almost identical and satisfactory. When we classified patients into the morning surge group (the highest quartile of morning systolic BP surge >36 mm Hg) and the non-morning surge group (the remaining 3 quartiles of morning BP surge), candesartan was superior in decreasing morning BP and morning BP surge.",2003.0,0,0
1224,12946547,"A randomized, double-blind, controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus.",Giuseppe Derosa; Arrigo F G Cicero; Leonardina Ciccarelli; Roberto Fogari,"When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered. The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period. Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed. Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m(2) in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m(2) in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05). Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population.",2003.0,0,0
1225,12948426,A comparison of outcomes with angiotensin-converting enzyme inhibitors and diuretics for hypertension in the elderly.,Norman M Kaplan; Donald G Vidt,,2003.0,0,0
1226,12948427,Angiotensin-converting enzyme inhibition or angiotensin receptor blockade in hypertensive diabetics?,Gozewÿn Laverman; Piero Ruggenenti; Giuseppe Remuzzi,"Hypertension increases the renal and cardiovascular risks in diabetic patients. The beneficial effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on renal and cardiovascular outcomes are discussed in this paper, with a particular focus on their optimal use in the hypertensive diabetic patient, with or without evidence of renal or cardiovascular disease. Although the mechanism of action of the two drug classes is not entirely similar, there is no evidence of differences in their clinical effects. Importantly, the achieved risk reduction with either drug is not similar across subsets of diabetic patients. Overt nephropathy of type 2 diabetes appears poorly responsive even to maximized renin-angiotensin system inhibition. This urgently calls for new interventions that may decrease renal and cardiovascular risk through other mechanisms than blood pressure lowering alone. Improving the outcome of type 2 diabetics is the major clinical challenge for the beginning of the third millennium.",2003.0,0,0
1227,12948433,"Clinical trials report. Chronic kidney disease: blood pressure, treatment goals, and cardiovascular outcomes.",Matthew R Weir,,2003.0,0,0
1228,12948434,RAAS escape: a real clinical entity that may be important in the progression of cardiovascular and renal disease.,Jay Lakkis; Wei X Lu; Matthew R Weir,"Interruption of the renin-angiotensin-aldosterone system (RAAS) at different levels is target-organ protective in several disease states; however, complete blockade is unlikely to be achieved due to escape mechanisms whenever blockade is attempted, incomplete knowledge of the role of all elements of the RAAS, and lack of pharmacotherapy against some elements that have been shown to contribute to disease states. Aldosterone has been overlooked as a mediator of RAAS escape and a key factor in target-organ injury despite the use of available RAAS blockers. Aldosterone is thought to play a role in the development of hypertension, alteration in vascular structure, vascular smooth muscle hypertrophy, endothelial dysfunction, structural renal injury, proteinuria, left ventricular remodeling, collagen synthesis, and myocardial fibrosis. Aldosterone receptor antagonists have been shown to antagonize all these effects in experimental models. Clinical trials with aldosterone antagonists showed an improvement in survival and left ventricular mass index in patients with congestive heart failure, and a reduction in urinary protein excretion and left ventricular mass index in patients with type 2 diabetes and early nephropathy who developed aldosterone synthesis escape. Consequently, aldosterone receptor antagonists may have specific benefits for reducing target-organ injury, particularly if there is evidence of RAAS escape.",2003.0,0,0
1229,12948435,How high should an ACE inhibitor or angiotensin receptor blocker be dosed in patients with diabetic nephropathy?,Marc S Weinberg; Nicholas Kaperonis; George L Bakris,"Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), two drug classes that effectively block the actions of the renin-angiotensin system (RAS), have unique capabilities as antihypertensive agents. Recent landmark clinical trials have demonstrated their important roles as primary therapy for the prevention of renal disease in diabetes. The optimal dosage of these RAS blockers required to slow the progression of renal disease or impair the development of cardiovascular risk is not known. However, data from many studies strongly support the use of the higher doses of ACE inhibitors or ARBs to reduce proteinuria. All studies of kidney disease progression demonstrate benefit on slowing only when blood pressure is reduced when using higher doses. In order to accrue the optimum benefit from ACE inhibitors and ARBs, the dose-response relationship for diabetic renal disease will have to be determined. The best strategy, ie, supramaximal doses of ACE inhibitors or ARBs or combining them, is still a matter of debate but may be resolved soon by results of ongoing studies.",2003.0,0,0
1230,12948437,Use of calcium antagonists in renal patients: therapeutic benefit or medical malpractice?,Douglas A Nigbor; Julia B Lewis,"In patients with kidney disease, control of hypertension is paramount in helping to slow down the progression of both diabetic and nondiabetic nephropathy. A significant amount of data have been published that suggest blockade of the renin-angiotensin system should be considered as first-line therapy for patients with kidney disease. Meanwhile, some studies have suggested that the use of calcium channel blockers may have deleterious effects on patients with kidney disease. This manuscript reviews the renal outcomes of trials in which calcium channel blockers were included in the management of patients with and without kidney disease. The data suggest that agents that block the renin-angiotensin system are superior to calcium channel blockers in protecting against progressive kidney disease. However, there is no conclusive evidence that calcium channel blockers are injurious to the kidney, and they may be particularly beneficial in post-renal transplant patients.",2003.0,0,0
1231,12962336,Predicting survival in cost-effectiveness analyses based on clinical trials.,Ulf G Gerdtham; Niklas Zethraeus,"This study deals with the question of how to model health effects after the cessation of a randomized controlled trial (RCT). By using clinical trial data on severe congestive heart failure patients, we illustrate how survival beyond the cessation of an RCT can be predicted based on parametric survival models. In the analysis, we compare predicted survival and the resulting incremental cost-effectiveness ratio (ICER) of different survival models with actual survival/ICER. Our main finding is that the results are sensitive to the choice of survival model and that an extensive sensitivity analysis in the CE analysis is required.",2003.0,0,0
1232,12963858,Treatment of hypertension in older patients: an updated look at the role of calcium antagonists.,John B Kostis,"Hypertension is common in adults aged 60 years or older. Apart from age, hypertension is the most powerful predictor of cardiovascular end-organ damage and its associated morbidity and mortality. Although diastolic blood pressure is regarded as an important risk factor, it is now clear that systolic blood pressure, especially prevalent among older adults, is a better predictor of cardiovascular morbidity and mortality. Fewer than 30% of hypertensive patients have blood pressure levels controlled to <140/90 mm Hg as recommended by current guidelines. Controlled trials have demonstrated the benefits of lowering blood pressure for all hypertensive individuals, including those aged 65 years or older. Calcium antagonists of the dihydropyridine subclass, which include nifedipine, amlodipine, felodipine, and nitrendipine, as well as other drug classes, are potent antihypertensive agents that may be suitable for treatment of hypertension in older adults. However, as with all antihypertensive agents, adverse effects may limit their use; peripheral edema is particularly troublesome for dihydropyridines. Newer dihydropyridine calcium antagonists expected to be approved for use soon, including lercanidipine and lacidipine, have been associated with efficacy comparable to currently available calcium antagonists but with a lower incidence of adverse effects, especially ankle edema. Antihypertensive agents with improved tolerability profiles offer the potential for improved blood pressure control.",2003.0,0,0
1233,1341608,Low-dose angiotensin converting enzyme inhibitors: effect on renal function in normo- and hypertensive type 1 diabetic patients.,A Ciavarella; A Mustacchio; A Silletti; R Franchi; M Levorato; C Campieri; L C Borgnino; G Capozzi; L Morotti; P Vannini,"To investigate the effect of low doses of the angiotensin converting enzyme inhibitor enalapril on renal haemodynamics and albuminuria in normotensive and hypertensive type 1 (insulin-dependent) diabetic patients with incipient or overt nephropathy. Twenty-two type 1 (insulin-dependent) diabetic patients with persistent microalbuminuria or macroalbuminuria and normal serum creatinine were studied. Of all patients, 16 males and 6 females, age 45 +/- 13 years, diabetes duration 19 +/- 11 years, insulin dose 38 +/- 11 U/day, 10 were normotensive and 12 were hypertensive. After 3 months of run-in period the patients were assigned to treatment with 5 mg or 10 mg enalapril based on the presence of normotension or hypertension respectively. Before and after 6 months of treatment, renal function was assessed by evaluation of glomerular filtration rate (99m Tc-DTPA), renal plasma flow (131-I iodohippurate), filtration fraction and renal vascular resistance. Mean arterial pressure, albumin excretion rate, urinary urea excretion and glycated haemoglobin were also determined. Administration of enalapril resulted in both groups of patients in a significant fall in mean arterial pressure, albumin excretion rate, glomerular filtration rate, filtration fraction, and renal vascular resistance. Decreasing albumin excretion did not correlate with a drop in systemic blood pressure or filtration fraction. No significant variations were observed in renal plasma flow, in urinary urea excretion or in glycated haemoglobin. Our results suggest that low doses of enalapril are effective in influencing renal haemodynamics and reducing urinary albumin excretion in both normotensive and hypertensive type 1 (insulin-dependent) diabetic patients with incipient or overt nephropathy. The lowering effect of the angiotensin converting enzyme inhibitor on albuminuria seems to be independent of the action on systemic blood pressure and renal haemodynamic changes.",1992.0,0,0
1234,1345049,"Effect of ketoprofen on blood pressure, endocrine and renal responses to chronic dosing with captopril in patients with essential hypertension.",J R Cusson; P du Souich; P Le Morvan; G Thibault; R Phillips; A Milot; P Larochelle,"The effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the blood pressure and renal function of essential hypertensive patients depend on the specific type of NSAID and antihypertensive drug administered. Twelve patients with essential hypertension, aged 35 to 59 years, stabilized (blood pressure less than 140/90 mmHg) with captopril, received ketoprofen (100 mg bid for 7 days) or matching placebo in a randomized double-blind cross-over fashion. A 3-week wash-out period was included between treatment periods. Blood pressure on the first and last days of the placebo treatment period (137 +/- 7 (SD)/80 +/- 8 and 139 +/- 11/81 +/- 9 mmHg) was similar to respective values during ketoprofen therapy (136 +/- 10/79 +/- 7 and 143 +/- 10/81 +/- 9 mmHg). The mean differences in systolic and diastolic blood pressures, at the end of the treatment periods, between ketoprofen and placebo were 4 (95% confidence intervals -5, +13) and 0 (-8, +8) mmHg, respectively. Ketoprofen had no effect on 24-h urinary sodium excretion (160 +/- 33 and 147 +/- 39 mmol/24 h for ketoprofen and placebo, respectively). Ketoprofen was without effect on glomerular filtration rate, renal plasma flow and filtration fraction. In conclusion, our data suggest that ketoprofen is a safe choice when short-term treatment with a NSAID is indicated in an essential hypertensive patient treated with a converting enzyme inhibitor such as captopril.",1992.0,0,0
1235,1345141,Hypertensive retinal vascular changes: relationship to left ventricular hypertrophy and arteriolar changes before and after treatment.,B Dahlöf; S Stenkula; L Hansson,"Eye-ground-photos were taken in twenty-eight previously untreated men with mild to moderate essential hypertension. The same eye was evaluated before and after 26 weeks of double-blind treatment with Enalapril or Hydrochlorothiazide. The vascular changes were assessed by using a more elaborate and refined grading than the Keith-Wagener-Barker scale. All photos were examined by the same observer without knowledge of blood pressure, type of treatment or the order in which the photos had been taken. There were significant positive correlations between the vascular alterations in the retina in the untreated state and left ventricular wall thickness (echocardiography), minimal vascular resistance in the calf (plethysmography) and blood pressure respectively. Treatment with Enalapril decreased the reflection of the retinal arterial wall significantly and reduced the narrowing of arteries and arterio-venous crossing phenomena non-significantly. Hydrochlorothiazide did not affect any of the retinal vascular changes. It can be concluded that this relatively simple technique of evaluating eye-ground-photos with a new grading scale, when used in non-malignant hypertension, gives a useful assessment of the degree of hypertensive target organ damage in the retina as well as in other important target organs, i.e. the heart and vascular beds. In addition, Enalapril positively affects hypertensive retinopathy in contrast to Hydrochlorothiazide, reflecting what happens to structural cardiovascular changes in the rest of the body.",1992.0,0,0
1236,1345260,Ambulatory blood pressure monitoring. A tool for more comprehensive assessment.,I Enström-Granath,"To investigate the usefulness of more comprehensive blood pressure measurements, made during daily life, in the diagnosis and treatment of hypertension. A blood pressure screening was carried out in middle-aged men and women in Kävlinge, a municipality in southern Sweden. Subjects were classified according to Swedish standard criteria. Ambulatory blood pressure (amb-BP) was recorded in a random sample of normotensives and borderline hypertensives as well as in all the untreated hypertensives identified at screening and willing to participate. A subgroup of borderline hypertensives also carried out self-measurements of blood pressure (self-BP) both at work and at home. The blood pressure lowering efficacy of atenolol 50 mg o.d. and enalapril 20 mg o.d. was compared in hypertensives at rest, during 24 hours, and during dynamic and isometric exercise. The efficacy of enalapril and lisinopril (two ACE inhibitors with different durations of action) were also compared, with special focus on the early morning hours. Men and women classified as normotensives clearly differed from those with hypertension, also when blood pressure was recorded with ambulatory technique. The number of correctly classified subjects did not differ between self-BP and office-BP; combining the two added little. Atenolol reduced blood pressure better during dynamic exercise than did enalapril, while there was no significant difference in effect between enalapril and lisinopril, not even 18-24 hours post-dose. More comprehensive blood pressure measurements should be considered in the evaluation of hypertension treatment. Office BP, however, seems a reasonably good tool for diagnosing hypertension.",1992.0,0,0
1237,1345261,Structural cardiovascular changes in essential hypertension. Studies on the effect of antihypertensive therapy.,B Dahlöf,"These studies were undertaken to evaluate different manifestations of structural cardiovascular changes and the effects of antihypertensive therapy in essential hypertension. A meta-analysis of 109 studies that had examined the effect of different pharmacological blood pressure lowering regimens on left ventricular structure, examined by echocardiography, was undertaken to increase the statistical power, to resolve uncertainty and to improve the accuracy of estimation of the magnitude of effect. Strict preset criteria were applied. The effect of different drugs in monotherapy and in particular first line antihypertensive therapies were compared, using an analysis of covariance (ANCOVA). ACE-inhibitors, beta-blockers and calcium antagonists all reduced left ventricular mass (LVM) through a reduction in wall hypertrophy, the effect being most pronounced with ACE-inhibitors. Conversely, diuretics reduced LVM mainly through a reduction of left ventricular volume. Previously untreated males (n = 28, 86 kg, 46 years, 27 kg/m2) with non-malignant essential hypertension (supine diastolic blood pressure (DBP) > 95 mmHg 3-4 times (in triplicate) on placebo) were randomized to long-term double-blind treatment with enalapril (E) or hydrochlorothiazide (H). There were no significant differences between the groups at baseline. Vascular alterations in the retina (eyeground photo, refined grading), cardiac morphology (M-mode echocardiography, ASE), structural vascular changes of the hand (plethysmography, minimal resistance (Rmin)), total peripheral resistance ((TPR), calculated from dye-dilution) and blood pressure (intraarterial) were significantly interrelated at baseline except LVM and Rmin. After 6 months of therapy, E reduced the signs of vascular changes in the retina as well as Rmin in the hand circulation, while H did not change or increased these structural vascular changes. The blood pressure lowering effect of E (mainly through lowering of TPR) tended to be more pronounced, measured both intraarterially and indirectly, than that seen with H (mainly through lowering of cardiac output), however, there were no significant differences. LVM decreased progressively with E while the effect of H was non-significant. E reduced wall thickness but not left ventricular diameter and also improved left ventricular distensibility significantly. The effect on cardiac morphology was significantly different between therapies when taking change in blood pressure into account. After the longest follow-up on monotherapy (18 months) E had reduced LVM by 2.7 g/mmHg and H (14 months) by 1.3 g/mmHg (significant for E only). In univariate analysis the changes in cardiovascular structure were significantly related to the changes in the Renin-Angiotensin-Aldosterone System (RAAS).(ABSTRACT TRUNCATED AT 400 WORDS)",1992.0,0,0
1238,1366257,Comparison between enalapril and lisinopril in mild-moderate hypertension: a comprehensive model for evaluation of drug efficacy.,I Enström; T Thulin; L H Lindholm,"The objective of this study was to compare enalapril with lisinopril in terms of blood pressure control at rest, during dynamic exercise test, during isometric exercise test, and during 24 h--with special focus on blood pressure control during the morning hours, 18-24 h post-dose. Furthermore, we compared ACE activity in serum before and after 4 weeks of drug treatment. A four-week double-blind, randomized parallel group study compared enalapril 20 mg o.d. with lisinopril 20 mg o.d. preceded by a 4-week single blind run-in period on placebo. Fifty-eight patients (49 males and 9 females, mean age 50.9) were recruited and 56 completed the study. Blood pressures at randomization were 161/108 and 164/106 for the enalapril and the lisinopril subjects, respectively. Echo: LVPWd 9.5 (normal range 6-12 mm) and IVSd 10.3 mm (normal range 6-12 mm). ANCOVA. Enalapril and lisinopril were equally effective in lowering blood pressure at rest, during dynamic and isometric exercise as well as during 24 h. The attained blood pressure levels during the early morning hours were for enalapril treatment 119/76 and 121/76 mmHg for lisinopril treatment. The ACE activity in serum 24 h post-dose was lower (p < 0.001) after treatment with lisinopril 8.0 (SD 3.3) mumol/min/1 than with enalapril 16.1 (SD 6.0). The corresponding values for placebo were 18.8 (SD 4.6) and 17.8 (SD 5.7). No difference was found in blood pressure lowering efficacy between enalapril and lisinopril even though the blood pressure changes were evaluated in a more comprehensive way than in earlier studies of these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)",1992.0,0,1
1239,13678865,Should all patients with coronary disease receive angiotensin-converting-enzyme inhibitors?,Harvey D White,,2003.0,0,0
1240,13678872,"Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).",K M Fox; EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators,"Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease.",2003.0,0,0
1241,14517164,"Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: the 4E-left ventricular hypertrophy study.",Bertram Pitt; Nathaniel Reichek; Roland Willenbrock; Faiez Zannad; Robert A Phillips; Barbara Roniker; Jay Kleiman; Scott Krause; Daniel Burns; Gordon H Williams,"Elevated renin-angiotensin-aldosterone system activity correlates with left ventricular hypertrophy (LVH) and cardiovascular risk, but the relative contributions of angiotensin II and aldosterone remain unclear. This study compared LVH regression during treatment with the selective aldosterone blocker eplerenone, enalapril, and their combination in patients with hypertension. A 9-month, double-blind, randomized study was performed in 202 patients with LVH and hypertension who received eplerenone 200 mg daily, enalapril 40 mg daily, or eplerenone 200 mg and enalapril 10 mg daily. At week 8, hydrochlorothiazide 12.5 to 25 mg and/or amlodipine 10 mg was added if diastolic blood pressure was >90 mm Hg. Change in left ventricular (LV) mass as assessed by MRI was the primary end point. Change in blood pressure, renin-angiotensin-aldosterone system hormones, albuminuria, and safety were also assessed. Eplerenone significantly reduced LV mass from baseline (-14.5+/-3.36 g; n=50) similarly to enalapril (-19.7+/-3.20 g; n=54; P=0.258), but eplerenone/enalapril (-27.2+/-3.39 g; n=49) was more effective than eplerenone alone (P=0.007). All treatments reduced systolic blood pressure and diastolic blood pressure from baseline (eplerenone, -23.8 and -11.9 mm Hg; enalapril, -24.7 and -13.4 mm Hg; and eplerenone/enalapril, -28.7 and -14.4 mm Hg, P=0.048, in systolic blood pressure compared with eplerenone alone). Cough was more common with enalapril than with eplerenone (P=0.033), and elevated potassium was more common with eplerenone. Eplerenone was as effective as enalapril in LVH regression and blood pressure control. The combination of eplerenone and enalapril was more effective in reducing LV mass and systolic blood pressure than eplerenone alone.",2003.0,0,0
1242,14522567,"Comparative impact of enalapril, candesartan or metoprolol alone or in combination on ventricular remodelling in patients with congestive heart failure.",Robert S McKelvie; Jean-Lucien Rouleau; Michel White; Rizwan Afzal; James B Young; Aldo P Maggioni; Peter Held; Salim Yusuf,"RESOLVD study patients were randomized to candesartan (C), enalapril (E), or C+E. Patients were later randomized to metoprolol CR (M) or placebo. Examine impact of C or E (C/E), C+E, C+M/E+M, C+E+M on ventricular remodelling in heart failure (HF) over 43 weeks. Four hundred and twenty-six of 768 patients receiving C, E, or C+E were randomized to either M or placebo. Patients were New York Heart Association class II-IV, ejection fraction (EF) <0.40 and 6-min walk distance <500 m. Ejection fraction (EF), cardiac volumes, blood pressures, heart rates, and neurohormones were measured. End diastolic volumes changed +29.4+/-6.4 ml for C/E, +16.6+/-10.4 ml for C+E, +19.7+/-6.5 ml for C+M/E+M, and -6.4+/-7.5 ml for C+E+M (P< or =0.01). End systolic volumes changed +22.9+/-5.8 ml for C/E, +11.9+/-9.1 ml for C+E, +6.0+/-5.7 ml for C+E/E+M, and -16.5+/-7.0 ml for C+E+M (P< or =0.001). Ejection fraction changed +0.01+/-0.01 for C/E, +0.01+/-0.01 for C+E, +0.03+/-0.01 for C+M/E+M, and +0.05+/-0.01 for C+E+M (P< or =0.0001). No significant differences for blood pressure or neurohormones; heart rate for C+M/E+M and C+E+M decreased (P< or =0.01) vs C/E or C+E. C+E+M had a modest but beneficial effect on cardiac function compared to the other groups. Combination of C+E+M has potential for providing HF patients with further benefit.",2003.0,0,0
1243,14527106,Effects of protocol-driven care versus usual outpatient clinic care on survival rates in patients with type 2 diabetes.,Wing Yee So; Peter C Y Tong; Gary T C Ko; Wilson Y S Leung; Chun-Chung Chow; Vincent T F Yeung; Wing-Bun Chan; Julian A J H Critchley; Clive S Cockram; Juliana C N Chan,"To determine whether clinical outcomes in patients with type 2 diabetes were improved by protocol-driven care in a Diabetes Centre compared with usual outpatient care. Descriptive analysis of a prospective cohort. During a median 7-year observational period, 91 patients with type 2 diabetes and no cardiovascular or renal complications were monitored by a nurse and a diabetologist in a clinical trial setting according to a structured protocol. Another 81 patients with comparable clinical characteristics were monitored by generalists at the medical clinic in the same hospital. Clinical end points, defined as death and cardiovascular and renal events, were evaluated in 1997 by review of case records. Patients receiving structured care had lower mortality (relative risk [RR] = 0.21; 95% confidence interval [CI] = 0.07, 0.65; P = .006) than the usual-care group, as well as a lower incidence of combined clinical end points (RR = 0.43; 95% CI = 0.22, 0.84; P = .01). In the usual-care group, patients who had no monitoring of glycosylated hemoglobin or plasma lipid levels during the entire observational period (8.6%) had a 14.6-fold (P < .01) and 15.7-fold (P < .01) increased risk of death and combined clinical end points, respectively, compared with those who had at least one measurement (60.5%). Management by protocol-driven care model improved survival and clinical outcomes in patients with type 2 diabetes. Definitive studies are required to confirm these findings and compare the cost effectiveness of these care models.",2003.0,0,0
1244,14587650,Effects of spironolactone and metoprolol on QT dispersion in heart failure.,Mehmet Akbulut; Yilmaz Ozbay; Erdoğan Ilkay; Ilgin Karaca; Nadi Arslan,"The effects of spironolactone or metoprolol added to a conventional treatment protocol on QT dispersion, which is accepted as a sudden cardiac death predictor, were evaluated in heart failure patients.? A total of 105 New York Heart Association class III patients were included in this study. The conventional treatment protocol was standardized by giving ramipril, furosemide, and digoxin to all patients for 3 weeks at the same doses. At the end of this period, the patients were divided into three groups. Conventional treatment was continued in group 1, 25 mg spironolactone was added in group 2, and 12.5 mg metoprolol was added in group 3. Patients were followed for 12 weeks and clinical and laboratory tests were conducted at 3 week intervals. No significant change in corrected QT dispersion was observed in group 1 at the end of 12 weeks (corrected QT dispersion: 80 +/- 2 msc to 79 +/- 2 msc, P: 0.22). However, corrected QT dispersion in group 2 was reduced by 32.5% (83 +/- 2 msc to 56 +/- 1 msc; P: 0.01). A 32.9% reduction in corrected QT dispersion (79 +/- 2 msc to 53 +/- 2 msc; P: 0.01) was observed in group 3. In conclusion, the addition of spironolactone or metoprolol to a conventional treatment in heart failure patients resulted in improved clinical conditions and the significant decrease in sudden death predictors corrected QT dispersion. The effects of spironolactone and metoprolol on corrected QT dispersion were similar.",2003.0,0,0
1245,14597462,"ALLHAT, or the soft science of the secondary end point.",Franz H Messerli,"The recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed that the primary end point, coronary heart disease, was identical in the chlorthalidone, lisinopril, and amlodipine groups. Yet the major conclusion of this trial was that thiazide diuretics are superior in preventing 1 or more major forms of cardiovascular disease and should be preferred for first-line antihypertensive therapy. This conclusion was based solely on an analysis of secondary end points and cost. As evidenced by the dictum to ""use thiazides for most patients with uncomplicated hypertension"" in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, this interpretation of ALLHAT broadly adumbrated these guidelines. Although diuretics will rightfully remain a cornerstone in antihypertensive therapy, we should remember (as we were told by the ALLHAT investigators) that secondary end points are ""soft data"" that should not form a basis for main conclusions or lead to a labeling of a drug class as preferred.",2003.0,0,0
1246,14600713,[Drug therapy in secondary prophylaxis after transient cerebral ischemia or cerebral infarction].,Rolf Salvesen,"Stroke is the third leading cause of death in western countries and the leading cause of dependence in activities of daily living. Efforts to reduce its prevalence should therefore be given the highest priority. Uncertainty prevails as to the significance of the various types of intervention. This review is based on personal experience, though mostly on a search for relevant literature in the Cochrane Library. Important measures are treatment of hypertension with target area 140/90 mm Hg, anticoagulation in patients with atrial fibrillation and other potential sources of cardioemboli, and for the remainder antiplatelet agents in the form of acetylsalicylic acid, probably preferably combined with dipyradimole. One should also consider drugs reducing serum lipids. Adequate secondary prophylaxis after transient ischaemic attack (TIA) or ischaemic stroke is of potential great benefit in reducing the incidence of new stroke, myocardial infarction or premature vascular death. Standardised guidelines may facilitate implementation of these measures, if they are regularly updated and adjusted to the needs of the individual patient.",2003.0,0,0
1247,14608527,Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients.,Dilek Yavuz; Mehmet Koç; Ahmet Toprak; Ihsan Akpinar; Ayliz Velioğlu; Oguzhan Deyneli; Goncagül Haklar; Sema Akalin,"Disturbed endothelial function is closely associated with hyperinsulinaemia and insulin resistance in essential hypertension. The aims of this study were: 1) to evaluate whether the two alternative drugs, angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (Ang II) antagonists, had comparable effects on glucose metabolism and endothelial function. 2) to determine whether they improve endothelial dysfunction through modulating insulin resistance and oxidative stress. Essential hypertensive patients were randomised into two groups: Twelve (nine patients in final analysis) patients were given enalapril (enalapril group), and twelve (nine patients in final analysis) were given losartan (losartan group). Twelve sex- and age-matched normotensive volunteers were included as controls. Before and after six months of treatment, endothelial function, insulin sensitivity and lipid peroxidation (TBARs) and NO metabolites (NOx) were evaluated. Endothelial function, measured as flow mediated dilatation (FMD), was improved in both of the treatment groups (p=0.0001). Calculated insulin sensitivity index also improved in the enalapril-treated group (p=0.05) but not in the losartan-treated group, compared with baseline levels. TBARS values decreased significantly in the enalapril group compared with baseline levels (p<0.001). FMD was positively correlated with insulin sensitivity index (r=0.32, p<0.05) and NOx levels (r=0.39, p=0.01) and negatively correlated with TBARS levels (r=-0.53, p=0.0002) in hypertensive patients. Inhibition of the renin-angiotensin system, either with ACE inhibitors or AT(1)-receptor blockers improves endothelial dysfunction. ACE inhibition has prominent effects on improving insulin sensitivity and decreasing oxidative stress in essential hypertensive patients.",2003.0,0,0
1248,14610160,"Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.",Marc A Pfeffer; John J V McMurray; Eric J Velazquez; Jean-Lucien Rouleau; Lars Køber; Aldo P Maggioni; Scott D Solomon; Karl Swedberg; Frans Van de Werf; Harvey White; Jeffrey D Leimberger; Marc Henis; Susan Edwards; Steven Zelenkofske; Mary Ann Sellers; Robert M Califf; Valsartan in Acute Myocardial Infarction Trial Investigators,"Angiotensin-converting-enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartan-and-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.",2003.0,0,0
1249,14657064,A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial.,Carl J Pepine; Eileen M Handberg; Rhonda M Cooper-DeHoff; Ronald G Marks; Peter Kowey; Franz H Messerli; Giuseppe Mancia; José L Cangiano; David Garcia-Barreto; Matyas Keltai; Serap Erdine; Heather A Bristol; H Robert Kolb; George L Bakris; Jerome D Cohen; William W Parmley; INVEST Investigators,"Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients, safety and efficacy of antihypertensive agents for coronary artery disease (CAD) have been discerned only from subgroup analyses in large trials. To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy (CAS) or a non-calcium antagonist strategy (NCAS). Randomized, open label, blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older, which was conducted September 1997 to February 2003 at 862 sites in 14 countries. Patients were randomly assigned to either CAS (verapamil sustained release) or NCAS (atenolol). Strategies specified dose and additional drug regimens. Trandolapril and/or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than 90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85 mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. Primary: first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse experiences, hospitalizations, and blood pressure control at 24 months. At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%) were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%) were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113 (52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years (mean, 2.7 years per patient), 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies (9.93% in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval [CI], 0.90-1.06). Two-year blood pressure control was similar between groups. The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5% (diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients. A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients.",2003.0,0,0
1250,7475056,Insulin sensitivity in obese hypertensive dyslipidemic patients treated with enalapril or atenolol.,Y Morel; A Gadient; U Keller; L Vadas; A Golay,"We evaluated the effects of enalapril [angiotensin converting enzyme (ACE) inhibitor] in comparison with atenolol (beta-blocker) on insulin sensitivity and serum lipoprotein concentration in obese hypertensive dyslipidemic patients. Twenty-eight hypertensive [mean blood pressure (MAP) 152 +/- 3/103 +/- 1 mm Hgl], obese [mean body mass index (BMI) 30 + 1 kg/m2A], dyslipidemic [total triglycerides 2.0 +/- 0.2 mM and/or high density lipoprotein (HDL) cholesterol 1.1 +/- 0.1 mM and low density lipoprotein (LDL) cholesterol 4.5 +/- 0.2 mM] outpatients were randomized in two groups receiving enalapril or atenolol for 12 weeks, in an investigator-blinded, parallel, comparative two-center trial. Insulin sensitivity was assessed by a modified insulin suppression test. Blood pressure (BP), insulin sensitivity, and serum lipoprotein concentrations were compared before and after each treatment and between the two treated groups. BP decreased significantly and comparably during enalapril and atenolol treatment (p < or = 0.01). The sensitivity to insulin improved by 15% (p = 0.03) in the enalapril group and worsened by 17% (p < or = 0.01) in the atenolol group. Serum lipoprotein concentrations were not modified by any treatment. The improvement in insulin sensitivity caused by enalapril treatment appears to be an advantage as compared with atenolol treatment in hypertensive obese and dyslipidemic patients, whereas the BP-lowering efficacy of the two drugs is similar. Because this effect has been reported with other ACE inhibitors, it appears to be characteristic of the entire class of ACE inhibitors.",1995.0,0,0
1251,7475338,Diagnosis and outpatient management of congestive heart failure.,B L Karon,"Congestive heart failure causes substantial patient morbidity and mortality in the United States. Symptoms and physical findings can be helpful in diagnosis but have limited sensitivity and specificity. Objective measurement of ventricular function is essential in virtually all patients in whom a diagnosis of heart failure is suspected. Reversible causes of heart failure must be sought. Outpatient management includes education and counseling, emphasis on and assessment of compliance with diet, and pharmacologic treatment. Angiotensin-converting enzyme inhibitors are the mainstay of treatment but are underused, and maximal doses are not given apparently because of concern about side effects. Diuretic therapy should be administered only as needed to manage fluid overload. Calcium channel blockers are relatively contraindicated in patients with impaired ventricular function. Patient follow-up should be guided by the results of the medical history and physical examination. Routine serial testing of ventricular function and exercise performance is discouraged.",1995.0,0,0
1252,7477219,A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group.,L Køber; C Torp-Pedersen; J E Carlsen; H Bagger; P Eliasen; K Lyngborg; J Videbaek; D S Cole; L Auclert; N C Pauly,"Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces mortality among survivors of acute myocardial infarction, but whether to use ACE inhibitors in all patients or only in selected patients is uncertain. We screened 6676 consecutive patients with 7001 myocardial infarctions confirmed by enzyme studies. A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction (ejection fraction, < or = 35 percent). On days 3 to 7 after infarction, 1749 patients were randomly assigned to receive oral trandolapril (876 patients) or placebo (873 patients). The duration of follow-up was 24 to 50 months. During the study period, 304 patients (34.7 percent) in the trandolapril group died, as compared with 369 (42.3 percent) in the placebo group (P = 0.001). The relative risk of death in the trandolapril group, as compared with the placebo group, was 0.78 (95 percent confidence interval, 0.67 to 0.91). Trandolapril also reduced the risk of death from cardiovascular causes (relative risk, 0.75; 95 percent confidence interval, 0.63 to 0.89; P = 0.001) and sudden death (relative risk, 0.76; 95 percent confidence interval, 0.59 to 0.98; P = 0.03). Progression to severe heart failure was less frequent in the trandolapril group (relative risk, 0.71; 95 percent confidence interval, 0.56 to 0.89; P = 0.003). In contrast, the risk of recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk, 0.86; 95 percent confidence interval, 0.66 to 1.13; P = 0.29). Long-term treatment with trandolapril in patients with reduced left ventricular function soon after myocardial infarction significantly reduced the risk of overall mortality, mortality from cardiovascular causes, sudden death, and the development of severe heart failure. That mortality was reduced in a randomized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infarction.",1995.0,1,1
1253,7484820,Physical working capacity after acute myocardial infarction in patients with low ejection fraction and effect of captopril.,L H Hartley; G Flaker; L Basta; F Menapace; S Goldman; B Davis; P Hamm; G Lamas; L Moye; C C Wun,"Previous studies after acute myocardial infarction (AMI) have reported conflicting results on the effects of angiotensin-converting enzyme inhibition on physical working capacity. In an effort to provide more insight into this subject, we examined the effects of captopril on working capacity of patients who had low ejection fractions but no congestive heart failure after AMI. One hundred sixty-six participants were recruited from 5 centers after randomization to either captopril or placebo for the Survival and Ventricular Enlargement study. Upright cycle ergometer tests were performed with continuous measurements of respiratory gases at 4, 12, and 24 months after AMI. Our study concurs with 2 of 3 previous post-AMI studies and supports the conclusion that working capacity is not affected by angiotensin-converting enzyme inhibition at 4 or 12 months after AMI in patients without congestive heart failure. In addition, no significant effect of captopril was noted at 24 months after AMI. Peak oxygen uptake tended to decrease between 12 and 24 months in the placebo group by an average (+/- SD) of -22 +/- 322 ml/min (n = 66), but to increase in the captopril group (+62 +/- 289, n = 57), a difference that was significant (Mann-Whitney chi-square, p = 0.02). This post-hoc observation suggests that a late beneficial effect may have been masked by inadequate study duration. Known benefits of captopril appear not to include an increase in working capacity within the first 24 months after AMI.",1995.0,0,0
1254,7484859,Effects of enalapril on heart rate variability in patients with congestive heart failure.,Y H Zhang; Y C Song; J Zhu; T H Hu; L L Wan,"Congestive heart failure (CHF) is characterized by sympathetic activation and parasympathetic withdrawal, and the magnitude of sympathoneural activation is associated with adverse outcome. Angiotensin-converting enzyme inhibitor therapy has been shown to reduce mortality and improve prognosis in patients with CHF, but whether this therapy improves cardiac autonomic control is not well known. This double-blind, placebo-controlled, crossover study examines the effects of enalapril on autonomic control in 12 patients with mild to moderate CHF by heart rate variability analysis. Compared with placebo, enalapril increased the SD of all normal RR intervals (SDNN) from 39 +/- 13 to 48 +/- 15 ms (p < 0.01), the SD of the average RR intervals for all 5-minute segments from 33 +/- 12 to 42 +/- 15 ms (p < 0.01), and the mean of the SDs of all RR intervals for all 5-minute segments (SDNN index) from 19 +/- 5 to 23 +/- 6 ms (p < 0.01). The root-mean-square successive differences and the percent differences between adjacent RR intervals > 50 ms were also increased from 17 +/- 8 to 21 +/- 8 ms (p < 0.01) and from 1.1 +/- 2.1 to 2.8 +/- 2.9% (p < 0.05). In addition, total, low-frequency, and high-frequency power were increased from 560 +/- 349 to 786 +/- 504 ms2/Hz (p < 0.01), from 125 +/- 107 to 179 +/- 135 ms2/Hz (p < 0.01), and from 46 +/- 32 to 94 +/- 78 ms2/Hz (p < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1255,7485134,"A randomized, placebo-controlled, multicenter trial evaluating alternate-day prednisone and fish oil supplements in young patients with immunoglobulin A nephropathy. Scientific Planning Committee of the IgA Nephropathy Study.",R J Hogg,,1995.0,0,0
1256,7485207,The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria. North American Microalbuminuria Study Group.,L M Laffel; J B McGill; D J Gans,"To determine whether angiotensin-converting enzyme (ACE) inhibition with captopril reduces the progression of microalbuminuria to overt proteinuria in normotensive patients with insulin-dependent diabetes mellitus (IDDM). This study was a prospective randomized, double-blind, placebo-controlled trial involving 26 centers in the United States and Canada. One hundred forty-three subjects, 14 to 57 years of age, with IDDM for 4 to 33 years, blood pressure < 140/90 mm Hg in the absence of antihypertensive therapy, and persistent albumin excretion 20 to 200 micrograms/min were randomized to double-blind treatment with captopril 50 mg or placebo BID. Albumin excretion rate (AER), blood pressure, and glycohemoglobin were determined every 3 months, and creatinine clearance (CrCl) and urea excretion were measured every 6 months. Within 24 months, 6.0% (4/67) of captopril-treated subjects and 18.6% (13/70) of placebo-treated subjects progressed to clinical proteinuria, defined as AER > 200 micrograms/min and at least 30% above baseline (risk reduction = 67.8%, P = 0.037). AER increased at an annual rate of 11.8% (95% confidence interval [CI] -3.3% to 29.1%) in the placebo group, while it declined by 17.9% (CI -29.6% to -4.3%) in the captopril group (P = 0.004). CrCl decreased by 4.9 mL/min per 1.73 m2 per year in the placebo group, while it remained stable in the captopril group (0.9 mL/min per 1.73 m2 per year, P = 0.039 between groups). Ten subjects required treatment for hypertension; 8 in the placebo group and 2 in the captopril group. There was little correlation between the 24-month changes in mean arterial blood pressure and AER in either group. Glycohemoglobin and urinary urea excretion did not differ between groups. After 24 months of therapy with captopril, compared with placebo, normotensive subjects with IDDM experienced significantly less progression of microalbuminuria to clinical proteinuria, reduced albumin excretion, and preserved CrCl rate. The ACE inhibitor, captopril, was well tolerated.",1995.0,0,0
1257,7487244,Clinical evaluation of different doses of intravenous enalaprilat in patients with hypertensive crises.,M M Hirschl; M Binder; A Bur; H Herkner; M Brunner; M Müllner; F Sterz; A N Laggner,"The appropriate dose of intravenous enalaprilat to be used in the treatment of hypertensive crisis is controversial. There has been no comparative study of the efficacy and safety of different dosages of enalaprilat in hypertensive patients. Sixty-five consecutive patients with hypertensive urgencies (systolic blood pressure > 210 mm Hg and/or diastolic blood pressure > 110 mm Hg) or emergencies (diastolic blood pressure > 100 mm Hg and evidence of end-organ damage, ie, angina pectoris, hypertensive encephalopathy, or congestive heart failure) admitted to an emergency department from January 1, 1994, to September 30, 1994, were identified. The patients were randomized to receive different doses of enalaprilat (0.625, 1.25, 2.5, and 5 mg). Response to treatment was defined as a stable reduction of systolic blood pressure to below 180 mm Hg and diastolic blood pressure to below 95 mm Hg within 45 minutes after the start of treatment and relief of symptoms in patients with hypertensive emergencies. In 41 (63%) of 65 patients, the treatment goal was reached. Twenty-four patients (37%) failed to achieve the goal of treatment within 45 minutes after administration of enalaprilat. The response rates in the 0.625-mg, 1.25-mg, 2.5-mg, and 5-mg groups were 67%, 65%, 59%, and 62%, respectively. The proportion of patients initially randomized who responded to treatment was not different between any of the four groups of enalaprilat doses. There were no significant differences according to enalaprilat dose with respect to changes in systolic, diastolic, and mean arterial blood pressure. No severe side effects were observed. Enalaprilat is a safe antihypertensive drug with moderate efficacy in the treatment of hypertensive crisis. As doses above 0.625 mg alter neither response rates nor the magnitude of blood pressure reduction, we recommend 0.625 mg as the initial dose in the treatment of hypertensive crisis.",1995.0,0,0
1258,7487694,Failure to recognise the association of life-threatening angio-oedema and angiotensin-converting enzyme inhibitor therapy.,J M Weiner,,1995.0,0,0
1259,7488449,"Failure of ""effective"" treatment for heart failure to improve normal customary activity.",J T Walsh; R Andrews; A Evans; A J Cowley,"To examine the effects of drug treatment on laboratory exercise tests in relation to measures of daily activity in patients with chronic heart failure. University teaching hospital. 18 patients with mild to moderate chronic heart failure (New York Heart Association functional class II-III) and 10 age matched healthy controls. Assessments were made before and after 12 weeks of vasodilator drug treatment. Exercise capacity was measured during two different types of treadmill exercise, one using a ramp protocol and the other a fixed work load. Corridor walk tests at three self selected speeds were also undertaken and measures of customary activity assessed from pedometer scores. Exercise times were significantly increased from baseline (P < 0.01) with both treadmill protocols after 12 weeks of drug treatment, with a positive correlation between the duration of treadmill exercise for both protocols (r = 0.69, P < 0.01). Corridor walk tests of 100 m at a self selected slow speed also improved (P < 0.02) but these did not correlate with the changes in treadmill exercise time. The pedometer scores of the patients with heart failure were greatly reduced compared with those of the controls (258 (45) x 10(2) v 619 (67) x 10(2) steps/week, P < 0.001) and after 12 weeks of treatment were unchanged (261 (42) x 10(2) steps/week). These data confirm the need to use different exercise protocols when assessing the benefits of drug treatment in patients with chronic heart failure. Treatments that seem effective with conventional laboratory based exercise tests may not improve daily activities. This may reflect a failure of apparently successful treatment and should be considered when interpreting clinical trials.",1995.0,0,0
1260,7490153,The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.,J A Staessen; L Bieniaszewski; F Buntinx; H Celis; E T O'Brien; R van Hoof; R Fagard,"The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1261,7490409,Severe hyponatremia associated with ramipril therapy in an old woman.,A Tilly-Gentric,,1995.0,0,0
1262,7496563,Effect of enalapril on erythrocytosis in hypertensive patients with renal disease.,B I Shand; R R Bailey; K L Lynn; R A Robson,"Treatment of hypertension with an angiotensin converting enzyme inhibitor (ACEI) may be associated with a decrease in haemoglobin concentration especially in patients with renal insufficiency. This open study in 19 patients with a variety of renal diseases with complicating hypertension investigated the effects of the ACEI, enalapril, on haemoglobin and plasma erythropoietin (EPO) concentrations. Blood samples were obtained at baseline and 2, 60 and 120 days after starting treatment with enalapril. By day 60 there was a significant decrease in mean haemoglobin concentration (mean decrease 7.4 g/l) that was sustained until day 120. Apart from a small, but significant, reduction by day 2, mean plasma EPO concentration remained constant throughout the study. The magnitude of the decrease in haemoglobin concentration was, however, significantly correlated with the baseline plasma creatinine concentration and creatinine clearance. These results suggested that the degree of renal insufficiency was important in determining the haematological response to ACE inhibition. While the mechanism of these changes remains unclear, our findings suggest that inhibition of the renin-angiotensin system, rather than decreasing EPO production, may reduce the erythropoietic activity of the hormone.",1995.0,0,0
1263,7496564,Normalization of structural cardiovascular changes during antihypertensive treatment with a regimen based on the ACE-inhibitor perindopril.,I Sihm; A P Schroeder; C Aalkjaer; M Holm; B Mørn; M Mulvany; K Thygesen; O Lederballe,"Untreated essential hypertension is associated with left ventricular hypertrophy (LVH) and structural changes in resistance vessels. The aim of this study was to establish the effect of perindopril based antihypertensive therapy on media thickness to lumen diameter (media:lumen) ratio of peripheral resistance vessels and left ventricular mass in essential hypertension. Twenty-five patients with newly diagnosed or poorly regulated essential hypertension were treated with perindopril. Insufficient treatment response (DBP > 90 mmHg) led to addition of isradipine, and hydralazine was used as a tertiary drug if necessary. Gluteal subcutaneous biopsies were taken surgically at baseline and after 9 months of successful treatment. Two small resistance arteries were isolated and mounted in a small vessel myograph, and media:lumen ratio (%) was measured under standardized conditions. Left ventricular mass was determined by echocardiography. Mean (SD) media:lumen ratio decreased from 9.8 (2.6) % to 7.8 (1.9) % (p < 0.05), while left ventricular mass decreased from 299 (75) g to 199 (53) g (p < 0.001). Correlation was found between changes in left ventricular mass index and media:lumen ratio (r = 0.62, p < 0.01). It is concluded that a perindopril based regimen efficiently normalizes resistance artery structure and left ventricular hypertrophy in essential hypertension within one year of treatment. The impact of these findings on the excess cardiovascular morbidity and mortality in arterial hypertension remains to be investigated.",1995.0,0,0
1264,7498206,Acute effect of captopril administration on baroreflex sensitivity in patients with acute myocardial infarction.,S A Marakas; M K Kyriakidis; A N Vourlioti; P N Petropoulakis; P K Toutouzas,"Depressed baroreflex sensitivity (BRS) after acute myocardial infarction (AMI) is considered an indication of decreased vagal and/or increased sympathetic tone. To determine the effect of angiotensin converting enzyme inhibitors (ACEI) on BRS after AMI we studied 27 patients with a first Q wave AMI, no signs of heart failure and no history of arterial hypertension or diabetes mellitus. An additional group of 10 patients with the same clinical characteristics served as controls. On the 5th day after the onset of AMI, three consecutive boluses of phenylephrine were given intravenously and baseline BRS was taken as the mean slope of the linear regression lines of RR intervals over systolic blood pressure. QT interval was also measured and corrected according to Bazett's formula (QTc). Consequently, a single oral dose of captopril 50 mg or placebo was given to treatment or control group patients, respectively; BRS and QTc were reassessed 1 h later. One hour after captopril administration BRS increased from 5.95 +/- 2.80 to 9.14 +/- 3.46 ms.mmHg-1 (P < 0.0001); QTc increased from 414 +/- 46 to 425 +/- 46 ms (P < 0.0001), systolic blood pressure decreased from 125 +/- 19 to 115 +/- 15 mmHg (P = 0.0002), while heart rate did not change significantly. Baseline BRS was correlated only with age (r = -0.74, P < 0.0001). In the control group, 1 h after placebo, no difference was observed in any variable compared to baseline. Captopril appears to improve BRS immediately in the early phase of AMI.",1995.0,0,0
1265,7498975,Antihypertensive treatment efficacy in type II diabetes mellitus. Dissociation between casual and 24-hour ambulatory blood pressure. Spanish Multicenter Study Group.,J G Puig; L M Ruilope; R Ortega,"Whole-day ambulatory blood pressure monitoring is used to confirm the diagnosis of hypertension and assess the response to antihypertensive therapy. Neither of these has been applied to patients with type II diabetes mellitus, in whom it has been proposed that the desirable blood pressure should be lower than in nondiabetics. This multicenter study was designed to examine whether there are differences in the efficacy of a first-line antihypertensive drug when assessed by casual and ambulatory blood pressure determinations in patients with type II diabetes mellitus in whom 24-hour ambulatory monitoring confirms or fails to confirm the diagnosis of hypertension. Forty-three patients (mean age, 57.7 years) with stable type II diabetes mellitus and mild hypertension (casual diastolic pressure, 90 to 104 mm Hg on at least two visits) were treated with an angiotensin-converting enzyme inhibitor (benazepril, 10 to 20 mg, once a day) for 8 weeks. Antihypertensive drug efficacy was assessed by casual (trough) and 24-hour ambulatory blood pressure monitoring. Diabetic patients were classified as nonconfirmed hypertensive if the mean 24-hour ambulatory diastolic pressure was below 85 mm Hg. Antihypertensive treatment significantly decreased both systolic and diastolic pressures when determined by either casual measurement (from a mean of 162.7/98.0 to 153.9/89.2 mm Hg; P < .001) or ambulatory monitoring (from a mean of 143.1/84.4 to 137.0/81.5 mm Hg; P < .05). Twenty-one patients (49%) were classified as confirmed hypertensive and 22 as nonconfirmed hypertensive. In confirmed hypertensive patients benazepril significantly reduced systolic and diastolic pressures when assessed by either casual or 24-hour ambulatory monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1266,7501201,Twenty commonly dispensed medications at a United States military installation and their significance to dentists.,A E Lentz; D G Kerns,"Understanding the clinical pharmacology of medications commonly used by dental patients is necessary when providing dental care. A significant number of patients may be taking medications that have the potential for adverse effects. The purpose of this paper is to familiarize dental practitioners with the clinical pharmacology of medications most likely to be encountered in a current military dental practice. Product activity reports (records of medications usage) were obtained from the main pharmacy at a United States Army Community Hospital. The product activity reports covered a 1-year period from December 31, 1992, to December 30, 1993. These reports were analyzed according to the number of medications dispensed to determine the 20 most commonly used medications.",1995.0,0,0
1267,7503006,"Comparison of effects on peak oxygen consumption, quality of life, and neurohormones of felodipine and enalapril in patients with congestive heart failure.",R J de Vries; M Queré; D J Lok; P Sijbring; J J Bucx; D J van Veldhuisen; P H Dunselman,"Angiotensin-converting enzyme (ACE) inhibition is currently the cornerstone of congestive heart failure (CHF) therapy, but these drugs are not tolerated in up to 20% of patients. For these patients, therapeutic alternatives with comparable efficacy are needed. Felodipine, a vasoselective dihydropyridine calcium antagonist with a slow onset of action and a long plasma half-life, may be such an agent. Therefore, the efficacy and safety of felodipine were examined and compared with enalapril using a double-blind design. We studied 46 patients with a left ventricular ejection fraction < 0.40, peak oxygen consumption < 20 ml.min-1.kg-1, and symptoms of CHF despite therapy with diuretics and digoxin. After 16 weeks of therapy, there were no statistically significant differences in peak oxygen consumption (felodipine +1.6, enalapril +2.5 ml.min-1.kg-1) and exercise tolerance (felodipine +61 seconds, enalapril +64 seconds). Quality-of-life parameters were affected slightly better by felodipine than by enalapril. Plasma norepinephrine decreased by 143 pg.ml-1 with enalapril and by 12 pg.ml-1 with felodipine (p < 0.20 between groups). Both drugs were generally well tolerated. These data suggest that felodipine and enalapril have comparable effects on exercise parameters in patients with CHF. Neurohumoral activation was not observed with either drug.",1995.0,0,0
1268,7503014,Ventricular late potentials and left ventricular function after early enalapril treatment in acute myocardial infarction.,A Junker; P Ahlquist; P Thayssen; K Angelo-Nielsen; H Mickley; M Møller,,1995.0,0,0
1269,7504126,"Effects of an angiotensin-converting enzyme inhibitor, lisinopril, on cerebral blood flow autoregulation in healthy volunteers.",P Démolis; C Carville; J F Giudicelli,"The effects of a single oral dose (20 mg) of lisinopril on systemic, carotid (pulsed Doppler), and cerebral (middle cerebral artery, transcranial Doppler) hemodynamics have been investigated over an 8-h period in eight healthy volunteers in a double-blind placebo-controlled crossover study. In addition, cerebral vasodilatory reserve was measured (acetazolamide test). Lisinopril did not affect systemic hemodynamics but it increased both common carotid artery blood flow (+26.2%, p < 0.01) and diameter (+4.5%, p < 0.05) after 8 h. Lisinopril did not affect middle cerebral artery mean blood flow velocity but increased cerebral resistance index (+8.1%, p < 0.05) at 4 h and cerebral vasodilatory reserve (+24.8%, p < 0.05). These data suggest that lisinopril produces a paradoxical vasoconstriction of the small cerebral arterioles. This vasoconstriction might be a compensatory mechanism to a dilation of large cerebral arteries, thus resulting in an unchanged cerebral blood flow.",1993.0,0,0
1270,7507638,"Effects of diltiazem, metoprolol, enalapril and hydrochlorothiazide on frequency of ventricular premature complexes.",V Papademetriou; P Narayan; P Kokkinos,"Ventricular arrhythmias occur frequently in patients with hypertensive left ventricular (LV) hypertrophy and have been associated with increased incidence of sudden death. In this study, the effect of various antihypertensive medications on ventricular arrhythmias was evaluated in 31 hypertensive patients with moderate to severe LV hypertrophy. Patients were assessed at baseline (after 3 weeks of placebo treatment) and after treatment with each of 4 monotherapies: diltiazem 120 or 240 mg/day, metoprolol 100 or 200 mg/day, enalapril 10 or 20 mg/day and hydrochlorothiazide 50 or 100 mg/day. Each drug therapy was administered for 4 weeks. The sequence of each treatment was determined at random. Echocardiographic measurements and electrocardiograms were obtained only at baseline. Biochemical measurements and 48-hour Holter monitoring were obtained at baseline and at the end of each treatment. All treatments resulted in a significant but similar decrease in blood pressure. In the group as a whole diltiazem decreased ventricular premature complexes (VPCs) by 65% (p < 0.05) and metoprolol by 52% (p = 0.07). Enalapril and hydrochlorothiazide had no effect. In 12 patients with > or = 5 VPCs/hour at baseline, diltiazem and metoprolol decreased VPCs by 66% (p < 0.05). It is concluded that in hypertensive patients with moderate to severe LV hypertrophy, both diltiazem and metoprolol significantly reduce VPCs.",1994.0,0,0
1271,7511740,Effects of angiotensin-converting enzyme inhibitors on glucose and lipid metabolism in essential hypertension.,A Oksa; M Gajdos; V Fedelesová; V Spustová; R Dzúrik,"Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma glucose and insulin levels, as well as total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before and after the 8- to 12-week treatment. Minor differences in the blood pressure (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors studied; only lisinopril improved glucose tolerance significantly; blood lipids were not changed by any drug. The entire patient population showed only a slight reduction in 1-h postload glucose after treatment. More obvious improvement in glucose tolerance was evident in hypertensive patients who were glucose intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup also showed a slight but not significant increase in HDL-cholesterol and a decrease in triglycerides levels. Only a slight change or no change in plasma glucose, insulin, and lipid values was noted in hypertensive patients with normal glucose tolerance (NGT) and insulin sensitivity. These favorable effects were expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide was added. The results indicate that a lack of stratification of hypertensive patients with regard to glucose tolerance or insulin sensitivity could be a confounding factor in evaluation of metabolic effects of ACE inhibitors.",1994.0,0,0
1272,7511751,Effects of lisinopril on stress-induced peak blood pressure and sodium excretion: a double-blind controlled study.,J P Fauvel; M Laville; N Bernard; A Hadj-Aïssa; S Daoud; E Thibout; N Pozet; P Zech,"A stress test was performed before (S1) and after a 1-month treatment period (S2) in patients with essential hypertension, randomly allocated to receive either an angiotensin-converting enzyme inhibitor (ACEI), lisinopril (n = 10), or placebo (n = 10). The two groups were similar with regard to systolic and diastolic blood pressure (SBP, DBP), body weight, renal function, and 24-h sodium excretion. At S1, stress induced a significant increase in SBP of 18 +/- 9 mm Hg and in DBP of 10 +/- 6 mm Hg and a significant reduction in sodium excretion from 258 +/- 105 to 204 +/- 72 mumol/min. Stress-induced sympathetic stimulation was assessed by a significant increase in urinary norepinephrine (NE) excretion from 21 +/- 10 to 26 +/- 10 micrograms/g creatinine. One-month treatment by placebo did not change stress-induced BP reactivity, sodium retention, or urinary NE excretion. In the lisinopril group, rest and stress BP were significantly reduced by the treatment. Stress-induced sodium retention was higher after 1-month placebo treatment (72 +/- 78 vs 48 +/- 67 mumol/min), whereas this retention was significantly reduced by lisinopril (13 +/- 27 vs 69 +/- 60 mumol/min).",1994.0,0,0
1273,7511753,Effects of acetylsalicylic acid on peripheral hemodynamics in patients with chronic heart failure treated with angiotensin-converting enzyme inhibitors.,J van Wijngaarden; A J Smit; P A de Graeff; W H van Gilst; S A van der Broek; D J van Veldhuisen; K I Lie; H Wesseling,"Cyclooxygenase inhibitors may affect the hemodynamic status of patients with heart failure adversely and may also block the vasodilatory effects of angiotensin-converting enzyme (ACE) inhibitors in such patients. Relatively low doses of the cyclooxygenase inhibitor acetylsalicylic acid (ASA) are now used routinely in ischemic heart disease, the most important cause of heart failure. Therefore, we investigated the hemodynamic interaction between ASA and captopril in heart failure. In a randomized, cross-over study, 13 patients with congestive heart failure (CHF) who were already receiving maintenance treatment with an ACE inhibitor received a single dose of 25 mg captopril combined with 236 mg ASA or placebo. Peripheral blood flow was studied noninvasively by venous occlusion plethysmography of the calves. Liver blood flow was estimated from indocyanine green (ICG) clearance. Administration of captopril alone significantly decreased blood pressure (BP), and ICG clearance. Calf blood flow remained unchanged. However, after arterial occlusion, hyperemic calf blood flow persisted for longer. Captopril alone did not significantly change the plasma levels of the vasodilating prostaglandins PGI2 and PGE2 or the vasoconstricting thromboxane A2 (TXA2). In contrast, captopril combined with ASA reduced the plasma levels of these vasoactive substances, with significant decreases in PGE2 and TXA2 as compared with captopril alone, yet the hemodynamic alterations after captopril plus ASA were similar to those observed after captopril alone. A single antithrombotic dose of ASA (236 mg) in 13 patients with CHF [New York Heart Association (NYHA) class II-IV] undergoing chronic treatment with ACE inhibitors had no discernible effect on hemodynamic status.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1274,7512469,Lipid profile during antihypertensive treatment. The SLIP Study Group. Study on Lipids with Isoptin Press.,A Libretti; M Catalano,"Some antihypertensive drugs adversely affect the plasma lipid profile, and this has to be taken into account when choosing treatment for hypertension because it may offset the beneficial blood pressure-lowering effect of these agents. In this study, the long term effects of verapamil sustained release (SR) 240mg daily and enalapril 20mg daily on plasma lipid levels were investigated in 931 patients with mild to moderate hypertension. Patients whose blood pressure was not effectively lowered after at least 1 month of monotherapy had either enalapril 20mg once daily added to their verapamil treatment or hydrochlorothiazide 12.5mg once daily added to their enalapril treatment. Blood pressure and lipid profile were assessed before and after 6 months of treatment. Of 864 evaluable patients, 563 patients (65.1%) were successfully treated with monotherapy and 220 patients (25.5%) required combination therapy. A total of 81 patients withdrew from the trial. Systolic and diastolic blood pressure were significantly reduced by treatment with either verapamil or enalapril, and heart rate was reduced slightly, but significantly, by both treatments. Total cholesterol, triglycerides and low density lipoprotein were significantly reduced by both treatments. High density lipoprotein levels were significantly increased in verapamil recipients, but not in enalapril recipients. Adverse effects occurred in 37 (3.9%) patients receiving verapamil SR and 25 (2.7%) patients receiving enalapril. In conclusion, long term treatment with the antihypertensive agents verapamil and enalapril, alone or in combination regimens, significantly improved the plasma lipid profile. Verapamil SR had the most beneficial effect on plasma lipid levels.",1993.0,0,0
1275,7512487,"Lowering blood pressure. How far, how fast?",A Roca-Cusachs,"There is a general consensus that high blood pressure (BP) must be lowered gradually. A reduction in BP beyond the limits of the autoregulatory curve may compromise perfusion of vital organs, resulting in organ ischaemia. However, a reduction in high BP offers protection against cerebral events, and some protection against coronary heart disease. The limited protection against coronary heart disease provided by BP reduction may be partially explained by the so-called 'J-shaped curve': a reduction in diastolic blood pressure below 85 mmHg may lead to a paradoxical increase in coronary events, although this effect is by no means well established. In addition, the incidence of several events associated with cardiovascular disease peaks during morning hours, at a time when some antihypertensive drugs are least effective. This may also explain the limited coronary protection achieved after administration of antihypertensive drugs.",1993.0,0,0
1276,7514156,Antiarrhythmic effect of converting enzyme inhibitors in congestive heart failure.,A Gürlek; C Erol; E Basesme,"In this study 24-h Holter electrocardiographic recordings were used to measure the effects of an angiotensin converting enzyme inhibitor, enalapril given for 4 weeks, on the frequency of cardiac arrhythmias in 24 patients (14 patients had enalapril, 30 patients had placebo) with congestive heart failure (New York Heart Association Functional Class 3) receiving maintenance therapy with digoxin and furosemide. Although the placebo group had no change in the frequence of arrhythmias, enalapril-treated patients showed significant decrease in the frequency of premature ventricular complexes couplet, bigemine VPS and ventricular tachycardia. Moreover, it was observed that six cases of atrial fibrillation returned to sinus rhythm. During enalapril treatment, some patients experienced increased serum potassium levels, but there was no change in serum digoxin levels. We also observed echocardiographic improvement in left ventricular function as well as clinical symptoms of congestive heart failure. Finally we observed that there was an antiarrhythmic effect of enalapril in congestive heart failure. We thought that the antiarrhythmic effect of enalapril in congestive heart failure was probably due to hemodynamic improvement.",1994.0,0,0
1277,7514874,"Effect of 1-year treatment with nitrendipine versus enalapril on urinary albumin and alpha 1-microglobulin excretion in microalbuminuric patients with type 1 diabetes mellitus. A randomized, single-blind comparative study.",E Jungmann; M Malanyn; N Mortasawi; E Unterstöger; T Haak; K D Palitzsch; J Scherberich; P M Schumm-Draeger; K H Usadel,"In order to compare the long-term effects of nitrendipine (CAS 39562-70-4) and enalapril (CAS 75847-73-3) on variables of glomerular and tubular function in type 1 diabetes mellitus, a single-blind, randomised comparative 1-year study was carried out in microalbuminuric patients (6 women, 14 men, age, 30-58 years, duration of diabetes, 3-41 years, HbA1 sigma 5.5-10%). 10 patients were treated with 20 mg/d nitrendipine, 10 patients were treated with 10 mg/d enalapril. On the average, urinary albumin excretion was decreased by 38 +/- 4% by nitrendipine (p < 0.01 vs. before treatment) and by 21 +/- 8% by enalapril (p < 0.05 vs. before treatment). The excretion of alpha 1-microglobulin decreased by 35 +/- 10% and by 39 +/- 9%, respectively (p < 0.05 vs. before treatment). Creatine clearance rose by 20 +/- 30% during nitrendipine treatment (p < 0.05 vs. before treatment) but was unchanged during enalapril treatment. Total kidney volume decreased by 23 +/- 4% (p < 0.01) and by 14 +/- 6% (p < 0.05), respectively. Blood pressure fell by 8 +/- 1% systolic and by 13 +/- 1% (diastolic) in nitrendipine-treated patients (both p < 0.01) and by 10 +/- 1% and 13 +/- 1% in enalapril-treated patients (both p < 0.01). Thus, nitrendipine long-term treatment of microalbuminuric type 1 diabetic appeared to be as effective as the treatment with enalapril in preventing or postponing the progression of diabetic nephropathy.",1994.0,0,0
1278,7516014,Effects of perindopril on serum lipids in hypertensive patients with hyperlipidemia.,M Middeke; W Krone,"The effect of the angiotensin-converting enzyme (ACE)-inhibitor perindopril on serum lipids and apolipoprotein concentrations were assessed in a multicenter, randomized, double-blind, placebo-controlled study in 51 hyperlipidemic patients treated for mild hypertension. Perindopril was given as a single morning dose (4 mg) for 6 weeks. During the treatment period, blood pressure (BP) was significantly (p < 0.001) reduced from 159/99 to 148/90 mm Hg by verum treatment and from 158/101 to 151/95 mm Hg (NS) by placebo treatment. Neither total cholesterol and triglycerides nor high-density-lipoprotein and apolipoprotein AI and B levels were significantly altered by drug treatment as compared with placebo. Although perindopril had good antihypertensive effect in patients with mild hypertension and hyperlipidemia, it had no adverse effects on lipid metabolism in these patients. Therefore, perindopril is recommended for antihypertensive treatment, especially in hypertensive patients with concomitant hyperlipidemia.",1994.0,0,0
1279,7516856,Selecting appropriate antihypertensive drug dosages.,G D Johnston,,1994.0,0,0
1280,7516858,The clinical potential of renin inhibitors and angiotensin antagonists.,R J Cody,"The renin angiotensin system is a major contributor to the pathophysiology of cardiovascular diseases such as congestive heart failure and hypertension. For this reason, attempts to specifically block this system have been a pharmacological goal for over 25 years. Blockade of the renin system has been attempted at 3 pivotal sites: the rate limiting angiotensinogen-renin step, conversion of angiotensin I to angiotensin II, and the active receptor sites for the terminal products of angiotensin II and aldosterone. Converting enzyme inhibitors have been successfully studied and utilised in clinical cardiovascular disorders, but questions persist regarding the specificity of their action. Thus, other more specific approaches remain under evaluation. Inhibition of the action of renin on angiotensinogen was demonstrated with early inhibitory peptides and in experimental studies with specific antibodies. Most currently available renin inhibitors are nonpeptides, which nonetheless require intravenous administration. An oral renin inhibitor with clinical effects has been evaluated in early human trials. Like renin inhibitors and converting enzyme inhibitors, specific angiotensin antagonists were studied early in the course of renin system pharmacological blockade. Early angiotensin antagonists were limited, due to the requirement for intravenous administration and because of their short half-lives. They also had the potential for mixed agonist/antagonist physiological and pharmacological effects, which could result in a pressor, rather than a depressor, response. The angiotensin receptor antagonists have the appeal of blocking the specific receptor at its target tissue site, analogous to other well described systems. Newer angiotensin antagonists do not have the limitations of the precursor peptides. Losartan (DUP753) is a specific angiotensin II AT1 receptor antagonist. It is orally effective without agonist activity, and has high receptor binding characteristics. Early studies indicate that it is a specific probe of the renin system, and is providing newer insights into the role of the renin system in cardiovascular disorders. Emerging clinical studies indicate that it is effective for blood pressure reduction and as a vasodilator. Aldosterone antagonists such as spironolactone have been available for decades. Spironolactone is being used in an ongoing trial to assess the impact of combined converting enzyme and aldosterone inhibition. Newer aldosterone antagonists could add to targeted blockade of aldosterone without the adverse effects of the precursor compound, and the potential for combined specific renin system blockade.",1994.0,0,0
1281,7521487,Regional oxygen consumption persists in dyskinetic canine myocardium.,C W Buffington; D P Strum; S Watanabe,"Regional myocardial O2 consumption was measured in anesthetized dogs both in baseline conditions and during intracoronary infusion of lidocaine, verapamil, sodium citrate, or 2,3-butanedione-monoxime (BDM). Despite regional hypokinesis and dyskinesis during drug infusion, regional O2 consumption was reduced only 30-40% by lidocaine, verapamil, and citrate and not at all by BDM. These results cast doubt on an important assumption of the ""hibernation"" theory: the protective matching of regional perfusion and contraction.",1994.0,0,0
1282,7521831,Race and hypertension. What is clinically relevant?,D R Rutledge,"Hypertension, once considered rare in Africa, occurs frequently in most Black populations outside of the continent as well as within more urban areas of Africa. The frequency of hypertension in Black citizens of the US is among the highest in the world. Pathophysiological mechanisms suggest the frequency of salt-sensitive blood pressure is more common in Black patients. More Black than White patients initially present with volume expansion. However, in Black patients there appears to be no significant relationship between plasma renin activity, plasma volume and blood pressure. The syndrome of insulin resistance has also been reported in African Americans. Future studies should address this issue, both because it relates to identifying individuals at risk for development of high blood pressure and because it has implications for initial selection of antihypertensive therapy. Hypertensive kidney disease is prevalent in Black people. Lowering the blood pressure with diuretic-based therapies has not been shown to delay or prevent the loss of kidney function in patients with this condition, suggesting that this treatment approach may not be optimal. Lifestyle modifications remain the initial therapeutic regimen. Because diuretics and beta-blockers have been shown to reduce cardiovascular morbidity and mortality in controlled clinical trials, they are preferred therapies. The Hypertension Detection and Follow-up Program showed significant reductions in morbidity and mortality in Black patients using primarily diuretic-based therapies. However, controversy persists regarding use of diuretics since some investigators believe that greater reductions in overall cardiovascular risk may be achieved in Black patients using other agents. These agents may eventually be able to exert a beneficial cardiovascular effect in addition to and independent of their blood pressure-lowering effect. Long term data documenting reduced morbidity and mortality rates with other agents are needed for all populations, particularly in Black hypertensive patients.",1994.0,0,0
1283,7523058,Exercise testing in heart failure. A critical review.,K Swedberg,"Exercise intolerance is one of the primary characteristics of chronic congestive heart failure (CHF). Therefore, exercise testing has been widely used in the assessment of CHF patients, both to define the severity of the disease and to assess the efficacy of pharmaceutical agents in clinical trials. A number of different exercise tests can be used, although maximal exercise testing is the most common. Maximal exercise capacity can be determined by measuring exercise duration during incremental exercise, or maximal oxygen (O2) consumption, or it can be estimated by anaerobic threshold. While baseline exercise testing in CHF patients accurately identifies and quantifies cardiac failure and determines prognosis, it is of limited value in assessing changes that occur as a result of drug therapy. A key drawback of exercise testing as a measurement of drug effect is the fact that exercise changes produced by drug intervention do not correlate well with changes in the mortality rate. Several examples of the lack of correlation between exercise testing and mortality rates have been observed in clinical trials with angiotensin converting enzyme (ACE) inhibitors and vasodilators. ACE inhibitors have a modest effect on maximal exercise capacity but they improve survival. It is thought that neuroendocrine activation more closely reflects mortality rates and also the changes in survival observed with pharmacological intervention compared with other modes of evaluation.",1994.0,0,0
1284,7523606,Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate.,K J Pienta; B Redman; M Hussain; G Cummings; P S Esper; C Appel; L E Flaherty,"Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival. We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.",1994.0,0,0
1285,7525196,"Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension.",L R Wiseman; D McTavish,"Trandolapril is a non-sulfhydryl prodrug which, after oral administration, is hydrolysed in the liver to its active diacid, trandolaprilat. Trandolaprilat inhibits the angiotensin converting enzyme (ACE) and displays similar pharmacodynamic properties to other ACE inhibitors, improving haemodynamic and cardiac parameters in patients with essential hypertension. Trandolapril 2 to 4mg once daily effectively controls blood pressure for at least 24 hours in patients with mild to moderate hypertension. In a small number of double-blind comparative trials, trandolapril had similar antihypertensive efficacy to that of atenolol, enalapril, hydrochlorothiazide, lisinopril and sustained release nifedipine, but was more effective than captopril. Combined therapy with trandolapril and hydrochlorothiazide or sustained release nifedipine had a significantly greater antihypertensive effect than either drug treatment alone. Further comparative trials are warranted to confirm these preliminary findings. The tolerability profile of trandolapril is similar to that of other ACE inhibitors, most adverse events being generally mild and transient in nature, and trandolapril lacks adverse effects on carbohydrate and lipid metabolism. Thus, trandolapril, with its favourable pharmacological profile and antihypertensive activity similar to that of agents currently used to treat patients with mild to moderate hypertension, is likely to provide a well tolerated option for the treatment of this disease. The results of ongoing and future clinical trials will determine its potential as a cardioprotective agent in patients following myocardial infarction.",1994.0,0,0
1286,7526050,Safety of concomitant potassium-sparing diuretics in angiotensin-converting enzyme inhibitor therapy in severe congestive heart failure. Xamoterol in Severe Heart Failure Study Group.,J Bergler-Klein; H Sochor; H Pouleur; R Pacher; G Porenta; D Glogar,"The safety of concomitant use of angiotensin-converting enzyme (ACE) inhibitors and potassium-sparing diuretics (PSD) in severe heart failure remains a controversial issue. The database of the recently reported double-blind international trial, ""Xamoterol in Severe Heart Failure,"" was investigated to elucidate this question. Of 516 patients with New York Heart Association (NYHA) class III-IV, despite diuretics and ACE inhibitor therapy, 352 were randomized to xamoterol, a beta 1 partial agonist, and 164 were randomized to placebo. During the 13-week study, 28% of all patients (xamoterol, 104; placebo, 42) received potassium-sparing diuretics. All groups were comparable in hemodynamics and dose of other diuretics. At study end, patients with or without PSD showed no significant differences in serum K+ or creatinine, independent of xamoterol or placebo therapy. Mortality rate was consistently lower: 4.6% in patients with PSD and 8.5% in patients without PSD, although statistical significance was not reached. As compared with baseline, K+ values of 6 patients with and 17 patients without PSD had increased by > 5.0 mM at study end (p = NS); 1 patient with and 11 patients without PSD had a creatinine level > 180 microM (p = NS). For 3 patients receiving PSD, and 2 patients not receiving PSD because of renal impairment, study was discontinued because of hyperpotassemia. No significant differences were noted in long and short action or different dosages of ACE inhibitors. PSD may be administered concomitantly with ACE inhibitors, but serum K+ should be monitored as with other diuretics.",1994.0,0,0
1287,7526056,Comparison of the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide in patients with moderate hypertension.,K Dickstein; T Aarsland; P Ferrari; M Todd; M Stimpel,"This parallel, double-blind trial was designed to evaluate the efficacy of three dose levels of moexipril versus placebo as add-on therapy to hydrochlorothiazide (HCTZ) in patients with uncomplicated moderate to severe hypertension. Two hundred patients (aged 25-74 years) with sitting diastolic blood pressure (DBP) between 95 and 114 mm Hg after 4 week treatment with HCTZ 25 mg once daily were randomized to placebo, or moexipril 3.75, 7.5 mg, or 15 mg. BP was measured at 22-26 h postdose at biweekly visits and at 1, 2, 3, and 4 h postdose after the first dose of double-blind medication. At endpoint, adjusted mean reductions from baseline sitting DBP were 8.4, 8.8, and 8.9 mm Hg in the moexipril 3.75-, 7.5-, and 15-mg groups, respectively, as compared with a reduction of 4.6 mm Hg in the placebo group (p = 0.003). The differences in systolic BP (SBP) reductions were statistically significant in favor of each of the moexipril groups over the placebo group at all trough time-points. Adjusted mean changes in sitting SBP were 10.9, 12.0, and 11.7 mm Hg, respectively, as compared with a reduction of 0.6 mm Hg in the placebo group (p < 0.001). Our results indicate that moexipril and HCTZ constitute a clinically valuable combination in treatment of patients with moderate to severe hypertension.",1994.0,0,0
1288,7527326,Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders.,G L Plosker; E M Sorkin,"Following systemic absorption, quinapril is converted by de-esterification to quinaprilat (the active diacid metabolite), an inhibitor of angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourable effects in cardiovascular disorders. Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of quinapril in the treatment of patients with hypertension or congestive heart failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with essential hypertension in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of hydrochlorothiazide to quinapril therapy improved response rates by approximately 10 to 20% in patients with hypertension. In general, blood pressure control with quinapril monotherapy was similar to that achieved with enalapril or other standard antihypertensive agents in comparative trials. Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with congestive heart failure has not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with hypertension or congestive heart failure receiving quinapril experienced a treatment-related adverse effects compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effective and well tolerated alternative to other ACE inhibitors for the treatment of hypertension and congestive heart failure. While effects of quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with coronary artery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.",1994.0,0,0
1289,7528299,Changes in plasma norepinephrine concentration and thrombocyte alpha 2-adrenoceptor density during long-term antihypertensive therapy with nitrendipine and captopril.,R Müller; H M Steffen; P Weller; C Kugel; T Freiheit; W Krone,"Antihypertensive drugs influence the sympathetic nervous system in different ways that may cause adverse or beneficial effects. We treated 48 hypertensive patients with either nitrendipine (10-20 mg twice daily, b.i.d.) or captopril (25-50 mg b.i.d.) for 16 weeks to evaluate changes in plasma catecholamines, platelet alpha 2- and lymphocyte beta 2-adrenoceptors. Blood pressure (BP) decreased from 153/95 to 135/87 mm Hg with captopril and from 155/99 to 137/89 mm Hg with nitrendipine. Treatment with nitrendipine significantly stimulated plasma norepinephrine (NE) from 327 +/- 37 to 446 +/- 50 pg/ml, and treatment with captopril resulted in a significant reduction in platelet alpha 2-adrenoceptor density from 265 +/- 39 to 171 +/- 26 fmol/mg protein. Despite having equal BP-lowering properties, captopril and nitrendipine have different effects on the sympathetic nervous system. Stimulation of plasma NE during long-term treatment with nitrendipine may contribute to possible adverse effects, whereas reduction in alpha 2-adrenoceptors induced by captopril may contribute to the vasodilating effect of angiotensin-converting enzyme (ACE) inhibition.",1994.0,0,0
1290,7528307,Noninvasive assessment of regional arteriolar and arterial dilating properties of lisinopril in healthy volunteers.,E Bellissant; C Thuillez; C Richer; E Pussard; J F Giudicelli,"The effects of single oral doses of lisinopril (5 and 20 mg) on systemic and regional hemodynamics were investigated noninvasively in a placebo-controlled, randomized, double-blind, cross-over study of 6 healthy male volunteers. Lisinopril induced a dose-dependent (significant after 20 mg) and long-lasting (< or = 8 h) decrease in mean arterial pressure (MAP, approximately 11% after 20 mg) that was related to a decrease in total peripheral resistance (TPR), because simultaneously heart rate (HR) and cardiac output (CO) were unchanged. Brachial artery flow (+42 and +47% after 5 and 20 mg, respectively) and diameter (+8 and +9%) increased significantly, whereas brachial vascular resistance (-31 and -38%) decreased significantly from 2 to 8 h after drug intake. Common carotid artery flow (+20 and +24%) also increased significantly, whereas corresponding resistance (-18 and -26%) decreased significantly during the same period. Finally, CO was significantly redistributed toward the brachial and, to a lesser extent, the carotid vascular beds after both doses of lisinopril. We conclude that in healthy subjects lisinopril, at non- or slightly hypotensive doses, dilates both arterioles and large arteries and that this vasodilation is not homogeneous, affecting preferentially the brachial rather than the carotid vascular bed.",1994.0,0,0
1291,7528854,The application of hematopoietic growth factors in drug-induced agranulocytosis: a review of 70 cases.,A Sprikkelman; J T de Wolf; E Vellenga,"Since 1989, granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF, G-CSF) have been increasingly applied in the treatment of drug-induced agranulocytosis. In order to evaluate the effectiveness of GM-CSF and G-CSF in the treatment of drug-induced agranulocytosis, we have studied all reported cases (n = 70) treated with GM-CSF and G-CSF, including ten patients treated during the last 2 years in The Netherlands. The results demonstrate that patients with a severe granulocytopenia (< 0.1 x 10(9)/l) treated with hematopoietic growth factors had a significantly faster recovery of the peripheral blood granulocytes compared to previous published studies. At the same time, a significantly lower mortality rate was observed. In patients with a severe granulocytopenia treated with GM-CSF or G-CSF a mortality rate of 5% was noted. No difference in granulocyte recovery was observed in patients treated with GM-CSF or G-CSF. The results of this review indicate that G-CSF and GM-CSF enhance the recovery of the myeloid lineage, resulting in a faster normalization of the peripheral blood granulocyte count and a reduced incidence of fatal complications.",1994.0,0,0
1292,7533694,Angiotensin converting enzyme inhibitors in Raynaud's phenomenon.,V F Challenor,"Patients with Raynaud's phenomenon exhibit reversible digital vasospasm, often in response to cold. While this condition often responds to simple physical measures, in severe cases, symptoms may require drug treatment. Arterial vasodilators have usually been tried in clinical practice, but recently ACE inhibitors have been tested in clinical trials of this condition. Case studies, noncomparative and placebo-controlled studies have shown mixed results of ACE inhibitor therapy in Raynaud's phenomenon. While these drugs reduced symptoms in some patients, the results were not consistent. On objective measures of improvement, such as evaluation of digital blood flow patterns, consistent statistically significant changes have also not been shown. However, well conducted dose-titration studies have not been performed in patients with Reynaud's phenomenon, and the objective methods of assessing this condition require refinement. The mode of action of ACE inhibitors is promising and these agents do not have significant adverse effects in this population. While at present ACE inhibitors cannot be recommended for the routine treatment of Reynaud's phenomenon, further controlled studies with newer ACE inhibitors, which may have improved peripheral activity, may change this view.",1994.0,0,0
1293,7537194,Doxazosin. An update of its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia.,B Fulton; A J Wagstaff; E M Sorkin,"Doxazosin is a long-acting alpha 1-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in the treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM) and respiratory disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have reported an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha 1-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures.(ABSTRACT TRUNCATED AT 400 WORDS)",1995.0,0,0
1294,7546494,Variations in magnesium and zinc in hypertensive patients receiving different treatments.,M A Rubio-Luengo; A Maldonado-Martín; B Gil-Extremera; L González-Gómez; J D Luna del Castillo,"We studied the influence of captopril, atenolol, and verapamil on serum and intraerythrocyte concentrations of magnesium and zinc in 30 normotensive control subjects (12 men and 18 women, aged 30 to 65 years, mean +/- SD 45.76 +/- 12.15 years) and 30 patients with untreated mild or moderate essential hypertension (14 men and 16 women, aged 30 to 65 years, mean +/- SD 49.50 +/- 13.58 years). Ten each of the hypertensive patients were treated with captopril, atenolol, or verapamil. Physical examination and biochemical analyses (serum Mg and Zn) were done in all participants at baseline, and in patients after 3 and 6 months of treatment. The results were compared according to a nested design with Neumann-Keuls test. We found no significant differences between controls and patients in serum and intraerythrocyte concentrations of Zn at the start of the study, although there was a significant decrease in serum Zn in patients after 3 (P < .01) and 6 months (P < .001) of treatment, regardless of the drug used. This decrease was thought to be attributable to the zincuric effect of captopril or to dietary measures, or both. Intraerythrocyte Zn was not significantly affected by antihypertensive treatment. Serum and intraerythrocyte concentrations of Mg were significantly lower (P < .001) in hypertensive than in normotensive subjects, and serum Mg in patients treated with verapamil was significantly lower (P < .05) than after treatment with captopril or atenolol. Serum Mg concentration was related directly with serum concentrations of high density lipoprotein cholesterol (r = 0.4043, P < .05). We conclude that supplementation with Mg may benefit patients with hypertension.",1995.0,0,0
1295,7546499,The efficacy and tolerability of enalapril in a formulation with a very low dose of hydrochlorothiazide in hypertensive patients resistent to enalapril monotherapy.,S J Guul; I Os; A J Jounela,"The antihypertensive efficacy and tolerability of formulations of enalapril and low (12.5 mg) and very low (6 mg) doses of hydrochlorothiazide (HCTZ) were compared with enalapril and placebo. Four hundred and two patients with mild to moderate essential hypertension were treated with 20 mg enalapril for 8 weeks. Patients (n = 296) with persistent supine diastolic blood pressure > 95 mm Hg after enalapril monotherapy were randomized to receive enalapril/placebo (group I), 6 mg enalapril/HCTZ (group II), or 12.5 mg enalapril/HCTZ (group III) for another 8 weeks in a double-blind design. The mean reductions in blood pressure were significantly larger in groups II and III compared to group I, 7.3 (95% CI, -9.0; -6.2), 7.7 (-9.2;-6.3), and 4.1 (-5.9;-2.9) mm Hg, respectively P < .01 for groups II and III compared to group I). No difference in side effects was observed between the three groups. A very low dose of 6 mg HCTZ acts synergistically when given together with enalapril, but is devoid of adverse metabolic effects.",1995.0,0,0
1296,7546762,Pharmacologic drugs for controlled hypotension.,L D Testa; J D Tobias,"Due to the risks of transfusion reactions and the transmission of infectious diseases, there has been increased interest in measures to limit intraoperative blood loss and avoid the need for homologous transfusion. Controlled hypotension is one technique that has been used to limit intraoperative blood loss. Several drugs have been used alone or in combination for controlled hypotension, including the inhalational anesthetics, direct acting vasodilators such as nitroglycerin and nitroprusside, beta adrenergic antagonists, and calcium channel blockers. Various drugs available to the clinician for controlled hypotension are reviewed.",1995.0,0,0
1297,7554545,Evaluation of antihypertensive effects of once-a-day isradipine and fosinopril: a double-blind crossover study by means of ambulatory blood pressure monitoring.,F Perticone; F Pugliese; A M Marcantonio; C Cloro; R Maio; P L Mattioli,"We compared the efficacy and tolerability of isradipine (ISR) and fosinopril (FOS) once-a-day administration in 17 outpatients, 9 men and 8 women, aged 35-65 years (mean +/- SD = 58 +/- 10 years), affected by mild to moderate primary systemic hypertension. The patients were given single-blind placebo for 2 weeks and thereafter, in double-blind, randomized, crossover sequence, ISR (5 mg) and FOS (20 mg), both for 4 weeks. At the end of each period, patients underwent 24-h noninvasive blood pressure (BP) monitoring by means of an A&D TM 2420 Monitor Model 7, with readings taken very 10 min during the day (from 7 A.M. to 11 P.M.), and every 20 min during the night (from 11 P.M. to 7 A.M.) Similarly, BP load (BPL) as percentage of systolic and diastolic BP reading > 140 and > 90 mmHg was investigated. Both ISR and FOS induced a highly significant (p < 0.0001) decrease in BP from 158/96 +/- 7/6 mmHg to 133/86 +/- 6/6 and to 132/83 +/- 10/7 mmHg, respectively. Mean BP decreased from 117 +/- 6 mmHg to 102 +/- 6 mmHg (ISR) (p < 0.0001) and to 99 +/- 8 mmHg (FOS) (p < 0.0001). Both ISR and FOS significantly (p < 0.0001) reduced systolic BPL from 78 +/- 16% to 44 +/- 13% and 28 +/- 12%, respectively, and diastolic BPL from 70 +/- 15% to 40 +/- 13% (p < 0.0001) and 35 +/- 13% (p < 0.0001), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1298,7555489,Captopril-induced acute pancreatitis.,N Jeandidier; M Klewansky; M Pinget,"To increase awareness concerning abdominal pain associated with the use of captopril, which is a molecule frequently used in diabetic patients. One case of acute pancreatitis associated with captopril, confirmed by a reintroduction, is described in a type II diabetes patient. Captopril and other angiotensin-converting enzyme inhibitors are very frequently prescribed in diabetic patients. Therefore, it is important to be aware of the possibility of pancreatitis linked to these molecules and to withdraw the treatment in case of severe unexplained abdominal pain.",1995.0,0,0
1299,7555530,Factors determining the blood pressure response to enalapril and nifedipine in hypertension associated with NIDDM.,J C Chan; M G Nicholls; C K Cheung; L K Law; R Swaminathan; C S Cockram,"To examine the factors that determine the blood pressure response to enalapril and nifedipine monotherapy in the treatment of hypertension associated with non-insulin-dependent diabetes mellitus (NIDDM). After a 6-week placebo baseline period, 102 hypertensive NIDDM patients were randomly assigned, double-blindly, to treatment with nifedipine retard (slow release) (n = 52) or enalapril (n = 50). The daily dosage of enalapril was increased, if required, from 10 to 20 to 40 mg and that of nifedipine from 40 to 60 to 80 mg at 4-week intervals during the 12-week titration period. Blood pressure, 24-h urinary albumin excretion (UAE), biochemical data, and serum angiotensin-converting enzyme (ACE) activity were measured at weeks -6, -4, 0, 4, 8, and 12. At week 0, venous blood was also sampled for baseline plasma atrial natriuretic peptide, renin, aldosterone, and serum insulin concentrations. At week 12, the mean daily dose of enalapril was 35 +/- 11.4 mg, and 27 (57%) patients were receiving the maximum daily dose of 40 mg. In the nifedipine group, the mean daily drug dose was 50 +/- 12.9 mg, and 4 (8%) were receiving the maximum daily dose of 80 mg. Despite a dose-dependent fall in the serum ACE activity in the enalapril group, the mean arterial pressure (MAP) was reduced by only 8 mmHg throughout the 12-week titration period compared to a decline of 15, 18, and 19 mmHg at weeks 0, 4, and 12, respectively, in the nifedipine group (P = 0.01 between groups). In the enalapril group, changes in MAP between weeks 0 and 12 correlated significantly with baseline plasma glucose (r = 0.45, P = 0.001) and aldosterone concentrations (r = -0.32, P = 0.02) and UAE (r = 0.3, P = 0.04). There was no statistically significant correlation between the changes in MAP and baseline plasma renin concentration. On multivariate analysis, the baseline renal function, glycemic control, and plasma aldosterone and serum insulin concentrations were all independently related to the changes in blood pressure in the enalapril-treated patients. No such statistical associations were observed in the nifedipine group. In hypertensive NIDDM patients, the activity of the renin-angiotensin-aldosterone system, the level of serum insulin, glycemic control, renal function, and proteinuria may be important determinants of the blood pressure response to ACE inhibition. Good glycemic control may optimize the antihypertensive efficacy of concomitant ACE inhibitor therapy.",1995.0,0,0
1300,7559888,Alterations in cortisol metabolism in insulin-dependent diabetes mellitus: relationship with metabolic control and estimated blood volume and effect of angiotensin-converting enzyme inhibition.,R P Dullaart; F L Ubels; K Hoogenberg; A J Smit; J J Pratt; J H Muntinga; W J Sluiter; B G Wolthers,"11 beta-Hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the interconversion of cortisol and its inactive metabolite, cortisone, and protects the mineralocorticoid receptor from activation by cortisol. Sodium and fluid retention is a well documented phenomenon in insulin-dependent diabetes mellitus (IDDM), but it is not known whether diabetes-associated alterations in cortisol metabolism contribute to its pathogenesis. Therefore, we evaluated some aspects of cortisol metabolism by measuring urinary metabolites of cortisol and cortisone in eight microalbuminuric and eight normoalbuminuric IDDM patients and eight matched control subjects. In both IDDM groups, the overnight excretion of tetrahydrocortisol (THF), allo-tetrahydrocortisol (allo-THF), and tetrahydrocortisone (THE) was lower than that in the control group (P < 0.05 to P < 0.01). Both the allo-THF/THF ratio, a parameter of 5 alpha/5 beta-reduction of cortisol, and the cortisol to cortisone metabolite ratio (THF+allo-THF/THE), which reflects the overall direction of the cortisol to cortisone interconversion, were lower in the IDDM groups (P < 0.05 to P < 0.01). In the combined subjects (n = 24), allo-THF, allo-THF/THF, and THF+allo-THF/THE were inversely correlated with hemoglobin A1c (r = -0.69, P < 0.001; r = -0.61, P < 0.01; and r = -0.58, P < 0.01, respectively). Upper arm segmental blood volume, estimated by an electrical impedance technique, was positively correlated with the cortisol to cortisone metabolite ratio in both the control subjects (r = 0.77; P < 0.05) and the IDDM patients in whom it was measured (r = 0.56; P < 0.05; n = 13), whereas the regression line was shifted leftward in IDDM (i.e. a lower ratio at the same blood volume; P < 0.03, by analysis of covariance). In seven microalbuminuric IDDM patients, the angiotensin-converting enzyme inhibitor, enalapril (10 mg daily for 6-12 weeks), resulted in a moderate further lowering of the cortisol to cortisone metabolite ratio (P < 0.05). The present data suggest a chronic hyperglycemia-related impairment in the reduction of corticoids to tetrahydro metabolites and an imbalance in 11 beta HSD. Altered 11 beta HSD activity is unlikely to be primarily responsible for the sodium and fluid retention in IDDM. Moreover, an additional mechanism of action of angiotensin-converting enzyme inhibition might be provided by an effect on 11 beta HSD activity.",1995.0,0,0
1301,7560247,Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.,B Beller; T Bulle; R C Bourge; H Colfer; R E Fowles; T D Giles; J Grover; J P Whipple; M B Fisher; M Jessup,"Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.",1995.0,0,1
1302,7560617,Cost-effectiveness of captopril therapy after myocardial infarction.,J Tsevat; D Duke; L Goldman; M A Pfeffer; G A Lamas; J R Soukup; K M Kuntz; T H Lee,"This study sought to assess the cost-effectiveness of captopril therapy for survivors of myocardial infarction. The recent randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed that captopril therapy improves survival in survivors of myocardial infarction with an ejection fraction < or = 40%. The present ancillary study was designed to determine how the costs required to achieve this increase in survival compared with those of other medical interventions. We developed a decision-analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80-year old survivors of myocardial infarction with an ejection fraction < or = 40%. Data on costs, utilities (health-related quality of life weights) and 4-year survival were obtained directly from the SAVE trial, and long-term survival was estimated using a Markov model. In one set of analyses, we assumed that the survival benefit associated with captopril therapy would persist beyond 4 years (persistent-benefit analyses), whereas in another set we assumed that captopril therapy incurred costs but no survival benefit beyond 4 years (limited-benefit analyses). In the limited-benefit analyses, the incremental cost-effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old patients. In the persistent-benefit analyses, incremental cost-effectiveness ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on age. The outcome was generally not sensitive to changes in estimates of variables when they were varied individually over wide ranges. In a ""worst-case"" analysis, incremental cost-effectiveness ratios for captopril therapy remained favorable ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients but were higher ($217,600/quality-adjusted life-year) for 50-year old patients. We conclude that the cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of myocardial infarction.",1995.0,0,0
1303,7560618,Cost-effectiveness analysis and clinical practice.,T S Rector; G S Francis,,1995.0,0,0
1304,7560723,Enalapril and peripheral neuropathy.,S Ahmad,,1995.0,0,0
1305,7562679,Characteristics of individuals who excrete versus retain sodium under stress.,J D Rollnik; P J Mills; J E Dimsdale,"To examine the role of stress on renal sodium excretion, we studied 27 normotensive and 21 hypertensive subjects. All subjects were placed on a standardized sodium diet. After water loading (2290 ml in 3 1/2 hr) they completed a 30 min baseline and a 30 min stress period (competitive videogame). Sixty-nine percent of the subjects increased (""excreters"") and 31% decreased (""retainers"") their sodium excretion under stress. In addition to increased potassium excretion (p < 0.006), excreters also manifested less of a stress associated increase in systolic (p = 0.055) and diastolic (p = 0.040) blood pressure and showed greater expression of anger (p < 0.02) than retainers. The same subjects were also studied to determin the effects of angiotensin converting enzyme inhibition (captopril 25 mg b.i.d.) on sodium excretion. On captopril, excreters now showed a retention of sodium (p < 0.001) and potassium (p < 0.01) under stress and no longer differed significantly in blood pressure reactivity. The results suggest that there are two different stress-related patterns of renal sodium excretion, that these patterns are related to blood pressure responses to stress, and may be related to anger expression. In addition, sodium excretion patterns under stress may be altered with certain type of antihypertensive medications.",1995.0,0,0
1306,7562882,Lisinopril administration improves insulin action in aged patients with hypertension.,G Paolisso; V Balbi; A Gambardella; G Varricchio; R Tortoriello; F Saccomanno; L Amato; M Varricchio,"Thirty elderly, mildly hypertensive patients were enrolled for a single-blind, randomised cross-over placebo controlled trial in which placebo and lisinopril (20 mg/day before breakfast) were given for 4 and 8 weeks, respectively. A wash-out period of 3 weeks between placebo and lisinopril was observed. In each patient a euglycaemic glucose clamp with simultaneous indirect calorimetry allowed us to determine whole body glucose disposal and substrate oxidation. Changes in morning SBP and DBP were also determined. Lisinopril vs. placebo significantly improved whole body glucose disposal (40.4 +/- 0.4 vs. 30.3 +/- 0.4 mumol/kg LBM x min; P < 0.01), non-oxidative glucose metabolism (18.1 +/- 0.7 vs. 10.9 +/- 0.6 mumol/kg LBM x min; P < 0.01) and fasting plasma potassium levels (4.8 +/- 3 vs. 4.4 +/- 0.4 mmol/l; P < 0.05). SBP (175 +/- 3.3 vs. 160 +/- 3.0 mm Hg; P < 0.001) and DBP (106 +/- 2.3 vs. 95 +/- 2.0 mm Hg; P < 0.001) were significantly reduced by lisinopril administration. After ACE inhibition, fasting plasma potassium levels correlated with the decline in mean arterial BP (r = -0.71; P < 0.006). In conclusion, lisinopril administration reduces arterial BP and improves insulin sensitivity in elderly hypertensive patients.",1995.0,0,0
1307,7562888,Measurement of trough-to-peak ratios of four anti-hypertensive drugs on the basis of 24 h ambulatory blood pressure monitoring: different methods may give different results.,G Gama; A Santos; J Polónia,"With 24 h ambulatory blood pressure monitoring (ABPM), the trough-to-peak (T/P) ratios (corrected for placebo) of atenolol 100 mg, cilazapril 2.5 mg, enalapril 20 mg and nifedipine-GITS 30 mg administered once daily for 4 weeks were determined in four groups of hypertensive patients. T/P ratios were calculated by three different methods: directly from the curves that averaged all individual 24 h profiles (A); averaging all individual T/P ratios after ABPM data were averaged for each patient over either 1 h intervals (B) or 3 h intervals (C). Methods B and C produced different values of T/P which, for each drug, were significantly higher with method C. With method A, nifedipine appeared to have the higher T/P. With methods B and C (which in contrast to method A, permitted statistical comparisons), differences between nifedipine and the other drugs were not significant. Meanwhile, method B appears to adhere most closely to FDA guidelines by taking more into account the interindividual variability of BP profile. Thus, we suggest that precise guidelines for measuring T/P on the basis of ABPM are needed, whereas for the comparison between drugs, both the mean value of the T/P and its variance must be determined.",1995.0,0,0
1308,7564347,Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man.,M McIntyre; R J MacFadyen; P A Meredith; J Menard; H R Brunner; J Insuasty; J L Reid,"We compared the response of the oral angiotensin II (Ang II) receptor antagonist (ARA) UP 269-6 with an angiotensin converting enzyme inhibitor (ACEI) enalapril 20 mg or placebo, during salt depletion in normal men. We also evaluated safety and tolerability. Sixteen healthy, normotensive male volunteers followed a standardised salt-depletion regimen for 3 days before each study day. Seven different doses of UP 269-6 (5, 10, 20, 40, 80, 120 and 180 mg) were administered double blind in a four-panel dose escalation, with enalapril and placebo randomised within each panel. Supine and erect blood pressure (BP) and heart rate (HR); serum and urinary electrolytes; plasma active renin (PAR), aldosterone, and Ang II were measured at intervals. Urinary electrolytes and aldosterone were measured for the 24 h before dosing and for 24 h after dosing. Dizziness and light-headedness on standing were reported after UP 269-6 at higher doses. Enalapril caused one episode of symptomatic postural hypotension. No other drug-related adverse events (AE) were noted. There was a dose-related decrease in supine and erect systolic and diastolic BP (SBP, DBP) with UP 269-6 at > or = 40 mg, with no change in HR. Based on the maximal decrease in mean arterial pressure (MAP), UP 269-6 at 180 mg had an effect largely comparable to that of enalapril 20 mg. There was a dose-related increase in PAR with UP 269-6. Although this was greater with UP 269-6 180 mg than with enalapril, serum and 24-h urinary aldosterone suppression was greater with enalapril than with any dose of UP 269-6.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1309,7564350,"Controlled multicenter study with quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.",R Romero; E Castellote; J Ocón; B Wagner,"In an 8-week, double-blind, randomized, active-controlled, multicenter study with three parallel treatment groups, we compared the efficacy and safety of once-daily 20 mg quinapril plus 12.5 mg hydrochlorothiazide (HCTZ) with each drug as monotherapy in patients with moderate to severe hypertension. Hypertensive out-patients with supine diastolic blood pressure (DBP) > or = 105 and < or = 120 mm Hg at the end of a 2- to 4-week placebo-baseline period were randomly assigned to one of the treatment groups. Of the 323 patients who were randomized to double-blind medication, 297 completed the study, but 6 patients were excluded for violations of protocol; therefore, statistical analysis was performed in 291 patients. Only 7 patients withdrew owing to lack of efficacy (2 receiving combination therapy). In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component in both evaluable data and intent-to-treat analyses. The incidence of adverse events (AE) was 24% in the quinapril monotherapy group, 14% in the combination therapy group, and 11% in the HCTZ monotherapy group. Orthostatic hypotension with related symptoms was observed in 4 patients (2 receiving quinapril monotherapy, 1 receiving HCTZ monotherapy, and 1 receiving combination therapy). Once-daily quinapril plus HCTZ provided increased reduction of DBP as compared with the monotherapies and was well tolerated in patients with moderate to severe hypertension.",1995.0,0,0
1310,7564352,Differential effects of a missed dose of trandolapril and enalapril on blood pressure control in hypertensive patients.,L Vaur; C Dutrey-Dupagne; J Boussac; N Genes; M Bouvier d'Yvoire; F Elkik; P A Meredith,"A double blind randomised comparison of two angiotensin-converting enzyme (ACE) inhibitors was made in a study in which ambulatory blood pressure was monitored over a steady-state dosage interval and the subsequent 24-h period, the latter being designed to mimic a missed dose of drug. The blood pressure responses on active therapy were compared to an identical recording made at the end of a 3-week placebo run in period. Eighty-eight essential hypertensives were treated with a morning dose of either trandolapril 2 mg or enalapril 20 mg. Mean systolic (SBP) and diastolic blood pressure (DBP) were calculated on each of the following periods: daytime (8:31 a.m.-10:30 p.m.), nighttime (10:31 p.m.-6:30 a.m.), and early morning (6:31 a.m.-8:30 a.m.). Trough/peak was calculated for each group both on active treatment and after a missed dose. Twelve patients were excluded from analysis before opening the randomisation code because of inadequate ambulatory blood pressure monitoring (ABPM) recordings. Demographic data, placebo-period office blood pressure, and ABPM recordings were not significantly different between the two groups. Both trandolapril and enalapril effectively reduced blood pressure over the 24-h period. Twenty four-hour ambulatory SBP and DBP decreased from 148 +/- 14/92 +/- 10 mm Hg to 135 +/- 14/83 +/- 10 mm Hg in the trandolapril group (p < 0.001). The same parameters decreased to a quite similar extent after enalapril, from 143 +/- 13/91 +/- 5 mm Hg to 133 +/- 15/83 +/- 8 mm Hg (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1311,7564362,"Double-blind comparison of antihypertensive treatment with ramipril and piretanide, given alone or in combination.",L Thijs; H Celis; W Kiowski; K Löffler; M Middeke; W Schulz; J Staessen; A Amery,"In a double-blind, randomized, multicenter trial, we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1312,7564369,"Antihypertensive effects of moexipril, a new ACE inhibitor, as add-on therapy to nifedipine in patients with essential hypertension.",B Persson; B R Widgren; A Fox; M Stimpel,"Moexipril is a new nonpeptide angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action. The antihypertensive efficacy and safety of moexipril as add-on therapy to nifedipine retard (20 mg b.i.d) was compared to placebo during 8 weeks in a double-blind trial with a parallel group design. A total of 203 patients with essential hypertension and a sitting diastolic blood pressure (DBP) > or = 95 mm Hg on nifedipine alone were randomly assigned to placebo or moexipril 3.75 mg o.d., 7.5 mg o.d., or 15 mg o.d.. At endpoint, the adjusted mean reductions in DBP from baseline were 6 mm Hg, 9 mm Hg (p < 0.01), and 9 mm Hg (p < 0.05) in the moexipril 3.75 mg, 7.5 mg, and 15 mg groups, respectively, compared to 5 mm Hg in the placebo group. All dosages of moexipril were well tolerated, and the overall percentages of patients who reported adverse experiences were smaller than in the placebo group. We concluded that moexipril as add-on therapy to nifedipine is well tolerated and gives additional antihypertensive effects.",1995.0,0,0
1313,7564719,Trumping the ACE.,J Vane,,1995.0,0,0
1314,7568661,Mania secondary to lisinopril therapy.,B P Skop; B J Masterson,,1995.0,0,0
1315,7572651,Effect of early enalapril therapy on left ventricular function and structure in acute myocardial infarction.,S P Schulman; J L Weiss; L C Becker; A D Guerci; E P Shapiro; N C Chandra; C Siu; J T Flaherty; V Coombs; J C Taube,"Infarct expansion starts within hours to days after transmural myocardial injury. Previous echocardiographic and left ventriculographic studies demonstrated that angiotensin-converting enzyme (ACE) inhibitor therapy limits left ventricular dilatation, particularly in patients with anterior wall acute myocardial infarction (AMI) or impaired left ventricular function. Forty-three patients with an acute Q-wave AMI were randomized within 24 hours of symptom onset to intravenous enalaprilat (1 mg) or placebo. Patients were then given corresponding oral therapy and followed for 1 month. Predrug and 1-month gated blood pool scans were obtained in 32 patients to evaluate changes in cardiac volumes and ejection fraction. Twenty-three patients underwent magnetic resonance imaging at 1 month to evaluate left ventricular infarct expansion. Blood pressure decreased at 6 hours but returned to baseline in both groups after 1 month of therapy. The change in cardiac volumes from baseline to 1 month differed between the placebo (end-diastolic volume +16 +/- 5 ml, end-systolic volume +8 +/- 6 ml), and enalapril (end-diastolic volume -8 +/- 9 ml and end-systolic volume -14 +/- 7 ml) groups (p < 0.05 vs placebo). Global and infarct zone ejection fractions improved significantly at 1 month in the enalapril group (+6 +/- 3% and 19 +/- 5%, respectively) but did not change over 1 month in the placebo group. Infarct segment length and infarct expansion index by magnetic resonance imaging were significantly less in those treated with enalapril, suggesting less infarct expansion in this group. Thus, early administration of enalaprilat to patients presenting with a first Q-wave AMI prevents cardiac dilatation and infarct expansion.",1995.0,0,1
1316,7573094,Granulocytopenia after combined therapy with interferon and angiotensin-converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.,M Casato; L P Pucillo; M Leoni; L di Lullo; A Gabrielli; D Sansonno; F Dammacco; G Danieli; L Bonomo,"The purpose of this study was to assess whether granulocytopenia observed in 3 of 38 patients with essential mixed cryoglobulinemia who were treated with low-dose interferon was due to the underlying disease or to synergistic toxicity of interferon with other drugs. Adverse effects of interferon therapy were monitored in 38 patients affected with type II essential mixed cryoglobulinemia. Patients were treated with 3 million units (MU), daily or on alternate days, of recombinant interferon-alpha 2a (35 patients) or with natural interferon-beta (3 patients). The duration of treatment ranged between 6 and 15 months; the total duration of follow-up, including after therapy, ranged between 8 and 93 months. None of 35 patients treated with interferon alone developed significant hematologic alterations. In addition, none of 7 patients treated with angiotensin-converting enzyme (ACE) inhibitors alone showed hematologic toxicity. Three patients who were treated with a combination of interferon and ACE inhibitors developed severe granulocytopenia a few days after starting treatment. Granulocytopenia subsided within 1 to 2 weeks after suspending therapy. Resumption of treatment with this drug combination produced a granulocytopenia relapse in 1 patient. In these 3 patients, interferon treatment alone, or ACE inhibitor monotherapy, was not followed by granulocytopenia. Although severe hematologic toxicity rarely develops in patients treated with low-dose interferon, granulocytopenia occurred in all 3 of our patients with mixed cryoglobulinemia who were treated with a combination of low-dose interferon-alpha 2a and ACE inhibitors. Neither drug alone was toxic in any of our cryoglobulinemic patients, indicating a high risk of severe hematologic toxicity for this drug combination, at least in patients with this disease. Physicians should be aware of this danger when using interferon treatment in patients with this, or possibly other, disorder(s) that also require antihypertensive therapy.",1995.0,0,0
1317,7576264,ACE inhibitors and impotence: a case series from the Spanish drug monitoring system.,A Carvajal; M T Lérida; A Sánchez; L H Martín; I M de Diego,,1995.0,0,0
1318,7576397,Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects.,L J Dominguez; M Barbagallo; W Kattah; D Garcia; J R Sowers,"To investigate the metabolic and renal effects of the nonsulfhydryl, tissue-active ACE inhibitor quinapril in diabetes and in hypertension, we studied 30 essential hypertensives and 24 non-insulin-dependent (type II) diabetic (NIDDM) subjects with hypertension. Systolic and diastolic blood pressures, plasma glucose, and insulin responses to an oral glucose load (75 g), lipid profile, and urinary albumin excretion were evaluated before and after 8 weeks' administration of quinapril (10 to 40 mg/day). Quinapril produced a significant and comparable reduction of arterial blood pressure in both groups. Mean arterial pressure decreased from 114.8 +/- 0.9 to 94.2 +/- 1.1 (-17.9 +/- 1.5%) in the essential hypertensive group and from 118.4 +/- 1.6 to 96.2 +/- 1.4 (-18.4 +/- 1.6%) in the diabetic hypertensive group. In both essential hypertensives and diabetic-hypertensive subjects with microalbuminuria, quinapril significantly and comparably reduced the urinary albumin excretion rate (UAE); UAE decreased from 32.5 +/- 5.5 micrograms/min to 14.7 +/- 3.7 micrograms/min (P < .05 v baseline) in the diabetic-hypertensive group and from 27.5 +/- 3.0 micrograms/min to 11.6 +/- 2.7 micrograms/min (P < .05 v baseline) in the essential hypertensives. Altogether, a direct correlation was found between the initial level of UAE and the UAE reduction after quinapril (delta UAE) (r = 0.706, p < .05). Insulin and glucose responses to an oral glucose tolerance test and the lipid profiles were not modified by quinapril treatment. The results confirm that quinapril is an effective antihypertensive agent that additionally reduces microalbuminuria in both hypertensive diabetics and in patients with essential hypertension, without altering insulin sensitivity and lipid profiles.",1995.0,0,0
1319,7576410,A management trial for Duchenne cardiomyopathy.,Y Ishikawa; J R Bach; Y Ishikawa; R Minami,"The physiatrist can now be instrumental in prolonging the survival of individuals with neuromuscular disease by using respiratory muscle aids. As a result, morbidity and mortality from cardiomyopathy are likely to increase for patients with generalized myopathies. One hundred consecutive patients with dystrophin-deficient muscular dystrophy and a mean age of 17.2 yr (range, 5-41) satisfied criteria for having dilated cardiomyopathy (DCM) and received digitalis and diuretics. Nine of the 14 patients were symptom-free, despite left ventricular ejection fractions (LVEFs) of 25-40%. The five patients with symptomatic heart failure had severe ventricular dilatation, with LVEFs < 25%. Two of the five patients died of heart failure within 1 yr. For the remaining three patients, we evaluated the addition of the angiotensin-converting enzyme (ACE) inhibitor enalapril and, subsequently, the use of beta-blockers to the therapeutic regimen. Addition of these medications, never before attempted in the management of cardiomyopathy associated with generalized myopathic disease, complemented each other in relieving symptoms and reversing signs of congestive heart failure and DCM. We conclude that the combination of ACE inhibitor and beta-blocker deserves further exploration for inclusion in any management regimen for the treatment of muscular dystrophy-associated cardiomyopathy.",1995.0,0,0
1320,7579052,"Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.",S Klahr; J A Breyer; G J Beck; V W Dennis; J A Hartman; D Roth; T I Steinman; S R Wang; M E Yamamoto,"In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.",1995.0,0,0
1321,7584934,A 12-month comparison of ACE inhibitor and CA antagonist therapy in mild to moderate essential hypertension--The GLANT Study. Study Group on Long-term Antihypertensive Therapy.,,"Patients with mild to moderate essential hypertension were treated mainly with an ACE inhibitor (delapril, n = 980) or a Ca antagonist (n = 956) for 12 months, and the incidence of cerebrovascular and cardiovascular events as well as drug-related side effects were compared between the two groups. There were no significant differences between the clinical backgrounds of the two groups. In both groups, the blood pressure was decreased significantly from 1 month of treatment onwards, with the degree of reduction being greater in the Ca antagonist group throughout the study period (p < 0.001). Cerebrovascular or cardiovascular events occurred in 11 out of 980 patients in the delapril group and 18 out of 956 patients in the Ca antagonist group (p = NS). Cerebrovascular disease developed in 5 delapril-treated patients and 11 Ca antagonist-treated patients, and heart disease developed in 5 and 7 patients, respectively (both p = NS). Discontinuation of treatment due to side effects was significantly more common in the delapril group than in the Ca antagonist group (p < 0.001). There was no significant difference in the incidence of cerebrovascular and cardiovascular events between the two groups, and the results suggested that blood pressure reduction per se did not necessarily lead to a parallel decrease in cerebrovascular and cardiovascular complications.",1995.0,0,0
1322,7585753,Short-term effects of captopril on exercise tolerance in patients with chronic stable angina pectoris and normal left ventricular function.,R Steffensen; P Grande; J K Madsen; S Rasmussen; S Haunsø,"A double-blind, placebo-controlled, crossover study was carried out to evaluate the short-term effects of captopril on exercise tolerance in 18 normotensive patients with chronic stable angina pectoris and normal left ventricular function. Captopril 25 mg (or placebo) was given twice, i.e. in the evening (10 p.m.) and the following morning (8 a.m.), prior to a maximal symptom-limited bicycle exercise test (11 a.m.). Captopril reduced the systolic and diastolic blood pressures at rest (p < 0.01) without causing any reflex tachycardia. The time to onset of S-T depression was prolonged (p < 0.05), and the maximal S-T depression was reduced (p < 0.02). No differences were found between captopril and placebo in total exercise duration or time to onset of angina. The effects of captopril on exercise-induced ischemia were demonstrated most clearly in patients who responded with a greater than 10 mm Hg fall in the resting systolic blood pressure. In conclusion, this study suggests that captopril has anti-ischemic properties, which may be of importance in the treatment of patients with chronic stable angina and normal left ventricular function. These beneficial effects probably relate to a reduction in afterload and myocardial wall stress and therefore a reduction in myocardial oxygen demand.",1995.0,0,0
1323,7585774,Angiotensin-converting enzyme inhibitors post-myocardial infarction.,J B Young,"Results from SOLVD, SAVE, AIRE, GISSI-III, ISIS-IV, and the Chinese Captopril Trial suggest that therapy with ACE inhibitors, at least with enalapril, captopril, ramipril, and lisinopril, induce significant reduction in morbidity and mortality rates in patients with ischemic heart disease, myocardial infarction, and a wide range of ventricular function and myocardial infarction. SOLVD and SAVE results, in particular, demonstrate improved survival and reduced major ischemic events in patients with depressed systolic ventricular function. SOLVD points out that institution of ACE inhibitor therapy need not be done immediately post-myocardial infarction to accrue benefit. GISSI-III and ISIS-IV, on the other hand, suggest that use of ACE inhibitor drugs early post-myocardial infarction produces significant, albeit small, benefits when drugs are begun early post-event in conjunction with other routinely used therapeutic strategies. The prospective, well-designed, and well-controlled nature of these clinical trials, the consistency of their findings, and the high level of morbidity and mortality in placebo groups establish the importance of preventing ischemic events with the prescribed ACE inhibitors. Particularly important is the fact that none of these clinical trials were designed to determine optimal dose or frequency of administration of the ACE inhibitors chosen. Targeting dose principles were utilized and clinicians wishing to generate similar results in their own patient population should choose one of the ACE inhibitors studied and administer it in the manner described in hopes of achieving outcomes similar to those detailed in the summarized clinical trials. Finally, recommendations regarding post-myocardial infarction therapy with ACE inhibitors can be summarized. Patients having acute or remote infarction should have an assessment of ventricular function. All patients with depressed systolic function, whether they are or are not symptomatic, should receive a trial of an appropriate ACE inhibitor. Patients suffering an acute myocardial infarction should have an assessment of ventricular function early and, if the ejection fraction is low (probably < 50%), an appropriately chosen ACE inhibitor should be begun after 24 hours have elapsed. ACE inhibitor therapy should be begun in combination with other proven effective post-myocardial infarction treatment strategies. In patients with normal systolic function, advantages of ACE inhibitor therapy are less clear, but patients with large anterior wall myocardial infarction will likely benefit, even without objective evidence of left ventricular systolic dysfunction. Concomitant utilization of thrombolytic agents, aspirin, and beta blockers should not interdict use of ACE inhibitor therapy.",1995.0,0,0
1324,7585859,Meta-analysis of three trials with quinapril in the treatment of mild-to-moderate hypertension in the Mexican population.,L Alcocer; G Novoa; D Sotres,"A meta-analysis was performed to examine the therapeutic effect of quinapril in the treatment of patients with mild-to-moderate hypertension. Data from three clinical trials conducted in Mexico and including a total of 426 patients were examined using a retrospective approach and statistical methods. The meta-analysis proved that quinapril induces positive diastolic and systolic responses at all the doses studied, particularly at the 10-mg dose. At this dose, 94.1% of patients reduced their diastolic blood pressure (DBP) by 10 mm Hg or attained a DBP of < or = 90 mm Hg. Overall, quinapril reduced DBP by between 14.8 and 24.8 mm Hg proportionally to the baseline DBP. Systolic blood pressure decreased 16 to 35.7 mm Hg from baseline levels. We conclude that the meta-analysis allowed a clearer and more dependable handling of the results regarding effectiveness and optimum dose of quinapril.",1995.0,0,0
1325,7586352,Radionuclide monitoring of cardiac adaptations to volume loading in patients with dilated cardiomyopathy and mild heart failure. Effects of angiotensin-converting enzyme inhibition.,M Volpe; M A Rao; A Cuocolo; R Russo; A Nappi; A F Mele; I Enea; B Trimarco; M Condorelli,"Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction. Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL.kg-1.min-1 for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction < 50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all P < .001), whereas ESV was progressively reduced (P < .001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA: F = 5.98, P < .001), ESV increased (P < .001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (P < .001), and ESV was reduced (P < .001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged. Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.",1995.0,0,0
1326,7586765,Captopril in acute myocardial infarction: beneficial effects on infarct size and arrhythmias.,W D Bussmann; G Micke; R Hildenbrand; H Klepzig,"It is known from experiments that angiotensin-converting enzyme inhibitors can limit infarct size. In a prospective, randomized, placebo-controlled double-blind study, 22 patients were given 1.5-2.0 mg captopril/h i.v., while 24 patients were given placebo. Medication was started between 2 and 18 h from the onset of infarction. The two groups were matched for age, infarct location, and time of intervention. With the exception of one patient in either group, all were concurrently given nitroglycerin. The necrosis parameters were provided by the quantitative measurement of the QRS complex. The Q wave decreased with captopril treatment (-0.003 mV), but increased with placebo (+0.14 mV, p < 0.05). The number of ventricular premature beats at 24 h from the start of treatment was 25/h with placebo, and 9/h with captopril (p < 0.02). Ventricular fibrillation occurred seven times in the placebo group, but did not occur in the captopril group. The creatine kinase infarct weight was 59 gram-equivalents (gEq) with placebo, and 45 gEq with captopril (p = NS). Mean arterial pressure was reduced by 12 mmHg with captopril treatment. The results show a beneficial effect of captopril on infarct size and electrical instability, over and above the effect of standard management with nitroglycerin and thrombolysis.",2001.0,0,0
1327,7587182,Drugs for hypertension.,,,1995.0,0,0
1328,7588185,Nonemergent hypertension. New perspectives for the emergency medicine physician.,A M Thach; P J Schultz,"The emergency medicine physician must evaluate and treat hypertensive patients in a variety of contexts, ranging from the compliant patient with well-controlled blood pressure who presents for an unrelated problem, to the patient with asymptomatic blood pressure elevation, to the patient with a true hypertensive urgency or emergency. Recently, the approach to the treatment of adult hypertension has been modified to take into account advances in the understanding of individual patient risk factors and relative risk of cardiovascular complications. Additionally, no data currently exist that show a benefit to acutely lowering the blood pressure of asymptomatic patients with severe blood pressure elevation, but there is data to suggest that it may be harmful, especially in patients with cardiovascular risk factors. From this perspective, the authors define hypertensive urgency and make recommendations for more careful deliberation in management decisions. This article, along with the article on hypertensive emergencies in this issue, provides an approach to the patient presenting to the emergency department with hypertension, elevated blood pressure, or both.",1995.0,0,0
1329,7588920,Neurohormonal changes after acute myocardial infarction. Relationships with haemodynamic indices and effects of ACE inhibition.,S G Foy; I G Crozier; A M Richards; M G Nicholls; J G Turner; C M Frampton; H Ikram,"To determine the neurohormonal response to angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarction, 36 patients presenting within 6 h of the onset of chest pain were studied in a single regional cardiology service. In this double-blind study, 13 patients were randomized to receive captopril, 12 patients received enalapril, and 11 patients received placebo, for 12 months. In patients receiving placebo, acute myocardial infarction was associated with activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, and stimulation of plasma brain natriuretic peptide and atrial natriuretic peptide levels. ACE inhibition did not significantly alter circulating levels of norepinephrine, brain natriuretic peptide or atrial natriuretic peptide. Compared with placebo, enalapril induced a steep decline in plasma ACE activity, and plasma angiotensin II levels were reduced by both ACE inhibitors. Using grouped data, circulating levels of brain natriuretic peptide at the zero sampling time were significantly higher than atrial natriuretic peptide values. Brain natriuretic peptide levels at 72 h were significantly correlated with the radionuclide left ventricular ejection fraction measured 5 days and 3 months after infarction. Similar associations were observed for atrial natriuretic peptide and norepinephrine. We confirm activation of the renin-angiotensin-aldosterone and sympathetic nervous systems after acute myocardial infarction. The atrial natriuretic peptide and brain natriuretic peptide and sympathetic nervous system responses to acute myocardial infarction were not significantly modified by ACE inhibition. Brain natriuretic peptide and atrial natriuretic peptide levels were significantly correlated with the left ventricular ejection fraction measured 5 days and again 3 months after myocardial infarction, and may prove a useful prognostic index.",1995.0,0,0
1330,7588925,Contractile state is the major determinant of functional outcome in patients with left ventricular dysfunction treated with enalapril.,I Mirsky; T Aoyagi; T Ihara; C van Eyll; M F Rousseau; H Pouleur,"Large-scale drug trials have focused primarily on mortality and morbidity and less on the functional state of the myocardium. A model was developed to assess myocardial contractile state in patients with left ventricular (LV) dysfunction and to address the questions of differences in function between patients with and without overt heart failure, effects of enalapril, and best predictors of functional outcome. Pressure-angiographic data were obtained from 16 patients with overt heart failure and 47 without heart failure. Repeat studies were conducted in 41 patients following 1 year's treatment with enalapril or placebo. Left ventricular silhouettes were divided into 18 segments to estimate regional ejection fraction, wall stress and myocardial damage (% myocardial damage). Contractile state was assessed and ranked by ejection rate-preload-afterload relationships and by a score method based on 10 myocardial and ventricular function parameters. End-diastolic and end-systolic volumes (EDV, ESV) were significantly greater (P < 0.001), ejection fraction (EF) lower (P < 0.009), % myocardial damage greater (P < 0.008) and contractile state more depressed in patients with overt heart failure. Changes in EDV and ESV (delta placebo vs delta enalapril) were significant (delta EDV, P < 0.003; delta ESV, P < 0.014). Directional shifts in the diastolic pressure-volume relationships with enalapril or placebo depended primarily on the basal contractile state and diastolic volume range. The best single predictors of post-treatment EF were the score index (a surrogate parameter for the contractile state) and ESV. Added benefits of enalapril include the prevention of further dilatation in patients with less depressed contractile state and delay in the onset of heart failure. Asymptomatic patients with LV dysfunction should also be considered for angiotensin converting enzyme (ACE) inhibitor therapy.",1995.0,0,0
1331,7589767,Antihypertensive efficacy and safe use of once-daily sustained-release diltiazem in the elderly: a comparison with captopril. The Dilcacomp Study Group.,J Nicaise; E Neveux; P Blondin,"The efficacy and safety of sustained-release diltiazem, 200-300 mg once daily was compared with that of captopril, 12.5-25 mg twice-daily, in 100 elderly patients (65-85 years old) with mild to moderate essential hypertension (supine diastolic blood pressure 95-115 mmHg). All patients received placebo for 2 weeks, followed by an 8-week double-blind period, and were randomized to either diltiazem (n = 50) or captopril (n = 50). Their blood pressure was measured at trough level at week 4 immediately before dosing, i.e. 24 h post diltiazem dose or 12 h post captopril dose. Also at week 4, in non-responders, diltiazem was increased from 200 to 300 mg once daily and captopril from 12.5 to 25 mg twice daily to achieve a target supine diastolic blood pressure reduction of at least 10 mmHg or a diastolic blood pressure below 90 mmHg. Supine diastolic blood pressure, at week 8, was significantly (P < 0.001) reduced from 102 +/- 1 to 90 +/- 1 mmHg with diltiazem and from 103 +/- 1 to 89 +/- 1 mmHg with captopril, bringing this parameter within normal limits for both groups. Supine systolic blood pressure was also significantly (P < 0.001) reduced. Target blood pressure was achieved in 68% of patients taking diltiazem and in 70% taking captopril. Distribution of adverse events was comparable in both groups; no significant changes in laboratory or electrocardiographic parameters occurred. Two serious events were reported with captopril: one sudden death and one cerebrovascular stroke. Sustained-release diltiazem once a day is a convenient, well tolerated, first line treatment for hypertension in the elderly, for whom the possibility of using two dose levels allows a close regimen adjustment, 200 mg being recommended as a starting dose.",1995.0,0,0
1332,7591740,ACE inhibitors for prophylaxis of migraine headaches.,W I Bender,"Seventeen patients with migraine headaches, occurring at least twice a month, were successfully treated with an ACE inhibitor for prophylaxis. Most were given enalapril, some used lisinopril. Duration of treatment ranged from 3 months to 3 years. Side effects were generally not noted. Cough occurred in four patients. The mechanism of action is unknown. The lack of side effects and the presence of clearly sustained benefit in this small group of migraineurs should prompt further study and use of this class of drugs for prophylaxis.",1995.0,0,0
1333,7594429,Alpha-blockade and calcium antagonism: an effective and well-tolerated combination for the treatment of resistant hypertension.,M J Brown; J E Dickerson,"To test whether the combination of calcium antagonism is additive with the other newer antihypertensives, namely alpha-blockers and angiotensin converting enzyme (ACE) inhibitors. Three-way double-blind, Latin-square crossover studies in two groups of 12 patients with essential hypertension. The three treatment periods were amlodipine, doxazosin (study A) or enalapril (study B), and the combination of amlodipine with the second drug. Each treatment was taken for 1 month, preceded by a 2-week single-blind run-in period, in which the patients received a low dose of doxazosin (study A) or enalapril (study B) to enable recruitment of patients with moderate or severe hypertension. Blood pressure, foot volume and plasma noradrenaline concentration were measured at the end of each run-in and treatment period. The combination of alpha-blockade and calcium antagonism caused a fall in supine and erect blood pressures. These falls were significantly greater than on either drug alone, and greater than the sum of the falls when taking the individual drugs. The combination of amlodipine and the ACE inhibitor was also additive. Both combinations with amlodipine were tolerated well by all patients. The combination of alpha-blockade and calcium antagonism has not previously been studied and should be useful for resistant hypertensives who have not tolerated beta-blockade or ACE inhibitors. The combination of ACE inhibition and calcium antagonism has previously been shown to be additive; its use as a positive control in the present studies suggests that the use of an active drug for a run-in period may be a useful design for permitting the study of patients from whom all treatment cannot safely be withdrawn.",1995.0,0,0
1334,7594444,Neutral endopeptidase versus angiotensin converting enzyme inhibition in essential hypertension.,B Favrat; M Burnier; J Nussberger; J M Lecomte; R Brouard; B Waeber; H R Brunner,"To evaluate the antihypertensive efficacy of sinorphan, an orally active inhibitor of neutral endopeptidase EC 3.4.24.11. The ability of sinorphan (100 mg twice a day) to lower blood pressure was compared with that of the angiotensin converting enzyme (ACE) inhibitor captopril (25 mg twice a day) using a randomized-sequence, double-blind crossover design in 16 patients with essential hypertension. Each treatment was administered for 4 weeks and treatments were separated by a 3-week placebo period. At the end of the last phase of treatment sinorphan was combined with captopril for a further 4-week period. The changes in systolic (SBP) and diastolic blood pressure (DBP) were monitored using repeated ambulatory blood pressure monitoring. When given as monotherapy for 4 weeks, neither sinorphan nor captopril significantly reduced the 24-h or the 14-h daytime mean SBP or DBP. However, a significant decrease in DBP was observed during the first 6 h after the morning administration of captopril. With sinorphan only a significant decrease in night-time SBP was found. With the combined therapy of sinorphan and captopril, significant decreases both in SBP and in DBP were observed, which were sustained over 24 h. After 4 weeks of sinorphan alone or in combination with captopril, no change in plasma atrial natriuretic peptide level was found. However, urinary cyclic GMP excretion increased transiently after administration of the neutral endopeptidase inhibitor. Neutral endopeptidase inhibition with sinorphan has a limited effect on blood pressure in hypertensive patients when given alone. However, simultaneous neutral endopeptidase and ACE inhibition induces a synergistic effect, and might therefore represent an interesting new therapeutic approach to the treatment of essential hypertension.",1995.0,0,0
1335,7596934,Effects of captopril and enalapril on renal function in elderly patients with chronic heart failure.,C A Haffner; M J Kendall; A D Struthers; A Bridges; D J Stott,"To compare the effects on renal function of captopril and enalapril in elderly patients with chronic heart failure. A multi-centre double-blind parallel-group comparison of the two angiotensin-converting enzyme (ACE) inhibitors, captopril (12.5 mg bid) and enalapril (2.5 mg bid). 80 elderly patients with chronic heart failure (41 in the captopril group, 39 in the enalapril group). The blood pressure and pulse rate response to the first dose of ACE inhibitor was assessed in all patients. Glomerular filtration rate (GFR) was measured radioisotopically by 99mTcDTPA or 51CrEDTA clearance after three and six months of each treatment. Subgroups were assessed for effective renal plasma flow (33 patients), exercise tolerance (25 patients) and by a symptom-oriented questionnaire (45 patients). No serious adverse effect on GFR was noticed. There was no significant difference between the two treatments in the mean baseline GFR or in changes from baseline at three and six months (captopril mean baseline GFR 49.6 ml min-1 1.76 m-2, enalapril 54.7 ml min-1 1.76 m-2; mean change (95% confidence interval) at three months captopril 12 ml min-1 (+3.0, +21.0), enalapril -2 ml min-1 (-13.0; +9.0); mean change at six months, captopril 3.7 ml min-1 (-6.7; +14.2), enalapril -6.0 ml min-1 (-21.0; +9.4). Significantly more patients given captopril had an improvement in GFR during the study period (26/31 compared with 20/31 enalapril-treated patients at three months, p = 0.0096, and 23/30 compared with 15/27 at six months, p = 0.021). There were no significant changes in effective renal plasma flow. Three patients treated with enalapril developed symptomatic hypotension within three days of starting treatment. Quality of life questionnaires revealed more gastrointestinal symptoms in the enalapril group (p = 0.039). Captopril seems marginally preferable to enalapril in the treatment of chronic heart failure in elderly patients.",1995.0,1,1
1336,7599749,Neurohormonal activation in patients with acute myocardial infarction or chronic congestive heart failure. With special reference to treatment with angiotensin converting enzyme inhibitors.,A Sigurdsson,"Neurohormonal activation may provide a pathophysiological link between acute myocardial infarction and chronic congestive heart failure, and modulation of neurohormonal activity may be an important therapeutic target in these conditions. Plasma neurohormones were studied in 55 patients with acute myocardial infarction. Angiotensin II, noradrenaline and ANP were elevated in the early phase but tended to normalize during the first week in patients without signs of heart failure. In patients with heart failure angiotensin II and noradrenaline remained elevated for 1 month and ANP for 4-6 months. During head-up tilt, angiotensin II and noradrenaline increased most in patients with heart failure. In patients with a first myocardial infarction there was a positive correlation between sustained neurohormonal activity and infarct size. Almost complete suppression of plasma ACE activity was achieved within 30 min in 48 patients treated with intravenous enalaprilat, initiated within 24 h from the onset of infarction. The drug was tolerated in dosages of 1.0-1.2 mg given over 1-2h. Patients with systolic blood pressure between 100 and 110 mmHg incurred a greater risk of hypotension than those with higher blood pressure at baseline. Tolerance was not worse among patients treated with intravenous diuretics, metoprolol or nitroglycerin. A total of 98 patients were randomized to treatment with enalapril or placebo, initiated within 24 h from onset of infarction and continued for 4-6 months. During treatment there were no significant differences in plasma levels of angiotensin II, aldosterone, ANP or catecholamines between groups. Echocardiographic recordings were performed in 28 patients. Among patients on placebo there was a positive correlation between plasma levels of noradrenaline at days 5-7 and the increase in left ventricular volumes during the study period, and an inverse correlation between plasma aldosterone at days 5-7 and the increase in left ventricular ejection fraction during the study. No such correlation was found among patients on enalapril. ANP levels at 1 month correlated inversely with the left ventricular ejection fraction at the same time. Plasma neurohormones were measured in 223 patients with mild or moderately severe chronic heart failure, randomized to treatment with ramipril or placebo for 3 months. There was wide variation in hormone levels. Noradrenaline and aldosterone correlated inversely with exercise duration at baseline. Noradrenaline correlated positively with the degree of symptoms. Aldosterone and ANP were reduced with ramipril compared with placebo. Noradrenaline was reduced among patients with baseline levels in the highest tertile. Plasma hormones were also measured at peak exercise in 54 patients. Hormonal levels at rest correlated strongly with those at peak exercise.(ABSTRACT TRUNCATED AT 400 WORDS)",1995.0,0,0
1337,7600744,Is ACE inhibition with lisinopril helpful in diabetic neuropathy?,A Reja; S Tesfaye; N D Harris; J D Ward,"Thirteen diabetic patients with hypertension (mean diastolic blood pressure 96.2 +/- 1.1 mmHg) were included in a study to assess the effects of lisinopril (20 mg day-1) on measures of nerve function. Patients had nerve conduction velocity (NCV), temperature discrimination threshold (TDT), and vibration perception threshold (VPT) measurements. At the end of 12 weeks of treatment with lisinopril, there was a significant improvement in median motor NCV (mean change +/- SEM 2.7 +/- 0.6 m s-1, p < 0.0001), median sensory NCV (2.1 +/- 0.9 m s-1, p = 0.03), peroneal motor NCV (1.0 +/- 0.4 m s-1, p = 0.03), and sural sensory NCV (1.9 +/- 0.7 m s-1, p = 0.01) values. There were also significant improvements in warm TDT and VPT. Diastolic BP decreased significantly, but there was no significant change in HbA1. Double blind controlled studies are now needed to confirm the effect of lisinopril on measures of nerve function.",1995.0,0,1
1338,7601014,Spirapril. A preliminary review of its pharmacology and therapeutic efficacy in the treatment of hypertension.,S Noble; E M Sorkin,"Spirapril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor prodrug which is converted to the active metabolite spiraprilat following oral administration, and which has been evaluated primarily for the treatment of hypertension. In dose-finding studies of patients with mild to severe hypertension, spirapril > or = 6 mg once daily produced reductions in blood pressure of approximately 10 to 18 mm Hg (systolic) and 7 to 13 mm Hg (diastolic) [24-hour postdose trough readings at the end of the treatment period]. Blood pressure normalisation (trough diastolic blood pressure < or = 90 mm Hg) had occurred in 29 to 50% of patients at the end of these investigations. The dose-response curve for spirapril appears to be flat for doses of 6 to 24 mg once daily. Comparisons with other ACE inhibitors are limited in number, and further studies are required before the relative antihypertensive efficacy of spirapril can be fully evaluated. However, in single, well controlled clinical trials, spirapril produced similar reductions in blood pressure to those seen with enalapril or captopril. When given as monotherapy or in combination with hydrochlorothiazide, spirapril may offer potential advantages over the calcium antagonist nitrendipine. Spirapril is generally well tolerated and produces an adverse event profile similar to that of other ACE inhibitors. Data from small studies suggest that spirapril can be used without dosage adjustment in patients with renal impairment, as a consequence of its dual renal and hepatic clearance mechanisms. This is in contrast to most ACE inhibitors, which are eliminated by a predominantly renal mechanism that results in accumulation of the active metabolite when renal function is impaired. However, the utility of spirapril in this patient group has yet to be fully determined because of conflicting data regarding its effects on renal function. Thus, spirapril is an effective antihypertensive agent which is well tolerated. Further comparative trials are needed to fully determine its efficacy with respect to other ACE inhibitors, and a better understanding of its effects on renal function will clarify its role in hypertensive patients with renal failure.",1995.0,0,0
1339,7607715,Differing mechanisms of action of angiotensin-converting enzyme inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group.,M R Weir; J M Gray; R Paster; E Saunders,"The antihypertensive effect of the angiotensin-converting enzyme inhibitor trandolapril administered in doses of 1, 2, and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind, randomized, placebo-controlled, parallel study design. Trandolapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite, trandolaprilat. After 6 weeks of double-blind treatment, trandolapril lowered baseline sitting diastolic pressure in both white and black patients. A comparison of the antihypertensive response of the two populations revealed that the black patients required between two and four times the dose of trandolapril to obtain a response similar to that observed in the white patients. A dose of 1 mg/d trandolapril resulted in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients; a similar response (-6.5 mm Hg) was observed in the black patients at 4 mg/d. In contrast to the population differences in blood pressure, the decreases in angiotensin-converting enzyme activity were similar for both populations. An evaluation of trandolaprilat levels revealed that there were no racial differences in the trandolaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition. Therefore, it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity. The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of trandolapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition.",1995.0,0,0
1340,7607751,Long term effects of ACE inhibitors on the erythrocytosis in renal transplant recipients.,S M Lal; H S Trivedi; G Ross,"Erythrocytosis is infrequently seen in renal transplant recipients. Both theophylline and angiotensin converting enzyme (ACE) inhibitors have been reported to decrease the elevated hematocrit (Hct) and hemoglobin (Hgb) levels. We studied the efficacy of the ACE inhibitors ramipril (n = 6) and enalapril (n = 1) in seven stable renal transplant recipients. Although the ACE inhibitors significantly reduced the elevated Hct and Hgb levels during the short and long term (Hct 53 +/- 1 vs 48.8 +/- 0.7%; Hgb 17.8 +/- 0.4 vs 16.7 +/- 0.3 vs 16.7 +/- 0.3 gm/dl, at 1 year), the clinical significance of these reductions remains unknown. During therapy there were no significant changes in the blood pressure, serum creatinine and potassium levels and the medications were well tolerated.",2001.0,0,0
1341,7608310,"Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring.",W B White; A Whelton; A A Fox; M Stimpel; P M Kaihlanen,"To assess the efficacy and time-dependent effects of once-daily moexipril, a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme (ACE) inhibitor, moexiprilat, we conducted a multicenter, double-blind, placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure (BP) recordings. Patients were included in the trial based on a minimum of 40% of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase; and the primary endpoint was change in 24-hour ambulatory diastolic BP. Patients were randomized to receive placebo, 7.5 mg of moexipril, or 15 mg of moexipril once daily. Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy. After the 7.5-mg dose, there were no significant changes in the acute or prolonged clinic BPs compared with placebo. Compared with adjusted mean changes for placebo, the 15-mg moexipril dose lowered clinic systolic BP, but not diastolic BP. In contrast, acute (1 day) reductions in 24-hour diastolic BPs were -2/-3 mm Hg, -6/-4 mm Hg, and -14/-9 mm Hg on placebo, 7.5 mg of moexipril, and 15 mg of moexipril, respectively (P < .01 for the 15-mg dose). Similarly, after long-term dosing for 8 weeks, reductions in 24-hour diastolic BPs were 1/-2 mm Hg, -6/-4 mm Hg, and -12/-9 mm Hg for the respective treatment groups (P < .01 for the 15-mg dose).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1342,7608448,Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure.,K Dickstein; P Chang; R Willenheimer; S Haunsø; J Remes; C Hall; J Kjekshus,"This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment. Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents. One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction < or = 35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing. No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed. The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.",1995.0,0,1
1343,7611276,Angiotensin-converting enzyme inhibition in diabetic nephropathy: ten years' experience.,H H Parving; P Rossing; E Hommel; U M Smidt,"The aim of our prospective study was to evaluate putative progression promoters, kidney function, and prognosis during long-term treatment with angiotensin-converting enzyme inhibition in insulin-dependent diabetes mellitus patients suffering from diabetic nephropathy. Eighteen consecutive hypertensive insulin-dependent diabetes patients with nephropathy (mean age, 33 years) who had not been treated previously were all treated with captopril in combination with frusemide or bendrofluazide. The four patients who were refractory to this regimen also received nifedipine. Treatment was continued for a median of 8.9 years (range, 6.3 to 9.8, years). Renal function was assessed every 6 months by measurement of glomerular filtration rate (GFR) (single-bolus 51Cr-EDTA technique) and albuminuria by radioimmunoassay. Baseline values (+/- SE) were mean arterial blood pressure 146/93 +/- 3/1 mm Hg, albuminuria (geometric mean +/- antilog SE) 982 +/- 1.2 micrograms/min, and GFR 98 +/- 5 mL/min/1.73 m2. Angiotensin-converting enzyme inhibition induced a significant reduction during the whole treatment period of blood pressure (137/85 +/- 3/1 mm Hg; P < 0.01) and albuminuria (392 +/- 1.4 microns/min; P < 0.01), and the rate of decline in GFR was 4.4 +/- 0.7 mL/min/yr, in contrast to previous reports of 10 to 14 mL/min/yr (natural history). Univariate analysis revealed a significant correlation between the rate of decline in GFR and mean arterial blood pressure (r = 0.58, P = 0.01), albuminuria (r = 0.67, P < 0.01), hemoglobin A1c (r = 0.69, P < 0.01), and serum total cholesterol concentration (r = 0.51, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
1344,7613498,The acute effect of perindopril upon effort capacity in congestive heart failure.,D Zdrenghea; O Angheloiu; G Icusca; D Timiş,"A number of 21 patients with congestive heart failure (CHF) of various etiologies were studied. All patients were subjected to a classical exercise testing (ET) on cycloergometer. The ET was repeated 24 hrs later, 6 hrs after the administration of 2 mg Perindopril (Coversyl). No statistically significant differences in duration and intensity of ET before and after Perindopril were noted for the whole group. But in 9 patients (42.8%) at least one effort level was gained. In these patients the peak double product (DP) was similar before and after Perindopril, but at submaximal effort DP was, at each level, lesser after Perindopril, suggesting a mechanism of afterload reduction in the improvement of effort capacity.",1994.0,0,0
1345,7614527,A comparison of captopril and digoxin in the treatment of patients with mild-to-moderate chronic congestive heart failure.,I Heck; B Lüderitz; H M Müller; H Esser,"In a double-blind study, 116 patients (mean age, 57.6 years) with mild-to-moderate chronic congestive heart failure who were in sinus rhythm were randomly assigned to receive 25 mg of captopril twice daily (up to 50 mg twice daily, if needed) plus hydrochlorothiazide (HCTZ) (group 1) or 0.1 mg of digoxin twice daily plus HCTZ (group 2) for 12 months. During a 3- to 4-week pretreatment stabilization period, group 1 received a mean of 37.7 mg of HCTZ daily and group 2 received 34.9 mg daily. After 6 weeks and 12 months of treatment, improvement was noted in both treatment groups on five measures of cardiac function: exercise tolerance, left ventricular end-diastolic diameter (LVEDD), ejection fraction, blood pressure, and heart rate. At 12 months, significantly greater improvement was noted in group 1 than in group 2 in exercise tolerance (from 329 seconds at baseline to 445 seconds at 12 months in group 1 and from 353 to 427 seconds in group 2; P < 0.05); LVEDD (from 60.5 to 56.5 mm in group 1 and from 60.3 to 57.9 mm in group 2; P < 0.05); and blood pressure (from 103.5 to 95.6 mm Hg in group 1 and from 101.9 to 97.0 mm Hg in group 2; P < 0.03). Clinical severity (New York Heart Association class) improved in both groups; 52% of the patients in group 1 and 41% in group 2 dropped an average of one functional class (P < 0.01). The results indicate that captopril combined with a diuretic is an effective initial treatment for patients with mild-to-moderate congestive heart failure.",1995.0,0,1
1346,7615575,Angiotensin-converting enzyme inhibitors and the role of nitric oxide and excitatory amino acids in improvement of cognition and memory.,J Marín; C Govantes,,1995.0,0,0
1347,7616816,Fatal aplastic anaemia associated with lisinopril.,B D Harrison; S T Laidlaw; J T Reilly,,1995.0,0,0
1348,7617115,Effects of body-weight loss and captopril treatment on proteinuria associated with obesity.,M Praga; E Hernández; A Andrés; M León; L M Ruilope; J L Rodicio,"We have identified 17 obese patients (body mass index, BMI, 37.9 +/- 4.1) with proteinuria > 1 g/day (1.3-6.4 g/24 h, mean 3.1 +/- 1.7). Their age was 34-70 years (48.3 +/- 10); 11 were females and 6 males. Six patients had only one functioning kidney and a sleep apnea syndrome had been diagnosed in 5. Renal biopsies, obtained in 5 cases, showed focal glomerulosclerosis in 2 cases, minimal changes in 2 and mesangial proliferation in 1. Nine patients (group 1) were treated with hypocaloric diets; body weight significantly decreased (BMI 37.1 +/- 3, 34 +/- 3.5 and 32.6 +/- 3.2 at 0, 6 and 12 months, respectively) as well as proteinuria (2.9 +/- 1.7, 1.2 +/- 1 and 0.4 +/- 0.6 g/24 h). There was a significant correlation between body weight loss and decrease in proteinuria (r = 0.69, p < 0.05). Eight patients (group 2) were treated with captopril, without dietary changes. BMI remained stable but proteinuria showed a dramatic decrease, similar to that in group 1 (3.4 +/- 1.7, 1.2 +/- 0.9 and 0.7 +/- 1 g/24 h, respectively). Renal function remained stable in both groups. In summary, both body weight loss and captopril treatment can induce a sharp decrease in obesity-related proteinuria.",1995.0,0,0
1349,7618614,Neurohumoral measurements as indicators of long-term prognosis after acute myocardial infarction.,T Omland; V V Bonarjee; R T Lie; K Caidahl,"The objective of this study was to evaluate the prognostic accuracy and usefulness of neurohumoral determination as a risk stratification tool after acute myocardial infarction (AMI) by comparing the long-term prognostic value of subacute neurohumoral measurements with other established indicators of adverse outcome. The study included 145 patients with documented AMI. During a median follow-up of 3.7 years, 30 cardiovascular and 6 noncardiovascular deaths occurred. By univariate analysis, plasma atrial natriuretic factor (ANF) and endothelin levels were strongly related to long-term cardiovascular mortality. In multivariate models, both peptides added prognostic information to that obtained from clinical evaluation, but not to that obtained from left ventricular ejection fraction (LVEF). Estimation of the area under the receiver-operating characteristic curve showed comparable prognostic accuracy for LVEF (0.7788), plasma ANF (0.7795), plasma endothelin (0.7493), and Killip classification (0.8203), meaning that for all these prognostic indicators, a randomly selected patient from the group of patients dying will have a test value larger than that of a randomly selected patient from the group of surviving patients 75% to 82% of the time. The clinical usefulness of neurohumoral determination in routine risk stratification after AMI appears to be limited since no additional prognostic information to that provided by objective evaluation of LV systolic function is obtained. However, in patients for whom objective assessment of LV performance is not readily available, measurement of plasma ANF and endothelin may be helpful in identifying asymptomatic patients at risk for cardiac death.",1995.0,0,0
1350,7618619,Failure of protective effect of captopril and enalapril on exercise and dipyridamole-induced myocardial ischemia.,G Longobardi; N Ferrara; D Leosco; A Nicolino; D Acanfora; G Furgi; N Guerra; A Papa; P Abete; F Rengo,"Fifteen patients with angiographic evidence of significant coronary artery disease, exertional myocardial ischemia, and positive dipyridamole echocardiographic test results at basal conditions and after 7 days of placebo treatment were prospectively studied to see whether captopril (containing sulfhydryl) and enalapril (nonsulfhydryl) modify myocardial ischemia induced by exercise testing and the effects of dipyridamole echocardiographic testing on regional myocardial contractility. Patients were randomized to captopril (150 mg/day in 3 separate doses) or enalapril (20 mg/day) for 1 week. At the end of this period each patient crossed over to the alternate regimen after a washout period of 7 days. Exercise stress testing and dipyridamole echocardiographic testing were repeated at the end of each treatment period. Neither captopril nor enalapril had a significantly greater anti-ischemic effect than placebo in any patient. Exercise duration, time to onset of ST-segment depression, maximal workload, degree of ST-segment depression, and rate-pressure product were not affected by either drug. Neither captopril nor enalapril improved dipyridamole-induced mechanical dysfunction or ST-segment depression.",1995.0,0,1
1351,7619356,"Comparison of moexipril, a new ACE inhibitor, to verapamil-SR as add-on therapy to low dose hydrochlorothiazide in hypertensive patients.",S G Chrysant; A A Fox; M Stimpel,"The antihypertensive effects of moexipril, a new angiotensin converting enzyme inhibitor, and verapamil-SR as add-on therapy to hydrochlorothiazide (HCTZ) were investigated in patients with moderate to severe (stages II and III) essential hypertension. Of 147 patients treated for 4 weeks with 25 mg/day HCTZ, 108 whose sitting diastolic blood pressure (SDBP) was 100 to 114 mm Hg inclusive were randomized to 7.5 mg/day moexipril (56 patients) and 180 mg/day verapamil-SR (52 patients) in addition to 25 mg/day HCTZ. If after 4 weeks of treatment the SDBP was > or = 90 mm Hg, the dose of moexipril was increased to 15 mg/day and that of verapamil-SR increased to 240 mg/day; the patients were followed for an additional 8 weeks. Blood chemistries, plasma renin activity, and plasma aldosterone were done during the study. Both moexipril and verapamil-SR were safe and well tolerated and decreased the sitting and standing blood pressure similarly (P < .001). This study demonstrated that the addition of moexipril and verapamil-SR to low dose HCTZ is effective for the treatment of moderate to severe hypertension.",1995.0,0,0
1352,7619667,"Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study.",R Wood,"1. We report a controlled retrospective cohort study of respiratory adverse reactions to ACE inhibitors. Bronchospasm and cough occurred at a higher rate in patients treated with ACE inhibitors, no links with sex, past history of bronchospasm, drug type or dose were found. 2. Cohorts of 1013 patients on angiotensin converting enzyme (ACE) inhibitors and 1017 patients on lipid lowering drugs (LLDs) were compared for the occurrence of new bronchospasm, relapse of previous bronchospasm, increase of current bronchospasm, and cough. 3. The prevalence of bronchospasm was 5.5% for patients on ACE inhibitors and 2.3% for patients on LLDs, P < 0.001. The relative risk of a bronchospasm adverse reaction for a patient on an ACE inhibitor compared with a patient on a LLD was 2.39, 95% confidence interval 1.47 to 3.90. 4. No ACE inhibitor specificity, or significant sex differences were found in the prevalence of bronchospasm or cough after correcting for bias implicit in the original cohorts. The bronchospastic reactions were not dose dependent. 5. The prevalence of a past history of bronchospasm in patients reporting ACE inhibitor-induced bronchospasm (16%) was not significantly different from the prevalence in patients on ACE inhibitors without an adverse reaction (13%), P = 0.447. 6. The prevalence of ACE inhibitor cohort cough was 12.3% and 2.7% in the patients on LLDs, P < 0.0001. Cough did not occur more commonly in patients on ACE inhibitors who had experienced any bronchospasm (28%) than in patients on LLDs with bronchospasm (27%).",1995.0,0,1
1353,7619668,Effect of dose adjustment on enalapril-induced cough and the response to inhaled capsaicin.,W W Yeo; K S Higgins; G Foster; P R Jackson; L E Ramsay,"1. In nine hypertensive patients with enalapril-induced cough the effect of altering the dose of enalapril on subjective cough and the cough response to inhaled capsaicin was examined in a random single-blind balanced cross-over study. They received three doses of enalapril, each for 3 weeks; the dose at entry (mean 10 mg daily); double this dose (mean 20 mg daily); and half this dose (mean 5 mg daily). 2. The cough response to inhaled capsaicin was also measured in two control groups: hypertensive patients on long-term enalapril treatment with no cough (n = 18), and hypertensive patients taking nifedipine (n = 17). 3. In patients with enalapril-induced cough there were significant dose-responses for enalapril as regards severity of cough (P < 0.05) and night time waking by cough (P < 0.05), but not for frequency of cough. Although the cough was less severe (P < 0.02) and caused less night time waking (P < 0.03) on the lowest dose of enalapril (mean 5 mg daily) it did not disappear completely in any patient. 4. The sensitivity to inhaled capsaicin did not differ significantly on the three doses of enalapril. The relative potency of capsaicin on enalapril 20 mg compared with enalapril 5 mg was 1.0 (95% CI 0.4-2.2). The wide confidence limits indicate that an important dose-dependent shift in capsaicin sensitivity is not excluded. 5. The sensitivity to inhaled capsaicin differed significantly between patients with enalapril-induced cough and both control groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1354,7624954,Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism.,G M Danovitch; N J Jamgotchian; P H Eggena; W Paul; J D Barrett; A Wilkinson; D B Lee,"Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.",1995.0,0,0
1355,7625425,Contemporary management of acute myocardial infarction.,W J Rogers,"Acute myocardial infarction, the leading cause of death in western society, has been the focus of more randomized clinical trial effort over the past decade than any other area of medicine. As a result of this worldwide effort, involving hundreds of thousands of patients with myocardial infarction, data have accumulated showing substantially lower mortality of acute myocardial infarction with simple interventions such as i.v. thrombolytic therapy, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors. Emergency coronary angioplasty appears to be a suitable alternative to i.v. thrombolytic therapy in skilled centers. Several previously recommended therapies (routine i.v. lidocaine, calcium channel blockers, magnesium, nitrates) have not been proved to be life-saving. Whether routine coronary arteriography should be employed after myocardial infarction remains controversial, but it is generally accepted that patients with evidence of residual ischemia after infarction, either spontaneous or provoked by stress testing, should undergo prophylactic coronary revascularization.",1995.0,0,0
1356,7626347,"Left ventricular volumes, ejection fraction, and plasma proatrial natriuretic factor (1-98) after withdrawal of enalapril treatment initiated early after myocardial infarction. CONSENSUS II Multi-Echo Study Group.",V V Bonarjee; T Omland; D W Nilsen; S Carstensen; J Berning; M Edner; K Caidahl,"To assess whether the reduction in left ventricular dilatation after acute myocardial infarction obtained by early administration of angiotensin converting enzyme inhibitors depends on continuous treatment. Prospective observational and cross sectional study of withdrawal of randomised treatment with enalapril or placebo. 106 patients on 6 months trial treatment after an acute myocardial infarction. Left ventricular volumes and ejection fraction as assessed by echocardiography and circulating proatrial natriuretic factor (1-98) before and 4-6 weeks after withdrawal of treatment. There were no significant changes (mean (SD)) in left ventricular systolic (0.7 (4.7) ml/m2) and diastolic (0.4 (6.6) ml/m2) volume indices, ejection fraction (-0.9 (6)%), and proatrial natriuretic factor (172 (992) pmol/l) after withdrawal of enalapril. The significantly lower left ventricular volumes observed with 6 months of enalapril therapy after acute myocardial infarction, as compared with placebo, were maintained 6 weeks after drug withdrawal. The results show that the benefit of 6 months of enalapril treatment initiated early after myocardial infarction is maintained for at least 6 weeks after drug withdrawal, suggesting that the treatment effect on left ventricular structure is not reversed by changes in loading conditions caused by subsequent drug withdrawal.",1995.0,0,0
1357,7628885,Characteristics and prognosis of non-participants of a multi-centre trial of long-term anticoagulant treatment after myocardial infarction.,P F van Bergen; J J Jonker; G P Molhoek; P H van der Burgh; R T van Domburg; J W Deckers; A Hofman,"Participants of a randomised trial may differ from eligible non-participants as a result of selection. We studied the distribution of prognostic factors and survival in eligible patients of a multi-centre trial of long-term oral anticoagulant treatment after myocardial infarction. All hospital survivors of myocardial infarction in one participating clinical centre of a multi-centre, randomised, double-blind, placebo-controlled trial of long-term anticoagulant treatment after myocardial infarction were screened for entry criteria. Subsequently, prognostic factors and survival of participants were compared with eligible but not randomised patients. The 350 participants were younger and were more often of male gender and more often smokers compared with 587 non-participants. Non-participants had more frequently suffered a previous myocardial infarction and were treated more often with diuretics and ACE-inhibitors, suggesting a higher proportion of patients with chronic heart failure in this group. Age, previous myocardial infarction and the use of diuretics at discharge were independent predictors of mortality, consent showed no association. Our findings indicate that participants of a clinical trial have a better prognosis during the first years following myocardial infarction compared to eligible non-participants as a result of a higher prevalence of cardiovascular risk factors associated with mortality in the non-participants.",1995.0,0,0
1358,7629487,Angio-oedema induced by enalapril.,T Forslund; H Tohmo; G Weckström; M Stenborg; S Järvinen,"We report the case of a patient who, 9 months after initiation of enalapril and hydrochlorothiazide combination treatment for hypertension, developed angio-oedema with near fatal outcome. Our patient was successfully intubated using a flexible bronchofiberoscope. This case demonstrates that patients given an angiotensin-converting enzyme (ACE) inhibitor may develop serious facial and laryngeal swelling even several months after the initiation of treatment. The occurrence of even mild swelling should lead to prompt cessation of the drug. Patients with incipient ACE inhibitor-related angio-oedema should, without any delay, be referred to hospital for emergency treatment.",1995.0,0,0
1359,7631621,Low-dose drug combination therapy: an alternative first-line approach to hypertension treatment.,L M Prisant; M R Weir; V Papademetriou; M A Weber; I A Adegbile; D Alemayehu; M P Lefkowitz; A A Carr,"To investigate the concept that the initial treatment of hypertension with low doses of two antihypertensives that have different modes of action and additive effects may achieve control of blood pressure and minimize the dose-dependent adverse effects seen with conventional monotherapy, a randomized, double-blind parallel group dose-escalation study was conducted. After a 4 to 5 week placebo washout period, 218 men and women with diastolic blood pressure between 95 and 114 mm Hg were randomly allocated to take: amlodipine (2.5 to 10 mg), enalapril (5 to 20 mg), and the low-dose combination of bisoprolol (2.5 to 10 mg) with 6.25 mg of hydrochlorothiazide (HCTZ). All drugs were administered once daily, titrated to optimal response, and taken for a total of 12 weeks. Blood pressure was measured 24 hours after dose. The response rates (either a diastolic blood pressure < or = 90 mm Hg or a decrease of diastolic pressure > or = 10 mm Hg) were 71% for bisoprolol-6.25 mg HCTZ, 69% for amlodipine, and 45% for enalapril. The mean decreases in systolic/diastolic blood pressure from baseline were 13.4/10.7, 12.8/10.2, and 7.3/6.6 mm Hg for bisoprolol-6.25 mg HCTZ, amlodipine, and enalapril, respectively. The mean change with enalapril was less than the other drugs (p < 0.01), although the once-daily dosing of enalapril and the maximum dose of 20 mg might not have been optimal for this agent.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1360,7633026,Angioedema caused by ramipril.,F Epeldo Gonzalo; L Boada Montagut; S T Vecina,,1995.0,0,0
1361,7635529,Theodore Cooper Memorial Lecture. Kallikreins and kinins. Some unanswered questions about system characteristics and roles in human disease.,H S Margolius,"Kinins can affect many aspects of cellular function, but their roles in human homeostatic mechanisms and disease are just beginning to be understood. In this brief review, some of the interesting new observations about kallikrein-kinin system characteristics, roles in cell behavior, and aberrancy in diseases of relevance to readers interested in hypertension will be discussed. Along the way, questions raised by these observations will be posed. They show that we still have much to learn about the contributions of kinins to human cardiovascular diseases but now have in addition both a strong rationale for asking them and the tools to make them operational.",1995.0,0,0
1362,7638466,Cardiovascular considerations in the management of neuromuscular disease.,Y Ishikawa; J R Bach; R J Sarma; T Tamura; J Song; S W Marra; Y Ishikawa; R Minami,,1995.0,0,0
1363,7641605,Guillain-Barré syndrome. Clinical manifestations and directions for treatment.,J Rees,"Guillain-Barré syndrome (GBS) is the commonest cause of acute neuromuscular paralysis in the developed world today. Patients present most commonly with a rapidly ascending paralysis together with sensory symptoms and variable autonomic involvement. The diagnosis is clinical, but lumbar puncture and nerve conduction studies are helpful in excluding other conditions. The improvement in prognosis in recent years is largely due to advances in respiratory intensive care management. Careful monitoring of cardiorespiratory function and in particular regular measurements of the vital capacity will help to predict which patients will require elective ventilation to prevent impending neuromuscular respiratory failure. The paralysed patient is susceptible to all the complications of immobility, in particular venous thromboembolism and hypostatic pneumonia, and good nursing care and physiotherapy are therefore mandatory. Autonomic involvement may predispose to cardiac arrhythmias and labile blood pressure. The prolonged nature of the illness predisposes to psychiatric complications, particularly depression, and this should be treated appropriately. Specific treatment is aimed at reducing the period of maximum disability. Both plasma exchange (PE) and intravenous immune globulin (IVIg) have been shown to be effective in randomised controlled trials. A multicentre trial is currently under way to determine whether PE or IVIg or PE followed by IVIg is the most effective treatment for this condition. Steroids alone have not been shown to be of value, although a trial is under way comparing the combination of IVIg and methylprednisolone with IVIg alone. The prognosis of GBS is generally good, with about 80% of patients making a full recovery, although about 5% die of complications.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1364,7643542,Increased glomerular filtration rate after withdrawal of long-term antihypertensive treatment in diabetic nephropathy.,H P Hansen; P Rossing; L Tarnow; F S Nielsen; B R Jensen; H H Parving,"Initiation of antihypertensive treatment (AHT) in hypertensive insulin-dependent diabetic (IDDM) patients with diabetic nephropathy (DN) induces a faster initial (0 to 6 months) and a slower subsequent (6 months to end of observation) decline in GFR [delta GFR (ml/min/month) approximately 1.5 vs. 0.35]. Whether this initial phenomenon is reversible (hemodynamic) or irreversible (structural damage) after prolonged AHT is not known. To elucidate these mechanisms we investigated 42 hypertensive IDDM patients (16F/26M, age 40 +/- 7 years, mean +/- SD) with DN receiving AHT (angiotensin converting enzyme inhibition, N = 30) for 6 (2 to 15) years [median (range)]. GFR (ml/min/1.73 m2), arterial blood pressure (BP, mm Hg) and albuminuria (mg/24 hr) were measured the last day on AHT and one month after withdrawal of AHT. The measured variables were all significantly elevated after withdrawal of AHT: GFR [mean(SEM)] from 76(4) to 81(4) (P < 0.0001), BP [mean(SEM)] from 140/82 (2/1) to 151/89 (2/1) (P < 0.0005) and albuminuria [geometric mean (antilog SEM)] from 704 (1.2) to 1122 (1.2) (P < 0.0001). A correlation between relative rise in systolic blood pressure (delta Sys%) and relative change in GFR (delta GFR%) was found (r = 0.44, P < 0.005). Our results render some support of the hypothesis that the faster initial decline in GFR is due to a functional (hemodynamic) effect of AHT, which does not attenuate over time, while the subsequent slower decline reflects the beneficial effect on progression of diabetic nephropathy.",1995.0,0,0
1365,7645558,Enalapril treatment of posttransplant erythrocytosis: efficacy independent of circulating erythropoietin levels.,M Perazella; P McPhedran; A Kliger; M Lorber; E Levy; M J Bia,"To determine the mechanism of action by which angiotensin-converting enzyme (ACE) inhibitors lower hematocrit in patients with posttransplant erythrocytosis, indices of red blood cell production and red blood cell destruction were obtained serially for 6 months from 10 renal transplant patients receiving treatment with enalapril for this problem. Before treatment, five patients had an elevated red blood cell mass, four had plasma volume contraction, and one had both. The mean hemoglobin concentration decreased by 2 g/dL (range, 0.5 to 3.3 g/dL), from 17 +/- 1 g/dL to 15 +/- 1 g/dL (P = 0.001) following 6 months of enalapril therapy. Similarly, the mean hematocrit decreased by 8% (range, 3% to 12%), from 52% +/- 2% to 44% +/- 3% (P = 0.001) during the same period. The mean reticulocyte count tended to decrease, although the change was not significant. The red blood cell mass decreased dramatically by 15% to 50%, from 32 +/- 9 mL/kl to 23 +/- 4 mL/kg (P = 0.008). Although serial erythropoietin levels declined steadily in two patients, there was no consistent change in the other patients. Mean levels decreased modestly, from 20 +/- 11 mU/mL at baseline to 12 +/- 5 mU/mL at 6 months, a change that was not statistically significant. Mean levels at each time point were not statistically different from the mean pretreatment value. Furthermore, during enalapril therapy, there was no correlation between mean circulating erythropoietin level and mean hematocrit (r = 0.43, P = 0.20) or hemoglobin concentration (r = 0.36, P = 0.30) or between changes in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1366,7648653,Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators.,G A Lamas; G C Flaker; G Mitchell; S C Smith; B J Gersh; C C Wun; L Moyé; J L Rouleau; J D Rutherford; M A Pfeffer,"In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries. The Survival and Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented MI and a left ventricular ejection fraction < or = 40%. They were randomized to the ACE inhibitor captopril (50 mg TID) or placebo 3 to 16 days after MI and were followed for an average of 3.5 years. Left ventricular ejection fraction, measured with radionuclide left ventriculography, was repeated at the end of the follow-up period. The 946 patients in whom the patency of the IRA was established before randomization form the basis of this study. At cardiac catheterization averaging 4.2 days after infarction, 30.7% of patients had an initially occluded IRA. After revascularization, 162 of the 946 patients (17.1%) were left with an occluded IRA at the time of randomization. The 162 patients with persistently occluded IRAs and 784 with patent IRAs had similar clinical baseline characteristics, but those with occluded arteries had a slightly lower ejection fraction than the 784 patients with patent infarct arteries (30% versus 32%, P = .01). Cox proportional-hazards analyses showed that the independent predictors of all-cause mortality were hypertension (relative risk [RR] 1.94, P < .001), number of diseased coronary arteries (RR 1.68, P < .001), occluded IRA (RR 1.49, P = .039), ejection fraction (RR 1.36, P < .001), age (RR 1.10, P = .030), and use of beta-adrenergic receptor blocking agents (RR 0.60, P = .007). Independent predictors of a composite end point consisting of cardiovascular mortality, morbidity, or reduction of ejection fraction of > or = 9 units were occluded IRA (odds ratio [OR] 1.73, P = .002), hypertension (OR 1.71, P < .001), number of diseased vessels (OR 1.38, P < .001), ejection fraction (OR 1.18, P = .003), use of beta-adrenergic receptor blocking agents (OR 0.67, P = .007), and randomization to captopril (OR 0.70, P = .009). IRA patency within 16 days after MI predicts a favorable clinical outcome, independent of the number of obstructed coronary arteries or of left ventricular function. The beneficial effect of ACE inhibition is independent of patency status of the IRA. These findings support the need for additional, prospective clinical trials of late reperfusion in MI patients.",2001.0,0,0
1367,7649579,Comparison of perindopril and amlodipine in cyclosporine-treated renal allograft recipients.,J Sennesael; J Lamote; I Violet; S Tasse; D Verbeelen,"The objective of this study was to compare the antihypertensive efficacy and influence on renal function of perindopril and amlodipine in cyclosporine-treated renal allograft recipients with mild to moderate hypertension. We conducted a randomized, double-blind, double-dummy crossover trial in ambulatory patients. Four phases were conducted: 2 weeks on placebo, 8 weeks of maintenance (perindopril or amlodipine), and 2 weeks of washout between treatment periods. Ten hypertensive patients with stable renal allograft function transplanted more than 6 months previously and receiving cyclosporine as part of their immunosuppressive regimen were studied. The patients were allocated to perindopril (2 or 4 mg/d) and amlodipine (5 mg/d) in a random sequence. If office diastolic pressure was greater than or equal to 90 mm Hg after 4 weeks, the dosage was doubled and continued for another 4 weeks. The main outcome measures were office and 24-hour ambulatory blood pressure changes after 8 weeks of active treatment and treatment and time effect on glomerular filtration rate and effective renal plasma flow. Perindopril and amlodipine were equally effective in lowering office blood pressure and similarly efficacious for the 24-hour period of the day. Neither drug affected glomerular filtration rate or effective renal plasma flow. Both agents demonstrated equivalent capacity (time x treatment, P = .955) to reverse renal vascular resistance (amlodipine from 0.35 +/- 0.02 to 0.30 +/- 0.02 mm Hg/mL per minute per 1.73 m2; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01) (time effect of all treatments together, P = .043).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1368,7649593,"Short- and long-term effects of antihypertensive drugs on arterial reflections, compliance, and impedance.",C T Ting; C H Chen; M S Chang; F C Yin,"This article reviews our work on the effects of different classes of antihypertensive agents on the hemodynamic alterations in essential human hypertension. Short-term studies were done during cardiac catheterization in young normotensive subjects (mean age, 33 years; range, 19 to 40) and several different age-matched (range, 25 to 53 years) groups of patients with essential hypertension. Aortic impedance, resistance, wave reflections, and compliance were calculated from high-fidelity recordings of ascending aortic pressure and flow signals during baseline and after nitroprusside, propranolol followed by phentolamine, phentolamine, captopril, and nifedipine, respectively, at doses sufficient to normalize blood pressure in each hypertensive group. Propranolol exacerbated all the hemodynamic parameters; these effects were only partially overcome by phentolamine. Among the other agents only phentolamine did not completely normalize compliance, and only captopril did not completely normalize wave reflections. The long-term study was a randomized, double-blind comparison of fosinopril and atenolol in 79 normotensive subjects and 79 essential hypertensive patients. Baseline 24-hour ambulatory blood pressures and carotid artery tonometry to index wave reflections were performed in all subjects and in hypertensive patients after 8 weeks of therapy. Both fosinopril and atenolol normalized blood pressure and lowered the elevated augmentation index, but fosinopril had a significantly larger effect than atenolol. Both short- and long-term beta-blockade did not have as beneficial an effect as the other agents. Thus, the differing hemodynamic effects of the various classes of antihypertensive agents might be a consideration in the choice of therapy.",1995.0,0,0
1369,7649665,Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure.,A Bharani; A Ganguly; K D Bhargava,"Twelve patients with refractory chronic congestive heart failure (Class IV NYHA), related to idiopathic dilated cardiomyopathy (10 patients); previous myocardial infarction (one patient) and peripartum cardiomyopathy (one patient), received Terminalia Arjuna, an Indian medicinal plant, as bark extract (500 mg 8-hourly) or matching placebo for 2 weeks each, separated by 2 weeks washout period, in a double blind cross over design as an adjuvent to maximally tolerable conventional therapy (Phase I). The clinical, laboratory and echocardiographic evaluation was carried out at baseline and at the end of Terminalia Arjuna and placebo therapy and results were compared. Terminalia Arjuna, compared to placebo, was associated with improvement in symptoms and signs of heart failure, improvement in NYHA Class (Class III vs. Class IV), decrease in echo-left ventricular enddiastolic (125.28 +/- 27.91 vs. 134.56 +/- 29.71 ml/m2; P < 0.005) and endsystolic volume (81.06 +/- 24.60 vs. 94.10 +/- 26.42 ml/m2; P < 0.005) indices, increase in left ventricular stroke volume index (44.21 +/- 11.92 vs. 40.45 +/- 11.56 ml/m2; P < 0.05) and increase in left ventricular ejection fractions (35.33 +/- 7.85 vs. 30.24 +/- 7.13%; P < 0.005). On long term evaluation in an open design (Phase II), wherein Phase I participants continued Terminalia Arjuna in fixed dosage (500 mg 8-hourly) in addition to flexible diuretic, vasodilator and digitalis dosage for 20-28 months (mean 24 months) on outpatient basis, patients showed continued improvement in symptoms, signs, effort tolerance and NYHA Class, with improvement in quality of life.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1370,7650220,The expanding role of angiotensin converting enzyme inhibitors in the management of hypertension.,J F Burris,"Angiotensin converting enzyme (ACE) inhibitors are increasingly important in antihypertensive therapy because of their efficacy, tolerability, and specific benefits in subsets of patients. They are pharmacologically diverse. Whereas most benefits have been proven with older agents (captopril, enalopril), newer agents, such as benazepril, quinapril, and ramipril, offer potential advantages that remain to be proven.",1995.0,0,0
1371,7652789,Usefulness and safety of treatment with captopril in posttransplant erythrocytosis.,E Hernández; J M Morales; A Andrés; B Ortuño; M Praga; J M Alcazar; G Fernández; J L Rodicio,,1995.0,0,0
1372,7654109,Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,B J Materson; D J Reda; R A Preston; W C Cushman; B M Massie; E D Freis; M S Kochar; R J Hamburger; C Fye; R Lakshman,"An important issue in clinical practice is how to treat patients whose blood pressure does not respond to the first antihypertensive drug selected. To analyze the antihypertensive response of patients who had failed to achieve their diastolic blood pressure goal (< 90 mm Hg at the end of 8 to 12 weeks of titration) with one of six randomly allocated drugs or placebo to the random allocation of an alternate drug. We initially randomized 1292 men with diastolic blood pressure of 95 to 109 mm Hg to treatment with hydrochlorothiazide, atenolol, captopril, clonidine hydrochloride, diltiazem hydrochloride (sustained release), prazosin hydrochloride, or placebo. Of 410 men in whom initial treatment failed, 352 qualified for randomization to the alternate drug. Of the 352 patients, 173 (49.1%) achieved their goal diastolic blood pressure, in 133 (37.8%) the alternate drug failed, and 46 (13.1%) left the study for various reasons. Overall response rates were as follows: diltiazem, 63%; clonidine, 59%; prazosin, 47%; hydrochlorothiazide, 46%; atenolol, 41%; and captopril, 37%. The best response rate for patients in whom hydrochlorothiazide failed was achieved with diltiazem (70%); after atenolol failure, clonidine (86%); after captopril failure, prazosin (54%); after clonidine failure, diltiazem (100%); after diltiazem failure, captopril (67%); and after prazosin failure, clonidine (53%). The combined response rate for patients initially randomized to an active treatment was 76.0%, which is similar to that achieved by the combination of two drugs in previous studies. We conclude that sequential single-drug therapy is a rational approach for treatment of hypertension in patients in whom initial drug therapy has failed.",1995.0,0,0
1373,7654275,Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials.,R Garg; S Yusuf,"To evaluate the effect of angiotensin-converting enzyme (ACE) inhibitors on mortality and morbidity in patients with symptomatic congestive heart failure. Data were obtained for all completed, published or unpublished, randomized, placebo-controlled trials of ACE inhibitors that were at least 8 weeks in duration and had determined total mortality by intention to treat, regardless of sample size. Trials were identified based on literature review and correspondence with investigators and pharmaceutical firms. Using standard tables, data were extracted by one author and confirmed where necessary by the other author or the principal investigator of the trial. Unpublished data were obtained by direct correspondence with the principal investigator of each study or pharmaceutical firm. The data for each outcome were combined using the Yusuf-Peto adaptation of the Mantel-Haenszel method. Overall, there was a statistically significant reduction in total mortality (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.67 to 0.88; P < .001) and in the combined endpoint of mortality or hospitalization for congestive heart failure (OR, 0.65; 95% CI, 0.57 to 0.74; P < .001). Similar benefits were observed with several different ACE inhibitors, although the data were largely based on enalapril maleate, captopril, ramipril, quinapril hydrochloride, and lisinopril. Reductions for total mortality and the combined endpoint were similar for various subgroups examined (age, sex, etiology, and New York Heart Association class). However, patients with the lowest ejection fraction appeared to have the greatest benefit. The greatest effect was seen during the first 3 months, but additional benefit was observed during further treatment. The reduction in mortality was primarily due to fewer deaths from progressive heart failure (OR, 0.69; 95% CI, 0.58 to 0.83); point estimates for effects on sudden or presumed arrhythmic deaths (OR, 0.91; 95% CI, 0.73 to 1.12) and fatal myocardial infarction (OR, 0.82; 95% CI, 0.60 to 1.11) were less than 1 but were not significant. Total mortality and hospitalization for congestive heart failure are significantly reduced by ACE inhibitors with consistent effects in a broad range of patients.",1995.0,1,1
1374,7655326,"Risk of renal cell cancer in relation to diuretics, antihypertensive drugs, and hypertension.",W H Chow; J K McLaughlin; J S Mandel; S Wacholder; S Niwa; J F Fraumeni,"Although recent data have suggested an association between renal cell cancer and the use of diuretics, it remains unclear whether these medications or hypertension is the important risk factor. In a population-based case-control study including 440 renal cell cancer cases, spouses of an additional 151 cases, and 691 controls, we assessed renal cell cancer risk associated with hypertension and use of diuretics and other antihypertensive medications. Risks increased with the use of diuretics or other drugs that lower blood pressure, especially among persons who reported no history of hypertension. After adjustment for hypertension, the use of diuretics alone was associated with a 40% excess risk (OR = 1.4; 95% CI = 0.8-2.2), while use of other antihypertensive drugs was linked to a 2-fold risk (OR = 2.0; 95% CI = 1.2-3.3). The excess risk was not restricted to any specific products, and no trend was observed with estimated lifetime consumption of any product. Furthermore, risk was not potentiated by the presence of both hypertension and the use of antihypertensive drugs. Among persons who did not use antihypertensive drugs, a history of hypertension was associated with a significant 40-50% excess risk of renal cell cancer. Excluding subjects with hypertension diagnosed within 5 years of cancer diagnosis or interview had only a small effect on risk. These findings suggest small effects on renal cell cancer risk associated with hypertensive disease and with the use of diuretics and other antihypertensive drugs, but it is difficult to disentangle the separate effects due to potential misclassification of highly correlated events.(ABSTRACT TRUNCATED AT 250 WORDS)",2001.0,0,0
1375,7657848,A multicenter comparison of adverse reaction profiles of isradipine and enalapril at equipotent doses in patients with essential hypertension.,B F Johnson; G M Eisner; F G McMahon; A K Jain; P Rudd; J R Sowers,"A multicenter, randomized, double-blind trial compared the safety and efficacy of the dihydropyridine isradipine with the angiotensin-converting enzyme (ACE) inhibitor enalapril given twice daily for mild hypertension. 160 patients received either isradipine (starting at 1.25 mg twice daily) or enalapril (starting at 2.5 mg twice daily) for 10 weeks. The dosage was increased if the average sitting diastolic blood pressure was > 90 mm Hg. Significantly greater mean reductions in systolic blood pressure were seen after 2, 6, and 8 weeks of isradipine. However, by the end of the trial, 83% of patients receiving isradipine and 78% receiving enalapril showed a decrease of at least 5 mm Hg in sitting diastolic blood pressure to a level below 96 mm Hg. Possible or probable drug-related adverse effects were reported in 36% of patients showing a good antihypertensive response to isradipine, and in 30% of those who responded to enalapril. There was a trend for a lower frequency of adverse effects in isradipine non-responders (25%) and a higher frequency in enalapril non-responders (43%). Pruritus, dizziness, edema, and fatigue were reported more often with isradipine, and cough and changed bowel habits were more common with enalapril. The relationship between the pattern of adverse effects and the extent of blood pressure reduction may be dependent on the mechanism of action of a drug. In responders, isradipine and enalapril showed differing patterns, but a similar overall incidence of adverse effects.",1995.0,0,1
1376,7661384,A comparative study of captopril and enalapril on endothelial cell function in congestive heart failure patients.,A B Bridges; M McLaren; J J Belch,"Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce the incidence of future coronary artery thromboses in postmyocardial infarction patients. A possible prothrombotic role for the angiotensin system has been postulated, and support for this has been provided by a recent study that demonstrated that an infusion of angiotensin increases levels of the prothrombotic plasminogen activator inhibitor (PAI). In the current study the authors have investigated the effect of two ACE inhibitors, captopril and enalapril, on tissue plasminogen activator (tPA) and PAI in 33 congestive heart failure (CHF) patients. Blood samples were obtained pretreatment and then at weeks 1, 12, and 24 after initiation of ACE inhibitor therapy for measurement of tPA antigen and PAI activity levels. The results of the study indicated that the initiation of ACE inhibitors had no significant effects on tPA antigen or PAI activity levels at the time points studied, and no significant differences were demonstrated between captopril and enalapril. The results suggest, therefore, that ACE inhibitors do not affect tPA antigen or PAI activity in CHF patients, and thus another mechanism is probably responsible for the observed decrease in coronary artery thromboses in post-MI patients treated with ACE inhibitors.",1995.0,0,0
1377,7661937,"ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group.",,"58,050 patients entering 1086 hospitals up to 24 h (median 8 h) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications to the study treatments (in particular, no cardiogenic shock or persistent severe hypotension) were randomised in a ""2 x 2 x 2 factorial"" study. The treatment comparisons were: (i) 1 month of oral captopril (6.25 mg initial dose titrated up to 50 mg twice daily) versus matching placebo; (ii) 1 month of oral controlled-release mononitrate (30 mg initial dose titrated up to 60 mg once daily) versus matching placebo; and (iii) 24 h of intravenous magnesium sulphate (8 mmol initial bolus followed by 72 mmol) versus open control. There were no significant ""interactions"" between the effects of these three treatments, and the results for each are based on the randomised comparison of about 29,000 active versus 29,000 control allocated patients. Captopril There was a significant 7% (SD 3) proportional reduction in 5-week mortality (2088 [7.19%] captopril-allocated deaths vs 2231 [7.69%] placebo; 2p = 0.02), which corresponds to an absolute difference of 4.9 SD 2.2 fewer deaths per 1000 patients treated for 1 month. The absolute benefits appeared to be larger (perhaps about 10 fewer deaths per 1000) in certain higher-risk groups, such as those presenting with a history of previous MI or with heart failure. The survival advantage appeared to be maintained in the longer term (5.4 [SD 2.8] fewer deaths per 1000 at 12 months). Captopril was associated with an increase of 52 (SD 2) patients per 1000 in hypotension considered severe enough to require termination of study treatment, of 5 (SD 2) per 1000 in reported cardiogenic shock, and of 5 (SD 1) per 1000 in some degree of renal dysfunction. It produced no excess of deaths on days 0-1, even among patients with low blood pressure at entry. Mononitrate There was no significant reduction in 5-week mortality, either overall (2129 [7.34%] mononitrate-allocated deaths vs 2190 [7.54%] placebo) or in any subgroup examined (including those receiving short-term non-study intravenous or oral nitrates at entry). Further follow-up did not indicate any later survival advantage. The only significant side-effect of the mononitrate regimen studied was an increase of 15 (SD 2) per 1000 in hypotension. Those allocated active treatment had somewhat fewer deaths on days 0-1, which is reassuring a bout the safety of using nitrates early in acute MI.(ABSTRACT TRUNCATED AT 400 WORDS)",1995.0,1,1
1378,7662221,Comparison of the hemodynamic and metabolic effects of low-dose hydrochlorothiazide and lisinopril treatment in obese patients with high blood pressure.,G M Reaven; C Clinkingbeard; J Jeppesen; P Maheux; D Pei; J Foote; C B Hollenbeck; Y D Chen,"Patients with high blood pressure tend to be insulin resistant, glucose intolerant, hyperinsulinemic, and dyslipidemic. Since these metabolic defects are accentuated by obesity, we thought it important to compare the effects of 3 months' treatment with either lisinopril (20 mg/day) or low dose hydrochlorothiazide (12.5 mg/day) on blood pressure and glucose, insulin, and lipoprotein metabolism in obese patients with hypertension. There were 14 patients in each group, and they were similar (mean +/- SE) in age (54 +/- 3 v 50 +/- 4 years), gender (nine men/five women), and body mass index (33.4 +/- 0.8 v 33.9 +/- 0.9 kg/m2). Patients treated with lisinopril had a somewhat greater fall in both systolic (18 +/- 3 v 10 +/- 3 mm Hg) and diastolic (12 +/- 2 v 8 +/- 1 mm Hg) blood pressure, but only the change in systolic pressure was statistically significant (P < .05). Plasma glucose, insulin, and triglyceride concentrations were measured at hourly intervals from 8 AM to 4 PM (breakfast at 8 AM and lunch at 12 PM), and there was a modest increase in all three variables following hydrochlorothiazide treatment (P < .05 to P < .09). However, daylong plasma glucose, insulin, and triglyceride concentration did not change with lisinopril treatment. Finally, neither the ability of insulin to mediate glucose disposal nor fasting lipid and lipoprotein concentrations, changed with either treatment. In conclusion blood pressure decreased significantly following treatment with either lisinopril (20 mg/day) or hydrochlorothiazide (12.5 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1379,7662225,Effect of antihypertensive treatment on the increased beta 2-adrenoceptor density in patients with essential hypertension.,M Bono; A Cases; J Calls; J Gaya; W Jiménez; J Carretero; F Rivera; L Revert,"The effect of different antihypertensive drugs on the increased surface beta 2-adrenoceptor density in essential hypertension was evaluated to elucidate whether the possible effect of the treatment on these receptors was secondary to blood pressure decreases or a specific effect of the drugs. Thirty-nine untreated essential hypertensive patients and 28 normotensive control subjects were studied in basal conditions. Hypertensive patients were randomly assigned to three treatment groups: bisoprolol (10 mg/day, n = 15), enalapril (20 mg/day, n = 12), and verapamil SR (240 mg/day, n = 12), and were studied before and after 1 month of treatment. Plasma catecholamines were determined by a radioenzymatic assay. Surface beta 2-adrenoceptors were measured in intact lymphocytes by radioligand binding assay using the hydrophilic ligand [3H]-CGP12177. beta 2-adrenoceptor density was increased in hypertensive patients (P < .01). After treatment, mean blood pressure decreased similarly in the three groups, while plasma catecholamines showed no significant changes in any group. beta 2-adrenoceptor number decreased only in bisoprolol-treated patients (P < .05). Mean blood pressure decreases correlated with beta 2-adrenoceptor decrements only in bisoprolol-treated patients (r = 0.65, P < .05). beta 2-adrenoceptor density correlated with plasma epinephrine levels in the control group (r = -0.50, P < .01), but not in hypertensive patients before treatment. This correlation was also observed in hypertensive patients treated with bisoprolol (r = -0.52, P < .05), but not in those treated with verapamil or enalapril. Our results suggest that bisoprolol treatment reduces the increased surface beta 2-adrenoceptor density and restores its regulation by epinephrine in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1380,7662226,Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension.,J H Levine; K C Ferdinand; P Cargo; H Laine; M Lefkowitz,"A factorial design was applied in this multicenter, double-blind, placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy, to evaluate safety, and to determine the effects on quality of life (QOL) of both drugs, alone and in combination. The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure (BP) of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout, were randomized to one of six treatment groups for 4 weeks of active treatment. Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo. The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only. The total number of adverse events reported was similar for all six treatment groups. QOL scores were unchanged from baseline and not different between treatment groups. The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL. Thus, combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy.",1995.0,0,0
1381,7662247,Effect of long-term antihypertensive therapy with angiotensin converting enzyme inhibitors on red cell sodium transport.,A de la Sierra; R Insa; M Compte; A Martínez-Amenós; C Sierra; G Hernández-Herrero; A Coca,"Several sodium transport abnormalities have been reported in erythrocytes from essential hypertensive patients. The possible modification of these parameters under antihypertensive treatment remains controversial. We have measured the maximal rates of the Na+/K+ pump, Na+/K+/Cl- cotransport, and Na+/Li+ countertransport and the rate constant of Na+ leak in erythrocytes from 22 essential hypertensive patient responders to angiotensin converting enzyme inhibitors quinapril or captopril, and from 17 patient nonresponders to these drugs. In the former group, sodium transport measurements were performed at the baseline placebo period and after 6 months of active treatment. The maximal rate of Na+/Li+ countertransport decreased significantly after 6 months of treatment, without differences between both groups of treatment. Angiotensin converting enzyme inhibitors did not significantly modify other sodium transport parameters. The basal activity of erythrocyte sodium transport was not different between patients who responded or not to antihypertensive treatment with those drugs, excluding a predictive value of these measurements concerning the response to angiotensin converting enzyme inhibitors.",1995.0,0,0
1382,7664505,Beneficial clinical effect of very early enalapril treatment in patients with acute left ventricular failure complicating myocardial infarction.,S Hüttl; J Nussberger; K Lehmann; J Hasford; H R Brunner; W Delius,"Acute myocardial infarction (AMI) leads to left ventricular dysfunction, the extent of which predicts mortality. We studied the effect of very early enalapril treatment in patients with left ventricular failure (Killip classification II-III) resulting from AMI. In a double-blind randomized trial, patients on conventional treatment were started on placebo (PL, n = 15) or 2.5 mg enalapril (EN, n = 15) twice daily as early as 24 to 30 h after AMI and were followed up over a period of 21 days. One patient died in each treatment group. There were three dropouts in the placebo group (progressive heart failure requiring antiotensin-converting enzyme inhibition) and one dropout in the enalapril group (malignant ventricular arrhythmias). Plasma atrial natriuretic peptide (ANP) and norepinephrine decreased similarly in both groups from elevated baseline concentrations. The patients with the highest baseline ANP levels died in both groups: EN: 579 fmol/ml (mean 65.3 +/- 34.4 fmol/ml), PL: 403 fmol/ml (mean 63.5 +/- 37.6 fmol/ml). Killip classification improved in 9 of 13 patients on enalapril but only in 5 of 11 patients on placebo. On echocardiography an increase in fractional shortening (FS) (3.2 +/- 7.5%, p < 0.05) was found with enalapril only. Patients on placebo required more diuretics, and plasma aldosterone increased threefold. Thus, very early enalapril treatment may help prevent left ventricular failure after AMI. Extremely high initial plasma ANP concentrations may predict an unfavorable outcome.",1995.0,0,0
1383,7666600,Angiotensin-converting enzyme inhibitor-induced anemia and treatment for erythrocytosis in renal transplant recipients.,S Satoh; T Kaneko; K Seino; T Abe; S Omori; J Sugimura; T Fujioka; T Kubo,"Erythrocytosis is not rare in renal transplant recipients, and phlebotomy is still the main treatment. Recently, the occurrence of angiotensin-converting enzyme (ACE) inhibitor induced anemia in patients on chronic hemodialysis and in renal transplant recipients has been reported. We herein report 5 transplant recipients whose hematocrit levels decreased while taking ACE inhibitors, including 2 patients treated with ACE inhibitors for erythrocytosis. The individual mean hematocrit values ranged from 35.0% to 54.7% before treatment and from 27.6% to 42.0% after treatment. The hematocrit level in the 2 patients with erythrocytosis decreased from 54.7% to 39.8% and 47.5% to 27.6%, respectively. Anemia improved after discontinuation or dosage reduction of the drugs. The patients were given the same immunosuppressive drugs, and had good renal function. ACE inhibitor-induced conspicuous anemia was not observed in the transplant recipient who received a kidney from a twin sibling and had not been taking any immunosuppressive drugs, nor in the 8 other patients with diabetes mellitus or chronic glomerulonephritis who served as controls. We conclude that ACE inhibitor-induced anemia may frequently arise in an immunosuppressed state. Based on these events, the ACE inhibitor can be used as a potent drug for erythrocytosis in post-transplant recipients.",1995.0,0,0
1384,7667995,Lisinopril therapy associated with acute pancreatitis.,M A Marinella; J E Billi,,1995.0,0,0
1385,7669262,ACE inhibitors. Drug interactions of clinical significance.,C Mignat; T Unger,"ACE inhibitors are used widely in the treatment of hypertension and congestive heart failure, but there is only limited information on adverse interactions between ACE inhibitors and other cardiovascular or noncardiovascular drugs. The present article provides an overview of this issue, with emphasis on those interactions having the greatest clinical implications. In patients who have been sodium and/or volume depleted by thiazide or loop diuretics, the additional use of ACE inhibitors can lead to an excessive reduction in blood pressure and symptomatic hypotension. An increase in serum potassium levels may occur after coadministration of potassium-sparing diuretics and ACE inhibitors, resulting in hyperkalaemia especially in patients with renal insufficiency. The incidence of acute renal failure may be associated with ACE inhibitor therapy when these drugs are combined with nonsteroidal anti-inflammatory agents and given to patients whose renal function becomes increasingly dependent on angiotensin II and prostaglandins. There is some evidence, albeit scant, linking ACE inhibitors with the induction of lithium toxicity in patients maintained on lithium, and with the occurrence of severe hypersensitivity reactions in patients undergoing haemodialysis, venom immunisation or concomitant allopurinol therapy.",1995.0,0,0
1386,7669481,Effects of different antihypertensive drugs on plasma fibrinogen in hypertensive patients.,R Fogari; A Zoppi; G D Malamani; G Marasi; A Vanasia; G Villa,"1. In order to evaluate whether treatment with different antihypertensive drugs would affect plasma fibrinogen levels, 118 mild to moderate essential hypertensive subjects, all males, aged 18 to 65 years, were randomly treated with amlodipine 10 mg, atenolol 100 mg, hydrochlorothiazide 25 mg or lisinopril 20 mg, all given once daily for 8 weeks. 2. Before and after 8 weeks' treatment, blood pressure (BP), heart rate (HR), fibrinogen, total cholesterol (TC), HDL-C, LDL-C, triglycerides (TG), plasma glucose, plasma uric acid, serum creatinine and serum potassium were evaluated. 3. All four medications significantly reduced BP values, although the BP lowering effect of lisinopril, amlodipine and atenolol was significantly greater compared with that of hydrochlorothiazide. 4. Plasma fibrinogen levels were unaffected by atenolol, hydrochlorothiazide and amlodipine, whereas they were significantly decreased by lisinopril (-11.2%, P = 0.002). This fibrinogen lowering effect was more evident in smokers (-17.7%) than in non smokers (-7.4%). 5. Atenolol and amlodipine did not significantly affect plasma lipids, hydrochlorothiazide increased TC, LDL-C and TG and reduced HDL-C; lisinopril increased HDL-C and decreased TC and LDL-C. 6. Hydrochlorothiazide increased plasma glucose and uric acid concentrations, which were unaffected by the other drugs. The diuretic also reduced serum potassium. 7. The results of this study indicate that lisinopril reduces levels of plasma fibrinogen and confirm that different antihypertensive drugs may elicit different metabolic effects, which may variously influence the overall risk profile of the hypertensive patients.",1995.0,0,0
1387,7670648,Ambulatory blood pressure monitoring in the evaluation of antihypertensive treatment: additional information from a large data base.,G Mancia; S Omboni; A Ravogli; G Parati; A Zanchetti,"Aims of our study were i) to compare in a large number of hypertensive subjects the relative effect of antihypertensive treatment on clinic (C) blood pressure (BP) and various ambulatory (A) BP components, and ii) to determine whether antihypertensive treatment affects BP variability. In 266 mild essential hypertensive outpatients (age: 18-78 years) CBP (trough measurements) and ABP (Spacelabs 90202 or 90207) were measured after 3 to 4 weeks of wash-out and after 4 to 8 weeks of treatment with an ACE-inhibitor (n = 135) or a calcium-antagonist (n = 131). ABP recordings were analyzed to obtain average 24 h, day-time (6 a.m. to midnight) and night-time (midnight to 6 a.m.) systolic and diastolic BP values and standard deviations (BP variabilities). Treatment reduced both CBP and ABP. Treatment-induced changes in CBP showed a poor correlation with those in 24h, day- and night-time BP (r never > 0.23) and the correlation was poor also when trough ABP (mean of last 2 h) was considered. Twenty-four hour, day- and night-time BP were similarly reduced by treatment with a direct relationship between the initial BP values and the subsequent BP falls. BP standard deviations were also reduced by treatment in relation to the pretreatment values but the overall reduction was small, limited to the day-time and proportional or less than proportional to the reduction in mean values, with no changes or an increase in variation coefficients. The effects of ACE-inhibitor and calcium-antagonist treatments were superimposable. Our results from a large data base show that antihypertensive treatment effectively reduces all ABP components. The reduction cannot be predicted by the concomitant fall in CBP but it relates to the initial ABP values. Treatment has a limited effect on BP variability, this being the case both for ACE-inhibitors and calcium-antagonists.",1995.0,0,0
1388,7671364,Effects of increasing maintenance dose of digoxin on left ventricular function and neurohormones in patients with chronic heart failure treated with diuretics and angiotensin-converting enzyme inhibitors.,M Gheorghiade; V B Hall; G Jacobsen; M Alam; H Rosman; S Goldstein,"Despite almost three centuries of use, the appropriate dosage of digitalis in patients with chronic heart failure and normal sinus rhythm has not been well studied. We studied 22 patients with heart failure who were receiving constant daily doses of digoxin, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. In 18 patients, the oral daily dose of digoxin was increased from a mean of 0.20 +/- 0.07 to 0.39 +/- 0.11 mg/day corresponding to an increase in the serum digoxin concentration from 0.67 +/- 0.22 to 1.22 +/- 0.35 ng/mL. Radionuclide and echocardiographic left ventricular ejection fraction; maximal treadmill time; heart failure score; serum concentrations of norepinephrine, aldosterone, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity were obtained before and after the increase in digoxin dose. Subsequently, 9 patients were randomized to receive digoxin and 9 to receive placebo and radionuclide ejection fraction measured after 12 weeks. With the higher dose of digoxin compared with the lower dose, there was a significant increase in radionuclide ejection fraction from 23.7 +/- 9.6% to 27.1 +/- 11.8% (P = .007). No significant changes were noted in heart failure score; exercise tolerance; serum concentrations of norepinephrine, atrial natriuretic factor, and antidiuretic hormone; and plasma renin activity. There was, however, an increase in serum aldosterone concentration. Twelve weeks after the patients were randomized to receive digoxin or placebo, there was a significant decrease in ejection fraction (from 29.4 +/- 10.4% to 23.7 +/- 8.9%) in the placebo group but not in patients who continued to receive digoxin (P = .002). The increase in maintenance digoxin dose, while maintaining serum concentrations within therapeutic range, resulted in a significant increase in left ventricular ejection fraction that was not associated with significant changes in heart failure score, exercise tolerance, and neurohumoral profile.",1995.0,0,0
1389,7673623,Isolated uvular angioedema associated with ACE inhibitor use.,D C Kuo; R A Barish,"Angioedema is a well-known complication of medical therapy with angiotensin-converting enzyme (ACE) inhibitors. Isolated uvular angioedema, a rare presentation of angioedema, in a patient taking lisinopril (Zestril) is described in this case report. Management of uvular edema is also reviewed.",1995.0,0,0
1390,7674690,Contemporary management of patients with heart failure.,J B Young,"Treatment of patients with heart failure has become extremely challenging. A complicated interplay of myocardial, hemodynamic, and humoral factors marking this condition requires a delicate balancing of medication use, procedural intervention, and lifestyle changes. Judicious prescription of therapies in stepwise fashion as the syndrome severity worsens (Fig. 2) is critical to success.",1995.0,0,0
1391,7674691,Early intervention in patients with heart failure and left ventricular dysfunction.,P C Deedwania,The focus of this article is to review the process of left ventricular remodeling and discuss the results of several published large clinical trials that have demonstrated the benefit of early intervention in heart failure to prevent left ventricular remodeling and progression of cardiac dysfunction. The knowledge gained from this review should help define a strategy for the internist to initiate therapy early in the course of development of heart failure.,1995.0,0,0
1392,7676758,"Enalapril in the treatment of mild-to-moderate heart failure in general medical practice: a prospective and multicentre study concerning 17,546 patients.",P Messner Pellenc; A Rudnicki; F Leclercq; R Grolleau,"The objective of this study was to test the efficacy and tolerability of a precise dosage regimen of enalapril in general medical practice, in combination with conventional therapy, in patients with mild-to-moderate (NYHA classes II and III) congestive heart failure (CHF). 17,546 patients were prospectively included in this multicentre study. After three months of treatment with enalapril, 53.9% of patients were asymptomatic (NYHA Class I) and 75.1% of patients improved by at least one class in the NYHA classification. 64.6% of patients reached maintenance dosage of 20 mg/day of enalapril and mean daily dosage for all patients was 16 mg. Outcome of functional symptoms according to NYHA class was more favourable with maintenance dosages of 15 and 20 mg/day of enalapril than with maintenance dosages of 5 and 10 mg/day of enalapril. Clinical and laboratory safety was good with low rates observed of the main adverse events: cough (1.74%), hypotension (0.34%), postular hypotension (0.30%), dizziness (0.31%) and hyperkaliema (0.13%); 1.4% of patients dropped out of the study because of such events. This extensive and open study confirms, in general medical practice, the feasibility, efficacy and tolerability of a dosage regimen of enalapril, which has been previously determined in controlled studies performed in specialized medical centres, for treatment of mild-to-moderate heart failure.",1995.0,0,1
1393,7695185,Prevention of post-PTCA restenosis.,D P Faxon; J W Currier,"Significant improvements in the success of angioplasty combined with a major reduction in complications have led to widespread use of the technique in the treatment of symptomatic patients with coronary disease. Restenosis, however, remains the most significant limitation of angioplasty, occurring in 20-50% of patients following a successful procedure. Over the past 10 years, more than 40 large randomized pharmacological trials have attempted to address this problem. Currently no single agent has clearly been shown to reduce restenosis. As a consequence of intensive research, improved understanding of the pathophysiology of restenosis as well as the design of clinical studies necessary to study the process has resulted. Recent experimental studies suggest that vascular remodeling may be as important as intimal hyperplasia, and future trials will need to address this aspect of the restenosis process. Current approaches to preventing restenosis include the use of combined drug therapy to attack several pathophysiological processes, local delivery of drug at the site of the injury to maximize drug effect, and the use of highly specific drugs including local gene therapy.",1995.0,0,0
1394,7697691,Efficacy and safety of benazepril plus hydrochlorothiazide versus benazepril alone in hypertensive patients unresponsive to benazepril monotherapy.,K Holwerda; R P Hoogma; C Oldenbroek; R C Huige; A Wester; J M Rijnierse,"A combination of benazepril 10 mg plus hydrochlorothiazide 12.5 mg once daily was investigated in the treatment of patients with mild-to-moderate essential hypertension who had not responded to monotherapy with benazepril 10 mg. Patients failing to respond to 4 weeks of benazepril 10 mg/d were randomized to continue with the monotherapy (n = 47) or receive the combination therapy (n = 46). After 4 weeks of double-blind treatment, reductions in blood pressure were significantly greater among patients given the combination than among those receiving benazepril alone: a 4.7 +/- 1.5 mm Hg difference in mean sitting diastolic blood pressure was noted in favor of the combination therapy (P = 0.0037). The incidence of adverse events, particularly cough, was lower with benazepril + hydrochlorothiazide than with benazepril alone; no notable changes in body weight or heart rate were seen in either group.",1994.0,0,0
1395,7698130,"An echocardiographic method for selecting high risk patients shortly after acute myocardial infarction, for inclusion in multi-centre studies (as used in the TRACE study). TRAndolapril Cardiac Evaluation.",L Køber; C Torp-Pedersen; J Carlsen; R Videbaek; H Egeblad,"The aim of our study was to examine if echocardiography can reproducibly be used in a multicentre study to select high risk patients with reduced left ventricular function early after an acute myocardial infarction (MI). In the TRAndolapril Cardiac Evaluation Study (TRACE) patients with reduced left ventricular systolic function were randomized 3-7 days post MI to receive either the ACE inhibitor trandolapril, or placebo. Twenty-seven Danish centres participated and 7001 consecutive MI patients were screened for entry. Local doctors and technicians who had received a brief but thorough training course recorded a two-dimensional echocardiographic examination on videotape 2-6 days after MI. Within 24 h, wall motion index (WMI) was visually assessed by one of two cardiologists (examiners) with considerable experience in echocardiography. A WMI of < or = 1.2 (corresponding to a left ventricular ejection fraction (LVEF) < or = 0.35) meant that the patient was eligible for randomization in the TRACE study. Two other experienced cardiologists with substantial experience in echocardiography (controllers) performed blind reassessment of 155 randomly chosen videotapes. We showed that 93% of the 7001 screened MIs had an assessable echocardiogram. WMI was < or = 1.2 in 37% of patients. The one-year mortality was inversely related to WMI, being 60%, 30%, 14% and 11% in patients with a WMI < 0.8, 0.8-1.2, 1.3-1.6 and > 1.6, respectively. In the random sample of 155 videorecordings that were reevaluated, 97% were found to be technically adequate for analysis both by the examiners and the controllers.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1396,7698136,Absence of effect on exercise capacity of 12-weeks treatment with ramipril in patients with moderate congestive heart failure. Ramipril Study Group.,T Gundersen; K Swedberg; O Amtorp; J Remes; B Nilsson,"Pharmacological therapy in cases of chronic congestive heart failure (CHF) is usually evaluated by maximal exercise time. To assess the effect of an angiotensin converting enzyme inhibitor, ramipril, 223 patients with moderate CHF were studied in 24 centres in four Nordic countries in a randomized, double-blind, placebo-controlled, parallel group design. The study drug was titrated from 1.25 mg to a maximum of 10 mg once daily (o.d) over a period of 4 weeks (mean dose 8 mg). A symptom-limited bicycle exercise test, starting at 30 watts and increasing by 10 watts.min-1, was used to evaluate exercise capacity. Reproducible tests were required at baseline, and the test was repeated after 4, 8 and 12 weeks of treatment. Seven deaths were recorded in the placebo group and one death in the ramipril group. A total of 195 patients completed 12 weeks of treatment (placebo group n = 91, ramipril group n = 104). The groups had similar baseline characteristics. Maximal exercise time was increased by mean (SD) 35 s (9) and 41 s (8) in the placebo and ramipril groups, respectively. The adjusted difference between the groups at 12 weeks was 9 s (12) (ns). A significant decrease in blood pressure and rate-pressure product at rest and at end of exercise was obtained by ramipril as compared with placebo. Significantly fewer patients deteriorated in NYHA class from baseline to 12 weeks of ramipril treatment compared to placebo (P = 0.012). Concomitant medication for CHF increased significantly in the placebo group as compared with ramipril-treated patients (P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1397,7700028,Remission of nephrotic range proteinuria in type I diabetes. Collaborative Study Group.,L A Hebert; R P Bain; D Verme; D Cattran; F C Whittier; N Tolchin; R D Rohde; E J Lewis,"The present study assessed the extent to which remission of nephrotic-range proteinuria occurred in patients with Type I diabetes enrolled in the Captopril Study, a placebo controlled multicenter clinical trial of captopril therapy in diabetic nephropathy. Of the 409 patients recruited into the Captopril Study, 108 had nephrotic-range proteinuria (> 3.5 g/24 hr) at entry in the Study (baseline). This group was the subject of the present study. Remission of nephrotic-range proteinuria was defined as follows: (1) Onset of the remission was taken as the date when proteinuria was first noted to be < or = 1.0 g/24 hr. (2) The reduction in proteinuria had to be sustained for a minimum of six months and until the end of the Captopril Study. (3) During the remission, the average of all 24 hour proteinuria measurements could not exceed 1.5 g. (4) Decline in renal function could not explain the reduced proteinuria. That is, the patient's serum creatinine during the entire period of observation in the Captopril Study had to remain at less than a doubling of the baseline serum creatinine. Remission of nephrotic-range proteinuria occurred in 7 of 42 patients assigned to captopril (16.7%, mean follow-up 3.4 +/- 0.8 years) and in 1 of 66 patients assigned to placebo (1.5%, mean follow-up 2.3 +/- 1.1 years; P = 0.005, comparing remission rate in captopril vs. placebo-treated patients).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
1398,7704289,Short term effects of pravastatin on blood pressure in hypercholesterolaemic hypertensive patients.,C J O'Callaghan; H Krum; E L Conway; W Lam; M A Skiba; L G Howes; W J Louis,"In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatin's rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks' treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks' treatment or 3 weeks' withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.",1994.0,0,0
1399,7706699,Effects of modulators of the renin-angiotensin-aldosterone system on cough. Losartan Cough Study Group.,Y Lacourcière; H Brunner; R Irwin; B E Karlberg; L E Ramsay; D B Snavely; T W Dobbins; E P Faison; E B Nelson,"To compare the incidence of cough in patients with a history of angiotensin converting enzyme (ACE) inhibitor-related cough who received losartan [a type 1 angiotensin II (Ang II) receptor antagonist], lisinopril (an ACE inhibitor) or hydrochlorothiazide (a diuretic). An international, multicentre, randomized double-blind, parallel-group controlled trial. Outpatient clinics at 20 tertiary care medical centres in 11 countries. One hundred and thirty-five patients with uncomplicated primary hypertension with a history of ACE inhibitor-related cough were randomly assigned to the double-blind treatment phase and completed the study. After confirming that the cough was ACE inhibitor-related by a single-blind rechallenge, followed by a placebo washout period, patients were randomly assigned to receive 50mg losartan, 20mg lisinopril or 25mg hydrochlorothiazide once a day for 8 weeks. Cough incidence, severity and frequency were assessed by a self-administered questionnaire and a visual analogue scale. The percentage of patients who complained of cough was significantly higher with lisinopril than with losartan or hydrochlorothiazide. The mean visual analogue scale scores for patients treated with lisinopril demonstrated that these patients coughed more frequently than those who received losartan or hydrochlorothiazide. The incidence of cough related to the type 1 Ang II receptor antagonist losartan is significantly lower than that observed with lisinopril, and similar to that observed with hydrochlorothiazide in patients with a rechallenged ACE inhibitor cough. Type 1 Ang II receptor antagonists represent a potential new treatment for hypertensive patients in whom ACE inhibitors are indicated, but who develop a cough with these agents.",1994.0,0,0
1400,7708426,Profound hypotension in a tetraplegic patient following angiotensin-converting enzyme inhibitor lisinopril. Case report.,J K Schmitt; K S Koch; M Midha,"We present the case of a 60 year old C6 complete tetraplegic patient who developed profound hypotension following initiation of the angiotensin-converting enzyme inhibitor lisinopril to control blood pressure. Other causes of hypotension, such as myocardial infarction and sepsis was ruled out. Inhibition of the renin-angiotensin-aldosterone system was the probable cause of hypotension. This case demonstrates the critical importance of the renin-angiotensin-aldosterone axis in the maintenance of blood pressure in tetraplegic patients, who may lack input from the brain to sympathetic neurons, and therefore have increased reliance on the renin-angiotensin-aldosterone axis for the maintenance of blood pressure. Angiotensin-converting enzyme inhibitors should be avoided in tetraplegic patients, unless other treatment modalities are ineffective.",1994.0,0,0
1401,7709462,Chronic angiotensin-converting enzyme inhibition may improve sodium excretion in cardiac transplant hypertension.,G K Schwietzer; A Hartmann; G Kober; E Jungmann; D Stratmann; M Kaltenbach; W Schoeppe,"Cyclosporine-associated hypertension (CAH) may be mediated in part by sodium and volume retention. To investigate this issue, we studied the effects of a calcium antagonist, nitrendipine (NIT, 10-20 mg b.i.d.), and a converting enzyme inhibitor, lisinopril (LIS, 10-20 mg o.d.), on blood pressure (office BP, 24 hr ambulatory BP), excretion of an acute sodium load (200 mmol/2 hr i.v.), glomerular filtration rate (insulin clearance), cumulative dopamine excretion, plasma atrial natriuretic peptide (ANP), and endothelin excretion in 8 patients with CAH after cardiac transplantation in a double-blind, randomized, crossover trial for 6 weeks. Five patients received a diuretic during the trial at a constant dose. Office diastolic BP (DBP) decreased significantly with LIS from 97 +/- 6 to 87 +/- 9 mmHg and with NIT from 96 +/- 7 to 92 +/- 12 mmHg. Ambulatory 24 hr DBP decreased significantly from 96 +/- 7 mmHg to 86 +/- 10 mmHg (LIS) and to 84 +/- 11 mmHg (NIT). Ambulatory DBP during the day was lowered significantly from 98 +/- 11 mmHg to 87 +/- 10 mmHg (LIS) and to 88 +/- 9 mmHg (NIT) and during the night from 95 +/- 9 mmHg to 86 +/- 8 mmHg (LIS) and to 79 +/- 7 mmHg (NIT). Cumulative sodium excretion 6 hr after an acute sodium load increased to 52 +/- 39 mmol (placebo), 96 +/- 44 mmol (LIS, P < 0.05 vs. placebo), and 71 +/- 34 mmol (NIT). Glomerular filtration rate, cumulative dopamine excretion, ANP, and endothelin excretion did not differ between either treatment group. We conclude, that: (1) both drugs were similar in lowering office BP and during the day, but NIT tended to be more effective during the night; and (2) cumulative sodium excretion during LIS was significantly increased compared with placebo. There was a similar trend during NIT also. Therefore, it is possible that chronic angiotensin-converting enzyme inhibition and possibly calcium antagonists might improve the sodium-retaining state in CAH independent of differences in blood pressure, ANP, dopamine, or renal function.",1995.0,0,0
1402,7711427,Effects of captopril treatment versus placebo on renal function in type 2 diabetic patients with microalbuminuria: a long-term study.,M Capek; C Schnack; B Ludvik; A Kautzky-Willer; M Banyai; R Prager,"We evaluated the renal effect of long-term antihypertensive treatment (12 months) with the angiotensin-converting enzyme inhibitor captopril compared to placebo in 15 type 2 diabetic patients with microalbuminuria. The patients were randomly allocated to captopril (n = 9) or placebo (n = 6). After 1-year therapy no significant decrease in blood pressure was demonstrated with captopril (139 +/- 17/80 +/- 9 versus 138 +/- 13/76 +/- 6 mmHg) or placebo (138 +/- 9/75 +/- 6 versus 135 +/- 14/79 +/- 10 mmHg). Only in a small hypertensive subgroup (n = 4) treated with captopril did we find a significant reduction in blood pressure (154 +/- 2/88 +/- 1 versus 142 +/- 7/78 +/- 5 mmHg, P < 0.05). The urinary albumin excretion rate did not change significantly either in the captopril group (95.6 mg/24 h, 25th percentile 138.4, 75th percentile 25.1; versus 127.8 mg/24 h, 25th percentile 29.3, 75th percentile 222) or in the placebo group (99.2 mg/24 h, 25th percentile 58.5, 75th percentile 125.8; versus 120.9 mg/24 h, 25th percentile 62.1, 75th percentile 179.7). There were also no alterations in renal blood flow or filtration rate. In the hypertensive subgroup treated with captopril a reduction in urinary albumin excretion rate after 3 and 6 months of treatment was observed (captopril 73.4 versus 24 and 41 mg/24 h, P < 0.05), but not after 12 months. Triglyceride and cholesterol levels remained constant before and after treatment while glycosylated hemoglobin decreased significantly after 12 months captopril (7.8 +/- 0.9 versus 6.9 +/- 0.7 mg%, P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
1403,7712685,Long term use of captopril or nifedipine in normotensive microalbuminuric patients with insulin-dependent diabetes mellitus.,H Bilo; E Kluitman; E van Ballegooie; B J Potter van Loon; K Bakker; B Michels; R Gans; A Donker,"Several studies have suggested that ACE-inhibition may be effective in postponing the onset of nephropathy in insulin-dependent diabetic subjects. In contrast, other drugs might have opposing effects. To study the long term effects of either captopril or nifedipine in normotensive, microalbuminuric patients with insulin-dependent diabetes mellitus, eighteen subjects received either placebo (n = 5, P), 20 mg nifedipine daily (n = 7, N) or 50 mg captopril daily (n = 6, C) for one year. Baseline clinical and laboratory variables were comparable in the three groups. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure did not differ between groups before and after one years medication. UAER did not change in the captopril and the placebo group (C: -12.6% (-58.1 to 51.8%)' P: -17.3 (-55.9 to 99.3%), medians and ranges. In contrast, in the patients that received nifedipine, UAER rose by 43.1% (-8.5 to 261.8%), (p < 0.05 Baseline vs one year, and one year nifedipine vs captopril and placebo). We therefore conclude, that long-term use of nifedipine increases UAER in normotensive microalbuminuric insulin-dependent subjects, in contrast to captopril or placebo. Whether this enhancement of microalbuminuria exerts an adverse effect on renal function in the long-term is yet unknown, but caution seems warranted.",1993.0,0,1
1404,7713100,"Dose-related effects of ACE inhibition in man: quinapril in patients with moderate congestive heart failure. The Study Group on Neurohormonal Regulation in Congestive Heart Failure: Lausanne, Switzerland; Berlin, Düsseldorf, Munich, Germany.",J Nussberger; E Fleck; H Bahrmann; W Delius; H P Schultheiss; H R Brunner,"Early treatment with ACE inhibitors of even moderate heart failure is clinically beneficial, even though haemodynamic measurements cannot adequately quantitate such improvement. Neurohumoral assessment is, however, supposed to be more accurate. In 55 patients with moderate heart failure (ejection fraction < or = 35%), we investigated the dose-dependent effects of ACE inhibition with quinapril taken orally (2.5, 5 or 10 mg b.i.d.) following a placebo-controlled, parallel design protocol over 12 weeks. Plasma components of the renin angiotensin system, catecholamines and ANF were measured together with haemodynamics both at rest and during exercise. Before ACE inhibitor treatment, median PRA, Ang I and II and catecholamines were normal, while ANF was increased. All these parameters, including ACE activity, rose during exercise. Chronic inhibition of ACE activity was dose-dependent and the maximal fall in Ang II occurred with quinapril 20 mg.day-1. Humoral changes appeared more assessible than haemodynamic alterations even though many of these changes were reasonably correlated. The effects of chronic ACE inhibition on circulating neurohumoral components in patients with moderate heart failure are small and dose-dependent. Since humoral changes are related to haemodynamics they should account for the clinical benefit. Appropriately high doses of ACE inhibitors should be chosen for treatment of heart failure.",1994.0,0,0
1405,7713103,Losartan in heart failure: preclinical experiences and initial clinical outcomes.,C S Sweet; E J Rucinska,"Losartan potassium (Cozaar) is an angiotensin II receptor antagonist (AT1 selective) which has undergone extensive clinical trials for the treatment of hypertension. This literature survey will review some of the pre-clinical findings with losartan in models of heart failure, and where appropriate, we will compare the haemodynamic findings in animals with similar studies completed in patients. The major conclusion from these trials is that losartan has clear haemodynamic benefits in patients in heart failure and that the drug appears to be well tolerated, with a low incidence of adverse experiences related to impaired renal function.",1994.0,0,0
1406,7717281,"Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension.",A I Goldberg; M C Dunlay; C S Sweet,"This report presents data on the safety and tolerability of losartan potassium (losartan), a selective antagonist of the angiotensin II AT-1 receptor, in approximately 2,900 hypertensive patients treated in double-blind clinical trials. In these studies, headache (14.1%), upper respiratory infection (6.5%), dizziness (14.1%), asthenia/fatigue (3.8%), and cough (3.1%) were the clinical adverse experiences most often reported in patients treated with losartan. These adverse experiences were also frequently reported in patients receiving placebo: 17.2%, 5.6%, 2.4%, 3.9%, and 2.6%, respectively. Dry cough as an adverse event was reported in 8.8% of patients treated with angiotensin-converting enzyme inhibitors, and in 3.1% and 2.6% of patients treated with losartan or placebo, respectively. Only dizziness was considered ""drug-related"" more often in losartan-treated (2.4%) than placebo-treated (1.3%) patients. In controlled clinical trials, losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences. Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3% and 2.8%, respectively, compared with placebo (3.7%). No laboratory adverse experiences were unexpected or of clinical importance. First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide, and withdrawal effects such as rebound hypertension were not observed in clinical trials. There were no clinically important differences in the clinical or laboratory safety profiles in the demographic subgroups for age, gender, or race. In controlled clinical trials, losartan demonstrated an excellent tolerability profile.",1995.0,0,0
1407,7719946,Pharmacologic management of congestive heart failure.,J M Wright,"This article is a review of the pharmacologic management of congestive heart failure (CHF) and a summary of the medical literature that guides current treatment strategies. Despite advances in the treatment of CHF, it remains a common diagnosis with a poor prognosis. Because CHF is a progressive syndrome with heterogeneous features of cardiac dysfunction, effective management requires combination therapies and evolving treatment strategies. The mechanism of action, goals of therapy, and demonstrated efficacy of each of the various agents used in the treatment of CHF are discussed.",1995.0,0,0
1408,7720758,Effect of captopril on myocardial beta-adrenoceptor density and Gi alpha-proteins in patients with mild to moderate heart failure due to dilated cardiomyopathy.,H Jakob; M Sigmund; T Eschenhagen; U Mende; M Patten; W Schmitz; H Scholz; J Schulte am Esch; M Steinfath; P Hanrath,"In end-stage heart failure due to idiopathic dilated cardiomyopathy beta 1-adrenoceptors are downregulated and Gi alpha-proteins are upregulated. The aim of the present study was to investigate the influence of the angiotensin-converting enzyme inhibitor captopril on beta-adrenoceptor density and Gi alpha-proteins in sequential endomyocardial biopsies. Nineteen patients with mild to moderate congestive heart failure due to idiopathic dilated cardiomyopathy (NYHA Class II-III) were studied before and after 8-11 weeks of therapy. Patients were randomised into a captopril and a control group; 9 patients received captopril 12.5-50 mg per day, (divided in 2-3 doses) p.o. in addition to ""conventional"" therapy with digoxin and diuretics, and 10 controls received ""conventional"" therapy only. Echocardiography, spiroergometry, right heart catheterisation and endomyocardial biopsies were performed before (baseline) and after treatment. Compared to baseline, captopril increased total beta-adrenoceptor density by selectively increasing beta 1-adrenoceptors (31.6 vs 41.2 fmol.mg-1; p < 0.05) but had no significant effect on Gi alpha-proteins. The results indicate that treatment with angiotensin-converting enzyme inhibitors partly restores myocardial beta 1-adrenoceptor density, and this action effect may contribute to the clinical improvement of patients with idiopathic dilated cardiomyopathy treated in this way.",1995.0,0,0
1409,7721386,Effect of antihypertensive treatment on small arteries of patients with previously untreated essential hypertension.,N K Thybo; N Stephens; A Cooper; C Aalkjaer; A M Heagerty; M J Mulvany,"In a double-blind randomized trial, the effects of treatment with an angiotensin-converting enzyme (ACE) inhibitor (perindopril) and a beta-blocker (atenolol) on small artery structure were compared in previously untreated essential hypertensive patients. Subjects (diastolic blood pressure > or = 100 and < or = 120 mm Hg) were randomly assigned to treatment for 12 months with either perindopril (n = 13, 4 to 8 mg/d) or atenolol (n = 12, 50 to 100 mg/d); the dosage was adjusted upward and in some cases combined (n = 5, perindopril; n = 2, atenolol) with thiazide diuretic to achieve target blood pressure (diastolic blood pressure below 90 mm Hg). Before and at the end of treatment, gluteal biopsies were taken under local anesthetic; from these biopsies, two small arteries were dissected and mounted on a myograph for morphometry. The reduction in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg) was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05). Perindopril treatment caused an increase in small artery diameter (231 +/- 14 to 274 +/- 13 microns, P < .05) and a reduction in the ratio of media thickness to lumen diameter (7.94 +/- 0.65% to 5.96 +/- 0.42%, P < .05), whereas atenolol had no effect (246 +/- 14 to 231 +/- 13 microns and 7.14 +/- 0.47% to 6.79 +/- 0.45%, respectively). The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area, suggesting that the change was due to ""remodeling.""(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1410,7721419,Comparison of effects of angiotensin I-converting enzyme inhibition and beta-blockade for 2 years on function of small arteries from hypertensive patients.,E L Schiffrin; L Y Deng,"The effect of treatment with two different antihypertensive agents on the function of small arteries from 17 patients with essential hypertension randomly assigned to receive either the angiotensin I-converting enzyme inhibitor cilazapril or the beta-blocker atenolol was investigated. Subcutaneous small arteries obtained from gluteal fat biopsies were studied on a wire myograph before treatment and at 1 and 2 years of treatment. Blood pressure was mildly elevated in both groups of patients (mean, 150/100 mm Hg) and was well controlled throughout the 2 years of treatment (mean, 130/85 mm Hg). We previously reported, in arteries from patients treated with cilazapril, an improvement at 1 year of treatment of the vasoconstrictor effect of endothelin-1, which had been significantly attenuated in the untreated hypertensive patients compared with normotensive subjects. After 2 years of treatment, this normalization of endothelin-1 response was still present in small arteries of patients treated with the angiotensin I-converting enzyme inhibitor, whereas in patients treated with atenolol, responses were still unchanged after 2 years of treatment. Endothelial function was tested by examining the response of norepinephrine-precontracted arteries to acetylcholine. Untreated hypertensive patients exhibited a slightly but significantly blunted vasorelaxation in response to 10 mumol/L acetylcholine compared with normotensive subjects. After 1 and 2 years of effective antihypertensive treatment, cilazapril-treated patients exhibited responses to acetylcholine that were not different from those of normotensive subjects, whereas atenolol-treated patients still had impaired responses.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1411,7722555,A case-control study of drugs and other determinants as potential causes of Guillain-Barré syndrome.,B H Stricker; M M van der Klauw; J P Ottervanger; F G van der Meché,"The Guillain-Barré syndrome is an inflammatory demyelinating polyneuropathy with an acute or subacute onset. The current case-control study was performed to investigate the possible role of drugs and other determinants in the causation of the Guillain-Barré syndrome. Patients were included as cases if they fulfilled the criteria for acute Guillain-Barré syndrome and were unable to walk 10 m independently and had been admitted to the hospital within 2 weeks of onset of the neuropathy. For every case, two controls without the disease were obtained from the general practitioner (GP) of the patient with Guillain-Barré syndrome. Controls had the same type of health care insurance, were of the same gender and age (within 5 years), and resident in the same area. By telephone, the GPs of the patients with Guillain-Barré syndrome were interviewed. There were 71 female and 75 male cases and 142 female and 149 male controls. Significantly more cases than controls had been prescribed drugs in the 3 months prior to the index date and also diagnoses or symptoms in cases were more common. Case patients used significantly more frequently antipropulsives (loperamide), penicillins (amoxicillin with or without clavulanic acid) and vaccines. Female controls used significantly more often oral contraceptives. More cases than controls suffered from infections of the respiratory, gastrointestinal or urinary tract prior to the onset of neurological symptoms. In a logistic regression analysis, symptoms concerning the gastrointestinal and respiratory system were strongly associated with the Guillain-Barré syndrome. The use of oral contraceptives was significantly lower in female cases which could be compatible with the hypothesis that these drugs are protective.",1994.0,0,0
1412,7723338,Effects of spirapril and captopril on regional blood flow in chronic congestive heart failure: a comparison between a short- and a long-acting angiotensin-converting enzyme inhibitor.,S A van den Broek; P A de Graeff; A J Smit; A R Girbes; ; W H van Gilst; H Hillege; D J van Veldhuisen; H Wesseling; K I Lie,"Spirapril is a new angiotensin-converting enzyme (ACE) inhibitor with a long duration of action. To determine whether duration of inhibition of serum ACE activity may affect regional blood flow (RBF), we compared spirapril with captopril, an ACE inhibitor with a short duration of action. Both the short- and long-term effects were studied in patients with mild to moderate congestive heart failure (CHF). Calf, renal, and hepatic BF measurements were performed in the morning before intake of the study medication; 24 h after the previous dose of spirapril (n = 9 patients) and 12 h after the previous dose of captopril (n = 9 patients). Serum ACE activity after 1, 6, and 12 weeks was significantly reduced in patients receiving spirapril, but not in those receiving captopril. The decrease in mean arterial pressure (MAP) was more pronounced in the spirapril group. Calf BF showed a slight but not significant increase in both spirapril- and captopril-treated patients. Effective renal BF increased significantly only in patients treated with spirapril. Although filtration fraction (FF) tended to decrease in the spirapril group, the decrease was significant only in the captopril group. No changes were observed in hepatic BF. Cerebral BF (CBF) measurements were performed after intake of the first dose of study medication and after 12 weeks, immediately after drug intake. Significant reduction in MAP in the two treatment groups both after the first dose and after 12 weeks did not affect CBF. Despite a significantly prolonged decrease in MAP and serum ACE activity in spirapril-treated patients, no marked differences in RBF were noted between the two ACE inhibitors.",1995.0,0,0
1413,7727181,Combining salicylate and enalapril in patients with coronary artery disease and heart failure.,L H Baur; J J Schipperheyn; A van der Laarse; J H Souverijn; M Frölich; A de Groot; P J Voogd; T F Vroom; V M Cats; M J Keirse,"To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease. Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo. Tertiary referral centre. 20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 0.40. Twelve patients completed the two parts of the study. Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids. The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed. The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A2 synthesis effectively in patients with heart failure and no further reduction by salicylate was found.",1995.0,0,0
1414,7731143,Vascular compliance in sodium-sensitive and sodium-resistant borderline hypertensive patients.,P Draaijer; M J Kool; L M van Bortel; F Nieman; P W de Leeuw; J P van Hooff; K M Leunissen,"Recently, we demonstrated a reduction in the compliance of the carotid, femoral and brachial arteries in sodium-sensitive subjects who had consumed a regular sodium intake of approximately 120 mmol per day, as compared to both sodium-resistant borderline hypertensive subjects and normotensive controls. Venous compliance was not different between the two borderline hypertensive groups and was only slightly lesser than in controls. Large artery compliance was studied using a non-invasive ultrasound vessel wall movement detector system, while venous compliance was determined by means of strain gauge plethysmography. The borderline hypertensive subjects were subsequently treated with enalapril 10 mg/day, felodipine 5 mg/day or placebo during six months. Despite similar reductions in blood pressure, enalapril induced a significant increase of the muscular femoral and brachial artery compliance, but not of the elastic carotid artery, while felodipine did not influence large artery compliance at all in the sodium-sensitive group. The effect of enalapril on muscular artery compliance was established through a dose-dependent increase in distension and not through a change in arterial diameter. Arterial compliance was not influenced by either of the drugs in the resistant group. Venous compliance was also not altered by the medication. In conclusion, femoral and brachial artery compliance in sodium-sensitive borderline hypertensive subjects, which was found to be lower than that of sodium-resistant subjects, improved with antihypertensive treatment with enalapril but not with felodipine, despite the similar reductions in blood pressure induced by both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1415,7732439,Patterns of medication use in patients with heart failure: a report from the Registry of Studies of Left Ventricular Dysfunction (SOLVD).,J B Young; D H Weiner; S Yusuf; C M Pratt; J B Kostis; M B Weiss; E Schroeder; M Guillote,"To determine patterns of medication use based on clinical variables in patients with heart failure, we analyzed data from 5,999 patients participating in the Registry of Studies of Left Ventricular Dysfunction (SOLVD). The Registry comprised a broad spectrum of patients with heart failure, including some with predominantly diastolic dysfunction. Drug use was determined in a population cross-sectional manner at the time of identification (74% hospitalized). The median number of drugs per patient was four, with diuretics taken by 62%, digitalis by 45%, angiotensin-converting enzyme inhibitors (ACE-I) by 32%, calcium channel blockers by 36%, antiarrhythmics by 22%, and beta-blockers by 18%. Only 18% were on the combination of ACE-I, diuretic, and digitalis. Stratification for diagnosis, heart failure symptoms, and ejection fractions demonstrated that triple-drug therapy (digitalis, diuretic, and ACE-I) was common only in those with ejection fractions less than .20 and several signs or symptoms of heart failure. Older patients were taking diuretics frequently (73% of patients older than 70 years of age), and our European center used fewer drugs overall, while prescribing digitalis about half as frequently as North American clinics. These data serve as the baseline for analysis of evolving therapeutic practice in patients with heart failure.",1995.0,0,0
1416,7733005,Effect of serum lipid concentrations on restenosis after successful de novo percutaneous transluminal coronary angioplasty in patients with total cholesterol 160 to 240 mg/dl and triglycerides < 350 mg/dl.,V Dzavik; K K Teo; S Yokoyama; R Modi; A Dinwoodie; J R Burton; W J Tymchak; T J Montague,,1995.0,0,0
1417,7733017,Racial difference in incidence of cough with angiotensin-converting enzyme inhibitors (a tale of two cities).,K S Woo; R M Norris; G Nicholls,,1995.0,0,0
1418,7733120,Enalapril reduces the albuminuria of patients with sickle cell disease.,R Y Aoki; S T Saad,"To evaluate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on albuminuria associated with sickle cell anemia. Two males and 6 females, mean age 22.8 +/- 5.5 years, with sickle cell anemia and albuminuria, received enalapril for 6 months. Before entry into the study, all had a urinary albumin concentration above 30 mg/L as determined by radioimmunoassay documented on three separate occasions at intervals of 15 to 30 days. Samples were collected before 10 AM after an oral water load of 10 mL/kg. Enalapril reduced 6 patients' pretreatment hyperalbuminuria to normal. One patient whose levels did not reach normal values experienced a reduction of 70%. Fractional excretion of sodium, potassium, and lithium did not change during the treatment. Mean arterial pressure decreased by 8.6 +/- 0.42 mm Hg. Two years after enalapril was discontinued, there were no changes in sodium, potassium, or creatinine levels of 7 patients who had received enalapril or in their mean arterial pressures. Urinary albumin concentration increased relative to pretreatment levels in 2 individuals, returned to pretreatment levels in 2, and remained below 30 mg/L in 2. Our results demonstrate that enalapril reduces albuminuria in patients with sickle cell anemia. After discontinuation of the drug, however, the albuminuria may increase to pretreatment levels or higher. Whether the reduction in urinary albumin concentration by angiotensin-converting enzyme inhibitors can delay the development of progressive renal failure in sickle cell anemia patients remains to be established.",1995.0,0,0
1419,7734095,Circulating endothelin-1 levels in lean non-insulin-dependent diabetic patients. Influence of ACE inhibition.,C Ferri; O Laurenti; C Bellini; M R Faldetta; G Properzi; A Santucci; G De Mattia,"To evaluate the effect of captopril on plasma endothelin-1 (ET-1) levels and insulin sensitivity, 15 lean normotensive men (51.6 +/- 3.8 years) affected by non-insulin-dependent diabetes mellitus (NIDDM) underwent 2-h euglycemic hyperinsulinemic clamp. Each patient was then assigned to receive either captopril (25 mg twice daily for 1 week) or placebo, in a double-blind randomized fashion, before repeating clamp. At baseline, plasma ET-1 levels were 0.77 +/- 0.25 pg/mL in captopril (n = 10) and 0.83 +/- 0.3 pg/mL in placebo patients (n = 5). A twofold increase in plasma ET-1 levels occurred during the 2-h insulin infusion in both groups (P < .05 after 60 and 120 min), with a rapid return to baseline after 30 min from insulin withdrawal. After 1 week of therapy, total glucose uptake significantly increased in captopril (from 3.71 +/- 1.70 mg/kg/min to 4.24 +/- 1.72 mg/kg/min, P < .03) but not in placebo patients. Plasma ET-1 levels significantly decreased after captopril therapy (0.48 +/- 0.25 pg/mL at time 0, P < .03 v pretreatment levels), but were unaffected by placebo. Moreover, captopril slightly reduced the magnitude of ET-1 increment during insulin infusion (0.65 +/- 0.28 pg/mL and 0.88 +/- 0.48 pg/mL at 60 and 120 min, respectively, P < .05 v time 0). As a consequence, during the second insulin infusion circulating ET-1 levels were significantly lower in captopril- than in placebo-treated patients at time 0 (P < .02), 60 (P < .002), 120 (P < .004), and 150 min (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1420,7734107,Duration of cough following cessation of ACE inhibitor therapy.,G Y Lip; J Zarifis; M Beevers; D G Beevers,,1995.0,0,0
1421,7736741,Invasive hemodynamic evaluation of sublingual captopril and nifedipine in patients with arterial hypertension after abdominal aortic surgery.,M Leeman; J P Degaute,"To examine the central hemodynamic and blood gas responses to sublingual captopril and nifedipine administration in patients with arterial hypertension after abdominal aortic surgery. Prospective, randomized, parallel-group clinical study. Twenty-nine-bed medical-surgical intensive care unit in a university hospital. Twenty patients with arterial hypertension (mean arterial pressure of > or = 115 mm Hg) the day after abdominal aortic surgery. Patients with bilateral renal artery stenoses, identified with the preoperative angiogram, were excluded. Pressures were measured using intravascular catheters and cardiac output was determined by thermodilution for 2 hrs after captopril 25 mg (n = 10) or nifedipine 10 mg (n = 10) was administered by the sublingual route. Captopril administration and nifedipine administration decreased mean arterial pressure (from 121 +/- 1 to 94 +/- 4 mm Hg and from 121 +/- 2 to 94 +/- 2 [sem] mm Hg, respectively), pulmonary arterial pressure, pulmonary artery occlusion pressure, and right atrial pressure (p < .001 for all variables). Changes in heart rate and in cardiac output were not significant. PaO2 decreased after nifedipine, from 101 +/- 8 to 81 +/- 3 torr [13.5 +/- 1.1 to 10.8 +/- 0.4 kPa] (p < .01), but not after captopril (104 +/- 9 to 100 +/- 7 torr [13.9 +/- 1.2 to 13.3 +/- 0.9 kPa]). Excessive or symptomatic decreases in blood pressure were not observed, nor was deterioration in renal function observed. Sublingual captopril and nifedipine were equally effective for the treatment of arterial hypertension after abdominal aortic surgery. Nifedipine, but not captopril, caused a deterioration in pulmonary gas exchange.",1995.0,0,0
1422,7737712,Different effects of fosinopril and atenolol on wave reflections in hypertensive patients.,C H Chen; C T Ting; S J Lin; T L Hsu; F C Yin; C O Siu; P Chou; S P Wang; M S Chang,"We conducted this study to compare the effects of fosinopril versus atenolol on peripheral blood pressure, central arterial wave reflection, and left ventricular mass in a group of patients with essential hypertension. We conducted a double-blind, randomized trial of fosinopril and atenolol in 79 hypertensive patients (52 men, 27 women; mean age, 45.8 +/- 8.5 years; range, 30 to 68 years). Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe. The extent of wave reflection was estimated by the augmentation index defined as the ratio of the amplitude of pressure wave above its systolic shoulder to the pulse pressure. The augmentation index, left ventricular mass index by two-dimensional echocardiography, and 24-hour ambulatory blood pressures were determined before and after 8 weeks of daily treatment with fosinopril (10 to 20 mg) or atenolol (50 to 100 mg) with or without diuretics and compared with those values in 79 normotensive control subjects. After 8 weeks of treatment, both drugs lowered 24-hour ambulatory peripheral systolic and diastolic pressures into the normal range to a similar extent (fosinopril, -18/-13 mm Hg; atenolol, -23/-17 mm Hg, both P = NS). On the other hand, whereas the elevated augmentation index in hypertensive patients compared with normotensive subjects (16 +/- 11% versus 10 +/- 8%) was completely normalized by fosinopril (-9.3 +/- 9.8%, P < or = .002), it was lowered by atenolol (-4.8 +/- 8.9%, P < .002) but to a significantly smaller extent (fosinopril versus atenolol effect, P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1423,7737713,Reduction of salt intake during converting enzyme inhibitor treatment compared with addition of a thiazide.,D R Singer; N D Markandu; F P Cappuccio; M A Miller; G A Sagnella; G A MacGregor,"A moderate reduction in salt intake lowers blood pressure in individuals with hypertension and improves blood pressure control in those taking a converting enzyme inhibitor. However, it is unclear how effective reduction of salt intake is compared with addition of other drugs, in particular, thiazide diuretics. We directly compared the separate effects on blood pressure of reducing sodium intake or adding a thiazide diuretic in the pressure of a converting enzyme inhibitor in a double-blind, randomized, crossover study. We studied 11 subjects with essential hypertension who had been taking 25 mg captopril twice daily for at least 1 month. In the double-blind study, after 1 month of captopril alone, supine blood pressure was 151 +/- 5/95 +/- 4 (SEM) mm Hg. With the addition of 25 mg hydrochlorothiazide once daily for 1 month, blood pressure fell to 137 +/- 5/87 +/- 3 mm Hg. When a moderate reduction in salt intake (from 206 +/- 26 to 109 +/- 20 mmol urinary sodium/24 h) was added to captopril for 1 month, blood pressure was reduced by a similar amount (to 137 +/- 4/90 +/- 3 mm Hg). Plasma potassium fell during the diuretic treatment (3.9 +/- 0.1 to 3.7 +/- 0.1 mmol/L, P < .05) but increased nonsignificantly during salt reduction (3.9 +/- 0.1 to 4.1 +/- 0.2 mmol/L). These results clearly demonstrate that moderate salt reduction, which can be easily achieved, is as effective as a thiazide diuretic in lowering blood pressure in the presence of a converting enzyme inhibitor and has the particular advantage that plasma potassium does not decrease.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1424,7737786,The consulting psychiatrist and the polydipsia-hyponatremia syndrome in schizophrenia.,V Vieweg; A Pandurangi; J Levenson; J Silverman,"The authors seek to extend understanding and treatment of hospitalized schizophrenics presenting with complications of polydipsia and dilutional hyponatremia. Attending physicians may ask the consultation/liaison psychiatrist to see schizophrenics with hyponatremically-induced delirium or other psychiatric syndromes. The referring physician may or may not have identified polydipsia and dilutional hyponatremia and their complications. This article will help the consultation/liaison psychiatrist recognize early evidence of water imbalance, describe evaluation, and provide somatic and behavioral treatment approaches to this life-threatening syndrome. Over the past ten years, the authors have treated more than 100 patients with the polydipsia-hyponatremia syndrome. The authors discuss their and others' experience with drugs that help and hinder patients suffering from dilutional hyponatremia. They review current key articles from the polydipsia-hyponatremia syndrome literature including articles identified via Medline search 1985-94. Schizophrenics with the polydipsia-hyponatremia syndrome most commonly present with polydipsia, polyuria, urinary incontinence, cognitive, affective, and behavioral changes, seizures, or coma. Quantitating polydipsia, hyponatremia, and diurnal changes in body weight facilitate therapeutic interventions. Treatment include patient and caregiver education, drug therapies to better treat psychosis and better treat osmotic dysregulation, behavioral interventions to interdict polydipsia, and diurnal weight monitoring. Once recognized, acute, subacute, and chronic complications of the polydipsia-hyponatremia syndrome are readily treatable. Besides treating the patient, consultation/liaison psychiatrists can teach their medical colleagues about this syndrome. In so doing, they will enhance the quality of their patients' lives and help the internist and surgeon feel more comfortable when working with schizophrenics.",1994.0,0,0
1425,7738212,Sequential monotherapy of hypertension.,M S Kochar; D Trottier; G Kotecki; M Forbes; V S Bamrah,"In most cases, the antihypertensive therapy for an individual patient is selected through a process of trial and error. This study determined if, by treating each hypertensive patient sequentially, with six antihypertensive drugs, one from each of the major classes, one could decide on the best possible drug for control of hypertension. In a randomized open-label crossover study, 19 patients (16 male and 3 female), 28-70 years of age with a sitting diastolic blood pressure of 95-110 mm Hg were given atenolol, captopril, clonidine, indapamide, prazosin, and verapamil in a sequential manner. Each drug was started at the minimum recommended or lower dose and titrated upwards every 2 weeks, if well tolerated, until blood pressure was controlled (diastolic BP < 90 mm Hg). If blood pressure was controlled, the drug was continued for another 2 weeks. A washout period of at least 2 weeks was allowed between drugs. Both systolic and diastolic blood pressures were reduced significantly with all of the six drugs. In 18 of the 19 patients, blood pressure was controlled with at least one of six drugs, frequently with the lowest dose. The authors conclude that if hypertension is not controlled with the lowest recommended dose of a drug, other antihypertensive drugs should be tried sequentially rather than increasing the dose or adding a second drug.",1994.0,0,0
1426,7739305,Hypoglycaemia associated with use of inhibitors of angiotensin converting enzyme.,R M Herings; A de Boer; B H Stricker; H G Leufkens; A Porsius,"The use of angiotensin-converting-enzyme (ACE) inhibitors has been associated with increased insulin sensitivity in diabetic patients. Although such an effect could be beneficial in the treatment of hypertension or congestive heart failure in diabetic patients, it might also precipitate severe hypoglycaemia. To test this hypothesis we carried out a nested case-control study, using data in the Dutch PHARMO system (1986-92), among diabetic patients treated with insulin or with oral antidiabetic drugs, who were admitted to hospital with hypoglycaemia. We identified 94 patients who had been admitted with hypoglycaemia and selected 654 controls from the same cohort. With adjustment for a wide range of potential confounding factors, hypoglycaemia was significantly associated with current use of ACE inhibitors (odds ratio 2.8 [95% CI 1.4-5.7]). Both among users of insulin and among users of oral antidiabetic drugs, use of ACE inhibitors was significantly associated with an increased risk of hospital admission for hypoglycaemia (2.8 [1.2-6.4] and 4.1 [1.4-12.2], respectively). Although ACE inhibitors have several advantages over other antihypertensive drugs in diabetes, the risk of hypoglycaemia should be taken into account. Further investigation of the mechanism is needed since as many as 13.8% of all hospital admissions for hypoglycaemia might be attributable to use of ACE inhibitors.",1995.0,0,0
1427,7742149,Reproducibility of angiotensin converting enzyme inhibitor induced cough: a double-blind randomised study.,V Charlon; S Dollow; J Fidel; C Hoglund; T Honkanen; I Kobrin; J McEwan; G McInnes; J R Viskoper; K S Woo,"1. The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect. 2. Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out. 3. Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made. 4. Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.",1995.0,0,0
1428,7743608,Special report on the ISIS-4 study.,,,1995.0,0,0
1429,7743619,Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy.,B Greenberg; M A Quinones; C Koilpillai; M Limacher; D Shindler; C Benedict; B Shelton,"Studies of Left Ventricular Dysfunction (SOLVD) demonstrated that enalapril therapy significantly improved the clinical course of patients with left ventricular (LV) dysfunction. The goals of this substudy were to evaluate changes in LV structure and function in SOLVD patients and to test the hypothesis that enalapril inhibits remodeling in patients with LV dysfunction. Patients entering both the prevention and treatment arms of SOLVD from 5 of the 23 clinical centers were recruited for this substudy. The 301 patients who participated underwent Doppler-echocardiographic evaluation according to standard protocol before randomization to either enalapril or placebo and again after 4 and 12 months of therapy. Recorded data were analyzed in a blinded fashion at a central core laboratory. Analysis of baseline clinical characteristics showed that patients enrolled in the substudy were generally representative of the SOLVD population, although prevention arm patients were slightly overrepresented in the substudy group (69.8% compared with 61.9% of remaining SOLVD patients). The enalapril group demonstrated significant reductions in the mitral annular E-wave-to-A-wave velocity ratio (due predominantly to a reduction in E-wave velocity), and this response was different from that seen in the placebo group (P = .030). Changes in the E-to-A ratio in the enalapril group correlated significantly with changes in plasma atrial natriuretic peptide (r = .56; P < or = .01). LV end-diastolic and end-systolic volumes increased in placebo but not enalapril-treated patients, and the differences in response between the treatment groups were significant (P = .025 and .019, respectively). LV mass tended to increase in placebo patients and to be reduced in enalapril-treated patients, and the difference in response between the groups was highly significant (P < or = .001). These data demonstrate that enalapril attenuates progressive increases in LV dilatation and hypertrophy in patients with LV dysfunction. The results support the possibility that the favorable effects of enalapril reported in the SOLVD trials were related to inhibition of LV remodeling.",1995.0,0,0
1430,7748046,Antiarrhythmic drug prescription in patients after myocardial infarction in the last decade. Experience of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico (GISSI).,F Avanzini; R Latini; A Maggioni; F Colombo; E Santoro; M G Franzosi; G Tognoni,"Recent clinical trials have shown increased, rather than decreased, mortality in patients treated with antiarrhythmic drugs after acute myocardial infarction. To determine whether these findings had an impact on prescription of antiarrhythmic drugs after acute myocardial infarction. We retrospectively analyzed the class I and III antiarrhythmic prescription data of 38,072 patients with acute myocardial infarction enrolled in three large randomized clinical trials endorsed by a highly representative sample (about 75%) of Italian coronary care units during the last 10 years. The first study was conducted in 1984 to 1985; the second, in 1988 to 1989; the pilot for the third, in 1991; and the third, in 1991 to 1994. Total class I and III antiarrhythmic prescriptions after acute myocardial infarction was halved during the last decade, from 11.9% at discharge and 14.4% at follow-up in 1984 to 1985 to 5.8% and 5.8%, respectively, in 1991 to 1994. The trend was independent of the different distributions in the three studies of the patients' characteristics associated with antiarrhythmic use (ie, age > or = 70 years, anterior acute myocardial infarction, ventricular fibrillation during hospitalization, and Killip class > or = 2 at randomization). The same decreasing trend was observed for each antiarrhythmic drug. The drug most widely used was amiodarone, accounting for about half of the antiarrhythmic prescriptions, followed by mexiletine hydrochloride and propafenone hydrochloride; flecainide acetate was dropped from the prescription list after the publication of the Cardiac Arrhythmia Suppression Trial results. The negative results of the recent clinical trials on class I antiarrhythmic drug use after acute myocardial infarction have been rapidly transferred into routine clinical practice in Italy, since the proportion of patients who received class I and III antiarrhythmic drugs after acute myocardial infarction was halved from the early 1980s to the early 1990s.",1995.0,0,0
1431,7751416,Dosing of antihypertensive medications in patients with renal insufficiency.,B L Carter,"The use of antihypertensive agents in patients with renal insufficiency necessitates careful consideration of dosages, titration, and monitoring. Renal function must be estimated to appropriately make dosage adjustments for antihypertensives that exhibit extensive renal elimination. Thiazide diuretics are useful in mild degrees of renal insufficiency but loop diuretics become necessary as renal function deteriorates further. With either class, low dosages should be used to prevent hypovolemia, hyponatremia, and hypokalemia which may worsen renal blood flow. Angiotensin-converting enzyme (ACE) inhibitors have become popular because they may have unique renal protective properties. All ACE inhibitors except fosinopril require reduced dosages and/or less frequent administration in patients with renal insufficiency. It is often necessary to use a diuretic with an ACE inhibitor and special dosing considerations are important. Due to demographic and physiologic characteristics of patients with renal insufficiency, beta blockers are often reserved for patients with other indications for beta blockers such as ischemic heart disease. Several beta blockers are eliminated primarily by the kidney and dosage reductions are necessary for these agents. Calcium antagonists may also have renal protective effects. Because calcium antagonists are metabolized extensively, significant dosage adjustments are not necessary. Data suggest that antihypertensives may slow the decline in renal insufficiency. The pharmacokinetics of several antihypertensives change with renal impairment because of reduced elimination. Therefore, dosage adjustments, slower titration, and less frequent administration are often necessary.",1995.0,0,0
1432,7751417,"Selected aspects of ACE inhibitor therapy for patients with renal disease: impact on proteinuria, lipids and potassium.",T Keilani; W Schlueter; D Batlle,"Overt proteinuria is often accompanied by hypercholesterolemia and is associated with increased lipoprotein(a) levels. These lipid abnormalities are probably involved in the high incidence of macrovascular complications associated with diabetic nephropathy and possibly other kinds of non-diabetic proteinuric renal disease. Over the last decade many studies have shown that ACE inhibitors can reduce urinary protein excretion but little attention was paid to the impact of this form of therapeutic intervention on the lipid profile. In this article we review our recent data showing that fosinopril administration was associated with significant decreases in both urinary protein excretion, serum total cholesterol levels, and plasma lp(a) levels. The use of ACE inhibitors in patients with renal impairment can result in the development of hyperkalemia as a result of suppression of angiotensin II-driven aldosterone secretion by the adrenal gland. Inhibition of aldosterone secretion may depend on the degree of inhibition of angiotensin II formation in the circulation and also locally in the adrenal gland. Because the various ACE inhibitors exhibit different degrees of ACE inhibition at the tissue level, we have postulated that angiotensin II-dependent aldosterone production will be inhibited to a lesser degree by agents that have low tissue affinity for the adrenal gland. The implication of this theoretical concept for the development of hyperkalemia in patients with impaired renal function treated with ACE inhibitors is discussed.",1995.0,0,0
1433,7751418,An individualized approach to the hypertensive patient with renal disease: six illustrative case studies.,W J Elliott,"One of the biggest challenges in medicine is the area of therapeutics, wherein the physician attempts to match the needs of the individual patient with a specific agent from the pharmacopeia, at the dose that might be best suited to treat the individual's problem. A great deal of the art of medicine is involved in this ""matching process,"" in which the scientific aspects of diagnosis and therapy meet with the physician's knowledge of clinical pharmacology. The abbreviated case histories of six patients who came to the author with specific questions regarding therapy of their hypertension and renal impairment illustrate the fact that one of any number of therapies might have reduced blood pressure in these patients, but in each, there was a specific reason to attempt a single approach first. If physicians could better understand and extrapolate the results of clinical research to the treatment of specific patients, choice of therapy might become more successful.",1995.0,0,0
1434,7751424,Single-dose and steady-state pharmacokinetics of fosinopril and fosinoprilat in patients with hepatic impairment.,N F Ford; K C Lasseter; D R Van Harken; J L Hammett; R Raymond; J Manning,"The single-dose and steady-state pharmacokinetics of the angiotensin-converting enzyme (ACE) inhibitor fosinopril and its active diacid, fosinoprilat, were evaluated in 6 healthy volunteers and 12 patients with alcoholic cirrhosis. Fosinopril was administered at a dosage of 10 mg once daily for 14 days. Results in the two groups were similar, with no evidence of accumulation of fosinoprilat in hepatically impaired patients. Mean (+/- SD) maximum observed plasma concentrations of fosinoprilat in the healthy subjects were 112.0 +/- 67.2 ng/mL after the first dose and 144.1 +/- 61.7 ng/mL at steady-state. Corresponding values for the hepatically impaired patients were 111.4 +/- 40.1 ng/mL and 140.2 +/- 50.9 ng/mL. The area under the serum concentration versus time curve for healthy volunteers was 790.7 +/- 431.0 ng.hr/mL after the first dose and 940.3 +/- 400.4 ng.hr/mL at steady-state. Similar values were noted in hepatically impaired patients: 926.0 +/- 293.9 ng.hr/mL and 1,255.4 +/- 434.0 ng.hr/mL for first dose and steady-state, respectively. No statistically significant differences were detected in fosinoprilat pharmacokinetic values between healthy and hepatically impaired subjects. Absence of accumulation can be attributed to the dual route of elimination of fosinoprilat reported in previous studies. Renal excretion of fosinoprilat in hepatically impaired patients prevents increased accumulation. The present findings suggest that the starting dose of fosinopril used in hypertensive patients with normal renal and hepatic function can also be used in patients with hepatic impairment secondary to cirrhosis.",1995.0,0,0
1435,7752175,Comparative effects of ramipril and nitrendipine on albuminuria in hypertensive patients with non-insulin-dependent diabetes mellitus and impaired renal function.,R Fogari; A Zoppi; C Pasotti; A Mugellini; P Lusardi; P Lazzari; L Corradi,"The purpose of this study was to compare the effects of ramipril and nitrendipine on urinary albumin excretion (UAE) in hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. Forty patients with mild hypertension with NIDDM and persistent albuminuria (> 300 mg/24h) were studied. After a 3-week run-in period on placebo, patients were randomly treated with ramipril 5 mg once daily or nitrendipine 20 mg once daily for 6 months, according to a double-blind design. Blood pressure (BP), UAE, creatinine clearance and glycosilated haemoglobin were evaluated at the end of the placebo period and after 1,3 and 6 months of active treatment. Both ramipril and nitrendipine significantly lowered BP values without affecting glucose homeostasis and renal function. Despite equivalent BP control, only ramipril afforded a significant reduction in UAE, thus suggesting that the antiproteinuric effect of ramipril is at least partially independent of its anti-hypertensive effect.",1995.0,0,0
1436,7752178,Different long-term metabolic effects of enalapril and atenolol in patients with mild hypertension. EGTA Group.,H Aberg; C Mörlin; H Lithell,"The primary objective in this multicentre, double-blind randomised, parallel study was to compare the metabolic effects of 12 months of treatment with an ACE inhibitor (enalapril) with those of a selective beta-blocker (atenolol) in patients with mild hypertension. The patients (35-69 years of age) were included if they were without antihypertensive drugs and after six months of nonpharmacological treatment had supine DBPs between 90 and 104 mmHg; 220 patients were randomised to enalapril (20 or 40 mg/day) and 218 to atenolol (50 or 100 mg/day). After 12 months of treatment, atenolol significantly increased the glucose concentrations at 60, 90 and 120 minutes after an oral intake of 75 g glucose (P < 0.01), while enalapril did not. Atenolol significantly increased fasting blood glucose and insulin concentration 120 minutes after glucose intake, while enalapril did not. Plasma total cholesterol and triglycerides increased significantly in patients having atenolol but not in those having enalapril. HDL cholesterol decreased significantly in the atenolol group but not in the enalapril group. The proportions of patients with clinical adverse experiences were similar in both treatment groups. These results indicate that enalapril does not influence either glucose tolerance or lipoprotein metabolism while atenolol does. These findings are consistent over the 12 month treatment period and confirm earlier short-term study results.",1995.0,0,0
1437,7752591,Plasma lipids and the progression of nephropathy in diabetes mellitus type II: effect of ACE inhibitors.,M Ravid; L Neumann; M Lishner,"Ninety-four normotensive type II diabetics with normal renal function and microalbuminuria were randomized to receive enalapril 10 mg/day or placebo and were followed for five years. In the patients treated by enalapril plasma creatinine values and albuminuria remained stable throughout the observation period. Their plasma total cholesterol decreased from an initial value of 245 +/- 27 mg/dl to mean study value of 236 +/- 29 mg/dl, and to a fifth year value of 232 +/- 27 mg/dl (P < 0.001). The changes in HDL cholesterol and triglyceride values were nonsignificant. In the placebo group there was a significant increase in albuminuria and a mean decline of 13% in reciprocal creatinine values during the five years. Plasma total cholesterol increased from an initial mean value of 246 +/- 24 to a mean study value of 252 +/- 25 mg/dl, and to a fifth year mean value of 259 +/- 32 mg/dl (P < 0.001). There was a significant correlation between both initial and mean plasma total cholesterol values, and the decline in renal function and the rise in albuminuria in the placebo treated patients. This correlation persisted after stratification for blood pressure. Treatment with enalapril did not eliminate these correlations. Cholesterol may be an additional risk factor for diabetic nephropathy. ACE inhibitors may have a modest cholesterol lowering effect in diabetic patients mediated, in part, through the decline in albuminuria.",1995.0,0,0
1438,7754939,Effects of early enalapril treatment on global and regional wall motion in acute myocardial infarction. CONSENSUS II Multi Echo Study Group.,S Carstensen; V V Bonarjee; J Berning; M Edner; D W Nilsen; K Caidahl,"Angiotensin-converting-enzyme inhibitor therapy can preserve left ventricular (LV) function and geometric features and improve survival in subsets of patients with acute myocardial infarction (AMI). We investigated the effect of enalapril treatment initiated < 24 hours after AMI on global and regional echocardiographic wall motion indexes obtained at 2 to 5 days and at 1 and 6 months in 428 consecutive patients enrolled in the randomized, placebo-controlled Cooperative New Scandinavian Enalapril Survival Study II. In anterior AMIs, the non-infarct-zone index deteriorated in the placebo group but remained unchanged in the enalapril-treated group (0.18 vs 0.02; p < or = 0.05), an effect related to attenuated LV volume expansion. No treatment effects were observed in nonanterior AMIs or in the entire unselected population. Thus in an unselected population with AMI, early enalapril treatment had no effect on LV function; yet in patients with anterior infarcts, LV function was maintained through preservation of function in the noninfarcted myocardium.",1995.0,0,0
1439,7755939,Effects of intensified blood-pressure reduction on renal function and albumin excretion in primary hypertension. Addition of felodipine or ramipril to long-term treatment with beta-blockade.,A Siewert-Delle; S Ljungman; M Hartford; J Wikstrand,"The effect of intensified blood pressure (BP) control with a reduction of the diastolic BP to < or = 85 mm Hg on renal function and urinary albumin excretion (UAE) was studied in 28 men with primary hypertension (aged 62 to 72 years) treated for 13 +/- 5 years with beta-blockade, diuretics, or hydralazine. They were compared with 25 normotensive (NT) men of similar age. At baseline (BL), glomerular filtration rate (GFR), renal plasma flow (RPF) (clearance of inulin and para-aminohippurate), and the UAE were studied. Thereafter, all antihypertensive drugs except beta-blockers were withdrawn and either felodipine (5 to 20 mg; n = 13) or ramipril (2.5 to 10 mg; n = 15) was added in a double blind, randomized fashion. Hydrochlorothiazide was added if necessary. The investigations were repeated after 6 weeks and 1 year of double-blind treatment. At BL, the BP and the renal vascular resistance (RVR) were significantly higher and GFR and RPF were significantly lower in both hypertensive groups than in NT. After 1 year, the BP treatment goal was reached by all patients in the felodipine group but only by two-thirds in the ramipril group in spite of addition of diuretics to 60% of the latter group. In the felodipine group, the BP, GFR, and RVR after 1 year no longer differed significantly from normal. The UAE and the fractional albumin clearance increased significantly after 1 year's treatment in the felodipine group but did not change in the ramipril group. The fractional albumin clearance, however, did not differ significantly from normal either at BL or after 1 year's treatment in any of the hypertensive groups. It is therefore possible to reduce BP and improve renal function in primary hypertension to levels not significantly different from normal after treatment with felodipine in combination with beta-blockade. Although this regimen increased the low UAE slightly, the fractional albumin clearance changed less and did not differ significantly from normal. The ramipril/beta-blocker combination reduced BP less and did not change the slightly reduced renal function or the UAE.",1995.0,0,0
1440,7756099,The renin angiotensin aldosterone system and frusemide response in congestive heart failure.,S Reed; P Greene; T Ryan; B Cerimele; U Schwertschlag; M Weinberger; J Voelker,"1. To test the hypothesis that basal renin angiotensin aldosterone system (RAAS) activity impairs the acute natriuretic response to frusemide in patients with mild or moderate congestive heart failure (CHF), we studied eight adult volunteers with preserved renal function, stable New York Heart Association Class II or III CHF, and echocardiographic evidence of left ventricular dysfunction due to myocardial infarction, hypertension, or both causes. 2. All patients received three dosing regimens administered in random order: (a) intravenous frusemide: 40 mg bolus then 40 mg h-1 for 3 h, (b) captopril: two 12.5 mg oral doses separated by 2 h, (c) combined dosing: the first captopril dose preceded the frusemide bolus by 30 min. Sodium balance on an 80 mmol day-1 sodium diet was documented prior to each dosing regimen. Sodium excretion was quantitated in urine collected at intervals until 3.5 h after initiating drug administration. During this time, urine output was replaced intravenously with an equivalent volume of 0.45% saline. 3. Captopril significantly lowered plasma angiotensin converting enzyme (ACE) activity and plasma aldosterone concentration, and raised inulin clearance. The drug had essentially no effect on the time course of magnitude of frusemide's natriuretic effect. Maximal fractional sodium excretion during frusemide infused by itself and in combination with captopril was 24.7 +/- 1.9% vs 28.2 +/- 3.8%, respectively (difference 3.5%; 95% CI, -4.0 to 11.0%; P > 0.05). Cumulative sodium excretion ending at 3.5 h was 429 +/- 53 mmol when frusemide was given alone and 455 +/- 69 mmol when captopril was added (difference, 26 mmol; CI, -121 to 174 mmol; P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1441,7758341,Effect of angiotensin-converting enzyme and calcium channel inhibition on progression of IgA nephropathy.,K M Bannister; A Weaver; A R Clarkson; A J Woodroffe,,1995.0,0,0
1442,7759715,Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. Captopril and Thrombolysis Study Investigators.,Y M Pinto; W H van Gilst; J H Kingma; H Schunkert,"This study sought to determine whether patients who are homozygous for the deletion (D)-type allele of the angiotensin-converting enzyme gene display augmented ventricular dilation after myocardial infarction. Recent evidence suggests that the deletion-type allele of the angiotensin-converting enzyme gene (DD genotype) is associated with an increased prevalence of myocardial infarction and myocardial hypertrophy. However, it is unknown whether the DD genotype is associated with adverse cardiac remodeling. To address this question we determined the genotype in patients enrolled in the Captopril and Thrombolysis Study (CATS), a prospective trial in which patients received either captopril or placebo during and after thrombolysis for a first anterior myocardial infarction. Cardiac volume was determined by echocardiography immediately after thrombolysis and at 1-year follow-up. The genotype for the angiotensin-converting enzyme was determined in 96 patients. Norepinephrine levels were assessed during and immediately after thrombolysis. Immediately after thrombolysis, cardiac volume did not differ between genotype groups. However, at 1-year follow-up, both end-systolic and end-diastolic left ventricular volumes were significantly greater in the DD-genotype group. Norepinephrine increased to higher levels in the DD-genotype group that received placebo therapy. Captopril treatment effectively blunted both the norepinephrine increase and cardiac dilation in the DD-genotype group. This exploratory study suggests that homozygosity for the angiotensin-converting enzyme deletion-type allele is associated with augmented neurohumoral activation as well as augmented cardiac dilation after an acute anterior myocardial infarction, an effect that may be susceptible to angiotensin-converting enzyme inhibition.",1995.0,0,0
1443,7759839,Hypertension and the vasculature: arterioles and the myogenic response.,A S Izzard; A M Heagerty,"This editorial was invited by the Journal of Hypertension as one of a series designed to examine our current knowledge of several aspects of the pathophysiology of hypertension. This article considers small arteries and arterioles. The conclusion that established hypertension is characterized by a normal cardiac output and a raised peripheral resistance represents the integration of findings from haemodynamic studies using a variety of models of the disease examined by several different techniques. In some ways it assumes that all vascular beds conform to the same pattern of responsiveness. However, given the obvious heterogeneity of functions performed by specialized tissues, the recognized variations in receptor populations and the differences in innervation found in the vascular wall throughout the circulation, this might not be the case. Resistance to blood flow occurs throughout the vascular tree, but the majority is found at the level of arterioles. Upstream small arteries demonstrate growth and remodelling changes which result in luminal narrowing, but the exact contribution of such vessels to resistance is still not known. Perhaps the most interesting recent finding in this context is that blood pressure can fall immediately after a pressor stimulus has been removed, despite the demonstration of such structural changes in small arteries. Furthermore, some whole-animal studies have been reported which fail to show the expected vascular amplification when the circulation is stressed in total. Viewing the vascular tree as an integrated circuit with specialized functions when nourishing specific tissues suggests that when the resistance in one vascular bed increases because of a constrictor challenge, this might not be representative of the circulation as a whole: indeed, resistance may fall elsewhere. It is probable that structural changes in small arteries represent the consequence of hypertension. The pathogenesis of hypertension may reside downstream in arterioles, where a myogenic response might play a fundamental role.",1995.0,0,0
1444,7762503,Effect of long-term enalapril therapy on neurohormones in patients with left ventricular dysfunction. SOLVD Investigators.,C R Benedict; G S Francis; B Shelton; D E Johnstone; S H Kubo; P Kirlin; J Nicklas; C S Liang; M A Konstam; B Greenberg,"The aim of this study was to compare the long-term effects of treatment with enalapril or placebo on plasma neurohormones in patients with left ventricular (LV) dysfunction. Elevated neurohormonal levels are associated with increased mortality in patients with congestive heart failure. Multiple studies have shown that angiotensin-converting enzyme inhibitors decrease mortality and morbidity in these patients. In Studies of Left Ventricular Dysfunction (SOLVD), enalapril significantly reduced mortality in patients with symptomatic LV dysfunction (treatment trial). In contrast, in patients with asymptomatic LV dysfunction (prevention trial), there was no significant reduction in mortality with enalapril therapy. The effect of enalapril was examined in 333 prevention trial and 129 treatment trial patients. Plasma norepinephrine (NE) and plasma renin activity were measured in these patients at baseline, and at 4 and 12 months of follow-up. In a subset of these patients, atrial natriuretic peptide (ANP) and arginine vasopressin were also measured. Analysis of covariance models were used to determine the effect of enalapril on each neurohormone. Participants in the treatment trial had significantly higher neurohormonal levels when compared with those in the prevention trial or normal control subjects. In the treatment trial, patients taking enalapril had a greater decrease in plasma NE levels than patients taking placebo (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1445,7762512,Angiotensin-converting enzyme inhibitor use in survivors of acute myocardial infarction.,J M Yim; T J Hoon; N Bittar; J L Bauman; E J Brown; C Celestin; B G Phillips; P H Vlasses,,2001.0,0,1
1446,7766338,Drug-induced mania.,M Peet; S Peters,"Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-existing bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically. Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with antipsychotic drugs or lithium.",1995.0,0,0
1447,7766339,Low dose combination antihypertensive therapy. Additional efficacy without additional adverse effects?,A M MacConnachie; D Maclean,,1995.0,0,0
1448,7768585,"A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension.",A H Gradman; K E Arcuri; A I Goldberg; L S Ikeda; E B Nelson; D B Snavely; C S Sweet,"The efficacy and safety of various doses of losartan potassium, a specific and selective angiotensin II receptor antagonist, were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a randomized, double-blind, parallel study. We randomly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10, 25, 50, 100, or 150 mg, enalapril maleate 20 mg, or placebo. After 8 weeks of treatment, mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing (trough) for losartan potassium 10, 25, 50, 100, and 150 mg, enalapril maleate 20 mg, and placebo were 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, 10.5/9.7, 14.7/11.2, and 3.8/5.6 mm Hg, respectively. Compared with mean changes in supine diastolic pressure in the placebo group, losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinically important and statistically significant reductions (P < or = .01) in blood pressure. At 24 hours after dosing, the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg. While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak (6 hours after dosing), doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing. To assess the once-daily effect of losartan potassium, trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1449,7769416,Angiotensin converting enzyme inhibitor associated cough: a population-based case-control study.,L E Visser; B H Stricker; J van der Velden; A H Paes; A Bakker,"The objectives of this study were to determine the risk for coughing as an adverse reaction to angiotensin converting enzyme (ACE) inhibitors under everyday circumstances in a large population and to study whether this adverse effect is more common in women. A population-based case-control study was used. The study was set in the practices of 161 Dutch general practitioners (GPs), in which all consultations, morbidity, mortality, medical interventions and prescriptions were registered during 4 consecutive 3-month periods in 4 consecutive groups of 40-41 GPs. The subjects were 2436 patients with incident coughing and up to 3 controls per case were obtained (total group: 7348 controls), matched for GP and a contemporary consultation in the same 3 months. All cases and controls were 20 years or older and had no notification of respiratory infections, influenza, tuberculosis, asthma, chronic bronchitis, emphysema, congestive heart failure, sinusitis, laryngitis, haemoptysis or respiratory neoplasms during the 3-month period. The results showed that cases were 3.6 times as likely as controls to have been exposed to ACE inhibitors (95% CI: 2.4-5.5) but after adjustment for potential confounders the odds ratio was 2.5 (95% CI: 1.6-3.9). The crude odds ratio for males was 2.7 (95% CI: 1.4-5.1) and for females 4.2 (95% CI: 2.4-7.5). The adjusted odds ratio for males was 1.8 (95% CI: 0.9-3.5) and for females 2.7 (95% CI: 1.5-4.8).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1450,7769797,"Responses to an orally active renin inhibitor, remikiren (Ro 42-5892), after controlled salt depletion in humans.",R J MacFadyen; C R Jones; J K Doig; H Birnbock; J L Reid,"The biological effects of dose-dependent inhibition of renin have rarely been extensively studied after oral (p.o.) dosing in humans. We studied remikiren (Ro42-4892), a selective renin inhibitor, in normal volunteers after activation of the renin-angiotensin system (RAS) based on salt depletion. Twelve normal men (28 +/- 9 years, 77 +/- 10 kg), comprising three consecutive dose panels of 4 subjects, received four treatments, double-blind and randomised 2 weeks apart: panel I, placebo (P), or 30, 100, and 300 mg, remikiren; panel II, placebo or 300, 600 mg, 1,000; panel III, placebo or 30, 600, and 1,000 mg. The RAS was activated by 40 mmol/day sodium diet plus frusemide (40 mg BDS), for 3 days before each study day. Data (mean +/- SD) were examined by repeated-measures analysis of variance (ANOVA). RAS activation was confirmed by 24-h urinary sodium excretion (screen, 142 +/- 74 mmol/24 h; prestudy, 66 +/- 33, 59 +/- 41, 78 +/- 4, 73 +/- 30 mmol/24 h) and increase in plasma renin activity (PRA) (screen, 0.8 +/- 0.3 ng AI/ml/h; before dosing, P, 6.5 +/- 3.1; 30 mg, 8.2 +/- 3; 100 mg, 9.4 +/- 5.7; 300 mg, 6.5 +/- 2.4; 600 mg, 5.2 +/- 2; 1,000 mg, 6.2 +/- 4.4 ng AI/ml/h).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1451,7774515,Ramipril. An updated review of its therapeutic use in essential hypertension and heart failure.,J E Frampton; D H Peters,"Ramipril is a second generation angiotensin converting enzyme (ACE) inhibitor. Like enalapril, it is a prodrug and is hydrolysed in vivo to release the active metabolite, ramiprilat, which has a long elimination half-life, permitting once-daily administration. The antihypertensive efficacy of ramipril has been confirmed in large-scale noncomparative studies conducted in general practice as well as in more rigorously controlled clinical trials. In the former, approximately 85% of patients with mild to moderate essential hypertension have responded successfully to treatment with ramipril 2.5 or 5 mg/day, while comparative trials indicate that the antihypertensive efficacy of the drug is equivalent to that of other established ACE inhibitors and the beta-adrenoceptor antagonist atenolol. As expected, the response rate to ramipril monotherapy is lower in patients with severe hypertension (around 40%), although the blood pressure lowering effect can be enhanced with the addition of a diuretic such as hydrochlorothiazide or piretanide. The antihypertensive efficacy of ramipril is maintained in patients with diabetes mellitus and preliminary data indicate that the drug has the beneficial effect of decreasing urinary albumin excretion in diabetic patients with nephropathy. Ramipril is superior to atenolol in causing regression of left ventricular hypertrophy, although the clinical significance of this effect per se remains to be established. The large-scale Acute Infarction Ramipril Efficacy (AIRE) study demonstrated that ramipril 5 or 10 mg/day significantly decreased the risk of all-cause mortality by 27% in patients with clinical evidence of heart failure after acute myocardial infarction, even if transient. The beneficial effect of ramipril was apparent by 30 days of treatment and appeared to be greatest in patients with more severe ventricular damage after infarction. Ramipril is well tolerated in general practice, with 5% or fewer patients discontinuing therapy because of drug intolerance. The data available suggest that ramipril shares a similar tolerability profile to that of other established ACE inhibitors. Thus, clinical data confirm ramipril as a useful alternative ACE inhibitor for the treatment of patients with mild to moderate hypertension, and indicate a beneficial effect of the drug in patients with clinical evidence of heart failure after acute myocardial infarction. It is also reasonable to assume that ramipril will be of value in the treatment of patients with more established heart failure or asymptomatic left ventricular dysfunction.",1995.0,0,0
1452,7778179,Comparison of the effects of enalapril and theophylline on polycythemia after renal transplantation.,E Ok; F Akçiçek; H Töz; S Kürşat; M Töbü; A Başçi; E J Mees,"Posttransplant erythrocytosis (PTE) is a potentially serious complication for which (apart from phlebotomy) two alternative treatments have been proposed: theophylline (Theo) and angiotensin-converting enzyme inhibitors. We investigated 28 patients with PTE, who were assigned to 3 matched groups. Group 1 (10 patients) received 10 mg of Enalapril (Ena)/day. After 2 months, mean hematocrit (Ht) had dropped from 0.57 (range 0.52-0.62) to 0.45 (0.34-0.49). Ena was stopped and, after a period of 3.8 +/- 0.3 months, Ht had risen again to baseline values (0.56, range 0.52-0.61) in 8 of them. These 8 patients were then given 5 mg/day Ena. Ht decreased more slowly, and after 3 months reached a mean of 0.49 (0.44-0.54). Group 2 (9 patients) received 600 mg/day Theo in 2 doses. After 2 months, Ht had decreased from 0.56 (0.52-0.61) to 0.52 (0.46-0.63), but in 5 patients, Ht remained above 0.51. After 1 month discontinuation of treatment, PTE persisted in 7 patients. These patients were given 10 mg/day Ena, whereupon Ht decreased from 0.55 (0.52-0.64) to 0.46 (0.40-0.53) after 2 months and to 0.41 (0.33-0.47) after 3 months. Group 3 did not receive medical treatment. After 3 months, PTE persisted in 8 out of the 9 patients and remained unchanged during the following 3 months. Mean values for Ht were: baseline, 0.55 (0.52-0.58); after 3 months, 0.56 (0.53-0.59); and after 6 months, 0.55 (0.52-0.60). We conclude that Ena is superior to Theo in the treatment of PTE. There were no resistant patients, but individual sensitivity differs. Its effect is dose dependent, reversible, and reproducible. Excessive Ht decrease may occur; thus, doses should be titrated individually.",1995.0,0,0
1453,7778548,Lack of long-term ventricular arrhythmia reduction by enalapril in heart failure. SOLVD Investigators.,C M Pratt; M Gardner; C Pepine; R Kohn; J B Young; B Greenberg; R Capone; J Kostis; M Henzlova; G Gosselin,"Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction < or = 35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 +/- 13 vs 84 +/- 13/hour), 4 months (100 +/- 15 vs 85 +/- 12/hour), or 12 months (80 +/- 12 vs 90 +/- 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 +/- 4.1 vs 1.9 +/- 0.4 runs/day), 4 months (16 +/- 12 vs 7.2 +/- 4.1 runs/day), or after 12 months of blinded therapy (11 +/- 7.0 vs 6.1 +/- 4.4 runs/day).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1454,7781377,Acute myocardial infarction. Then and now.,J Simmons; H J Willens; K M Kessler,"Dramatic changes in the management of acute myocardial infarction (AMI) have occurred in the past decade. While previous management strategies were primarily supportive, current strategies focus on achieving and maintaining patency of the infarct-related artery restoring blood flow to jeopardized myocytes, preserving left ventricular function, and preventing recurrences and complications in addition to promoting healing. Restoration of blood flow can be achieved pharmacologically with thrombolytic agents or mechanically with percutaneous transluminal coronary angioplasty (PTCA). Early use of antiplatelet agents and anticoagulants helps maintain patency of the infarct-related arteries and prevents thromboembolic complications. Administration of beta-blockers and angiotensin enzyme inhibitors are more specific means of conserving myocardium and preserving ventricular function. Additionally, several strategies for preventing arrhythmias such as prophylactic lidocaine use and routine long-term suppression of premature ventricular contractions with antiarrhythmic drugs are no longer routinely advocated. Basically, in the era prior to the eighth decade of this century, the primary direction of the therapeutic strategy for AMI was to reduce the oxygen demands in the infarcted myocardium; whereas in the subsequent years, the emphasis shifts to improvement in oxygen delivery, via thrombolysis, PTCA, and coronary artery bypass graft surgery. These interventional changes, when added to greater sophistication in the use of drugs to reduce oxygen demands, resulted in significant lowering of myocardial mortality.",1995.0,0,0
1455,7783096,Favourable interaction of calcium antagonist plus ACE inhibitor on cardiac haemodynamics in treating hypertension: rest and effort evaluation.,S Di Somma; A Carotenuto; M de Divitiis; A Paulucci; M Galderisi; A Cuocolo; O de Divitiis,"The aim of the study was to evaluate the effects of verapamil sustained release (SR) 240 mg, enalapril and their combination on blood pressure (BP) and cardiac haemodynamics at rest and during exercise in 20 patients with moderate essential hypertension (seven men and 13 women, mean age +/- s.d. 53.7 +/- 15.8 years). After a 4 week placebo run-in period, patients were randomly allocated to received verapamil SR 240 mg once daily or enalapril 20 mg once daily for 4 weeks in a double-blind fashion. Patients whose diastolic blood pressure (DBP) was still > or = 95 mm Hg at the end of this period received verapamil SR plus enalapril for an additional 4 weeks. At the end of the placebo, single and combined treatment periods, resting and exercise (bicycle ergometry) haemodynamics were evaluated by radionuclide ventricular angiography (technetium-99m) and the following parameters were assessed: BP, heart rate, double product, systemic vascular resistances (SVR), cardiac output (CO), stroke volume (SV), ejection fraction (EF) mean ejection rate (mER) and peak filling rate (PFR). Both verapamil SR and enalapril monotherapies significantly reduced resting and exercise BP (P < 0.01), with a BP normalisation (DBP < or = 95 mm Hg) of five of 10 and 4 of 10 patients respectively. A greater BP fall and a normalisation of 11 of 11 patients was obtained in non-responders to monotherapy, when treated with verapamil SR and enalapril (P < 0.01). Verapamil SR also reduced heart rate at rest and during exercise (-11.8% and -18.4%, respectively, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1456,7786644,ACE inhibitors after myocardial infarction: selection and treatment for all.,A J Coats,,1995.0,0,0
1457,7786645,ACE inhibitors after myocardial infarction: patient selection or treatment for all?,H S Lindsay; A G Zaman; J C Cowan,,1995.0,0,0
1458,7786657,Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group.,W A Littler; D J Sheridan,"To compare the effects of felodipine and placebo in patients with New York Heart Association functional class II or III and stable congestive heart failure despite treatment with an angiotensin converting enzyme inhibitor, diuretic, or digoxin, or any combination of these three drugs. 252 patients were randomised in a double blind, parallel group study after a 2-4 week placebo run-in to oral treatment with either felodipine extended release formulation or placebo 2.5-10 mg twice daily given in addition to existing background medication for a further 12 weeks. Patients aged 18-75 years of either sex with chronic congestive heart failure due to ischaemic heart disease, hypertensive heart disease, or dilated cardiomyopathy with or without secondary mitral insufficiency that was stable during the preceding two months were included in the study. Treadmill exercise tests according to the modified Naughton protocol were performed at baseline, and after six, 11, and 12 weeks of treatment. Signs and symptoms of heart failure were assessed at every visit. Physical examination was performed and left ventricular ejection fraction measured at baseline and after 12 weeks. Mean (SD) baseline exercise test times increased from 434 (162) s and 480 (157) s for felodipine and placebo groups respectively to 541 (217) s and 591 (218) s at 12 weeks or the last visit. The change in exercise from baseline to last visit was 107 (141) s for patients given felodipine and 112 (128) s for those given placebo (P > 0.20). There was also no difference between treatments with respect to the other efficacy variables. There were few deaths in the study (felodipine n = 3, placebo n = 2). More patients who received felodipine were withdrawn from treatment (n = 29) than those who received placebo (n = 17). The most common adverse events of the 54 and 28 cited as reasons for withdrawal in the felodipine and placebo groups respectively were increased need for non-study heart failure treatment (n = 10; 8%)--that is, starting new medication or changes in the dosage of existing treatment for patients given felodipine, and nausea (n = 4; 3%) for those given placebo. Patients withdrawn from the study due to increased need for non-study heart failure treatment rapidly stabilised and recovered. Felodipine has not been shown to be of benefit in patients with mild to moderate heart failure.",1995.0,0,0
1459,7786658,Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril.,J N Townend; J Doran; C J Lote; M K Davies,"To investigate the role of prostaglandins in maintaining circulatory homoeostasis in chronic heart failure and the hypothesis that an increase in vasodilatory prostaglandin synthesis may contribute to the actions of angiotensin converting enzyme inhibitors in heart failure. Randomised, double blind, placebo controlled studies. Cardiac output and renal and limb blood flow were measured after oral indomethacin 50 mg or placebo followed by ""open"" intravenous infusion of prostaglandin E2 (study A). In a second study the same measurements were made after oral indomethacin 50 mg or placebo was given 30 min before ""open"" captopril (study B). Blood pressure was measured using a mercury sphygmomanometer. Cardiac output was determined by Doppler interrogation of blood flow in the ascending aorta and echocardiographic measurement of aortic root diameter. Renal blood flow was calculated from the effective renal plasma flow measured by p-aminohippurate clearance and the haematocrit, and glomerular filtration rate by endogenous creatinine clearance. Limb blood flow was measured by venous occlusion plethysmography using mercury in silastic strain gauges. The concentration of plasma prostaglandin E2 was measured by radioimmunoassay. University department of cardiovascular medicine. 12 patients with chronic stable heart failure before starting treatment with angiotensin converting enzyme inhibitors. Indomethacin resulted in adverse effects on cardiac output, systemic vascular resistance, renal blood flow, glomerular filtration, urinary sodium excretion, and calf vascular resistance. Changes were reversed with infusion of prostaglandin E2. Pretreatment with indomethacin resulted in the attenuation of the acute increase in cardiac output and decrease in systemic vascular resistance that occurred with captopril. Similarly, an increase in renal blood flow with captopril was attenuated by indomethacin. The acute adverse effects of indomethacin on central and peripheral haemodynamic and renal function suggest that prostaglandins have a significant role in the regulation of peripheral blood flow and renal function in patients with stable chronic heart failure. The attenuation by indomethacin of captopril induced improvements in haemodynamic function and renal blood flow is consistent with the hypothesis that captopril may act in part via an increase in prostaglandin synthesis.",1995.0,0,0
1460,7786697,Early intravenous magnesium administration in acute myocardial infarction.,J S Fernandes,,1994.0,0,0
1461,7787145,The study of the effect of intensity of blood pressure management on the progression of type 1 diabetic nephropathy: study design and baseline patient characteristics. Collaborative Study Group.,R A Rodby; R Rohde; J Evans; R P Bain; W S Mulcahy; E J Lewis,"A randomized, prospective, clinical trial has been initiated to continue follow-up in a subset of the patients previously enrolled in the recently completed Study of Angiotensin-Converting Enzyme Inhibition (ACEi) in Type 1 Diabetic Nephropathy. In that study, the use of captopril was associated with a 48% reduction in the risk of doubling the serum creatinine and a 50% reduction in the risk of experiencing dialysis, transplantation, or death, compared with the use of placebo. These effects were independent of captopril's effect on the blood pressure. This study is designed to determine whether the level of mean arterial blood pressure (MAP), using the ACE inhibitor ramipril as the primary therapy, is associated with an improved prognosis of diabetic nephropathy with respect to (1) the rate of decline in renal function; (2) the rate of progression to end-stage renal failure; (3) the clinical course of proteinuria; (4) morbidity; and (5) mortality. Patients are randomized into one of two distinct blood pressure control groups, an Intensive Group #1, MAP < or = 92 mm Hg; and a Moderate Group #2, MAP 100 to 107 mm Hg. Patients previously enrolled in the ""Study of ACEi in Type 1 Diabetic Nephropathy"" whose serum creatinine was less than 4.0 mg/dL (354 mumol/L) were eligible for randomization into this study. All patients will receive ramipril (2.5 to 10.0 mg/day) as the primary therapy, with the addition or removal of other antihypertensive agents as needed to achieve the assigned blood pressure goal.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1462,7788682,Effects of ACE inhibition on left ventricular dimensions and haemodynamics in systemic hypertension: a radionuclide and echocardiographic study.,I C Haznedaroglu; Y Erdem; L Tokgözoglu; M Caglar; S Kes; N M Sayinalp; S Yörükan,"The aim of this study was to assess the effects of Angiotensin Converting Enzyme (ACE) inhibition on cardiac systolic and diastolic parameters and left ventricular muscle mass in hypertensive patients. For this purpose 30 patients (22 female and eight male) with mild to moderate essential hypertension, aged 47 +/- 2 years, were treated with enalapril maleate (MK 421, an ACE inhibitor) for six weeks. They underwent M-mode and Doppler echocardiography and radionuclide ventriculography at the beginning and after six weeks of enalapril treatment. In this study all patients treated with the ACE inhibitor enalapril responded with a significant decrease in mean arterial pressure (p < 0.001). A significant reduction in left ventricle and mass index were shown after six weeks of treatment with enalapril (p < 0.01). Total peripheral resistance and end-systolic stress decreased in the same time course (p < 0.001). Ejection fraction increased in both examinations after six weeks of therapy with enalapril, but this increase was not statistically significant. In radionuclide examinations, time to peak filling rate decreased significantly after six weeks of enalapril therapy (p < 0.02). Despite these improvements in cardiac systolic and diastolic parameters, cardiac output and stroke volume decreased slightly after enalapril treatment. We concluded that enalapril improves diastolic and systolic parameters in LV function but causes slight decreases in cardiac output and stroke volume in addition to lowering blood pressure.",1995.0,0,0
1463,7789045,Investigation of the mechanism of beta 2-agonist-induced activation of the renin-angiotensin system.,E A Millar; G T McInnes; N C Thomson,"1. We have previously described activation of the renin-angiotensin system in asthma, and also by high-dose nebulized beta 2-agonists. In this study we sought to determine the mechanism responsible. 2. The influence of the angiotensin-converting enzyme inhibitor, lisinopril, on the response of the renin-angiotensin system and serum potassium to nebulized salbutamol was investigated in a randomized, double-blind, crossover study in eight healthy volunteers using a factorial block design. On study days, subjects received lisinopril 20 mg orally or identical placebo tablets followed 3 h later by nebulized salbutamol or placebo inhalation; plasma renin, angiotensin II, serum angiotensin-converting enzyme and potassium were measured at intervals for 120 min after inhalation. 3. Following salbutamol, plasma renin and angiotensin II concentrations were increased significantly compared with placebo [mean (SEM) plasma renin of 61.7 (15.6) mu-units/ml and angiotensin II of 17.7 (5.4) pg/mol 15 min after salbutamol, P < 0.05 versus placebo]. Baseline plasma renin concentrations were increased [160.1 (20.6) mu-units/ml] and baseline plasma angiotensin II concentrations were reduced [1.4 (0.1) pg/ml] by lisinopril, P < 0.05 versus placebo in each case. Inhibition of angiotensin-converting enzyme completely inhibited this salbutamol-induced rise in plasma angiotensin II [mean (SEM) plasma angiotensin II of 1.5 (0.4) pg/ml 15 min after salbutamol, P < 0.05 versus placebo] but had no effect on the changes in plasma renin concentrations after the beta 2-agonist [mean (SEM) plasma renin of 198.4 (18.9) mu-units/ml 15 min after salbutamol].(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1464,7793393,Clinical characteristics and mortality of patients screened for entry into the Trandolapril Cardiac Evaluation (TRACE) study.,L Køber; C Torp-Pedersen,"In mortality studies of patients after acute myocardial infarction (AMI), exclusion of patients during selection from the screened population may be important for evaluating the impact of trials, but data on patients excluded from studies are rarely presented. In the Trandolapril Cardiac Evaluation (TRACE) trial of the angiotensin-converting enzyme inhibitor trandolapril versus placebo in patients with left ventricular (LV) systolic dysfunction shortly after AMI, medical history, infarct complication, and survival were accounted for in all patients screened for entry. A total of 7,001 consecutive enzyme-confirmed AMIs were screened for entry in 27 Danish coronary care units. The 1-year mortality of all screened AMI cases was 23% (95% confidence interval 22% to 24%). The target population of the TRACE trial were patients with LV systolic dysfunction (echocardiographically determined wall motion index < or = 1.2, n = 2,606 within 6 days of AMI. The 1-year mortality of this group was 34 +/- 2%. Patients with wall motion index > 1.2 (n = 3,920) had a 1-year mortality of 12 +/- 1%. were excluded. A total of 1,749 were included in the study. The excluded and included groups had a 1-year mortality of 54 +/- 3% and 24 +/- 2%, respectively. The result of the TRACE study will be applicable to two thirds of the patients with LV systolic dysfunction; however, even with this high figure, care should be taken in extrapolating the result to the general population with reduced LV function after AMI since the group excluded from the study had a higher mortality than those who were included.",1995.0,1,1
1465,7794571,Progressive improvement in the structure of resistance arteries of hypertensive patients after 2 years of treatment with an angiotensin I-converting enzyme inhibitor. Comparison with effects of a beta-blocker.,E L Schiffrin; L Y Deng; P Larochelle,"To investigate the effects of antihypertensive drugs on resistance artery structure, 17 essential hypertensive patients were randomly assigned to be treated with an angiotensin I-converting enzyme inhibitor, cilazapril, or a beta-blocker, atenolol, for 2 years. Blood pressure was well controlled throughout the 2 years. Before starting treatment, at the end of the first year and at the end of the second year, patients were subjected to gluteal subcutaneous fat biopsies, from which resistance-size arteries were dissected to be studied. The media width to lumen diameter ratio of arteries from patients in the cilazapril group was 7.5 +/- 0.3% before starting treatment, and decreased significantly (P < .05) to 6.3 +/- 0.2% at the end of the first year, and to 5.8 +/- 0.2% at the end of the second year, at which time it was not different from that of arteries from normotensive subjects (5.2 +/- 0.2%). In patients treated with atenolol, resistance arteries exhibited a media-to-lumen ratio of 8.0 +/- 0.6% before treatment, 8.1 +/- 0.5% after 1 year of treatment, and 7.9 +/- 0.3% at the end of the second year of treatment, all significantly higher (P < .01) than that of arteries from normotensive subjects. Thus, treatment for 2 years with the angiotensin I-converting enzyme inhibitor cilazapril resulted in progressive normalization of the structure (media-to-lumen ratio) of gluteal subcutaneous fat resistance arteries of essential hypertensive patients, whereas there was no change in patients treated with the beta-blocker atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1466,7794577,The effect of enalapril with and without hydrochlorothiazide on insulin sensitivity and other metabolic abnormalities of hypertensive patients with NIDDM.,A Shamiss; J Carroll; E Peleg; E Grossman; T Rosenthal,"The effect of 20 mg of enalapril with and without 12.5 mg of hydrochlorothiazide on glucose metabolism insulin sensitivity and lipids was evaluated in hypertensive non-insulin-dependent diabetes. Ten mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus were treated for 8 weeks with 20 mg enalapril once a day, and then divided into two groups of 5 patients each for a second 8 weeks of treatment with enalapril alone or in combination with hydrochlorothiazide, 12.5 mg once a day. Blood pressure, fasting plasma glucose, lipids and insulin, glycosylated hemoglobin, and insulin sensitivity were measured at baseline and after 8 and 16 weeks. Results were analyzed by the ANOVA test for repeated measures and all values are given as mean +/- SD. Diastolic blood pressure decreased significantly after the first and second period of enalapril and after the combination of enalapril and hydrochlorothiazide. Glycosylated hemoglobin dropped significantly after the first and second period of enalapril monotherapy. Plasma triglycerides and fasting plasma insulin decreased significantly after the 16 weeks of enalapril. Insulin-mediated glucose uptake increased significantly after 8 and 16 weeks of monotherapy with enalapril. No significant difference was observed in any of the metabolic characteristics, including insulin sensitivity, between the values after 8 weeks of enalapril alone and the final values of the enalapril-treated and the enalapril/hydrochlorothiazide-treated groups. It is concluded that enalapril improves some of the metabolic parameters, including insulin sensitivity, of hypertensive diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1467,7795397,Effect of oral captopril (SQ 14225) on intraocular pressure in man.,C Costagliola; R Di Benedetto; L De Caprio; R Verde; L Mastropasqua,"The effects of the angiotensin converting enzyme (ACE) inhibitor captopril (SQ 14225) on intraocular pressure (IOP) were studied. Four groups were analyzed: group A, ten control subjects; group B, ten hypertensive patients with normal IOP; group C, ten normotensive patients with primary open angle glaucoma (POAG); and group D, ten hypertensive patients with POAG. Systolic and diastolic blood pressure, heart rate, pupil diameter, IOP and total outflow facility were recorded at baseline and at 1-h intervals up to 3h after an oral dose of 25 mg captopril or placebo, given in a randomized, double-blind cross-over fashion. The alternative treatment was given a week later. Captopril significantly lowered IOP in all patients, with no effects on heart rate and pupil diameter. Blood pressure changed only in patients with hypertension (groups B and D). Total outflow facility, measured by conventional tonography, increased significantly in all groups. These findings indicate that oral captopril could represent a new antiglaucomatous compound.",1995.0,0,0
1468,7799699,Inhaled sodium cromoglycate in angiotensin-converting enzyme inhibitor cough.,M R Hargreaves; M K Benson,"Cough is a frequent side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the effects of inhaled sodium cromoglycate in 10 patients with ACE-inhibitor cough in a double-blind crossover study. After a 2-week run-in, patients were randomised to either 2 weeks' inhaled sodium cromoglycate or placebo followed by a further 2 weeks on the other treatment. Patients kept a cough diary during each study period. Cough severity was recorded on a scale from 0 to 12. At the end of each study period the cough threshold to inhaled capsaicin was measured. 9 patients reported a reduction in cough after sodium cromoglycate. Median (range) daily cough scores during run-in and placebo periods were 3.6 (1.9-6.4) and 4.1 (0.6-8.1), respectively (p > 0.05). Median daily cough score after sodium cromoglycate was 1.8 (0.4-3; p < 0.01). There was a significant relation between initial cough severity and benefit from sodium cromoglycate; and cough-reflex sensitivity to inhaled capsaicin was significantly reduced. Inhaled sodium cromoglycate is an effective treatment for ACE-inhibitor cough. Its effect may be due to suppression of afferent vagal activity.",1995.0,0,0
1469,7803945,"The Hypertension in the Very Elderly Trial (HYVET). Rationale, methodology and comparison with previous trials.",C J Bulpitt; A E Fletcher; A Amery; J Coope; J G Evans; S Lightowlers; K O'Malley; A Palmer; J Potter; P Sever,"The Hypertension in the Very Elderly Trial (HYVET) is a multicentre, open, randomised, controlled trial. The aim of this trial is to investigate the effect of active treatment on stroke incidence in hypertensive patients over the age of 80 years. Secondary end-points include total cardiovascular mortality and morbidity. Entry criteria include a sustained sitting systolic blood pressure of 160 to 219mm Hg plus a sustained sitting diastolic pressure of 95 to 109mm Hg. Also required is a standing systolic blood pressure of at least 140mm Hg. Patients must give their informed consent, and be free of congestive heart failure requiring treatment, gout, renal failure or a recent cerebral haemorrhage. Patients are to be randomised to 3 groups-(i) no treatment; (ii) treatment with a diuretic [bendroflumethiazide (bendrofluazide)]; or (iii) treatment with an angiotensin converting enzyme (ACE) inhibitor (lisinopril). Starting dosage for bendroflumethiazide and lisinopril is 2.5 mg/day. In order to achieve goal sitting systolic and diastolic blood pressures (< 150/80 mm Hg), a doubling of the dosage is allowed. Furthermore, slow release diltiazem (120 mg/day increasing to 240 mg/day if required) may be added to the medication of the actively treated groups. These drugs have been chosen as inexpensive and appropriate representatives of their therapeutic classes. 700 patients in each group (a total of 2100) will be sufficient to detect a 40% difference in cerebrovascular events between no treatment and active treatment (alpha = 0.01, 1-beta = 0.90). These numbers will also detect a difference in total mortality of 25% and in cardiovascular mortality of 35%. The pilot phase of the trial has been started with support from the British Heart Foundation. Centres which are interested in taking part should contact C.J. Bulpitt or any of the other authors.",1994.0,0,0
1470,7805462,Combined therapy of captopril and spironolactone for refractory congestive heart failure.,Y L Han; M Tong; Q M Jing; X L Hu; J Q Liu,"It is traditionally considered that angiotensin--converting enzyme inhibitor (ACEI) and spironolactone could not be used simultaneously because of the assumed risk of hyperkalemia. However, despite ACEI therapy edema and congestive status remain in some of the patients with severe congestive heart failure (CHF). In order to seek an effective therapy for these patients, we observed the efficacy and safety of captopil plus spironolactone in patients with refractory CHF, with strict monitoring of renal function, serum and urine electrolytes and blood pressure (BP). Thirty-five patients with refractory CHF and New York Heart Association functional class IV without renal dysfunction, hypotension and hyperkalemia, whose plasma aldosterone (ALD) level in 88.6% of them was above normal value, were randomly assigned to group A (n = 16, captopril alone) and B (n = 19, captopril plus spironolactone) for a 4-week treatment. The dosage of both drugs was individually adjusted in time according to the results of serum potassium and renal function. The improvement in dyspnea--fatigue ratings, urinary volume and Na+/K+ ratio in group B was more significant than that in group A, and the plasma ALD level in group B decreased obviously while it remained high in group A after therapy. Two patients in group B who had had normal plasma ALD level with urinary Na+/K+ ratio > 1.0 before the therapy did not exhibit any clinical improvement. A strong negative correlation was found between plasma ALD level and urinary Na+/K+ ratio (correlation coefficient -0.689, P < 0.01). None of the patients had obvious hyperkalemia and hypoaldosteronism.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1471,7807504,Speed and duration of dose titration with the angiotensin converting enzyme inhibitor quinapril: relationship with efficacy in patients with moderate hypertension.,M R Weir,"Most antihypertensive agents, including ACE inhibitors, are routinely dose titrated upwards every two weeks in both clinical trials and clinical practice to achieve control of systemic pressure. Two separate clinical trials assessing comparative antihypertensive efficacy of quinapril versus other ACE inhibitors (enalapril and captopril) were conducted in a double-blind fashion in patients with moderate to severe hypertension already receiving a diuretic (study I: entry DBP > or = 105 and < or = 120 mmHg while taking 25 mg hydrochlorothiazide; study II: DBP > or = 110 and < or = 130 mmHg while taking 25 mg chlorthalidone). In study I, 88 patients were randomised to receive quinapril (10-40 mg twice daily) which was titrated upwards every one to two weeks as necessary to reduce DBP < or = 90 mmHg (titration period six weeks, followed by an additional six weeks of therapy during which open-labelled beta-blocker therapy could be added for nonresponders). In study II, 84 patients were randomised to receive quinapril (5-20 mg twice daily) which was titrated upwards every four weeks as necessary to reduce DBP < or = 90 mmHg (titration period 16 weeks, followed by a 12-week maintenance period). Both cohorts of patients were demographically slightly dissimilar because there were more females and higher baseline DBP in study II versus study I (60% vs 34%, and 115.0 vs 109.1 mmHg, respectively) and more blacks (26% vs. 0%) and heavier patients (90 kg vs. 73 kg) in study I versus study II.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1472,7810360,Angioedema and angiotensin-converting enzyme (ACE) inhibitors.,J R Varma; G A Nixon,,1994.0,0,0
1473,7810540,Angiotensin-converting enzyme inhibitors may cause renal dysfunction in patients on long-term lithium treatment.,K Lehmann; E Ritz,"Anecdotal observations suggest that renal dysfunction may occur when unadjusted doses of angiotensin-converting enzyme inhibitors are administered to patients on long-term lithium treatment. Although no systematic experimental studies or controlled clinical observations are available, lithium is known to activate the renin angiotensin system through several mechanisms. In addition, direct interactions between lithium and angiotensin II may take place on a cellular level. We propose that (1) renal function should be closely monitored when patients on lithium treatment are given angiotensin-converting enzyme inhibitors and that (2) doses of both drugs should be chosen with caution to avoid serious drug interaction.",1995.0,0,0
1474,7811401,Mechanisms of unpredictable adverse drug reactions.,M J Rieder,"Adverse drug reactions are common problems associated with therapy, and are major sources of morbidity and mortality. There are numerous types of drug reactions, including predictable drug reactions such as side effects, toxicity, drug interactions and secondary effects that can be anticipated when planning therapy. There are also a number of unpredicted adverse effects, which are unexpected consequences of therapy. The least severe unpredicted adverse drug reaction is intolerance, which appears to be an exaggeration of pharmacological or toxic effects of the drug among vulnerable subsets of patients. Some of the most severe and life-threatening adverse drug reactions are allergic. These adverse effects can be mediated by a number of mechanisms, including the development of drug-specific IgE, serum-sickness-like reactions in response to drug-antibody complexes, direct release of inflammatory mediators, or involvement of the immune system by mechanisms that are poorly understood. Idiosyncratic adverse drug reactions are a heterogeneous group of adverse effects that are not predictable from the pharmacological actions of the drug. Many of these reactions occur as a consequence of pharmacogenetic variations in drug bioactivation and drug or metabolite detoxification or clearance. The physician must be vigilant for the possibility of unpredictable adverse drug reactions during or after therapy. Research currently underway may afford the opportunity to predict, and hopefully prevent, some of these adverse reactions in the future.",1994.0,0,0
1475,7814158,"Effects of the administration of captopril, metoprolol and of the captopril-metoprolol combination as adjuvant therapy during thrombolysis in acute myocardial infarction.",P Di Pasquale; S Paterna; V Bucca; G Maringhini; M Magatti,"The aim of the study was to verify, during thrombolysis in patients with anterior acute myocardial infarction, the safety and effects of beta-blockers or ACE-inhibitors and their combination in the short and long term. One-hundred sixty-six patients hospitalized within 4 h from the onset of the symptoms (first episode), eligible for thrombolysis, Killip class I-II, were randomized (single blind) into four groups. Group A (42 patients) received 6.25 mg captopril (orally) 15 min before thrombolysis and metoprolol (i.v.) not later than 1 h, and orally afterwards. Group B (42 patients) received 6.25 mg captopril 15 min before thrombolysis. Group C (37 patients) received metoprolol not later than 1 h. Group D (45 patients) received thrombolysis only. Later (day 3), groups C and D also received captopril. We checked ventricular arrhythmias (first 2h) from thrombolysis, creatine kinase peak, creatine kinase peak normalization time, late ventricular arrhythmias at Holter test pre-discharge (Lown's class > 2). At follow-up (mean 30.5 +/- 2 months), mortality was evaluated for reinfarction and ventricular failure. Age and sex were similar. Early ventricular arrhythmias: Group A, five cases; Group B, five cases; Group C, 15 cases; Group D, 16 cases. Creatine kinase peak: Group A, 1875 +/- 220 U/l; Group B, 1566 +/- 168 U/l; Group C, 2274 +/- 212 U/l; Group D 2103 +/- 232 U/l. Creatine kinase peak normalization time: Group A, 57.7 +/- 3 h; Group B, 58.1 +/- 3 h; Group C, 72.7 +/- 3 h; Group D, 69.5 +/- 2 h (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1476,7817618,The influence of chronic treatment with betablockade and angiotensin converting enzyme inhibition on the peripheral blood flow in hypertensive patients with and without concomitant intermittent claudication. A comparative cross-over trial.,L L Van de Ven; J T Van Leeuwen; A J Smit,"In a comparative cross-over trial we examined the influence of the betablocker bisoprolol and the ACE-inhibitor lisinopril on the peripheral blood flow of 2 groups of hypertensive patients with and without concomitant intermittent claudication. In 11 patients with hypertension without peripheral arterial obstructive disease and 11 patients with hypertension and claudication we assessed the blood pressure, leg blood flow, vascular resistance, walking distance, transcutaneous oxygen consumption and Laser-Doppler flow after treatment of one month with 10 mg bisoprolol once daily or 20 mg lisinopril once daily. The walking distance of patients with claudication improved in all patients while participating in an exercise program. For both treatment groups this improvement was significant (p < 0.05) compared to baseline, from 264 m at baseline to 313 m with bisoprolol and to 400 m with lisinopril. The difference was not significant between the both drugs. In patients without peripheral vascular obstructive disease we found a significant (p < 0.05) reduction in blood flow for both drugs. The peripheral blood flow parameters of 38 legs showed no statistical significant effect of bisoprolol nor lisinopril on the local vascular resistance at rest, after occlusion or after exercise.",1994.0,0,0
1477,7818958,Neurohormonal activation in patients with mild or moderately severe congestive heart failure and effects of ramipril. The Ramipril Trial Study Group.,A Sigurdsson; O Amtorp; T Gundersen; B Nilsson; J Remes; K Swedberg,"To describe neurohormonal activation in patients with mild or moderate heart failure and how it may be modified by treatment with ramipril. Cardiology departments at 24 hospitals in Denmark, Finland, Norway, and Sweden. 223 patients with mild or moderately severe congestive heart failure who were taking diuretics with or without digitalis. Randomised, double bind, multicentre, placebo controlled comparison of ramipril and placebo. Venous blood samples were drawn at rest, before blind treatment, and after 12 weeks of treatment with the study drug. A probability prediction score for mortality derived by stepwise linear discriminant from neurohormone data in the first cooperative north Scandinavian enalapril survival study (CONSENSUS I) was used to assess combined activity of the different neurohormonal systems. Plasma concentrations of atrial natriuretic peptide were raised at baseline but angiotensin II, aldosterone, and noradrenaline concentrations were within normal limits. There was, however, a wide interindividual variation. Plasma noradrenaline concentration and prediction score were higher among patients with class III congestive heart failure according to the New York Heart Association's classification than among patients with class II congestive heart failure (P < 0.05). There was a modest but significant inverse correlation between exercise duration at baseline and plasma noradrenaline concentration (r = -0.21, P = 0.0023), aldosterone concentration (r = -0.14, P = 0.04), and prediction score (r = -0.24, P = 0.0004). Prediction score at baseline was significantly higher among those who died (n = 10) than among survivors (P = 0.03). Angiotensin converting enzyme activity was suppressed and plasma concentrations of aldosterone and atrial natriuretic peptide were reduced after 12 weeks of treatment with ramipril compared with placebo. In patients with the most pronounced neurohormonal activation at baseline (highest third of noradrenaline concentration or prediction score), noradrenaline concentration and prediction score were significantly lower after 12 weeks of taking ramipril compared with placebo. Patients with a prediction score in the highest third at baseline had a higher heart rate than to those in the lowest third (P = 0.003). Neurohormonal activation is associated with the degree of symptoms and the severity of disease in mild or moderately severe congestive heart failure. Treatment with ramipril attenuates neurohormonal activation. This effect is most pronounced among patients with the highest circulating concentrations of neurohormones before the start of treatment.",1994.0,0,0
1478,7819003,Analysis of hypertension in children post renal transplantation--a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).,H J Baluarte; A B Gruskin; J R Ingelfinger; D Stablein; A Tejani,"Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the persistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medications used to treat this hypertension and to determine the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therapy to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.",1994.0,0,0
1479,7821188,"American Diabetes Association meetings, 1994. Complications of diabetes mellitus.",Z T Bloomgarden,,1994.0,0,0
1480,7828296,Comparison of five antihypertensive monotherapies and placebo for change in left ventricular mass in patients receiving nutritional-hygienic therapy in the Treatment of Mild Hypertension Study (TOMHS).,P R Liebson; G A Grandits; S Dianzumba; R J Prineas; R H Grimm; J D Neaton; J Stamler,"Increased left ventricular mass (LVM) by echocardiography is associated with increased risk of cardiovascular disease. Thus, it is of interest to compare the effects of both pharmacological and nonpharmacological approaches to the treatment of hypertension on reduction of LVM. Changes in LV structure were assessed by M-mode echocardiograms in a double-blind, placebo-controlled clinical trial of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five classes of antihypertensive agents: (1) diuretic (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin mesylate), (4) calcium antagonist (amlodipine maleate), or (5) angiotensin-converting enzyme inhibitor (enalapril maleate). Echocardiograms were performed at baseline, at 3 months, and annually for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that appeared at 3 months and continued for 48 months. The chlorthalidone group experienced the greatest decrease at each follow-up visit (average decrease, 34 g), although the differences from other groups were modest (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). Within-group analysis showed that changes in weight, urinary sodium excretion, and systolic BP were moderately correlated with changes in LVM, being statistically significant in most analyses. NH intervention with emphasis on weight loss and reduction of dietary sodium is as effective as NH intervention plus pharmacological treatment in reducing echocardiographically determined LVM, despite a smaller decrease in blood pressure in the NH intervention only group. A possible exception is that the addition of diuretic (chlorthalidone) may have a modest additional effect on reducing LVM.",2001.0,0,0
1481,7829724,Enalapril-induced lichen planus-like eruption.,S V Roten; C Mainetti; R Donath; J H Saurat,,1995.0,0,0
1482,7830033,Contrasting effects of angiotensin converting inhibitor and alpha-1-antagonist on albuminuria in insulin-dependent diabetes mellitus patients with nephropathy.,H Holdaas; A Hartmann; K J Berg; H Langberg; L Blystad; P Fauchald,"The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha-1 (alpha-1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin-dependent diabetes mellitus patients with nephropathy. The study consisted of a four-week run-in period, a four-week active treatment period, a four-week wash-out period and a second four-week active treatment period. The study was performed in the out-patient clinic at a university hospital. Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 micrograms min-1), mild to moderate hypertension (diastolic blood pressure 85-115 mmHg) and serum creatinine level below 200 mumol L-1 were included in the study. The effect of the drugs on albumin and total protein excretion, beta-2-microglobulin, proximal tubular enzyme markers and renal haemodynamics. Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 +/- 281 micrograms min-1 to 742 +/- 246 micrograms min-1 (P < 0.01) and total protein excretion from 2.0 +/- 0.4 g per 24 h to 1.3 +/- 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 +/- 0.02 to 0.23 +/- 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N-acetyl-beta-glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of beta-2-microglobulin. However, neither the excretion of beta-2-microglobulin nor the enzyme markers were affected by either drug. Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.",1995.0,0,0
1483,7834934,Neuroendocrine activation in relation to left ventricular function in chronic severe congestive heart failure: a subgroup analysis from the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).,S V Eriksson; P Eneroth; J Kjekshus; J Offstad; K Swedberg,"Left ventricular (LV) function and plasma levels of cardiovascular hormones were examined in patients with severe chronic congestive heart failure (CHF), randomized to placebo or enalapril, in addition to conventional therapy. M-mode echocardiography and plasma hormone concentrations were available at baseline and after 6 weeks of treatment. There was a significant relationship between LV systolic function and levels of angiotensin-II and norepinephrine. Enalapril increased LV fractional shortening (FS%) (13.3 +/- 5.6 to 15.4 +/- 5.8, p < 0.05) and decreased the systolic time interval index (0.58 +/- 0.14 to 0.48 +/- 0.15, p < 0.05) concurrent with a significant decrease in angiotensin-converting enzyme activity and in aldosterone, angiotensin-II, and norepinephrine concentrations after 6 weeks. No changes were found in the placebo group. However, there was no direct relationship between the amount of change in neurohormones and improvement in LV function after 6 weeks. These findings indicate that in patients with severe chronic CHF, severe LV systolic dysfunction is associated with high plasma levels of angiotensin-II and norepinephrine, which can be favorably modified by enalapril. This may be of importance for prolonging life in severe heart failure. The lack of relationship between changes in individual hormones and systolic function suggests complex dynamic interaction. It is, therefore, not sufficient to predict changes in LV function by measuring changes in only one hormone.",1994.0,0,0
1484,7837215,Lisinopril versus slow release nifedipine in patients with essential hypertension: a multicentre study.,H G Predel; H J Kramer,"The present study was performed to investigate the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitor lisinopril compared with those of the calcium channel blocker nifedipine in 293 patients with mild to moderate essential hypertension (supine diastolic blood pressure (DBP) 95-115 mmHg) in a multicentre, randomised, double-blind parallel group study after a two week single-blind placebo run-in period. Thus, the haemodynamic effects as well as side-effects during antihypertensive treatment were examined in 146 patients receiving lisinopril (20 mg once daily) and in 147 patients receiving slow release nifedipine (20 mg twice daily) who entered the six weeks' treatment period. From the analysis of efficacy one patient from the lisinopril and two patients from the nifedipine groups were excluded because their supine DBP after run-in was < 95 mmHg. Adverse reactions, mostly transient during the initial treatment period, and withdrawals occurred in six (4.1%) and three (2.1%) patients of the lisinopril group and in 12 (8.2%; NS) and three (2.0%) patients of the nifedipine group, respectively. After the six weeks' treatment period the lisinopril group showed 19 nonresponders (supine DBP > or = 95 mmHg) of the remaining 142 patients and the nifedipine group revealed 20 nonresponders of the remaining 142 patients. Initial supine and standing heart rates were similar in both groups. Supine heart rate fell significantly in the lisinopril group, whereas standing heart rate in this group and supine and standing heart rates in the nifedipine group did not change significantly with treatment. Thus, lisinopril proved to be as effective and safe as nifedipine with responder rates of 86.6% and 85.9%, respectively.",1994.0,0,0
1485,7841571,Lisinopril overdose and management with intravenous angiotensin II.,L E Trilli; K A Johnson,"This report describes a case of lisinopril overdose managed in part with an infusion of angiotensin II in a patient with dilated cardiomyopathy and reviews other literature reporting angiotensin-converting enzyme (ACE) inhibitor overdose. Information concerning this patient was obtained through review of the medical chart, conversation with the attending physician, and personal involvement late in the course of the patient's therapy. We conducted MEDLINE and PAPERCHASE searches of the English language literature (restricted to human studies) from 1976 to the present, manually searched Current Contents and references from each publication reviewed, and contacted the manufacturer of lisinopril for any further references they could provide. All case reports that described an ACE inhibitor overdose. Case reports were evaluated for the ACE inhibitor involved, amount ingested, and therapeutic management. Ten patients with ACE inhibitor overdose have been reported, most of whom required only intravenous fluids for blood pressure support. The case presented here is the second report in which the patient's blood pressure was not adequately controlled with fluid and traditional vasopressors and required an infusion of angiotensin II. Although only a few cases of ACE inhibitor overdose have been reported, it is possible that with widespread use of these agents, overdose may become a more common problem. Management of ACE inhibitor overdose should include general supportive care, gut decontamination when possible, intravenous fluids, and vasopressors if necessary. Intravenous angiotensin II may be effective in situations in which traditional vasopressors fail, and is a physiologically rational treatment.",1994.0,0,0
1486,7843751,"Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients.",M R Goldberg; T E Bradstreet; E J McWilliams; W K Tanaka; S Lipert; T D Bjornsson; S A Waldman; B Osborne; L Pivadori; G Lewis,"We investigated the effects of angiotensin II (Ang II) type 1 receptor blockade with losartan on the renin-angiotensin-aldosterone system in hypertensive patients (supine diastolic blood pressure, 95 to 110 mm Hg). Qualifying patients (n = 51) were allocated to placebo, 25 or 100 mg losartan, or 20 mg enalapril. Blood pressure, plasma drug concentrations, and renin-angiotensin-aldosterone system mediators were measured on 4 inpatient days: end of placebo run-in, after first dose, and 2 and 6 weeks of treatment. Plasma drug concentrations were similar after the first and last doses of losartan. At 6 weeks, 100 mg losartan and 20 mg enalapril showed comparable antihypertensive activity. Four hours after dosing, compared with the run-in day, 100 mg losartan increased plasma renin activity 1.7-fold and Ang II 2.5-fold, whereas enalapril increased plasma renin activity 2.8-fold and decreased Ang II 77%. Both drugs decreased plasma aldosterone concentration. For losartan, plasma renin activity and Ang II increases were greater at 2 than at 6 weeks. Effects of losartan were dose related. After the last dose of losartan, plasma renin activity and Ang II changes were similar to placebo changes by 36 hours. These results indicate that long-term blockade of the feedback Ang II receptor in hypertensive patients produces modest increases of plasma renin activity and Ang II that do not appear to affect the antihypertensive response to the antagonist.",1995.0,0,0
1487,7843758,Hypertension after renal transplantation. Calcium channel or converting enzyme blockade?,M R van der Schaaf; R J Hené; M Floor; P J Blankestijn; H A Koomans,"We compared the effects of 4 weeks of calcium channel blockade (amlodipine) or converting enzyme inhibition (lisinopril) on blood pressure and renal hemodynamics in a double-blind crossover trial in a group of 20 hypertensive cyclosporine-treated renal transplant patients. Amlodipine (10 mg) was more effective than the same dose of lisinopril in controlling hypertension (mean 24-hour arterial pressure, 111 +/- 9 and 115 +/- 9 mm Hg, respectively; P < .05). Blood pressure during both treatments was lower than during placebo (124 +/- 12 mm Hg, P < .05). Compared with placebo, amlodipine treatment was associated with a significant increase in glomerular filtration rate (10 +/- 20%, P < .05) and effective renal plasma flow (27 +/- 20%, P < .01) and a decrease in renal vascular resistance (23 +/- 18%, P < .01). Renal hemodynamics did not change during lisinopril. Neither drug had an effect on proteinuria. The data indicate that amlodipine is more effective than lisinopril in controlling hypertension in cyclosporine-treated patients and that treatment with amlodipine but not with lisinopril is accompanied by an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance. The data suggest that the renin-angiotensin system does not play a main role in determining cyclosporine-associated changes in renal hemodynamics and has a limited role in determining cyclosporine-associated hypertension.",1995.0,0,0
1488,7843761,Ramipril-induced regression of left ventricular hypertrophy in treated hypertensive individuals. HYCAR Study Group.,M Lièvre; P Guéret; C Gayet; R Roudaut; M C Haugh; S Delair; J P Boissel,"The objective of this trial was to assess the effects of 6-month daily treatment with two doses of ramipril on left ventricular mass and the dependence of this on blood pressure changes in hypertensive patients with left ventricular hypertrophy. After a selection phase of 4 to 6 weeks with patients under antihypertensive therapy with 20 mg furosemide daily, 115 patients with either controlled or uncontrolled hypertension and left ventricular hypertrophy were randomized in a double-blind manner to receive either placebo (n = 40), 1.25 mg (low dose, n = 38), or 5 mg (regular dose, n = 37) ramipril daily for 6 months. Treatment with furosemide was continued unchanged during this phase. The main outcome measured was left ventricular hypertrophy regression as assessed from central blind reading of echocardiograms recorded at randomization and after 6 months. No significant differences were observed for changes in casual or ambulatory blood pressure between the three groups. Left ventricular mass index was found to be significantly reduced in patients receiving 5 mg ramipril compared with those receiving placebo (-10.8 +/- 3.7 versus +4.1 +/- 4.0 g/m2, P = .008); in patients receiving 1.25 mg ramipril, the difference was close to borderline significance compared with placebo (-7.0 +/- 4.3 g/m2, P = .06). Similar results were observed for changes in left ventricular mass (-20.3 +/- 6.6 and -13.0 +/- 7.8 g in the 5- and 1.25-mg ramipril groups, respectively, versus +9.1 +/- 7.2 g in the placebo group; P = .004 and .04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1489,7843782,Feasibility study of N-of-1 trials with blood pressure self-monitoring in hypertension.,G Chatellier; M Day; G Bobrie; J Menard,"The objective of this study was to assess individual responses to antihypertensive treatment by N-of-1 trials using blood pressure self-monitoring in 79 patients of both sexes referred to a hypertension clinic. Thirty-five patients who remained untreated (study 1) and 44 N-of-1 trial participants (study 2) were consecutively selected if their clinic blood pressure was between 160/95 and 220/115 mm Hg and there were no hypertensive complications. Blood pressure was measured daily at home for 21 days (three consecutive measures, morning and evening). Each N-of-1 trial was a single-blind treatment consisting of two successive 10-day treatment pairs, each pair comprising 5 days of placebo followed by 5 days of 20 mg enalapril once daily in the morning. Study 1 showed no significant blood pressure regression toward the mean over 20 days and justified the choice of 5-day treatment periods in study 2. In study 2, blood pressure fell significantly 12 hours after the first administration of enalapril and rose within 24 hours of the end of the 5-day active treatment period. Using evening blood pressure values (12 hours after enalapril intake) from the first treatment pair, 33 patients were classified as responders (diastolic blood pressure fall > or = mm Hg). In 16 of these 33 patients, the fall in blood pressure above 6 mm Hg was not maintained in the morning, 24 hours after drug intake. Response reproducibility was tested by comparison with the second treatment pair: the observed agreement was only 0.71 (chance-corrected agreement: 0.34) when defined according to both evening and morning values.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1490,7848615,Female preponderance for lisinopril-induced cough in hypertension.,I Os; B Bratland; B Dahlöf; K Gisholt; J O Syvertsen; S Tretli,"In a double-blind double-dummy multicenter study, patients with mild to moderate essential hypertension were randomized to receive either nifedipine (n = 416, 47.6% women) or lisinopril (n = 412, 50% women), and side effects were registered by specific questioning, by spontaneous reports, and by use of visual analog scales. Cough was spontaneously reported to occur in 8.5% with lisinopril compared to 3.1% with nifedipine. Women treated with lisinopril reported cough spontaneously three times more often than men, 12.6% v 4.4%, whereas no differences between the sexes were observed during the placebo period or during nifedipine treatment. Similar gender differences were observed during specific questioning. Furthermore, nonsmokers reported an increase in cough more often than did smokers.",1994.0,0,0
1491,7848623,Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions in mild hypertension.,P A Abraham; S R Mascioli; C A Launer; J M Flack; P R Liebson; K H Svendsen; G A Grandits; J A Opsahl; J A Schoenberger; R H Grimm,"Renal effects of mild hypertension and therapy have not been established. Since urinary albumin and N-acetyl-beta-D-glucosaminidase excretions reflect renal effects of hypertension, they were related to blood pressure, other cardiovascular risk factors, cardiac target organ effects, and response to therapy in mild hypertension (diastolic blood pressure 85-99 mm Hg). Participants were from two clinics of the Treatment of Mild Hypertension Study (TOMHS), a multicenter randomized, double-blind, controlled trial. Participants received nutritional-hygienic therapy and one of five active drugs or placebo. Urinary albumin and N-acetyl-beta-D-glucosaminidase excretions were assessed prospectively using office ""spot"" collections from one clinic (n = 213) and retrospectively using overnight collections from the other clinic (n = 210). Relationships were determined between protein excretions and blood pressure, age, gender, race, blood glucose, cholesterol concentrations, and indices of body mass and left ventricular mass and function at baseline. Treatment effects were assessed after 3 to 12 months. Spot and overnight albumin excretions related positively to baseline systolic blood pressure by univariate analyses. Spot albumin excretion related positively to systolic blood pressure, age, creatinine clearance, and left ventricular function while overnight albumin excretion related positively to left ventricular mass and female gender by multiple regression analyses. Spot, but not overnight, albumin excretion declined significantly with active drug therapy. N-acetyl-beta-D-glucosaminidase excretion did not relate to blood pressure or decline with therapy. The combined results suggest albumin excretion correlates with blood pressure, decreases with antihypertensive drug therapy, and is associated with greater left ventricular function and mass, as well as glomerular filtration rate, even at mild levels of hypertension.",2001.0,0,0
1492,7848788,A multicentre study to compare the therapeutic efficacy of sustained-release diltiazem and enalapril in the treatment of patients with mild to moderate hypertension.,R J Weir; P S Lee; D S Clegg; S Hemingray; G P Belgrave; E Walter,"A 14-week study was conducted in order to compare the efficacy and tolerability of a twice-daily sustained-release diltiazem preparation (120 or 180 mg) and once-daily enalapril (10 or 20 mg). Patients not achieving an adequate response after 6 weeks on monotherapy were given a combination therapy of twice-daily diltiazem 120 mg and once-daily enalapril 10 mg. Of the 147 patients admitted to the study, 70 received diltiazem and 77 received enalapril; 17 patients subsequently received combination therapy. Blood pressure reductions in patients completing 12 weeks of therapy were (sitting values): diltiazem 120 mg, 10.2/15.2 mmHg; diltiazem 180 mg, 19.1/14.7 mmHg; enalapril 10 mg, 25.7/17.5 mmHg; enalapril 20 mg, 19.6/14.0 mmHg; and combination therapy, 24.6/15.1 mmHg. No significant differences in the incidence level of individual symptoms were seen between the two groups: 34 (49%) in the diltiazem, 37 (48%) in the enalapril group; and, between weeks 6 and 12, 9 (53%) patients taking combination therapy. Two patients withdrew from the enalapril group and 8 from the diltiazem group. No unexpected side-effects were seen during the study and no deaths occurred in any treatment group. Twice-daily sustained-release diltiazem 120 or 180 mg was shown to be an effective antihypertensive agent and equal in efficacy and patient acceptability to once-daily enalapril 10 or 20 mg. Combination therapy effectively lowered blood pressure in patients in whom monotherapy was ineffective.",1994.0,0,0
1493,7850941,Differential effects of chronic oral antihypertensive therapies on systemic arterial circulation and ventricular energetics in African-American patients.,B P Cholley; S G Shroff; J Sandelski; C Korcarz; B A Balasia; S Jain; D S Berger; M B Murphy; R H Marcus; R M Lang,"A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MVO2). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MVO2. Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MVO2, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744 +/- 398 versus 1290 +/- 215 dyne-s/cm5) and increased arterial compliance (ACL; 1.234 +/- 0.253 versus 1.776 +/- 0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740 +/- 292 versus 1437 +/- 290 dyne-s/cm5) and increased ACL (1.214 +/- 0.190 versus 1.569 +/- 0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or ACL. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MVO2 per beat was reduced with these agents. Stress-time index, a measure of MVO2 per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MVO2 coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol. The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MVO2 in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MVO2 with each drug may provide a more physiological approach to the treatment of systemic hypertension in indivi",1995.0,0,0
1494,7851032,The influence of ACE-inhibition on myocardial mass and diastolic function in chronic hemodialysis patients with adequate control of blood pressure.,F X Roithinger; C Punzengruber; M Wallner; W Ulbrich; O Pachinger; R Kramar; F C Prischl,"The objectives of this study were to evaluate the specific effect of the ACE-inhibitor lisinopril on myocardial mass and diastolic function in uremic patients using a protocol designed to leave blood pressure unchanged. Nineteen hemodialysis patients (7 males; mean age: 55 +/- 13 years; mean time on dialysis: 44 +/- 35 months) received lisinopril for 6 months in addition to their preexistent antihypertensive treatment regimens (mean: 1.4 +/- 0.8 drugs). Doses of antihypertensive drugs were adjusted to keep both systolic and diastolic blood pressure stable. Nine patients were withdrawn from lisinopril treatment after 43 +/- 33 days because of hypotension (n = 4), withdrawn consent (n = 3), stroke (n = 1) and cough (n = 1). Seven of them were further studied as controls. Ten patients received 6.4 +/- 4 mg lisinopril as a mean for 6 months. Mean myocardial mass, calculated by M-mode echocardiography, was 324 +/- 103 g before, and 313 +/- 79 g after 6 months of lisinopril treatment. In the control patients, myocardial mass was 318 +/- 110 g initially, and after 6 months, it was 334 +/- 159 g. Early and late transmitral diastolic flow velocities were not significantly influenced by lisinopril. Throughout the study, both the systolic and diastolic 24-h mean blood pressure levels remained stable (systolic: before: 145 +/- 19 mmHg, at 6 months: 147 +/- 17 mmHg; diastolic: before: 87 +/- 12 mmHg, at 6 months 87 +/- 10 mmHg). Thus, no specific effect of lisinopril on regression of myocardial hypertrophy or improvement of diastolic function could be observed within a 6-month period in this small group of hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1495,7851072,Hypertension in Diabetes Study. III. Prospective study of therapy of hypertension in type 2 diabetic patients: efficacy of ACE inhibition and beta-blockade.,,"The Hypertension in Diabetes Study (HDS) is an ongoing, multicentre, prospective randomized intervention trial of therapy of hypertension (> or = 160 and/or > or = 90 mmHg) in Type 2 diabetic patients. It compares tight blood pressure control (aim: < 150/85 mmHg) versus less tight control (aim: < 180/105 mmHg) and, within the tight control group, an ACE inhibitor, captopril, versus a beta blocker, atenolol. We report the efficacy, side-effects of treatment, biochemical responses and incidence of hypoglycaemia in 755 patients (mean age 57 years, blood pressure 150/94 mmHg) followed for 2 years. At 2 years, blood pressure was 143/84 in the tight control and 156/90 mmHg in the less tight control group (p < 0.0001). Blood pressure reduction, adherence to therapy, incidence of side-effects and of hypoglycaemia were similar on captopril and on atenolol. Patients on atenolol had a greater increase in body weight (+2.3 vs +0.7 kg, p < 0.01) and a non-significant trend to a greater increase in triglyceride than patients on captopril. A large blood pressure difference between the tight control and less tight control groups was obtained, with captopril and atenolol having similar hypotensive effects. The study has the potential to determine whether strict blood pressure control reduces the incidence of diabetic complications and whether ACE inhibitor or beta-blocker therapy is clinically advantageous.",1994.0,0,0
1496,7852748,The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-L-arginine in patients with essential hypertension.,D Lyons; J Webster; N Benjamin,"The nitric oxide (NO) system is abnormal in essential hypertension and the response of the forearm vascular bed to local intra-arterial infusions of NG-monomethyl-L-arginine (L-NMMA) is diminished in patients with untreated essential hypertension. Animal data suggest that treatment of hypertension may restore normal NO-mediated responses. We have prospectively examined the effect of standard antihypertensive therapy on the responsiveness to local intra-arterial infusions of L-NMMA in 18 newly diagnosed hypertensive patients. This was a double-blind, randomized, parallel-group study. Patients were randomized to treatment with 10 mg enalapril daily, 5 mg amlodipine daily or matched placebo for 6 weeks (with dose titration after 2 weeks if necessary). Forearm blood flow during direct infusion into the brachial artery of L-NMMA (1, 2 and 4 mumol/min) was measured using venous occlusion plethysmography at the beginning and end of the 6-week treatment period. Both enalapril and amlodipine reduced blood pressure significantly compared with placebo. After 6 weeks of antihypertensive therapy, forearm blood flow (+/- SEM) in response to the maximum dose of L-NMMA (4 mumol/min) was reduced by 54.8 (6.9)% (P = 0.012), 58.9 (7.0)% (P = 0.016) and 33.1 (3.0)% (P = 0.17) in the enalapril, amlodipine and placebo groups, respectively. There was no significant difference between enalapril and amlodipine treatment groups. The forearm arterial responsiveness to L-NMMA in newly diagnosed patients with essential hypertension returns to normal with normalization of blood pressure by antihypertensive drugs with different modes of action. It remains to be determined whether this phenomenon is a consequence of the change in pressure per se or a result of the action of either drug by a common or separate mechanism.",1994.0,0,0
1497,7852749,"Within-patient correlation between the antihypertensive effects of atenolol, lisinopril and nifedipine.",S Attwood; R Bird; K Burch; B Casadei; A Coats; J Conway; M Dawes; D Ebbs; A Farmer; J Robinson,"To investigate whether there are definable subgroups of patients with essential hypertension who respond specifically to particular antihypertensive drugs. Randomized cross-over comparison of the antihypertensive effect of 50 mg atenolol per day, 10 mg lisinopril per day and 20 mg nifedipine retard twice a day. Ambulatory blood pressure monitoring was used to assess the blood pressure level both for recruitment and at the end of each treatment period. The treatment periods lasted 4 weeks and were preceded by 4 weeks of placebo. Seventy-two untreated hypertensive patients with a mean age of 52 (SD 8.4) years were recruited from six general practices and from the hospital outpatient clinic. Sixty-eight patients completed the trial. To assess the within-patient correlations among the blood pressure responses to each drug and explore the possible role of simple characteristics, such as the initial blood pressure, plasma renin concentration and age, in identifying the responders to a particular drug. Systolic/diastolic blood pressure fell significantly with each agent (P < 0.001): atenolol reduced it by 16.3 +/- 13.3/9.9 +/- 8.8, lisinopril by 14.8 +/- 15.0/9.4 +/- 9.1 and nifedipine by 11.6 +/- 12.3/6.7 +/- 8.3 mmHg. There was a low degree of correlation between the changes in blood pressure with the three drugs in individual patients. With each drug there was a small percentage (8.9-14.7%) of non-responders. The initial level of systolic blood pressure was weakly correlated with the antihypertensive effect of nifedipine (r = 0.47, P < 0.001) and plasma renin concentration was related to the effect of atenolol (r = 0.32, P < 0.01). Age did not predict the blood pressure response to any agent. The low level of the correlation between the blood pressure changes with the three drugs suggests that different mechanisms may be involved in the aetiology of essential hypertension. Plasma renin concentration and the initial level of systolic blood pressure contribute only weakly to the identification of responders to the three drugs.",1994.0,0,0
1498,7853327,Relationship between change in erythrocyte sodium and antihypertensive response to enalapril.,H Herlitz; B Dahlöf; O Jonsson; L Hansson,"To investigate the effects of enalapril and hydrochlorothiazide on erythrocyte sodium and potassium in relation to their effects on BP, 28 men (mean age 46 years, range 22-64 years) with previously untreated essential hypertension (casual DBP > or = 95 mmHg) were randomised to enalapril (n = 14) or hydrochlorothiazide (n = 14) treatment. BP was also measured intraarterially (brachial artery) and the mean arterial pressure (MAP) recorded. Intraerythrocyte sodium and potassium were measured by flame photometry at baseline and after 26 weeks of active treatment in the hypertensive patients and also in 28 age- and sex-matched normotensive control subjects. There was a significant positive relationship between intra-arterial BP and intraerythrocyte sodium in untreated hypertensives, but there was no significant difference in mean intraerythrocyte sodium or potassium content between hypertensive and normotensive subjects at baseline. The distribution of values of intraerythrocyte sodium, however, differed between hypertensive and normotensive subjects. Supine MAP was lowered from 113 +/- 4 to 97 +/- 3 mmHg and from 110 +/- 3 to 102 +/- 2 mmHg on enalapril and hydrochlorothiazide treatment, respectively. BP reduction with enalapril was associated with a significant decrease in intraerythrocyte sodium (P = 0.02), while hydrochlorothiazide had no effect. There was no significant correlation between delta MAP and delta intraerythrocyte sodium after 26 weeks in any of the groups. Intraerythrocyte potassium did not change on treatment with either drug. In conclusion, there wa a significant relationship between intra-arterial BP and intraerythrocyte sodium in untreated hypertensives. Both enalapril and hydrochlorothiazide reduced BP effectively while enalapril only reduced intraerythrocyte sodium.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1499,7857732,Association between reduced heart rate variability and left ventricular dilatation in patients with a first anterior myocardial infarction. CATS Investigators. Captopril and Thrombolysis Study.,J H Dambrink; Y S Tuininga; W H van Gilst; K H Peels; K I Lie; J H Kingma,"Reduced heart rate variability has been identified as an important prognostic factor after myocardial infarction. This factor is thought to reflect an imbalance between sympathetic and parasympathetic activity, which may lead to unfavourable loading conditions and thus promote left ventricular dilatation. 298 patients in a multicentre clinical trial were randomised to captopril or placebo after a first anterior myocardial infarction. All patients were treated with streptokinase before randomisation. In the present substudy full data including heart rate variability and echocardiographic measurements were available from 80 patients. Patients were divided into two groups: those with a reduced (< or = 25) heart rate variability index and those with normal heart rate variability index (> 25). Heart rate variability was evaluated by 24 h Holter monitoring before discharge. Left ventricular volumes were assessed by echocardiography before discharge and three and 12 months after myocardial infarction. Extent of myocardial injury, severity of coronary artery disease, functional class, haemodynamic variables, and medication were also considered as possible determinants of left ventricular dilatation. Before discharge end systolic and end diastolic volumes were not different in the two groups. After 12 months in patients with a reduced heart rate variability, end systolic volume (mean (SD)) had increased by 6 (14) ml/m2 (P = 0.043) and end diastolic volume had increased by 8 (17) ml/m2 (P = 0.024). Left ventricular volumes were unchanged in patients with a normal heart rate variability. Also, patients with left ventricular dilatation had a larger enzymatic infarct size and higher heart rates and rate-pressure products. A reduced heart rate variability index before discharge was an independent risk factor for left ventricular dilatation during follow up. Measurement of heart rate variability after three months had no predictive value for this event. Assessment of the heart rate variability index before discharge, but not at three months, gave important additional information for identifying patients at risk of left ventricular dilatation.",1994.0,0,0
1500,7857733,Influence of angiotensin converting enzyme inhibition on relation of atrial natriuretic peptide concentration to atrial pressure in heart failure.,H Berglund; O Nyquist; B Beermann; M Jensen-Urstad; E Theodorsson,"To examine the relation between haemodynamics and atrial natriuretic peptide concentration during short term angiotensin converting enzyme inhibition. Patients were randomly allocated to receive placebo or one of three doses of the angiotensin converting enzyme inhibitor ramipril. Cardiac units of two tertiary referral hospitals. 38 Patients with stable congestive heart failure caused by ischaemic heart disease. Data were collected over a 24 hour period and assessed with the aim of distinguishing between the haemodynamic effects on plasma concentrations of atrial natriuretic peptide and the direct effects of the study drug, vasopressin concentrations, and angiotensin converting enzyme activity. Pulmonary capillary wedge pressure was the main predictor of the plasma concentration of atrial natriuretic peptide. A higher plasma concentration of this peptide with a given pulmonary capillary wedge pressure was found after 24 hours of treatment with 2.5 mg and 5 mg of ramipril. Plasma concentration of the active metabolite, change in arginine vasopressin concentration or degree of angiotensin converting enzyme inhibition did not significantly predict change in plasma concentration of atrial natriuretic peptide or in the ratio of atrial natriuretic peptide concentration to pulmonary capillary wedge pressure. A gradual increase in plasma concentration of atrial natriuretic peptide with a given pulmonary capillary wedge pressure, occurs during short term high degree inhibition of angiotensin converting enzyme. The causative mechanisms are yet to be identified. Such a change in the relation between central haemodynamics and atrial natriuretic peptide concentration may contribute to the beneficial effects of angiotensin converting enzyme inhibition in patients with congestive heart failure due to ischaemic heart disease.",1994.0,0,0
1501,7857734,"Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic peptide to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure.",M Yoshimura; H Yasue; H Tanaka; K Kikuta; H Sumida; H Kato; M Jougasaki; K Nakao,"Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B type or brain natriuretic peptide (BNP) are increased in patients with congestive heart failure (CHF). To examine the haemodynamic and hormonal responses, especially of ANP and BNP, to oral administration of an angiotensin-converting enzyme (ACE) inhibitor in patients with CHF and in controls. 12 patients with CHF and 11 controls. Haemodynamic variables and plasma concentrations of ANP, BNP, and other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth. Pulmonary capillary wedge pressure and systemic vascular resistance decreased significantly in both groups. The cardiac index increased only in the CHF group. In patients with CHF pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac index were significantly changed from 1 to 12 hours after alacepril administration. Plasma ANP and BNP decreased significantly after alacepril was given to the CHF group: neither concentration changed in the control group. In the CHF group plasma ANP was significantly lower between 1 and 6 hours and was highly significantly correlated with pulmonary capillary wedge pressure. Plasma BNP, however, was significantly lower between 6 and 24 hours after alacepril and was not correlated with pulmonary capillary wedge pressure. The response of plasma BNP after alacepril administration occurred later and lasted longer than the plasma ANP response. This may indicate that the mechanisms of synthesis, secretion, or degradation of the two peptides are different.",1994.0,0,0
1502,7859051,Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension.,S Nielsen; A Schmitz; R E Knudsen; J Dollerup; C E Mogensen,"In a double-blind, double-dummy, randomized, multi-centre study, the effects of bendroflumethiazide vs. enalapril on blood pressure, glycaemic control, lipoprotein concentrations and albuminuria were compared in non-proteinuric, hypertensive type 2 diabetic patients; they were treated for 20 weeks with either bendroflumethiazide 2.5-5.0 mg (n = 59) or enalapril 10-20 mg (n = 55). Age, fasting plasma glucose, HbA1c and BMI were similar in the groups. Systolic and diastolic blood pressure were reduced in both groups. Bendroflumethiazide was accompanied by minor but significant elevations in fasting plasma glucose and serum C-peptide. HbA1c was increased during both treatments. Lipoproteins and urinary albumin/creatinine ratio were stable. Bendroflumethiazide caused a decrease in serum potassium and an increase in serum urate. No significant correlations were observed between the decline in blood pressure and changes in the metabolic risk factors. Baseline levels of age, sex, BMI, blood pressure or urinary albumin/creatinine ratio were not related to changes in blood pressure, metabolic parameters or urinary albumin/creatinine ratio.",1994.0,0,0
1503,7859244,A postmarketing surveillance evaluation of quinapril in 3742 Canadian hypertensive patients: the ACCEPT Study. Accupril Canadian Clinical Evaluation and Patient Teaching.,P Larochelle; B Haynes; N Maron; S Dugas,"The Accupril Canadian Clinical Evaluation and Patient Teaching (ACCEPT) study was a multicenter, 6-month, open-label, postmarketing surveillance study where the efficacy and safety of quinapril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in a general population of patients with essential hypertension. Participating physicians followed their normal office procedures for the initiation of quinapril therapy (a dose of 10 mg QD in the majority of cases). The dose was titrated to blood pressure response, generally at 2-week intervals, for a maintenance dose of 10 mg QD to 20 mg QD in most cases (86% at 6 months) and not to exceed 40 mg QD. The use of concomitant antihypertensive medications was left to the discretion of the physician. By random assignment, physicians obtained patient informed consent on either a detailed form that listed possible quinapril side effects or a less specific form, which did not list particular side effects. The purpose of using two different forms was to assess any potential association between the frequency of adverse-event reporting and patient's awareness of quinapril side effects. The patients also received an educational package that provided general information on hypertension and lifestyle modifications known to reduce cardiovascular risk factors. An intent-to-treat analysis included data from 3742 patients in whom the median age was 56 years and the median duration of hypertension was 5 years. The demographic characteristics of these patients were similar to those identified in Canadian hypertensive patients in a recent population-based survey. Nearly 80% of the ACCEPT study patients had more than one cardiovascular risk factor, in addition to hypertension. Among 2979 patients receiving quinapril at 3 months, 77% were stabilized. Among 2517 patients continuing to receive quinapril at 6 months, 84% were stabilized. Greater declines in both diastolic and systolic blood pressures were evident among patients who continued to receive quinapril as part of an antihypertensive regimen than among those who discontinued quinapril treatment. Blood pressure responses to quinapril were similar in newly diagnosed patients and those with a history of hypertension. A total of 980 patients (26.2%) reported one or more adverse events. Cough was most frequently reported and was deemed as definitely related to quinapril therapy by the treating physician in 3.6% of cases. Serious adverse events occurred in 55 patients (1.5%) and were assessed as possibly related to quinapril in only three patients.(ABSTRACT TRUNCATED AT 400 WORDS)",1994.0,0,0
1504,7859801,Angiotensin converting enzyme inhibition does not affect response to exogenous angiotensin II in the forearm of mild-moderate hypertensive patients.,D Lyons; J Webster; N Benjamin,"It has been proposed that the suppression of endogenous levels of angiotensin II by angiotensin converting enzyme inhibition, may result in up-regulation of vascular AT1 receptors. This study evaluated the effects of orally administered enalapril on angiotensin II induced vasoconstriction in the human forearm of patients with mild-moderate hypertension. Patients received in random order, enalapril (20 mg) or matched placebo daily for 2 weeks. Forearm blood flow response to increasing doses of angiotensin II was measured using venous occlusion plethysmography at the beginning of the study and at the end of each 2 week treatment period. Treatment with enalapril significantly reduced plasma angiotensin II levels and supine blood pressure compared to placebo. The percentage reductions in forearm blood flow in the infused arm, in response to the maximum dose of angiotensin II (50 pmol.min-1) were 53.2% at baseline, 51.4% on placebo and 59.5% on enalapril. The differences were not significantly different. This study demonstrates that suppression of plasma angiotensin II does not enhance the response to exogenous intra-arterial angiotensin II in the human forearm of mild-moderately hypertensive patients.",1994.0,0,0
1505,7859897,"Effects of captopril on ambulatory blood pressure, renal and cardiac function in microalbuminuric type 1 diabetic patients.",K W Hansen; F Klein; P D Christensen; K Sørensen; P H Andersen; J Møller; E B Pedersen; J S Christiansen; C E Mogensen,"To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients. Randomized, double blind placebo controlled study of two years duration. University clinic. Twenty-two patients without hypertension. Patients received 50 mg Captopril or placebo twice a day. Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months. Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35). Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.",2000.0,0,1
1506,7860471,Ramipril vs captopril in mild to moderate hypertension.,V H Yajnik; D J Vatsraj; H K Acharya; N V Yajnik; N R Vyas; H B Vakil,"Ramipril 5 mg once daily was compared to Captopril 50 mg twice daily in a randomised, double-blind, parallel group study in 60 patients with a diastolic blood pressure between 95 to 120 mmHg over a period of 2 months. Both drugs in the dose regimen used in this study exerted a similar anti-hypertensive effect at the end of 2 months of treatment resulting in a fall of supine diastolic blood pressure with Ramipril = 19.27 +/- 3.34 mmHg and Captopril = 19.15 +/- 2.63, in patients receiving the drugs without the diuretic. The mean fall in supine diastolic blood pressure 4 hours after the first dose of Ramipril was 6.5 mmHg and Captopril 8 mmHg. None of the patients developed first dose hypotension or orthostatic hypotension and there was no significant alteration of the heart rate in either group. The serum K+ levels remained unchanged in both groups of patients. Both drugs were well tolerated and there were no adverse effects observed on the liver, kidney, blood sugar or haemopoietic system. Based on the results of this study, it can be concluded that the antihypertensive efficacy of 5 mg ramipril in a once daily dose is equivalent to 50 mg captopril given twice daily. However an appreciably greater number of patients reported improvement in the ""quality of life' parameters with ramipril as compared to captopril. Thus for the routine treatment of mild to moderate arterial hypertension, ramipril offers reliable antihypertensive efficacy in a once daily dose, thereby helping to improve patient compliance and making the treatment more economical.",1994.0,0,1
1507,7861706,Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members.,B J Barrett; R Foley; J Morgan; D Hefferton; P Parfrey,"We tested the hypothesis that overactivity of the renal and systemic renin-angiotensin system is important to the pathogenesis of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Up to 21 normotensive subjects with ADPKD and creatinine clearance > 70 ml/min/1.73 m2 were compared to 12 unaffected controls from the same families. Blood pressure, serum chemistry, sodium excretion, plasma renin and serum aldosterone and atrial natriuretic peptide (ANP) levels were measured at baseline, after acute sodium depletion, and after chronic higher sodium intake with and without enalapril. Effective renal plasma flow was measured by paraaminohippurate clearance in the higher sodium state, before and during an intravenous infusion of angiotensin II at 3 ng/kg/min. This was to test whether, by analogy to non-modulating essential hypertension, renal blood flow would fall to a lesser extent in the ADPKD subjects. The groups were comparable at baseline apart from a higher supine mean arterial pressure in the ADPKD group (median 91 vs. 81 mm Hg, P = 0.002). There were no significant differences between ADPKD and control subjects in blood pressure or hormonal response to sodium depletion. During chronically higher sodium intake, serum ANP was significantly higher (median 130 vs. 81 ng/liter, P = 0.0006) and plasma renin tended to be higher (median 20.5 vs. 13.5, P = 0.08) in ADPKD than in control subjects. The ADPKD group had a higher renal vascular resistance (median 7420 vs. 5915 dyn.sec.cm-5, P = 0.009) before angiotensin, but tended to have a lower percentage rise in resistance during angiotensin (median 31.5 vs. 46, P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1508,7866597,"The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results.",L Hansson; A Zanchetti,"The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter trial being conducted in 26 countries. Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular morbidity and mortality in hypertensive patients. In addition, the study will examine the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) or placebo. In the HOT Study, basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily. If target blood pressure is not reached, additional antihypertensive therapy with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent is given. Further dosage adjustments are made in accordance with a set protocol. As a fifth and final step, a diuretic may be added. Inclusion of patients was stopped on April 30, 1994. At that time 19,196 patients had been randomized. There were 9,055 (47%) women and 10,141 (53%) men with an average age of 61.5 +/- 7.5 (SD) years. At enrollment, 52% of patients were receiving antihypertensive treatment. These patients entered a wash-out period of at least 2 weeks before randomization. The average randomization blood pressure in untreated patients was 169 +/- 14/106 +/- 3 mmHg and in the treated patients 170 +/- 14/105 +/- 3 mmHg. On August 15, 1994, blood pressure data were available for 14,710 and 10,275 patients, who had completed 3 and 6 months treatment, respectively. The average reduction in diastolic blood pressure was 22 mmHg after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1509,7866603,Discordance of anti-ischemic and hemodynamic effects of captopril in stable coronary artery disease.,B R Winkelmann; G Matheis; P Kleist; S Pötter; D Wohltmann; M Kaltenbach,"The role of angiotensin converting enzyme (ACE) inhibition in patients with coronary artery disease without concomitant disease such as heart failure or hypertension has not been elucidated. In this double-blind, cross-over, randomized trial of the ACE inhibitor captopril, its antianginal and anti-ischemic effects were studied during monotherapy and in the presence of an organic nitrate. Thirty-seven patients (34 men, three women) with stable coronary artery disease and exercise-induced ST-segment depression were enrolled. After a washout phase without medication they received placebo, isosorbide dinitrate (ISDN) 20 mg twice daily, captopril 12.5 mg twice daily, and the combination of both for 1 week each, after which exercise tolerance, blood pressure and heart rate (supine, standing and 24 h profile), and peripheral arterial vasodilatation (finger pulse plethysmography) were assessed. Thirty-three patients completed all phases of the study. Exercise-induced anginal symptoms occurred in 17 patients, and asymptomatic ischemia was seen in the other 16 men. In comparison with ISDN, the anti-ischemic effects of captopril were minimal, despite a similar reduction in blood pressure. Compared with baseline, 1 week of placebo reduced the sum of ST-segment depression, the main efficacy parameter, by 10% (NS), captopril by 19% (NS), ISDN by 37% (P < 0.001) and the combination of captopril and ISDN by 42% (P < 0.001; NS versus ISDN). No patient remained completely free of exercise-induced angina during treatment with captopril; however, three patients after ISDN and seven patients after the combination did (P < 0.05). Blood pressure at rest decreased at peak effect by 9-10% systolic (P < 0.001) with monotherapy and by up to 7% diastolic (P < 0.001), and during combined therapy with captopril and ISDN by 18% systolic (P < 0.001) and 12% diastolic (P < 0.001). Significantly enhanced circulatory effects of captopril plus ISDN versus ISDN were found for blood pressure (P < 0.001) and peripheral arterial vasodilation (P < 0.01). The reflex tachycardia induced by ISDN in the upright position (5 beats/min) was not blocked by captopril during combined therapy. The antianginal and anti-ischemic effects of captopril alone were marginal, despite significant circulatory effects after short-term administration. Although captopril in combination with ISDN resulted in a significant further blood-pressure-lowering effect and increased peripheral arterial vasodilatation, the magnitude of potentiation of the anti-ischemic nitrate effects was, in contrast, small. Only exercise-induced angina was further improved by the use of the combination. No paradoxical worsening of ischemia or angina was seen after captopril. Thus, although captopril has no place as first-line therapy for ischemia, its use in combination with ISDN could be advantageous for long-term prognosis.",1994.0,0,0
1510,7867683,Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects.,J X Sun; A Cipriano; K Chan; V A John,"Pharmacokinetic interaction between benazepril (ACE inhibitor) and amlodipine (calcium channel blocker) was studied in 12 healthy subjects. Single doses of benazepril hydrochloride (10-mg tablet) and amlodipine besylate (tablet equivalent to 5 mg amlodipine) were administered alone or in combination according to a three-way, Latin-Square, randomized cross-over design. Serial blood samples were collected following each administration for the determination of benazepril and its active metabolite benazeprilat and amlodipine. The mean values of AUC (0-4 h), Cmax and Tmax for benazepril given as combination versus given alone were 161 vs 140 ng.h.ml-1, 168 vs 149 ng.ml-1, and 0.5 vs 0.6 h. The mean values of AUC (0-24 h), Cmax and Tmax for benazeprilat after benazepril given as combination versus given alone were 1470 vs 1410 ng.h.ml-1, 292 vs 257 ng.ml-1, and 1.7 vs 1.5 h. The mean values of AUC (0-144 h), Cmax and Tmax for amlodipine given as combination versus given alone were 118 vs 114 ng.h.ml-1, 2.5 vs 2.3 ng.ml-1, and 8.3 vs 9.0 h. The differences in these pharmacokinetic parameters between the combination and monotherapy treatments were not statistically significant based on ANOVA. The results of this study indicate that no pharmacokinetic interaction existed between the two drugs.",1994.0,0,0
1511,7868871,Does lipophilicity of angiotensin converting enzyme inhibitors selectively influence autonomic neural function in human hypertension?,R A Wu; M T Kailasam; J H Cervenka; R J Parmer; B P Kennedy; M G Ziegler; D T O'Connor,"Angiotensin II has both central nervous system and peripheral effects on autonomic function. Ramipril is among the more lipophilic angiotensin converting enzyme (ACE) inhibitors, and hence can penetrate the central nervous system readily. We investigated whether rampiril has selective effects on autonomic control of the circulation in human hypertension, compared with the more hydrophilic ACE inhibitor enalapril. Blood pressure, hemodynamics and measurements of autonomic function were obtained in 13 essential hypertensive subjects after 10 days on placebo, and after crossover monotherapy with 10 days on enalapril versus 10 days on ramipril. Both enalapril and ramipril lowered systolic, diastolic and mean arterial blood pressures significantly, with no reflex increase in heart rate. Plasma renin activity increased substantially on each of the ACE inhibitors. There were no significant effects of either agent on plasma catecholamines (norepinephrine or epinephrine) or chromogranin A, biochemical indices of efferent sympatho-adrenal outflow. There were also no significant changes after either agent in baroreflex sensitivity (to high- and low-pressure stimuli), the response to cold stress or sympathetic (alpha-adrenergic) participation in blood pressure maintenance. There was a marginal effect of ACE inhibition on alpha 1-adrenergic pressor sensitivity, but the two compounds did not differ significantly in this respect. Autonomic control of circulatory function was maintained well after either lipophilic (ramipril) or hydrophilic (enalapril) ACE inhibitors, and the lipophilic compound ramipril had no additional effects on autonomic function beyond those shown by the hydrophilic agent enalapril.",1994.0,0,0
1512,7869013,Efficacy and acceptability of perindopril in essential hypertension.,A Sukonthasarn; R Ratanaprakarn; B Koanantakul; P Ngam-Ukos,"The clinical efficacy and acceptability of once-daily perindopril (4 to 8 mg) monotherapy and in combination with hydrochlorothiazide (50 mg/day) was studied in mild to moderate stable essential hypertensive patients in 4 centres in Thailand. After 2-4 weeks of placebo run-in period, patients received active treatment for 3 months starting with 4 mg perindopril once daily. Dose titration was at second and third month of active treatment if the supine DBP was > 90 mmHg. The dose was doubled and if necessary, 50 mg/day hydrochlorothiazide was added in the last month. The results in 95 patients showed that the mean reduction in supine SBP/DBP at 1, 2 and 3 months of treatment was 10.3/8.0, 13.2/8.7 and 19.1/13.7 mmHg respectively. At the end of the study, 80 per cent of the patients showed normalisation of the supine diastolic blood pressure (supine DBP < or = 90 mmHg) with 30 per cent receiving combined therapy of perindopril and hydrochlorothiazide. There was no significant change in routine haematology or serum biochemistry except for slight increase of potassium levels in patients receiving 8 mg perindopril monotherapy. The incidence of side effects and withdrawal from treatment were quite low. Cough was the major side effect reported comprising 13.6 per cent with only 1 case withdrawn. The study confirms the previous studies that perindopril had satisfactory antihypertensive efficacy and acceptability profiles.",1994.0,0,0
1513,7869731,"Evaluation by 24-hour ambulatory blood pressure monitoring of efficacy of benazepril 20 mg plus hydrochlorothiazide 25 mg fixed combination as compared to captopril 50 mg [corrected] plus hydrochlorothiazide 25 mg fixed combination in treating mild to moderate hypertension: a double-blind, within-patient, placebo-controlled study.",R Fogari; A Zoppi; F Tettamanti; D Tettamanzi; P Lusardi; M Motolese,"In a double-blind, placebo-controlled, three-period cross-over, randomized study we evaluated the efficacy and tolerability of a fixed combination of benazepril 20 mg and hydrochlorothiazide 25 mg (BN + HCT) as compared with the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg (CP + HCT) by ambulatory blood pressure monitoring (ABPM) in patients with mild to moderate hypertension. Eighteen outpatients, 16 men and 2 women aged 41-58 years, were randomized to receive BN + HCT, CP + HCT, or placebo, all administered once daily for 4 weeks according to a three-period cross-over arranged in a 3 x 3 latin square design. Patients were checked after an initial 3-week washout period and every 4 weeks thereafter. At each visit, 24-h ABPM was performed by a noninvasive device (Spacelabs 5300); causal BP and heart rate (HR) were also measured. Both fixed combinations had a clear-cut antihypertensive effect in comparison with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1514,7871179,"Cost-effectiveness analysis in heart disease, Part III: Ischemia, congestive heart failure, and arrhythmias.",J Kupersmith; M Holmes-Rovner; A Hogan; D Rovner; J Gardiner,"Cost-effectiveness analyses were reviewed in the following diagnostic and treatment categories: acute myocardial infarction (MI) and diagnostic strategies for coronary artery disease (CAD), coronary artery bypass graft (CABG) surgery, percutaneous transluminal coronary angioplasty (PTCA), congestive heart failure (CHF), and arrhythmias. In the case of acute MI, coronary care units, as presently used, are rather expensive but could be made much more efficient with more effective triage and resource utilization; reperfusion via thrombolysis is cost-effective, as are beta-blockers and angiotensin-converting enzyme (ACE) inhibitors post-MI in appropriate patients. Cost-effectiveness of CAD screening tests depends strongly on the prevalence of disease in the population studied. Cost-effectiveness of CABG surgery depends on targeting; eg, it is highly effective for such conditions as left-main and three-vessel disease but not for lesser disease. PTCA appears to be cost-effective in situations where there is clinical consensus for its use, eg, severe ischemia and one-vessel disease, but requires further analysis based on randomized data; coronary stents also appear to be cost-effective. In preliminary analysis, ACE inhibition for CHF dominates, ie, saves both money and lives. Cardiac transplant appears to be cost-effective but requires further study. For arrhythmias, implantable cardioverter defibrillators are cost-effective, especially the transvenous device, in life-threatening situations; radiofrequency ablation is also cost-effective in patients with Wolff-Parkinson-White syndrome apart from asymptomatic individuals; and pacemakers have not been analyzed except in the case of biofascicular block, where results were variable depending on the situation and preceding tests.",1995.0,0,0
1515,7872342,Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor.,M Kohno; T Horio; K Yokokawa; K Yasunari; M Ikeda; M Minami; N Kurihara; T Takeda,"Secretion of brain natriuretic peptide (BNP), a cardiac hormone, is accelerated via hypertrophied ventricles in experimental hypertension. The present study examined whether regression of left ventricular (LV) hypertrophy by long-term treatment with an angiotensin-converting enzyme inhibitor (ACEI) affects plasma BNP concentration in patients with essential hypertension. Thirty-one hypertensive patients with LV hypertrophy were treated with ACEI (16 with enalapril; 15 with lisinopril) for 1 year. Serial changes were recorded in LV mass index, LV systolic function, and plasma concentrations of BNP and atrial natriuretic peptide (ANP). ACEI therapy significantly reduced LV mass index at 6 months, and more so at 1 year. Septal and posterior wall thicknesses were also reduced. Plasma BNP and ANP were markedly elevated at study entry, but only BNP levels correlated with LV mass index. Both peptide levels declined after 6 months, and this decline was enhanced at 1 year. There was a close relation between BNP decline and LV mass index reduction overall and with enalapril and lisinopril separately. Changes in ANP and in LV mass index were not related. Long-term ACEI therapy can reduce elevated plasma BNP. In this study, changes in BNP reflected the magnitude of regression of LVH. Plasma BNP may be a useful marker for LVH during antihypertensive therapy in patients with essential hypertension and LVH.",1995.0,0,0
1516,7875757,Lisinopril improves aortic compliance and renal flow. Comparison with nifedipine.,H Shimamoto; Y Shimamoto,"We compared the systemic and regional hemodynamic effects of nifedipine and lisinopril in 26 elderly hypertensive patients with the use of the pulsed Doppler ultrasound technique. Nifedipine is a dihydropyridine calcium antagonist, and lisinopril is an angiotensin-converting enzyme inhibitor. The study had a single-blind crossover design: nifedipine and lisinopril were given for 8 weeks each after washout periods of 4 weeks. Both nifedipine and lisinopril significantly reduced mean arterial pressure to the same extent (P < .01); cardiac output remained unchanged in both nifedipine- and lisinopril-treated groups. Lisinopril increased renal flow significantly (P < .01), but nifedipine did not. Common carotid, vertebral, celiac, and superior mesenteric arterial and diaphragmatic and terminal aortic flows did not show a significant change with either nifedipine or lisinopril. The specific action of lisinopril on the thoracic aorta was a marked improvement of aortic compliance compared with nifedipine, which might be partly responsible for an increase in renal flow. Lisinopril may provide more desirable regional hemodynamic effects and additional benefits for elderly hypertensive patients.",1995.0,0,0
1517,7876404,Angiotensin-converting enzyme inhibitors and cough: a prospective evaluation in hypertension and in congestive heart failure.,D Ravid; M Lishner; R Lang; M Ravid,"Angiotensin-converting enzyme inhibitors (ACE-I) have become the mainstem of antihypertensive therapy and first-choice agents for vasodilatation in congestive heart failure (CHF). A typical dry cough is the main cause for discontinuation of ACE-I therapy. Data about the incidence, course, and clinical significance of this side effect are conflicting. This study determined the incidence of cough in ACE-I treated patients with hypertension and with CHF and to appreciate its clinical significance; 268 ACE-I treated patients, 164 with hypertension and 104 with CHF were prospectively followed for at least 1 year and specifically questioned about cough and other side effects. In those in whom cough developed, a second and then a third ACE-I were tried. Cough developed in 50 (18.6%) of the 268 patients; 23 patients with hypertension (14%) had coughs 24.7 +/- 17.1 (SD) weeks after initiation of therapy; 27 patients with CHF (26%) had coughs 12.3 +/- 12 (SD) weeks after the start of ACE-I therapy (P = 0.005). All but three patients had coughs also on the second and third ACE-I. The time from the beginning of therapy to the onset of cough was significantly shorter with the second than the first drug. ACE-I agents had to be discontinued in 50% of the patients in whom coughs developed, most of them in the CHF group. In the others, cough was well tolerated or disappeared during subsequent months. The incidence of cough, which necessitated discontinuation of ACE-I treatment, was 4% among patients with hypertension and 18% among patients with CHF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1518,7877194,Effects of captopril and nadolol on renal hemodynamics in patients with essential hypertension.,Z H Zhu; R An; Y X Zhang; P L Gong; H Chen; F D Zen,"The randomized single-blind study was designed to compare the effects of captopril (Cap) and nadolol (Nad) on renal hemodynamics in 60 patients with essential hypertension. They were divided into two groups at random. Cap was given in dosage of 37.5-75 mg/d per os and Nad 40-80 mg/d. The results show that both drugs increase the blood volume distributed to the kidneys from cardiac output (renal blood flow/cardiac output), Cap increasing 10% (P < 0.05) and Nad 8% (P < 0.05). Renal vascular resistance (RVR) is lowered by the two drugs, 13% (P < 0.05) by Cap and 11% (P < 0.05) by Nad. These suggest that both drugs facilitate the maintenance of renal blood circulation in patients with essential hypertension, being beneficial for long-term treatment of hypertension.",1994.0,0,0
1519,7877544,Efficacy of pravastatin in combination with captopril in hypertensive patients.,C J O'Callaghan; H Krum; E L Conway; W Lam; M A Skiba; L G Howes; W J Louis,"To determine the efficacy of pravastatin in the treatment of primary hypercholesterolaemia in patients being treated with captopril for hypertension. A double-blind parallel group study comparing 12 weeks of pravastatin therapy (20-40 mg/day) with placebo. 25 patients (age, 37-73 years) with mild-to-moderate hypertension and hypercholesterolaemia (total cholesterol level, 5.5-8.8 mmol/L). Pravastatin reduced total cholesterol levels by 22% (from 7.1 +/- 0.29 [SEM] to 5.5 +/- 0.25 mmol/L; P < 0.001) and low-density-lipoprotein cholesterol levels by 32% (from 5.0 +/- 0.32 to 3.4 +/- 0.28 mmol/L; P < 0.001) in four weeks and these levels were maintained for the 12 weeks of therapy. Pre-pravastatin values returned three weeks after stopping therapy. Levels of total cholesterol, cholesterol fractions and triglycerides remained constant or deteriorated in the placebo group. Pravastatin therapy was well tolerated. An integrated coronary risk score showed a 40% reduction in risk. This study indicates that pravastatin (combined with captopril) is an effective cholesterol-lowering drug, but that treatment needs to be maintained.",1995.0,0,0
1520,7882821,Effect of fosinopril on cardiac and metabolic parameters in patients with NIDDM.,I M Holdaway; G D Gamble; G A Sanders; S C Greaves; E M Ellis-Pegler; N Sharpe,"To determine whether the angiotensin-converting enzyme (ACE) inhibitor fosinopril can favorably alter cardiac function in non-insulin-dependent diabetes mellitus NIDDM) patients who have either normal blood pressure (BP) or mild, untreated hypertension. Fifty-five NIDDM subjects with normal BP or mild, untreated hypertension were randomized to treatment with the ACE-inhibitor fosinopril or placebo for 6 months in a randomized, double-blind trial to determine the effect of fosinopril on echocardiographic measurements. Left ventricular mass index (LVMI) fell by 6.5 +/- 4.7% (mean +/- SD) with fosinopril and increased by 8.6 +/- 3.5% during placebo treatment (P < 0.02), and isovolumic relaxation time improved significantly in those with elevated baseline levels (P = 0.02). Systolic BP fell significantly, but this did not correlate with the change in LVMI, suggesting a possible direct action of fosinopril on the heart. Fosinopril appears to have significant cardiac benefits in patients with NIDDM who have normal or mildly elevated BP. These benefits are achieved without adversely affecting renal status and without impairing metabolic control of diabetes.",1994.0,0,0
1521,7882823,Enhanced pressor responsiveness to norepinephrine in type II diabetes. Effect of ACE inhibition.,A Ciavarella; A Mustacchio; C Ricci; M Capelli; P Vannini,"To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on the pressor responsiveness to norepinephrine in type II diabetes. Eight normotensive subjects, eight mild-to-moderate hypertensive type II diabetic patients, and eight nondiabetic patients with essential hypertension were studied before and after 4 weeks of being administered enalapril. The pressor response to norepinephrine was assessed by infusing the hormone in an antecubital vein at incremental doses of 30 ng.kg-1.min-1 for periods of 5 min until reaching an increase of 20 +/- 2 mmHg in mean arterial pressure (MAP) measured by an automatic device at 1-min intervals. An effective dosage of norepinephrine that increased MAP by 20 mmHg (EDNE 20) was thereafter calculated. Before and during the last minute of norepinephrine infusion at maximum dosage, a venous blood sample was drawn to determine plasma renin activity (PRA), aldosterone, and norepinephrine levels. In the three groups of patients, blood pressure and aldosterone were reduced while PRA was raised following ACE inhibition. Basal and maximum postinfusion levels of norepinephrine were not modified by enalapril. The EDNE 20 was basally lower in diabetic patients and remained unchanged after ACE inhibition, contrary to that observed in nondiabetic patients with essential hypertension. Both normotensive and hypertensive type II diabetic patients have an increased pressor responsiveness to norepinephrine that is not modified by therapeutic doses of enalapril, contrary to what is observed in nondiabetic patients with essential hypertension.",1994.0,0,0
1522,7884789,Combined effect of a low fat diet and doxazosin on blood pressure control and blood lipids. Hunter Hypertension Research Group.,,"Doxazosin, a once daily alpha-blocking drug has been demonstrated to reduce both BP and hyperlipidaemia, related risk factors for premature vascular disease. This study was designed to see if a low fat diet altered the favourable effect of doxazosin on blood lipids in adults with mild to moderate hypertension and mild to moderate hypercholesterolaemia (5.6-8.0 mmol/l). Following a six week period on a low fat diet, patients were randomly allocated to additional doxazosin (2-8 mg/day) or enalapril (5-20 mg/day) treatment for a further 10 weeks. Forty-four of 55 subjects completed the study. A low fat diet reduced mean body weight by 2 kg without significantly altering blood lipids (total and HDL cholesterol, triglycerides). Doxazosin (4.5 +/- 2.9 mg/day) and enalapril (12.5 +/- 6.5 mg/day) produced a comparable lowering of sitting and standing BP at all visits and also produced similar 24h BP control. The expected increase in HDL cholesterol concentration previously noted in this patient population in association with doxazosin treatment was not detected suggesting that the low cholesterol-high carbohydrate diet, at least acutely, attenuates this potentially beneficial effect on plasma lipids. In summary, doxazosin has a comparable tolerability and BP lowering ability to enalapril. However, its ability to increase HDL cholesterol may be reduced in patients on low fat diets.",1994.0,0,0
1523,7884791,Long-term efficacy and safety of moexipril in the treatment of hypertension.,W B White; A A Fox; M Stimpel,"The purpose of this study was to assess the long-term efficacy and safety of moexipril, a new angiotensin-converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in patients with hypertension. The patient population consisted of 281 hypertensive men and women, 30-84 years old, with seated diastolic BP between 95 and 114 mmHg. The study was a two year multicenter (22 centers), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse side-effects and laboratory studies were assessed following moexipril dosing at 7.5, 15 or 30 mg once daily or 15-30 mg daily in combination with 12.5 mg hydrochlorothiazide if the DBP was > or = 90 mmHg. The primary measure of efficacy was change from baseline in seated DBP. Secondary outcome measures included changes in seated SBP, heart rate, laboratory parameters and subjective complaints. Following one year of therapy in 183 patients, the BP fell 13/14 mmHg among patients receiving moexipril monotherapy and 18/15 mmHg those receiving combined therapy compared with baseline (P < 0.001 for both). After two years of treatment, reductions were similar in 161 patients. Forty-four (16%) patients were prematurely withdrawn from the study because of inadequate therapeutic response and 34 (12%) secondary to adverse experiences. There were no changes in pulse rate or postural BP reductions. Four adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril: fatigue (3%), headache (2%), dizziness (3%) and increased cough (5%).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
1524,7885123,"Oral captopril versus placebo among 13,634 patients with suspected acute myocardial infarction: interim report from the Chinese Cardiac Study (CCS-1)",,"13,634 patients entering 650 Chinese hospitals up to 36 h after the onset of suspected acute myocardial infarction (MI) were randomised between one month of oral captopril (6.25 mg initial dose, 12.5 mg 2 h later, and then 12.5 mg three times daily) or matching placebo. Captopril was associated with a non-significant reduction in 4-week mortality (617 [9.05%] captopril-allocated vs 654 [9.59%] placebo-allocated deaths; 2p = 0.3). There was a significant excess of hypotension, mostly early after the start of treatment, but no evidence of any adverse effect on early mortality (even among patients who were hypotensive at entry). Taken together with the other trials of converting enzyme inhibitors started early in acute MI, these results indicate that such therapy is generally safe and typically prevents about 5 deaths per 1000 patients treated for the first month.",1995.0,0,1
1525,7885524,Treatment of patients with IVCS and gross oedema and ascites with diuretic combination and ACE-inhibitors: relation to baseline PRA and PAC.,A A Van Vliet; R Kröger; R Dubbelman; W W Ten Bokkel-Huinink,"(1) To assess plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in patients with inferior vena cava syndrome (IVCS). (2) To study in an open fashion the efficacy of loop diuretic treatment, single, or in combination with an ACE-inhibitor or with spironolactone. In 13 patients PRA and PAC were measured and related to urinary sodium excretion (UNa). Highly elevated PRA and PAC were found in recently developed IVCS. The correlation coefficient between PAC and UNa was -0.61, p < 0.05. In 10 patients the influence of captopril (C)] at maximum tolerable doses with or without furosemide (F) was evaluated. Mean tolerated dose of C amounted to 8.8 mg t.i.d. (range 2-25), achieving a PAC reduction of 26%. Efficacy of F was severely blunted when PAC exceeded the low-normal range. Spironolactone addition at 100 mg/day in non-responders to F or to F and C, induced immediate natriuretic responses except in a patient with 7-70 fold increase in PAC. (1) In IVCS loop diuretic efficacy is attenuated by aldosterone activation; (2) complete aldosterone suppression with captopril is difficult to achieve due to dose restriction; (3) spironolactone is favoured for a synergistic response.",1995.0,0,0
1526,7885528,Chronic hepatitis caused by lisinopril.,H T Droste; R A de Vries,ACE inhibitors are used world-wide for treatment of hypertension and cardiac failure; liver damage is a rare but potentially severe side-effect of these drugs. In this case report we describe a patient with chronic liver damage due to lisinopril.,1995.0,0,0
1527,7887385,Effects of fosinopril on exercise tolerance and clinical deterioration in patients with chronic congestive heart failure not taking digitalis. Fosinopril Heart Failure Study Group.,E J Brown; P H Chew; A MacLean; K Gelperin; J P Ilgenfritz; M Blumenthal,"A total of 241 men and women with mild to moderately severe chronic heart failure (New York Heart Association functional class II [90%] or III) and a mean (+/- SD) left ventricular ejection fraction of 25 +/- 7%, entered a 24-week, prospective, double-blind, placebo-controlled trial of 10 or 20 mg/day of fosinopril, a phosphinic acid angiotensin-converting enzyme inhibitor. Patients received concomitant diuretic therapy but not digitalis. Primary end points were mean change in maximal treadmill exercise time and occurrence of prospectively defined clinical events indicative of worsening heart failure (most to least severe): death, withdrawal for worsening heart failure, hospitalization for worsening heart failure, need for supplemental diuretic or emergency room visit for worsening heart failure, and no event. At study end point, treadmill exercise time had improved in the fosinopril versus the placebo group (+28.4 vs -13.5 seconds, p = 0.047). New York Heart Association functional class had improved at end point more frequently (24% vs 13%) and deteriorated less frequently (18% vs 32%) in the fosinopril group (p = 0.003). More patients treated with fosinopril (66% vs 50%) remained free of clinical events indicative of worsening heart failure, and fosinopril-treated patients had less severe clinical events (p = 0.004). Dyspnea, fatigue, and paroxysmal nocturnal dyspnea improved more often and worsened less often in this group (p < or = 0.002), and edema showed a trend toward improvement (p = 0.088). These clinical benefits did not require concomitant digitalis therapy. Fosinopril was associated with an acceptable safety profile.",2001.0,0,1
1528,7888377,Pemphigus vulgaris induced by captopril.,A Butt; S M Burge,,1995.0,0,0
1529,7889195,Role of the renin-angiotensin system in hypertension in the elderly.,M Nagano; J Higaki; H Mikami; T Ogihara,"Although the activity of the renin-angiotensin system is known to decrease with age, the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in the elderly. To examine the role of the renin-angiotensin system in hypertension in the elderly, we evaluated the antihypertensive response to enalapril and to TCV-116, an angiotensin II type-1 receptor antagonist, in elderly patients with essential hypertension. A single oral dose of enalapril (10 mg) increased plasma renin activity (PRA) and reduced the angiotensin II concentration, whereas a single oral dose of TCV-116 (4 mg) increased both PRA and the angiotensin II concentration. Blood pressure was significantly reduced by these drugs from 4 h after administration. Basal levels of PRA and angiotensin II declined with age. However, the changes in blood pressure produced by either TCV-116 or enalapril did not correlate with age. These results suggest that the activity of the renin-angiotensin system in plasma declines with age, and that the extrarenal renin-angiotensin system may play a role in hypertension in the elderly.",1994.0,0,0
1530,7891796,Effect of long-term therapy with captopril on proteinuria and renal function in patients with non-insulin-dependent diabetes and with non-diabetic renal diseases.,H H Liou; T P Huang; V M Campese,"Several studies have shown that long-term therapy with angiotensin-converting enzyme inhibitors may reduce urinary protein excretion and decrease the rate of progression of renal disease in patients with insulin-dependent diabetes mellitus more effectively than conventional antihypertensive drugs. Only few studies, however, have been performed in patients with non-insulin-dependent diabetes mellitus (NIDDM). To compare the effects of captopril with more conventional drugs on proteinuria and progression of renal disease, we conducted a prospective, 18-month study in 42 proteinuric (> 500 mg/day) NIDDM and, for comparison, in 31 nondiabetic patients with a variety of renal diseases (NDRD). Twenty-four NIDDM patients were treated with captopril and 18 with conventional drugs. Eighteen NDRD patients received captopril, and 13 received conventional drugs. Baseline proteinuria and glomerular filtration rate (GFR) were not different among groups. The blood pressure decreased equally in all group of patients, irrespective of whether they received captopril or conventional drugs. Urinary protein excretion, however, decreased significantly only in NIDDM and NDRD patients treated with captopril. The GFR decreased only in patients treated with conventional drugs, but not in those treated with captopril. The rate of decline in GFR in NIDDM patients treated with captopril was significantly lower than in patients treated with conventional drugs. However, in NDRD patients treated with captopril, the rate of decline in GFR was not different from that in patients treated with conventional drugs. The reduction of urinary protein excretion was poorly correlated with changes in blood pressure or with changes in renal function and renal hemodynamics. Serum potassium increased significantly in patients treated with captopril.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
1531,7899882,Pleural and mediastinal disorders related to drug use.,W T Miller,The full range of mediastinal and pleural effects of a variety of drugs both therapeutic and illicit has been reviewed. The importance of clinical information in making the diagnosis of these drug-induced disorders is emphasized.,2001.0,0,0
1532,7900628,Angiotensin-converting enzyme inhibitors and beta-blockers in long-term treatment of dilated cardiomyopathy.,V Regitz-Zagrosek; B Leuchs; J Krülls-Münch; E Fleck,"This double-blind, randomized, long-term study investigated the effects of the angiotensin-converting enzyme inhibitor enalapril and the beta-blocker metoprolol on clinical, hemodynamic, angiographic, and neurohormonal parameters in patients with dilated cardiomyopathy and moderate cardiac functional impairment (left ventricular ejection fraction [LVEF] 35% +/- 6%). After 12 months of treatment, a 12% reduction in 24-hour heart rate was observed in both groups (p < 0.05), whereas heart rate during exercise was reduced only in the metoprolol group. Echocardiographic fractional shortening increased (enalapril: 17% +/- 6% to 21% +/- 7%; metoprolol: 21% +/- 9% to 29% +/- 7%; both p < 0.05), as did the angiographic LVEF (enalapril: 35% +/- 7% to 43% +/- 12%, p = 0.1; metoprolol: 34% +/- 7% to 44% +/- 9%, p < 0.05), whereas ventricular volume decreased. Initially, both groups were comparable in terms of all parameters investigated. After 12 months fractional shortening was greater, and the heart rate at 50 W was lower in the beta-blocker group. At the doses used, the effect of the beta-blocker on dilated cardiomyopathy with moderate functional impairment was at least as great as that of the angiotensin-converting enzyme inhibitor.",1995.0,0,0
1533,7903217,Comparative renal and cardiac effects of tertatolol and enalapril in essential hypertension.,J Ribstein; G Du Cailar; R Brouard; A Mimran,"The influence of a 3-month antihypertensive treatment on cardiac structure and renal function was assessed in patients with uncomplicated essential hypertension randomly allocated to treatment by the nonselective beta-blocker tertatolol or the angiotensin-converting enzyme inhibitor enalapril. Both tertatolol and enalapril treatments were associated with a similar decrease in mean arterial pressure (-26 +/- 6 and -15 +/- 2 mm Hg, respectively, both p < 0.05 in comparison with baseline values) and left ventricular mass (echocardiography: -48 +/- 17 vs. -18 +/- 6 g) but no change in glomerular filtration rate (DTPA clearance). Renal vascular resistance decreased similarly in both groups. Urinary albumin excretion was not significantly modified in either group. These results indicate that a consistent reduction in arterial pressure by either treatment was associated with a proportional change in left ventricular geometry and no alteration in renal function.",1993.0,0,1
1534,7904616,Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature.,M K Kuechle; E Stegemeir; B Maynard; L E Gibson; K M Leiferman; M S Peters,"Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure. Our purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type. Six patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS). Histopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug. Drug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.",1994.0,0,0
1535,7906178,Critical review of data supporting affective disorder caused by nonpsychotropic medication.,T D Long; R G Kathol,"Since the first reports of depressions associated with the use of reserpine, reports of affective syndromes related to the use of medications have proliferated in the literature. We chose to review controlled and uncontrolled studies, comprehensive reviews with comparisons of controlled studies, and case reports where sheer numbers indicated a relationship existed between affective syndromes and nonpsychotropic medications. Our findings suggest a relationship between the use of reserpine or lipophilic beta-blockers and depressive symptoms, but no clear evidence to support such a relationship with alpha-methyldopa, clonidine, calcium-channel blockers, or ACE-inhibitors. Glucocorticoids are related to both depressive symptoms and mania. Patients on anabolic steroids should be monitored for evidence of mania, rage, depression, and suicidality. There is no clear evidence that oral contraceptives are related to depressive symptoms. Our review does not support a close relationship between the use of H2 blockers, anticonvulsants, levodopa or antiarrhythmics, or antibiotics to affective syndromes.",1993.0,0,0
1536,7908164,"Progression of left ventricular dysfunction secondary to coronary artery disease, sustained neurohormonal activation and effects of ibopamine therapy during long-term therapy with angiotensin-converting enzyme inhibitor.",M F Rousseau; M A Konstam; C R Benedict; J Donckier; L Galanti; J Melin; D Kinan; S Ahn; J M Ketelslegers; H Pouleur,"Left ventricular function and neurohormonal status in patients with heart failure remaining symptomatic during therapy with angiotensin-converting enzyme inhibitors were assessed, and the effects of dopaminergic receptor stimulation in this setting were determined. Neurohormonal and left ventricular function (radionuclide angiography) data were obtained in 19 patients with symptomatic ischemic heart failure. Measurements were repeated after 4 to 6 weeks of therapy with the dopamine agonist ibopamine (100 mg, 3 times/day) or placebo administered in a double-blind, randomized, parallel group design. At baseline, despite therapy with enalapril, the angiotensin II levels (mean 39.4 pg/ml; p < 0.01 vs controls) were significantly increased, as were plasma norepinephrine (497 +/- 240 pg/ml; p < 0.01 vs controls), endothelin-1, atrial natriuretic peptide and arginine vasopressin. Moreover, in comparison with pretreatment values, left ventricular ejection fraction had decreased substantially (-9.1%) in patients with plasma norepinephrine > or = 600 pg/ml, but not in those with lower values of norepinephrine. With ibopamine, plasma norepinephrine decreased from 516 +/- 241 to 391 +/- 208 pg/ml (n = 8; p < 0.025 vs placebo), whereas it increased with placebo. In conclusion, the neurohormonal control provided by an angiotensin-converting enzyme inhibitor is reduced in a large subset of patients during prolonged therapy; ibopamine appears to be a potentially useful drug to improve neurohormonal control in this setting.",1994.0,0,0
1537,7908910,Immunohistochemical study of graft-versus-host reaction (GVHR)-type drug eruptions.,J Osawa; K Kitamura; S Saito; Z Ikezawa; H Nakajima,"Skin biopsies of graft-versus-host reaction (GVHR)-type drug eruptions in the acute phase were compared immunohistochemically with those in the chronic phase and also with non-GVHR type drug eruptions in the acute phase. Predominance of CD8+ T cells in the epidermal infiltrates, reduction in the number of epidermal OKT6+ dendritic cells (Langerhans cells), and increased expression of HLA-DR and ICAM-1 on keratinocytes were observed in the acute phase of GVHR-type, but not in either the chronic phase of GVHR-type or the acute non-GVHR type. These findings were similar to those of previous reports on skin lesions of acute GVH disease (GVHD) seen after bone marrow transplantation. Therefore, immunohistochemistry is not useful for differential diagnosis between acute GVHR-type drug eruptions and acute cutaneous GVHD. These findings also indicate that similar immunomechanisms may be involved in the pathogenesis of both GVHR-type drug eruptions and cutaneous GVHD.",1994.0,0,0
1538,7910229,GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico.,,"GISSI-3 is a multicentre randomised clinical trial to assess the efficacy of lisinopril, transdermal glyceryl trinitrate (GTN), and their combination in improving survival and ventricular function after acute myocardial infarction (AMI). Between June, 1991, and July, 1993, 19,394 patients were randomised from 200 coronary care units in Italy. Eligible patients presented within 24 h of symptom onset and had no clear indications for or against the study treatments. In a factorial design patients were randomly assigned 6 weeks of oral lisinopril (5 mg initial dose and then 10 mg daily) or open control as well as nitrates (intravenous for the first 24 h followed by transdermal GTN 10 mg daily) or open control. Complete clinical data and 6-week follow-up were available for 18,895 (97.4%) patients randomised. Two-dimensional echocardiographic data were available for 14,209 patients. Overall 6-week mortality was 6.7%. Lisinopril, started within 24 h from AMI symptoms, produced significant reductions in overall mortality (odds ratio 0.88 [95% CI 0.79-0.99]) and in the combined outcome measure of mortality and severe ventricular dysfunction (0.90 [0.84-0.98]). In the same trial the systematic administration of transdermal GTN did not show any independent effect on the same outcome measures (0.94 [0.84-1.05] and 0.94 [0.87-1.02]). Systematic combined administration of lisinopril and GTN also produced significant reductions in overall mortality (0.83 [0.70-0.97]) and in the combined endpoint (0.85 [0.76-0.94]). The favourable effect of lisinopril alone or with GTN was clear also in the predefined high-risk populations (elderly patients and women) for the combined endpoint. These findings were obtained in a population intensively exposed to recommended treatments (thrombolysis 72%, beta-blockade 31%, and aspirin 84%); non-protocol treatment with angiotensin-converting-enzyme inhibitors and nitrates was allowed for specific clinical indications. No excess of unfavourable clinically relevant events in the treated groups was reported.",1994.0,1,1
1539,7912475,Different effects between antihypertensive drugs on nephrotic-range proteinuria in renovascular hypertension.,T Ishimitsu; H Yagi; M Ohkubo; Y Nakamura; S Yagi,"A 61-year-old man developed renovascular hypertension characterized by nephrotic-range proteinuria. When he was treated with a calcium channel blocker, glomerular filtration fraction was 0.26 and massive proteinuria ranging from 10 to 15 g/day persisted. An angiotensin-converting enzyme inhibitor markedly reduced the proteinuria to 1-2 g/day with a filtration fraction of 0.20. After the antihypertensive drug was switched to a beta-blocker, the filtration fraction was 0.23 and urinary protein excretion was 3-4 g/day. Blood pressure control was comparable by each drug. These findings suggest a role of intraglomerular hydraulic mechanism in the etiology of massive proteinuria in renovascular hypertension.",1994.0,0,0
1540,7913333,Cutaneous vasculitis.,R E Hiltz; T R Cupps,"Cutaneous vasculitis and vasculopathic processes continue to be difficult to define, diagnose, and treat. Historically, the complexity of these disorders has been compounded by imprecision in terminology and classification and the presence or absence of underlying systemic illness. Approaching the literature with consistent diagnostic constraints and accepted terminology can, it is hoped, eliminate some of the ambiguity. During the past year, several case reports and brief communications regarding cutaneous vasculitis or vasculopathies have appeared, as well as thoughtful basic science reports whose authors have attempted to further the understanding of the underlying pathophysiology. Recent technologic advances have produced recombinant cytokines, growth factors, and thrombolytics that have been used therapeutically for a variety of medical illnesses. The role of these agents in the treatment of cutaneous vasculitis and vasculopathies has varied from provocative in some to therapeutic in others. A number of these reports are discussed.",1994.0,0,0
1541,7913676,"Dermatology Days Symposium: Ocean City, Maryland: June 17-19, 1993.",M H Lowitt; J W Burnett,,1994.0,0,0
1542,7915733,Prognostic value of neurohumoral activation in patients with an acute myocardial infarction: effect of captopril.,J L Rouleau; M Packer; L Moyé; J de Champlain; D Bichet; M Klein; J R Rouleau; B Sussex; J M Arnold; F Sestier,"This study attempted to evaluate whether neurohumoral activation at the time of hospital discharge in postinfarction patients helps to predict long-term prognosis and whether long-term therapy with the angiotensin-converting enzyme inhibitor captopril modifies this relation. Neurohumoral activation persists at the time of hospital discharge in a large number of postinfarction patients. The Survival and Ventricular Enlargement (SAVE) study demonstrated that the angiotensin-converting enzyme inhibitor captopril improves survival and decreases the development of severe heart failure in patients with left ventricular dysfunction (left ventricular ejection fraction < or = 40%) but no overt postinfarction heart failure. In 534 patients in the SAVE study, plasma neurohormone levels were measured a mean of 12 days after infarction. Patients were then randomized to receive captopril or placebo and were followed up for a mean (+/- SD) of 38 +/- 6 months (range 24 to 55). The association between activation of plasma neurohormones at baseline and subsequent cardiovascular mortality or the development of heart failure was assessed with and without adjustment for other important prognostic factors. By univariate analysis, activation of plasma renin activity and aldosterone, norepinephrine, atrial natriuretic peptide and arginine vasopressin levels were related to subsequent cardiovascular events, whereas epinephrine and dopamine levels were not. By multivariate analysis, only plasma renin activity (relative risk 1.6, 95% confidence interval [CI] 1.0 to 2.5) and atrial natriuretic peptide (relative risk 2.2, 95% CI 1.3 to 3.8) were independently predictive of cardiovascular mortality, whereas the other neurohormones were not. Only plasma renin activity and aldosterone, atrial natriuretic peptide and arginine vasopressin were independent predictors of the combined end points of cardiovascular mortality, development of severe heart failure or recurrent myocardial infarction. Except for 1-year cardiovascular mortality, the use of captopril did not significantly modify these relations. Neurohumoral activation at the time of hospital discharge in postinfarction patients is an independent sign of poor prognosis. This is particularly true for plasma renin activity and atrial natriuretic peptide. Except for 1-year cardiovascular mortality, captopril does not significantly modify these relations.",1994.0,0,0
1543,7917078,Adverse effects of alpha 1-adrenergic blocking drugs.,S G Carruthers,"Earlier nonselective alpha 1-adrenergic blocking drugs such as phentolamine and phenoxybenzamine are now restricted to the pharmacological management of alpha 1-adrenergic crisis and phaeochromocytoma. Prazosin, the first selective alpha 1-blocker approved for the treatment of hypertension, became available in the mid-1970s. Additional alpha 1-blockers such as doxazosin and terazosin have been introduced during recent years. The undesirable effects of all members of this class are similar. Most adverse events can be attributed to reversible competitive antagonism of postsynaptic alpha 1-adrenergic receptors in tissues that sustain high levels of alpha-adrenergic sympathetic tone, e.g. resistance arteries, capacitance veins and the urinary bladder outflow tract. Orthostatic hypotension with a sensation of intense faintness and occasional syncope, can occur shortly after the initial dose. Aggravating factors include upright posture, intravascular volume depletion and concurrent administration of other medications that lower blood pressure, including all other classes of antihypertensive drugs. The problem is reduced or avoided by the choice of low starting doses, beginning treatment at bedtime and by minimising other risks. Among overall adverse effects, asthenia, dizziness, faintness and syncope predominate and occur in 10 to 20% of patients, leading to discontinuation of therapy in about half that number. Infrequent adverse events include headache, drowsiness, palpitations, urinary incontinence and priapism. Some patients experience a 1 to 2kg bodyweight gain which may be associated with secondary hyperaldosteronism. Tolerance appears to develop to the benefits of alpha 1-blockade in patients with congestive heart failure, but not in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1544,7917158,"Comparative effects of quinapril, atenolol, and verapamil on blood pressure and forearm hemodynamics during handgrip exercise.",J Cléroux; M Beaulieu; N Kouamé; Y Lacourcière,"We compared the effects of angiotensin-converting enzyme inhibition with quinapril to those of selective beta-blockade with atenolol and calcium channel blockade with verapamil in 10 hypertensive subjects in a randomized double-blind placebo-controlled crossover study. All antihypertensive agents reduced baseline mean arterial pressure equally and did not modify forearm vascular resistance compared to placebo. In response to sustained handgrip exercise, both quinapril and verapamil, but not atenolol, attenuated the pressor response. However, verapamil was associated with an exaggerated increase in forearm vascular resistance during handgrip, whereas quinapril did not alter this response compared to placebo. It is concluded that quinapril and verapamil reduce the pressor response during isometric exercise by quantitatively different effects on the vasoconstrictor response in, as well as outside of, skeletal muscles.",1994.0,0,0
1545,7919557,Cough induced by quinapril with resolution after changing to fosinopril.,M N Sharif; B L Evans; G B Pylypchuk,"To report a case of chronic, nonproductive cough secondary to the angiotensin-converting enzyme (ACE) inhibitor quinapril, with complete resolution after switching to another ACE inhibitor, fosinopril. All relevant articles from January 1985 through February 1993 were identified, primarily through MEDLINE search and review of pertinent articles' bibliographies. A 68-year-old woman developed a dry, irritating cough within one month of starting quinapril therapy for the treatment of essential hypertension. The patient was a nonsmoker with no respiratory illnesses. The cough continued for the duration of therapy with quinapril. One month after changing to fosinopril therapy, the patient reported complete resolution of the cough. She remains cough-free to date. Cough induced by ACE inhibitors is a frequently documented adverse effect. It is severe enough to require discontinuation of therapy in 1-10 percent of patients. The cough is considered to be a class-related adverse effect with cross-reactions between ACE inhibitors routinely reported. At this time, changing to another ACE inhibitor or additive therapy with nonsteroidal antiinflammatory drugs is not recommended. Discontinuation of the ACE inhibitor results in rapid alleviation of the cough, although this is not always necessary, as most patients may experience a cessation or decrease in cough. We report a case of cough following the administration of quinapril, with complete resolution after changing to the alternative ACE inhibitor fosinopril in a patient with essential hypertension. Cough has been encountered commonly after the administration of ACE inhibitors. Frequency of cough is variable and although this complication has been described as a class effect, patients with a persistent, severe ACE inhibitor-induced cough may benefit from a trial of fosinopril therapy. This may be particularly useful in patients unable to tolerate an alternative class of antihypertensive agents.",1994.0,0,0
1546,7923309,Effect of combination therapy with atenolol and the angiotensin-converting enzyme inhibitor benazepril.,M Bursztyn; I Gavras; L Gourley; J DeSilva; J Whalen; H Gavras,"The purpose of this study was to determine whether patients whose blood pressure failed to normalize while receiving monotherapy with atenolol would experience further blood pressure lowering by adding the angiotensin-converting enzyme (ACE) inhibitor benazepril hydrochloride to their treatment regimen. Seventy-four of the original 127 patients treated with atenolol met the criteria for entry into the 4-week, double-blind phase of the study, in which either benazepril 10 mg twice daily (increased after 1 week, if necessary, to 20 mg twice daily) or placebo was added to atenolol. At end point, 46% of the benazepril group had achieved an excellent or good response (ie, diastolic blood pressure [DBP] < 90 mm Hg or a decrease of > or = 10 mm Hg below the baseline) compared with 14% of the placebo group (P < 0.01). The mean fall in DBP at end point was -5.6 mm Hg in the benazepril group and -3.7 mm Hg in the placebo group. Because six patients in the benazepril group experienced an increase of blood pressure that offset the fall observed in the responders, the difference in DBP response between the benazepril group and the placebo group was not statistically significant. We conclude that adding benazepril to the regimen of patients whose blood pressure is inadequately controlled while receiving atenolol monotherapy can produce an additional decrease in blood pressure in almost half the patients.",1994.0,0,0
1547,7923656,Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators.,J D Rutherford; M A Pfeffer; L A Moyé; B R Davis; G C Flaker; P R Kowey; G A Lamas; H S Miller; M Packer; J L Rouleau,"In the Survival and Ventricular Enlargement (SAVE) trial, recurrent myocardial infarction (MI) was the most important predictor of a poor outcome and conferred a sevenfold increase in risk of death. The purpose of this study was to determine the predictors of recurrent MI in study participants and to examine the influence of the angiotensin-converting enzyme inhibitor captopril on this and other myocardial ischemic events. The 2231 patients had survived the acute phase of MI (3 to 16 days) and had a radionuclide ventricular ejection fraction < or = 40%. Patients were randomly assigned to receive double-blind treatment with either placebo or captopril and were followed for an average of 42 months. The influence of captopril on recurrent MI, cardiac revascularization procedures, and hospitalization with unstable angina was examined. The likelihood of recurrent MI was greater in patients with an MI or functional disability before the index infarction and higher systolic pressure (all P < .001) but was not influenced by baseline left ventricular ejection fraction. Therapy with captopril reduced the risk of development of recurrent MI by 25% (95% confidence intervals, 5% to 40%; P = .015) and the risk of death after recurrent MI by 32% (95% confidence intervals, 4% to 51%; P = .029). Captopril-assigned patients were also less likely to require cardiac revascularization procedures (P = .010), but hospitalization for unstable angina was unaltered. When all three of these major coronary ischemic events were considered together, captopril therapy reduced the risk (14% risk reduction; 95% confidence intervals, 0% to 26%; P = .047). In post-MI patients with asymptomatic left ventricular dysfunction, long-term administration of captopril reduced recurrence of MI and the need for cardiac revascularization but had no influence on the rate of hospitalization with a discharge diagnosis of unstable angina. The finding that the recurrence of MI was independent of left ventricular ejection fraction suggests that captopril could be useful in preventing recurrent MI in patients with more preserved left ventricular function. The need for cardiac revascularization was reduced in patients receiving long-term captopril therapy, suggesting either an anti-ischemic effect or the ability of the angiotensin-converting enzyme inhibitor to modify the atherosclerotic process in survivors of MI.",1994.0,1,1
1548,7924541,Nonpharmacologic therapy improves functional and emotional status in congestive heart failure.,J B Kostis; R C Rosen; N M Cosgrove; D M Shindler; A C Wilson,"To compare the effects of a multimodal nonpharmacologic intervention to digoxin and to placebo in patients with congestive heart failure receiving background therapy with angiotensin-converting enzyme inhibitors. Randomized, parallel assignment to three treatment groups of 20 patients with congestive heart failure (New York Heart Association Class II and III). Nonpharmacologic treatment program included the following: (1) graduated exercise training, three to five times per week; (2) structured cognitive therapy and stress management; and (3) dietary intervention aimed at salt reduction and weight reduction in the overweight. Digoxin was titrated to achieve a blood level between 0.8 and 2.0 ng/ml. Placebo and digoxin were administered in a randomized, double-blind fashion. Echocardiographic ejection fraction improved (p < 0.05) in the digitalis group (change = +4.4 +/- 6.5) compared with both placebo (change = -3.2 +/- 3.9) and nonpharmacologic therapy (change = -3.2 +/- 3.9). The nonpharmacologic treatment program was well tolerated by all patients and resulted in significant improvement (p < 0.05) in exercise tolerance (digoxin = +51 +/- 50 s, placebo = +91 +/- 76, nonpharmacologic therapy = +182 +/- 139), as well as Beck Depression Inventory score (digoxin = +1.2 +/- 4.4, placebo = +2.0 +/- 4.2, nonpharmacologic therapy = -5.0 +/- 4.2), Hamilton Scale scores of anxiety (digoxin = +3.0 +/- 6.8, placebo = +6.0 +/- 2.6, nondrug therapy = -5.2 +/- 5.4), and depression (digoxin = +1.0 +/- 4.9, placebo = +5.0 +/- 5.0, nonpharmacologic therapy = -6.6 +/- 10.1). In addition, weight loss was significantly greater with nonpharmacologic therapy (digoxin = +0.32 +/- 1.76 kg; placebo = -1.35 +/- 1.44 kg; nonpharmacologic therapy = -4.37 +/- 4.50 kg) compared with both digoxin and placebo. Nonpharmacologic therapy improved functional capacity, body weight, and mood state in patients with congestive heart failure. In contrast, digoxin improved ejection fraction without corresponding changes in exercise tolerance or quality of life.",1994.0,0,0
1549,7924573,Symptomatic hemodynamic and hormonal effects of intravenous captopril in patients with heart failure.,H Wu; H Y Zhao,"Since only oral preparations of captopril are clinically available, intravenous captopril was studied in 10 patients with mild heart failure and in 20 severe. The results showed that intravenous captopril may rapidly reduce cardiac preload and afterload, increase cardiac output, inhibit renin-angiotensin-aldosterone system, and depress plasma levels of catecholamine. After captopril infusion, a rapid symptomatic improvement occurred and the infusion could be well tolerated in patients with acute or severe heart failure. In addition, reversing hyponatremia and hypokalemia or improving azotemia may benefit the patients with acute or severe heart failure.",1994.0,0,0
1550,7925510,Acute intervention with captopril during thrombolysis in patients with first anterior myocardial infarction. Results from the Captopril and Thrombolysis Study (CATS).,J H Kingma; W H van Gilst; C H Peels; J H Dambrink; F W Verheugt; R P Wielenga,"The study was designed to examine the safety and efficacy of acute interventional use of captopril on left ventricular volumes, ventricular arrhythmias and neurohormones during thrombolysis in patients with a first anterior myocardial infarction, within 6 h of onset of symptoms. Left ventricular dysfunction and prognosis after myocardial infarction can be improved by angiotensin converting enzyme inhibition started after the ischaemic phase. Experimental evidence suggests that intervention during thrombolysis may lead to even further benefit. In a randomized, double-blind placebo-controlled trial, 298 patients with a first anterior myocardial infarction, eligible for thrombolytic therapy were treated with captopril 6.25 mg or placebo, started immediately upon streptokinase infusion and titrated to 25 mg t.i.d.. The efficacy of captopril by an intention-to-treat-analysis to reduce left ventricular volumes, ventricular arrhythmias, neurohumoral activation and enzymatic infarct size was measured. During dose titration, mean blood pressure and heart rate were similar in both groups. However, hypotension after the first dose was reported in 18 patients on placebo and 31 patients on captopril (P < 0.05). At discharge, 80% of patients were on study medication. Left ventricular volumes were significantly increased in both groups at 3 months, but they tended to be lower in the captopril group; however, the differences were not statistically significant. The incidence of accelerated idioventricular rhythm and non-sustained ventricular tachycardia in captopril patients was lower than in placebo patients (P < 0.05), parallelled by transiently lower norepinephrine levels (P < 0.05) upon thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,1,1
1551,7925516,"Quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension.",T Lenz; K L Schulte; B Wagner; J Lilienthal; R Gotzen,"This 8-week, double-blind, multicentre study compared the efficacy and safety of the combination of quinapril and hydrochlorothiazide (HCTZ) with each drug as monotherapy. Outpatients with moderate to severe hypertension defined as supine diastolic blood pressure (DBP) > or = 105 mmHg and < or = 120 mmHg at the end of a 2 to 4-week placebo-baseline period were randomly assigned to one of the three treatments: once-daily 10 mg quinapril plus 12.5 mg HCTZ or monotherapy with these doses. After 4 weeks, the doses were to be doubled for the remaining 4 weeks. Three hundred and sixty-eight patients were randomized to double-blind medication; 346 completed the study. Seven patients withdrew due to lack of efficacy. Four patients withdrew due to side effects. In all three treatment groups, clinically significant reductions in DBP were achieved. Combination therapy was statistically more effective than each component taken as monotherapy. Adverse events were infrequent in all treatment groups. No patients experienced symptomatic hypotension or orthostatic hypotension.",1994.0,0,0
1552,7925517,Long-term efficacy and safety of pimobendan in moderate heart failure. A double-blind parallel 6-month comparison with enalapril. The Pimobendan-Enalapril Study Group.,W J Remme; H P Krayenbühl; G Baumann; M H Frick; M Haehl; G Nehmiz; W Baiker,"In view of growing scepticism as to the efficacy and safety of agents with predominant phosphodiesterase inhibiting properties in heart failure, the clinical efficacy and safety of pimobendan, a calcium-sensitizing and partially phosphodiesterase-inhibiting compound, was compared with enalapril in 242 patients with mild to moderate heart failure (NYHA classification II-III) despite diuretics and digitalis, and abnormal haemodynamics at baseline. Patients were randomly assigned to either pimobendan (average 10.3 mg.day-1, n = 119), or enalapril (average 10.7 mg.day-1, n = 123) in a double-blind fashion for 6 months. Forty-two pimobendan and 37 enalapril patients stopped the treatment, five pimobendan and six enalapril due to worsening of failure without death, whereas 13 and eight patients, respectively, died from cardiac disorders (ns). Other reasons for discontinuation and adverse events not leading to discontinuation were also comparable. Although Holter analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events. NYHA classification improved similarly in both groups, from 2.51 to 2.16 (pimobendan) and from 2.40 to 2.06 (enalapril). The number of patients needing a change in background therapy or hospitalization did not differ between the two groups. Haemodynamic variables at rest were improved by both compounds after 6 months. In contrast, only enalapril improved haemodynamics during exercise, and reduced the cardiothoracic ratio. The primary endpoint, exercise capacity, increased significantly during the first 3 months by 45 and 53 s, under pimobendan and enalapril, respectively, but, although unchanged thereafter, the improvement was no longer statistically significant at 6 months in either group.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
1553,7926346,"Captopril and atenolol are equally effective in retarding progression of diabetic nephropathy. Results of a 2-year prospective, randomized study.",L D Elving; J F Wetzels; H J van Lier; E de Nobel; J H Berden,"The progression of diabetic nephropathy can be positively influenced by maintaining a low blood pressure level. This has been shown in studies with conventional antihypertensive treatment as well as with ACE inhibitors. Whether the latter group of drugs is more effective remains to be proven and was the aim of our study. In a prospective randomized study we compared the effects of ACE inhibition and beta-blockade on retarding progression of renal function in IDDM patients with an early stage of overt diabetic nephropathy. Twenty-nine patients were studied for 2 years, 15 were randomized for treatment with captopril and 14 for atenolol. Every 6 weeks blood pressure and urinary albumin and total protein excretion were measured. GFR was measured every 6 months as 51Cr-EDTA clearance. Baseline values for blood pressure, renal function and albuminuria were identical in the two groups. The effect of both drugs on blood pressure was not significantly different. In the captopril-treated patients MAP before and after 2 years was 110 +/- 3 (SEM) and 100 +/- 2 mm Hg, respectively and in the atenolol-treated patients 105 +/- 2 vs 101 +/- 2 mm Hg. Both drugs reduced albuminuria and total proteinuria to the same extent. With captopril albuminuria decreased from 1549 (989-2399) to 851 (537-1380) mg/24 h and proteinuria from 2.5 (1.6-3.8) to 1.2 (0.8-1.8) g/24 h. With atenolol albuminuria decreased from 933 (603-1445) to 676 (437-1047) mg/24 h and proteinuria from 1.5 (1.0-2.4) to 0.9 (0.6-1.5) g/24 h.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1554,7927956,Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.,R Genthon,"In a double-blind, parallel-group multicentre study, the efficacy and safety of a fixed low-dose combination of ramipril 2.5 mg and hydrochlorothiazide (HCT) 12.5 mg was compared with each of the component drugs when given as monotherapy. After a four-week placebo run-in, patients were randomized to receive either ramipril 2.5 mg (n = 218) or HCT 12.5 mg (n = 220), or the fixed-dose combination of ramipril 2.5 mg and HCT 12.5 mg (n = 222), for a period of eight weeks. At the end of the study, in which 624 patients had completed treatment, it was found that the decrease in supine diastolic blood pressure (the main efficacy parameter) was greater in the ramipril-HCT combination group than in either the ramipril or the HCT monotherapy groups, the difference being statistically significant when compared with the HCT group (-14.3, -13.1 and -12.4 mm Hg, respectively). Reductions in standing DBP and supine and standing systolic blood pressure (SBP) were also greatest in the combination group. The incidence of adverse events was lower in the combination group than in either of the monotherapy groups, and there were no serious clinically significant laboratory abnormalities in the combination group.",1994.0,0,0
1555,7927959,Effect of increasing doses of lisinopril on proteinuria of normotensive patients with IgA nephropathy and normal renal function.,R Palla; V Panichi; V Finato; M Parrini; B Andreini; A M Bianchi; L Giovannini; M Migliori; A A Bertelli,"The antiproteinuric effect of angiotensin converting enzyme (ACE) inhibition in patients with renal disease is well known, but the results of clinical studies appear to vary considerably from a partial decrease to a fall of 100% in urinary protein excretion. This may have been due to the use of different doses of ACE inhibitor, different renal pathology and non-standardized sodium intake. In 16 proteinuric patients with biopsy-proven IgA nephropathy, with normal renal function and blood pressure, maintained at controlled sodium intake < or = 80 mEqII, the efficacy of increasing doses of the ACE inhibitor lisinopril was studied. The lisinopril doses were 5, 10, 15 and 20 mg, administered for 4 weeks. Between each dose increment a placebo period of 3 weeks was interposed. Proteinuria stepwise decreased from the control period by 39%, 44%, 61% and 67% with lisinopril at 5, 10, 15 and 20 mg, respectively. The blood pressure decreased by 22% with lisinopril 5 mg; a similar fall was observed with the dose increment. Although the glomerular filtration rate remained unchanged, the renal plasma flow increased by 21%, 26%, 24% and 28% and the filtration fraction increased by 28% mean. The ACE plasma levels decreased by 33%, 64%, 76% and 83%. A close correlation was found between an increase in lisinopril dosage and the fall in urinary protein excretion (r = 0.88, p < 0.001). The antiproteinuric effect of lisinopril is dose-related and may be attributable to some extent to the fall in systemic (and intraglomerular) blood pressure, but it is best attributed to the modification of glomerular sieving function.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1556,7928331,Ketorolac (Toradol) induced lithium toxicity.,V Iyer,"A case of lithium neurotoxicity in a patient with cluster headache, resulting from coadministration of ketorolac is reported. While lithium interaction with many other NSAIDs is well-known, ketorolac has not been incriminated.",1994.0,0,0
1557,7930196,Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy.,M Lin; H T Chiang; S L Lin; M S Chang; B N Chiang; H W Kuo; M D Cheitlin,"This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation. We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial. Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up. At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m2, p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m2, p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m2, p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2 value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01). Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.",1994.0,0,0
1558,7932518,Comparison of the efficacy and tolerability of an angiotensin converting enzyme inhibitor (lisinopril) versus a calcium channel antagonist (diltiazem SR) in the treatment of moderate to severe hypertension.,M R Weir; T Fagan; S Chrysant; W Flamenbaum; P M Kaihlanen; M Lueg; D Anzalone,"One hundred and ten patients (mean age 50.6 years) with moderate to severe essential hypertension (DBP between 105 and 116 mmHg) were randomised to eight weeks of double-blind treatment with lisinopril (n = 56) or diltiazem SR (n = 54). Fourteen patients withdrew from therapy; six patients withdrew because of adverse events (lisinopril, n = 3; diltiazem SR, n = 1) and lack of BP control (lisinopril, n = 1; diltiazem SR, n = 1). Both monotherapies were titrated upward (lisinopril 20-40 mg daily, diltiazem SR 120-180 mg twice daily) to achieve an office DBP < 90 mmHg. Hydrochlorothiazide (HCTZ; 25 mg daily) was added to monotherapy after week 4 if patients did not reach the BP goal (i.e. non-responders). After four weeks of therapy, 72% of patients (74 of 103) were nonresponders. At eight weeks of therapy, 66 patients (lisinopril, n = 32; diltiazem SR, n = 34) had received HCTZ. At week 8, 53% of lisinopril and 36% of diltiazem SR patients met the response criteria. Mean office DBP decreased from baseline -18.1 +/- 8.6 mmHg for lisinopril patients and -15.9 +/- 10.1 mmHg for diltiazem SR patients at week 8. Lisinopril was as effective as diltiazem in reducing systolic and diastolic office BP at week 4 (p > 0.1). Likewise, at weeks 4 and 8, no statistically significant differences were detected between treatments (p > 0.05) for systolic and diastolic ambulatory BP averaged over 24 hours. Both treatments were well tolerated and showed important antihypertensive efficacy in patients with moderate to severe BP elevation.",1994.0,0,0
1559,7934452,ACE inhibition after myocardial infarction: can megatrials provide answers?,G Ertl; B Jugdutt,,1994.0,0,1
1560,7936476,Once daily lisinopril and captopril in hypertension: a double blind comparison using ambulatory monitoring.,S Mann; K P O'Brien,"To validate and compare the 24-hour antihypertensive efficacy of the angiotensin-converting-enzyme inhibitors, captopril and lisinopril. A randomised, doubleblind, doubledummy crossover study was performed with single-blind placebo run-in and washout periods and titration opportunities during therapeutic phases (captopril 25mg, 50mg and 100mg daily, lisinopril 10mg, 20mg and 40mg daily). The study was monitored using standard office blood pressure measurements, clinical and laboratory assessment. 24 patients of either sex and between 18 and 70 years with essential hypertension were enrolled, 20 met randomisation criteria (of sitting diastolic pressure 95-115mmHg), 3 withdrew from the study during its active phase and one was excluded from analysis having been found retrospectively to have not met randomisation criteria at the appropriate visit. Predetermined endpoints were blood pressure levels during different time periods of ambulatory monitoring performed at the end of each placebo or treatment phase. In the 17 patients who completed the protocol, lisinopril produced a greater reduction of blood pressure at all time periods although the differences were not all statistically significant. The differences were most marked 19-24 hours post dosage time when pressures (systolic/diastolic) during lisinopril therapy were lower than during captopril by 18.0/14.5 mmHg (p < 0.001 for both). As measured by clinic pressures, lisinopril also achieved a considerably higher degree of blood pressure control with less dose titration. In this study, lisinopril proved a more effective once daily antihypertensive agent than captopril, especially in the last 6 hours of the 24-hour dosage interval.",1994.0,0,1
1561,7937273,Effect of long-term angiotensin-converting enzyme inhibitor therapy on arterial oxygen saturation in patients with mild to moderate heart failure.,E J Stanek; A R Nara; K P Strohl; R N Nair; M J Decker; M A Munger,"To evaluate the effects of angiotensin-converting enzyme (ACE) inhibition on continuous pulse oximetry recordings of arterial oxygen saturation (SpO2). Open-label study. Cardiology clinics at two large teaching hospitals. Eight patients with New York Heart Association Functional Class (NYHA FC) II-III heart failure. Patients were studied after an ACE inhibitor washout (baseline, B), and after 3 months following resumption of therapy (ACE). Monitoring times for B and ACEI were approximately 22 hours. Reduction trends were observed for number (190 +/- 170 vs 125 +/- 67 B vs ACEI), magnitude (8.2 +/- 1.4% vs 7.5 +/- 1.8%), and duration (2.45 +/- 2.8 vs 1.35 +/- 0.8 min) of desaturations/monitoring period, and for nadir SpO2/desaturation (88.1 +/- 1.5% vs 89.9 +/- 3.3%). The B desaturation index [(cumulative desaturation time/monitoring period time) x 100, a measure of hypoxic stress or burden] decreased from 19.4 +/- 8.1% to 11.9 +/- 8.1% at ACEI (p = 0.024). Long-term ACE inhibitor therapy improves the profile of SpO2 values over time in patients with NYHA FC II-III heart failure.",1994.0,0,0
1562,7937415,Congestive heart failure. Current and future strategies to decrease mortality.,R E Hobbs; B Czerska,"The prevalence of and mortality from congestive heart failure increase with advancing age. The most important prognostic indicators are exercise tolerance and left ventricular function. Currently, drug treatment consists of digitalis, diuretics, and ACe inhibitors. Future management may include medications to modulate the extracardiac mechanisms of decompensation and newer surgical techniques to assist or replace the failing heart.",1994.0,0,0
1563,7940662,Atypical reactions associated with use of angiotensin-converting enzyme inhibitors and apheresis.,H G Owen; M E Brecher,"Anaphylactic or atypical reactions, characterized by flushing, hypotension, dyspnea, and bradycardia, have been reported in patients undergoing hemodialysis, low-density lipoprotein apheresis, IgG affinity column apheresis, therapeutic plasma exchange, and desensitization immunotherapy while receiving angiotensin-converting enzyme (ACE) inhibitor therapy. Records were reviewed of 299 consecutive patients undergoing therapeutic plasma exchange with colloid replacement at the University of North Carolina Hospitals from September 1981 through December 1993. Charts were selected for further analysis if atypical reactions (flushing or hypotension defined as a mean decrease in blood pressure of 20 torr or greater) occurred during apheresis or if there was concurrent administration of an ACE inhibitor. Fourteen (4.7%) of 299 patients were receiving ACE inhibitor therapy at the time of apheresis; all 14 experienced an atypical reaction. In contrast, 20 (7%) of 285 patients not receiving ACE inhibitors developed atypical reactions (p < 0.001). The 14 ACE inhibitor patients accounted for 41 percent (14/34) of all patients having atypical reactions during apheresis. Patients receiving ACE inhibitor therapy who are undergoing therapeutic plasma exchange with albumin replacement solutions are at high risk (100%) for atypical reactions. It is recommended that ACE inhibitors be withheld for at least 24 hours before that procedure.",1994.0,0,0
1564,7940808,Enalapril and cyclosporin in renal transplant patients and rats.,C J Ferguson; C von Ruhland; B Shrestha; P J Griffin; R H Moore; J R Salaman,,1994.0,0,0
1565,7940809,Role of ACE inhibitors in the treatment of erythrocytosis in patients with renal allograft.,F Pisani; G Tisone; E Alciati; G Vennarecci; E Pieragostini; C U Casciani,,1994.0,0,0
1566,7946163,"Electrolyte changes and metabolic effects of lisinopril/bendrofluazide treatment. Results from a randomized, double-blind study with parallel groups.",A Haenni; P E Andersson; L Lind; C Berne; H Lithell,"The metabolic effects of lisinopril and bendrofluazide therapy were studied in 61 patients with essential hypertension in a randomized, double-blind study with parallel groups. The insulin sensitivity index, measured by hyperinsulinemic euglycemic clamp test, decreased by 22% (P < .01) during bendrofluazide treatment and by 15% (NS) during lisinopril treatment. The initial insulin response at intravenous glucose tolerance test (IVGTT) increased by 21% (P < .05) during lisinopril treatment but decreased by 13% (P < .05) during treatment with bendrofluazide, and in addition, the glucose disappearance rate decreased by 9% (P < .05) in the latter group. During oral glucose tolerance test (OGTT), the area under the glucose curve (AUCglucose) increased by 17% (P = .05) in the bendrofluazide-treated group but decreased by 19% (P = .05) in the lisinopril group, although there was no difference between the drug effects on AUCinsulin. The LDL/HDL cholesterol ratio increased during bendrofluazide treatment. The serum potassium concentration decreased by 10% (P = .0001) during bendrofluazide treatment but increased by 6% (P = .0001) in the lisinopril-treated group. The change in serum potassium was correlated to the change in initial insulin response and glucose disappearance rate at IVGTT, and inversely correlated to the change in AUCglucose at OGTT. In conclusion, alterations in serum potassium balance may affect the initial insulin release and glucose disposal. Bendrofluazide treatment decreases the serum potassium concentration, reduces the initial insulin release and the glucose disposal, and, in addition, impairs insulin sensitivity. Lisinopril treatment increases serum potassium concentration and the initial insulin response, and decreases AUCglucose, but does not improve insulin sensitivity per se.",1994.0,0,0
1567,7949498,Close clinical observation minimizes the complications of beta-blocker withdrawal.,G Eisele; L L Gilmore; E B Blanchard,"To determine whether beta-blocker withdrawal under close medical supervision poses undue risks. Retrospective case review. Data extracted from previous study. 114 hypertensive subjects tapered from beta-blocker therapy. Subjects were a subset of patients originally studied for blood pressure medication withdrawal and biofeedback training. Frequency of symptoms and adverse effects reported by subjects during medication taper to the study nurse. Symptoms were no more likely to occur with beta-blocker withdrawal than with withdrawal of other types of antihypertensive medications. Most adverse effects were classified as minor. Two subjects experienced major symptoms. One subject required reinstitution of beta-blockers for palpitations, and another exhibited angina upon beta-blocker withdrawal. In well-screened patients under careful monitoring, withdrawal from beta-blockers appears to present a small, manageable risk.",1994.0,0,0
1568,7950612,Randomised controlled trial of enalapril and beta blockers in non-diabetic chronic renal failure.,T Hannedouche; P Landais; B Goldfarb; N el Esper; A Fournier; M Godin; D Durand; J Chanard; F Mignon; J M Suo,"To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. Open randomised multicentre trial with three year follow up. Outpatient departments of six French hospitals. 100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. 17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.",1994.0,0,0
1569,7951496,A case of aldosterone producing adenoma associated with high PRA after long-term angiotensin converting enzyme inhibitor treatment.,A Kasuga; I Takei; S Tasaka; H Shibata; H Maruyama; T Saruta; K Kataoka,"A 62-year-old patient with non-insulin dependent diabetes (NIDDM) was admitted to our hospital for blood pressure control. He had been treated with angiotensin converting enzyme inhibitor (ACEI) for 7 years and showed marked hypokalemia with increased urinary potassium excretion. Hormonal examination revealed a normal plasma aldosterone concentration and increased plasma renin activity (PRA, 13.4 ng/ml/h), so potassium losing nephropathy was suspected. After discontinuation of the ACEI, PRA decreased to normal. An adrenal adenoma was found on abdominal magnetic resonance imaging (MRI) and adrenalectomy was performed to confirm aldosterone producing adenoma (APA). Although ACEIs are said not to alter PRA in APA, this drug was primarily responsible for the increased PRA in this case. This is a rare case of APA, which showed markedly increased PRA during ACEI treatment.",1993.0,0,0
1570,7954561,Nitrendipine vs. captopril in essential hypertension: effects on circadian blood pressure and left ventricular hypertrophy.,T Machnig; K H Henneke; G Engels; G Pongratz; M Schmalzl; J Gellert; K Bachmann,"Both nitrendipine and captopril have been shown to reverse left ventricular hypertrophy in hypertensive patients. So far, no study allowed a true comparison of these drugs in this regard and with respect to their potential of reducing circadian blood pressure. Therefore, a total of 86 patients with newly diagnosed arterial hypertension and echocardiographic evidence of left ventricular hypertrophy underwent randomized treatment with captopril (n = 43) or nitrendipine (n = 43). Eighteen patients had to be put on a combination therapy of nitrendipine and captopril during the course of the study to control blood pressure effectively. Before and after the 6th and 38th weeks of treatment all patients underwent ambulatory 24-hour blood pressure monitoring, M-mode echo assessment of left ventricular mass and Doppler evaluation of left ventricular filling. The 24-hour blood pressure data were smoothed with a Fourier series and then compared with a normotensive reference profile with respect to blood pressure load and variability. The daytime and nighttime mean and the office blood pressure were also analyzed. Substance-specific profiles of action were obtained by subtracting the smoothed profiles after therapy from the profiles before therapy. After 38 weeks ambulatory blood pressure had decreased from 152 +/- 11/101 +/- 7 to 137 +/- 13/87 +/- 10 mm Hg on nitrendipine and from 147 +/- 11/99 +/- 6 to 134 +/- 13/89 +/- 9 mm Hg on captopril. The substance-specific profiles calculated for captopril and nitrendipine showed a balanced antihypertensive effect throughout the day and the night. The mean percentage decreases in left ventricular muscle mass under nitrendipine was 15% and did not differ significantly from the decrease of 21% under treatment with captopril (p < 0.001). There is no significant association between the reduction in blood pressure and the regression of left ventricular hypertrophy. In patients with disturbances of left ventricular diastolic function the early-to-late diastolic left ventricular flow ratio and the isovolumetric relaxation time were improved independent of the drug used. It is concluded that a long-term therapy with captopril and nitrendipine leads to a comparable degree of circadian blood pressure reduction and regression of hypertensive left ventricular hypertrophy.",1994.0,0,0
1571,7956268,Patient perception of a long-term clinical trial: experience using a close-out questionnaire in the Studies of Left Ventricular Dysfunction (SOLVD) Trial. SOLVD Close-out Working Group.,M J Henzlova; G H Blackburn; E J Bradley; W J Rogers,"A close-out questionnaire was distributed to the participants in a long-term heart failure trial, Studies of Left Ventricular Dysfunction (SOLVD). The respondents' primary motivation for enrollment, positive and negative experiences, and reported changes in habitual behavior was analyzed. Seventy-four percent (N = 3522) of the eligible patients responded to the survey. The most commonly cited reason for enrollment was recommendation by the primary physician. A wish ""to contribute to medical science"" and ""to help others"" was also a frequent incentive. A majority of the respondents were satisfied with participation and would be willing to participate in a future clinical trial. Most negative experiences included transportation to and from the clinic and frequent staff changes. A significant number of the patients reported changes in their smoking habits, alcohol intake, and diet despite the absence of behavioral interventions in the study protocol. There were minor differences between attitudes and perceptions of the male and female participants. No differences were found between patients who had previously participated in a clinical trial and those who had not.",1994.0,0,0
1572,7957538,Metabolic effects of long-term angiotensin-converting enzyme inhibition with fosinopril in patients with essential hypertension: relationship to angiotensin-converting enzyme inhibition.,R Reneland; P E Andersson; A Haenni; H Lithell,"Fifty patients with mild to moderate essential hypertension were randomized to receive either 20 mg fosinopril daily for 16 weeks or placebo for 4 weeks followed by 12 weeks of 50 mg atenolol daily. Prior to these 16 weeks there was a placebo wash-out period of 2-6 weeks. Blood pressure measurements, euglycaemic, hyperinsulinaemic glucose clamps, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and after 4 and 16 weeks. Blood lipid status was evaluated at baseline and 16 weeks. The insulin sensitivity index (M/I) increased by 12% during the prolonged placebo period, and subsequently decreased by 12% during treatment with atenolol in that group. A post-hoc analysis of covariance indicated that the increase in insulin sensitivity during the initial 4 weeks may have been due to carry-over effects from previous antihypertensive treatment. Fosinopril increased glucose disappearance during IVGTT at 4 and 16 weeks (k values 1.46 and 1.33 vs 1.10 at baseline) but had no effect on insulin sensitivity. The change in insulin sensitivity and serum triglycerides during treatment with fosinopril was related to angiotensin-converting enzyme inhibition in serum. In conclusion, carry-over effects from previous antihypertensive medication were indicated in this study, probably because of an insufficient wash-out period in many patients. Therefore, 4 weeks of placebo wash-out in all patients is advisable in this kind of investigation.",1994.0,0,0
1573,7957539,Effects of glycopyrrolate on capsaicin-induced cough in normal volunteers treated with captopril.,M van Wyk; D K Sommers; J R Snyman,"The effects of inhibition of angiotensin converting enzyme (ACE) and glycopyrrolate on cough caused by inhaled capsaicin were investigated in a double-blind, randomised cross-over study in twelve normal volunteers. The capsaicin challenge was performed before and 2 h after dosing with 75 mg captopril or matched placebo given orally, and 20, 40 and 60 min after giving 1 mg glycopyrrolate i.v. to each subject. Captopril and placebo did not alter the cough response when compared to baseline. Glycopyrrolate, however, caused a significant increase in the threshold sensitivity (D2) from baseline, and a significant decrease in the total cough response at 40 and 60 min both after captopril and placebo. The D2-baseline and D2-40 min after glycopyrrolate (mean SD), respectively, were 3.2 (1.0); 17.9 (4.2) after placebo and 2.5 (8.5); 23.6 (6.9) after captopril. Elimination of vagal influences implies attenuation of the effects of tachykinins but not those prostaglandins. We postulate that tachykinins, such as substance P, play a more important role than prostaglandins in capsaicin-induced cough. We conclude that the vagus is important in the capsaicin-induced cough reflex, but, as suppression of this reflex by glycopyrrolate was delayed, the relevant receptors are either poorly accessible peripheral receptors or they are located in the central nervous system.",1994.0,0,0
1574,7968030,Management of hypertensive emergencies.,N M Kaplan,,1994.0,0,0
1575,7968725,Angiotensin converting enzyme inhibitors and diabetic renal disease. ACE inhibitors may prevent progression from incipient to clinical nephropathy.,R E Gilbert; G Jerums,,1994.0,0,0
1576,7969680,Urinary angiotensin II: a marker of renal tissue activity?,G Reams; D Villarreal; Z Wu; J H Bauer,"The methodology for the collection, extraction, separation and measurement of urinary angiotensin II [the octapeptide, ANG(1-8)] is described. To determine the origin of urinary ANG(1-8), mean arterial pressure, renal hemodynamics and the arterial, renal venous and urinary concentrations of ANG(1-8) were examined prior to and following the constant intra-arterial infusion of tritiated angiotensin II [3H-ANG(1-8)] in graded doses of 0.5, 2.0 and 2.5 ng/kg/min in 5 uninephrectomized, anesthetized female dogs. The infusion of 3H-ANG-(1-8) had no significant effect on mean arterial pressure, glomerular filtration rate, renal blood flow or urine flow rate. The mean concentration of ANG(1-8) in the urine was 3.7 fmol/ml. None or only trace amounts of 3H-ANG(1-8) were detected in the urine in spite of marked increases in renal arterial 3H-ANG(1-8) concentrations. These observations suggest that urinary ANG(1-8) was derived de novo from the intrarenal generation of angiotensin II. In addition, plasma and urinary concentrations of ANG(1-8) were assessed in patients with essential hypertension undergoing treatment with either a diuretic (n = 14) or an angiotensin-converting enzyme inhibitor (n = 14). Although the concentrations of plasma ANG(1-8) responded appropriately to the respective therapies, the urinary excretion of ANG(1-8) was not different following either therapy. These data suggest that ANG(1-8) collected from the urinary bladder may not occur in adequate concentrations to accurately assess the activity of the intrarenal renin-angiotensin system.",1994.0,0,0
1577,7973905,Reversible hyperkalemia during antihypertensive therapy in a hypertensive diabetic patient with latent hypoaldosteronism and mild renal failure.,K Uchida; S Azukizawa; S Nakano; M Kaneko; T Kigoshi; S Morimoto; A Matsui,"A 66-year-old hypertensive diabetic patient with latent hypoaldosteronism and mild renal failure was treated by adding enalapril, an angiotensin converting enzyme inhibitor, to the furosemide and nifedipine regimen because of an insufficient antihypertensive response for 1 month. Seven days after enalapril addition, the blood pressure was significantly reduced, but frank hyperkalemia occurred with a marked rise in BUN and a slight increase in serum creatinine. Plasma renin activity (PRA) and plasma aldosterone (PA) values remained low before and during enalapril therapy. Transient treatment with sodium polystyrene sulfate after enalapril withdrawal improved the hyperkalemia and renal function, but PRA and PA levels were low. PA and its precursor steroids also responded poorly to graded angiotensin II infusion and rapid ACTH injection. Latent hypoaldosteronism probably predisposed this patient to frank hyperkalemia with progressive dehydration and slightly reduced renal function during antihypertensive therapy.",1994.0,0,0
1578,7977316,Long-term treatment with either enalapril or nitrendipine stabilizes albuminuria and increases glomerular filtration rate in non-insulin-dependent diabetic patients.,P Ruggenenti; L Mosconi; L Bianchi; L Cortesi; M Campana; G Pagani; G Mecca; G Remuzzi,"The effect of short- (98 days) and long-term (1 year) treatment with nitrendipine (10 to 40 mg/d) and enalapril (5 to 20 mg/d) on kidney function was studied prospectively in a parallel group design in 16 microalbuminuric non-insulin-dependent diabetic patients with mild hypertension and biopsy-proven diabetic glomerulopathy. At the end of the short-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 83.5 +/- 3.5 mm Hg (P < 0.001) in the nitrendipine group and from 96.7 +/- 2.5 to 86.7 +/- 5.6 mm Hg (P < 0.001) in the enalapril group. Both overnight urinary albumin excretion rate and albumin fractional clearance tended to increase in the nitrendipine group and to decrease in the enalapril group, whereas the glomerular filtration rate and the renal plasma flow were similar to baseline in both study groups. At the end of the long-term treatment period diastolic blood pressure significantly decreased from 95.4 +/- 2.5 mm Hg to 86.0 +/- 6 mm Hg (P < 0.005) in the nitrendipine group and from 96.7 +/- 2.1 to 90.8 +/- 4.3 mm Hg (P < 0.05) in the enalapril group. Overnight urinary albumin excretion and albumin fractional clearance were similar to baseline in both study groups. The glomerular filtration rate significantly increased from 70.2 +/- 14.2 to 96.8 +/- 20.4 (P < 0.05) in the nitrendipine group and from 58.9 +/- 10.7 to 78.5 +/- 11.0 (P < 0.05) in the enalapril group. The renal plasma flow also significantly increased from 456.6 +/- 165.3 to 597.2 +/- 178.9 (P < 0.01) in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1579,7981011,Haemodynamic response and pharmacokinetics after the first dose of quinapril in patients with congestive heart failure.,I B Squire; R J Macfadyen; K R Lees; W S Hillis; J L Reid,"1. Twenty-four elderly patients with stable, chronic congestive heart failure, NYHA II-IV, requiring addition of an ACE inhibitor to their existing therapy were randomised to receive double-blind a single dose of quinapril 2.5 mg p.o. or matching placebo after 24-48 h supervised diuretic withdrawal. 2. The effect of treatment on resting supine blood pressure, heart rate, plasma angiotensin converting enzyme (ACE) and circulating plasma renin activity was compared between groups over the first 24 h after dosing. The pharmacokinetic profiles of quinapril and the active metabolite quinaprilat were determined. 3. Compared with placebo, quinapril caused a statistically significant but modest fall in blood pressure from 3 to 10 h post dose. The maximum fall of 12 mm Hg (95% C.I. 5.4-18.5) was seen at approximately 5 h. Circulating ACE activity was 40% inhibited within 1 h. Maximum ACE inhibition (83.6%, 95% C.I. 76.7-90.5) was observed at 3 h. ACE remained 60% inhibited at 24 h post dose. tmax for quinapril was seen at 2.6 +/- 1.2 h. while tmax for quinaprilat was at 3.6, +/- 0.8 h. 4. Treatment with quinapril was associated with a significant rise in plasma renin activity (PRA) of 8.83 ng AI ml-1 h-1 (95% C.I. 0.30-17.96) compared with placebo. 5. Compared with placebo, quinapril 2.5 mg inhibits plasma ACE by over 60% for 24 h and reduces blood pressure for at least 10 h in patients with stable, chronic congestive heart failure. The blood pressure fall, although moderate and well tolerated, is more sustained than previously described for quinapril in heart failure.",1994.0,0,0
1580,7983291,A multi-center analysis of the use of enalapril and lisinopril in elderly hypertensive patients.,D W Hawkins; W D Hall; M B Douglas; G Cotsonis,"To evaluate the clinical use and adverse effects of enalapril and lisinopril in elderly hypertensive subjects. A multi-center, retrospective, drug use evaluation survey. Ambulatory care clinics at 14 VA and 14 academic medical centers. 422 elderly (> 60 years of age) patients with hypertension and no clinical evidence of congestive heart failure. At least 3 consecutive months of anti-hypertensive therapy with either enalapril or lisinopril. Blood pressure, serum creatinine, serum potassium, concomitant disease states, concurrent medications, and documentation of any adverse event that might be related to ACE inhibitor therapy. There were no significant differences in systolic and diastolic blood pressures, serum creatinine, or serum potassium between enalapril- and lisinopril-treated patients at baseline and after 3 months of therapy. Both treatments resulted in a significant reduction in diastolic blood pressure. There was no significant difference in the incidence of adverse effects between the two treatments. Significantly more patients were dosed on a twice daily regimen of enalapril than lisinopril. The data from this retrospective study confirm the safe and effective use of enalapril and lisinopril, two long-acting ACE inhibitors, in elderly hypertensive patients.",1994.0,0,1
1581,7985599,Long-term metabolic effects of antihypertensive drugs.,L Lind; T Pollare; C Berne; H Lithell,"In short-term studies (4 to 6 months) we have reported that antihypertensive treatment with beta-adrenergic blockade and thiazide diuretics induced insulin resistance, hyperinsulinemia, and a deranged lipid profile; the ACE inhibitor captopril increased insulin sensitivity without affecting serum lipids. In the present study, 65 of the original 149 patients with essential hypertension included in the short-term studies were reexamined after treatment for 2 to 3 years. The hyperinsulinemic euglycemic clamp method showed that the significant decrease in insulin sensitivity (p < 0.01) induced by treatment with pindolol, propanolol, metoprolol, atenolol, or hydrochlorothiazide after 4 to 6 months persisted after 2 to 3 years of treatment. Furthermore, the increase in insulin sensitivity reported for captopril after 6 months (p < 0.05) was not significantly altered during long-term treatment. Also, the raised levels of very low-density lipoprotein triglycerides (p < 0.01) and reduced levels of high-density lipoprotein cholesterol (p < 0.01) induced by most of the beta-adrenergic blockade without intrinsic sympathomimetic activity and hydrochlorothiazide persisted. Captopril, on the other hand, did not significantly affect the lipids during prolonged treatment. In conclusion, the magnitude of the metabolic effects induced by antihypertensive treatment during short-term studies was of the same order after long-term treatment over 2 to 3 years and were not significantly different from the results in the short-term studies.",1994.0,0,0
1582,7986459,Effects of exercise and therapy on ventricular emptying and filling in mildly hypertensive patients.,I P Clements; K R Bailey; P K Zachariah,"Left ventricular (LV) filling was studied in 18 healthy subjects and 19 mildly hypertensive patients before and after 50% and 70% of maximal supine exercise using radionuclide ventriculography. In addition, in the hypertensive patients, the effects of oral verapamil and lisinopril treatment on LV filling before and after exercise were studied. At rest, hypertensive patients compared with healthy subjects had a lower peak filling rate, ratio of peak filling to peak emptying rate, first-half filling fraction, and a longer isovolumic duration. With exercise, LV filling measures were not different between healthy subjects and hypertensive patients. In the hypertensive patients at rest, compared with before treatment, lisinopril prolonged isovolumic duration and verapamil had no effect on LV filling; at 50% maximal exercise compared with before treatment, verapamil shortened the time to peak filling rate and isovolumic duration and increased first-half filling fraction but, at 70% maximal exercise, verapamil had no effect, whereas lisinopril did not alter exercise LV filling at either exercise level. Thus, the early abnormal LV filling in mildly hypertensive patients is influenced by therapeutic interventions both at rest and with exercise.",1994.0,0,0
1583,7986464,Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.,D Raccah; M Pettenuzzo-Mollo; O Provendier; L Boucher; J A Cozic; R Gorlier; P Huin; J Sicard; P Vague,"Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1584,7987868,Patient characteristics in cases of chronic severe heart failure with different degrees of left ventricular systolic dysfunction.,S V Eriksson; J Kjekshus; J Offstad; K Swedberg,"It has not been determined previously whether patients with severe chronic congestive heart failure differ in demographic characteristics with respect to left ventricular systolic dysfunction (LVD). In patients with severe chronic congestive heart failure in NYHA IV, an optional protocol in the CONSENSUS-I trial was designed to ascertain whether there were any differences in patient characteristics regarding the degree of LVD defined as left ventricular fractional shortening (FS). A subgroup of 54 patients from the CONSENSUS-I trial were evaluated with M-mode echocardiography. Patients with FS above median (14%) were older (74 +/- 7 vs. 68 +/- 7, p < 0.01), more often female (48 vs. 15%, p < 0.05) and had lower heart rates (77 +/- 15 vs. 95 +/- 17, p < 0.01). Analysis of the 2-year follow-up from the end of the trial was also performed. In the placebo group, patients with FS > 14% had significantly better prognosis than patients with FS < 14%. In the enalapril-treated group no such difference in survival was seen. The difference between the original treatment groups remained, despite the fact that treatment with enalapril was then made available to all surviving patients. In conclusion, patients with advanced chronic congestive heart failure and less severe LVD have different demographic characteristics than patients with more severe LVD. In the placebo group, but not in the enalapril group, prognosis was better in patients with less severe LVD.",1994.0,0,0
1585,7988608,Quality of life on enalapril after acute myocardial infarction.,O Ekeberg; T O Klemsdal; S E Kjeldsen,"Quality of life was assessed 4-6 months after an acute myocardial infarction in a randomized double-blind study of enalapril versus placebo. Quality of life was evaluated using the Nottingham Health Profile (NHP), the Physical Symptoms Distress Index (PSDI), the Work Performance Scale (WPS) and the Life Satisfaction Index (LSI). The study comprised 36 women (aged 46-85 years, mean 68) and 96 males (aged 39-81 years, mean 62). Quality of life did not differ significantly between patients treated with enalapril versus placebo. The scores were (enalapril vs placebo, mean +/- SE): average NHP 15.4 +/- 2.3 vs 17.1 +/- 2.3; PSDI 9.5 +/- 1.0 vs 10.8 +/- 0.9; WPS 19.8 +/- 2.0 vs 19.4 +/- 1.4; LSI 24.1 +/- 1.0 vs 22.5 +/- 1.4. Men reported a better quality of life than women on most assessments, and non-smokers and ex-smokers better than smokers. Patients with moderate or severe angina pectoris had a worse quality of life measured by PSDI and NHP than patients with minimal or no angina pectoris. Patients with congestive heart failure had a higher PSDI than those without (13.6 +/- 1.7 vs 9.4 +/- 0.7, P < 0.05), while no significant differences were observed in the NHP scores. In conclusion, quality of life was similar in enalapril and placebo-treated patients after an acute myocardial infarction. However, it was reduced in patients with angina pectoris or heart failure and in those who continued smoking.",1994.0,1,1
1586,7989705,Lymphocyte reactivity to ex-vivo drug antigens in drug-induced hepatitis.,V A Maria; L Pinto; R M Victorino,"The diagnosis of drug-induced hepatitis is usually based on clinical criteria, with emphasis on both the temporal relationship between drug intake and liver injury and the exclusion of alternative causes. In vitro tests of lymphocyte sensitization to drugs are considered to have a low sensitivity. We investigated the possibility of detecting lymphocyte reactivity to drugs in drug-induced hepatitis by analyzing the lymphocyte proliferative responses to ex-vivo drug or metabolite antigens to improve the sensitivity of the in vitro test. Lymphocyte proliferative responses to five different concentrations of the drug and to ex-vivo drug antigens (serum collected from normal subjects after the ingestion of the drugs) were analyzed in 25 patients with a clinical diagnosis of drug-induced hepatitis, 27 healthy subjects and 10 individuals with a recent exposure to the same drugs without development of adverse drug reactions. In seven of the 25 patients, lymphocyte reactivity to drugs was detected (28%). The use of sera collected from healthy volunteers after drug intake (ex-vivo drug antigens) and the addition of a prostaglandin inhibitor to the cultures allowed the detection of lymphocyte sensitization in seven additional cases, increasing the detection ability from 28% to 56%. We suggest that the use of ex-vivo drug antigens may represent a significant contribution to the identification of the drug involved in cases of drug-induced hepatitis.",1994.0,0,0
1587,7990098,The Hypertension in the Very Elderly Trial (HYVET).,C J Bulpitt; A E Fletcher; A Amery; J Coope; J G Evans; S Lightowlers; K O'Malley; A Palmer; J Potter; P Sever,,1994.0,0,0
1588,7990904,The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. The Survival of Myocardial Infarction Long-Term Evaluation (SMILE) Study Investigators.,E Ambrosioni; C Borghi; B Magnani,"Left ventricular dilatation and neuroendocrine activation are common after acute anterior myocardial infarction. Long-term treatment with an angiotensin-converting-enzyme (ACE) inhibitor may improve outcome by attenuating these processes. We investigated whether the ACE inhibitor zofenopril, administered for six weeks after anterior myocardial infarction, could improve both short-term and long-term outcome. A total of 1556 patients were enrolled within 24 hours after the onset of symptoms of acute anterior myocardial infarction, and they were randomly assigned in a double-blind fashion to receive either placebo (784 patients) or zofenopril (772 patients) for six weeks. At this time we assessed the incidence of death or severe congestive heart failure. The patients were reexamined after one year to assess survival. The incidence of death or severe congestive heart failure at six weeks was significantly reduced in the zofenopril group (55 patients, 7.1 percent), as compared with the placebo group (83 patients, 10.6 percent); the cumulative reduction in the risk of death or severe congestive heart failure was 34 percent (95 percent confidence interval, 8 to 54 percent; P = 0.018). The reduction in risk was 46 percent (95 percent confidence interval, 11 to 71 percent; P = 0.018) for severe congestive heart failure and 25 percent (95 percent confidence interval, -11 to 60 percent; P = 0.19) for death. After one year of observation, the mortality rate was significantly lower in the zofenopril group (10.0 percent) than in the placebo group (14.1 percent); the reduction in risk was 29 percent (95 percent confidence interval, 6 to 51 percent; P = 0.011). Treatment with zofenopril significantly improved both short-term and long-term outcome when this drug was started within 24 hours after the onset of acute anterior myocardial infarction and continued for six weeks.",1995.0,1,1
1589,7992988,Effects of antihypertensive therapy on serum lipids.,B L Kasiske; J Z Ma; R S Kalil; T A Louis,"To compare and contrast the effects of antihypertensive agents on serum lipids and blood pressure in different patient populations. A MEDLINE search and bibliographies from recent comprehensive reviews were used to identify trials that provided sufficient data to calculate the change in one or more serum lipid values measured before and after antihypertensive therapy. 474 controlled and uncontrolled clinical trials investigated the effects of 85 antihypertensive agents on lipids and blood pressure in more than 65,000 patients. Data on triglyceride and total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels; blood pressure; patient characteristics; and study design. Differences in the effects of agents, adjusted for differences in patient populations and study design, were examined using multiple linear regression analysis that was weighted by study quality and inverse variance. Diuretics caused relative increases in cholesterol levels (regression coefficient = 0.13 mmol/L; 95% CI, 0.09 to 0.18 mmol/L) that were greater with higher doses (additional effect of high dose, 0.12 mmol/L; CI, 0.04 to 0.20 mmol/L) and were worse in blacks than in nonblacks (additional effect in blacks, 0.13 mmol/L; CI, 0.01 to 0.26 mmol/L). Beta-blockers caused increases in triglyceride levels (0.35 mmol/L; CI, 0.31 to 0.39 mmol/L) that were substantially smaller for agents with intrinsic sympathomimetic activity (amelioration of beta-blocker increase, -0.21 mmol/L; CI, -0.27 to -0.16 mmol/L). When combined with cardioselectivity, beta-blockers with intrinsic sympathomimetic activity favorably affected lipids and reduced both total (-0.14 mmol/L; CI, -0.24 to -0.04 mmol/L) and LDL cholesterol levels (-0.17 mmol/L; CI, -0.28 to -0.07 mmol/L). alpha-Blockers beneficially affected total cholesterol (-0.23 mmol/L; CI, -0.28 to -0.18 mmol/L), LDL cholesterol (-0.20 mmol/L; CI, -0.25 to 0.15 mmol/L), triglycerides (-0.07 mmol/L; CI, -0.11 to -0.03 mmol/L), and, in younger persons, HDL cholesterol (0.02 mmol/L; 0.01 to 0.04 mmol/L). Converting enzyme inhibitors reduced triglycerides (-0.07 mmol/L; CI, -0.12 to -0.02 mmol/L), and, in patients with diabetes, total cholesterol (-0.22 mmol/L; CI, -0.34 to -0.10 mmol/L). Vasodilators reduced total (-0.22 mmol/l; CI, -0.30 to -0.10 mmol/L) and LDL cholesterol (-0.22 mmol/L; CI, -0.29 to -0.11 mmol/L) and increased HDL cholesterol (0.06 mmol/L; CI, 0.02 to 0.09 mmol/L). With the exception of calcium antagonists, nearly all antihypertensive agents affect serum lipids. These effects differ among patient populations.",1995.0,0,0
1590,7994448,Hemodynamic and humoral effects of low-dose aspirin in treated and untreated essential hypertensive patients.,A Magagna; B Abdel-Haq; S Favilla; S Taddei; A Salvetti,"Aspirin at low doses is used as an inhibitor of platelet aggregation and is frequently administered to essential hypertensive patients with arterial thrombotic complications. However, it is unknown whether aspirin can modify blood pressure values either in treated or untreated hypertensive patients, as described for other non steroidal anti-inflammatory drugs. Thus 30 patients. 10 with mild uncomplicated and untreated essential hypertension, 10 with essential hypertension under chronic treatment with captopril, 50 mg bid, and 10 with essential hypertension under chronic treatment with atenolol, 100 mg oid, received aspirin, 100 mg oid, and the corresponding placebo for one month, according to a double blind randomized cross-over design. At the end of each treatment, blood pressure, heart rate, generated serum thromboxane B2 and urinary excretion of thromboxane B2 and 6 keto prostaglandin F1 alpha and plasma renin activity were measured. Both in treated and untreated essential hypertensive patients, aspirin administration did not affect blood pressure, heart rate and urinary 6 keto prostaglandin F1 alpha, while it significantly reduced serum and urinary excretion of thromboxane B2 and plasma renin activity. In conclusion, while the present data confirm that low doses of aspirin selectively inhibit thromboxane B2 synthesis, they indicate that aspirin at 100 mg oid can be administered to treated and untreated essential hypertensive patients without any harmful effect on blood pressure values.",1994.0,0,0
1591,7994817,Angiotensinergic versus nonangiotensinergic hemodynamic effects of converting enzyme inhibition in patients with chronic heart failure. Assessment by acute renin and converting enzyme inhibition.,W Kiowski; J Beermann; P Rickenbacher; R Haemmerli; M Thomas; F Burkart; T Meinertz,"The contribution of nonangiotensinergic effects of converting enzyme inhibitors to their hemodynamic effects in patients with chronic heart failure is not clear. A comparison of the effects of renin and converting enzyme inhibition should help to clarify this issue. Thirty-six patients with chronic heart failure (New York Heart Association class II or III) were randomly assigned to receive double-blind either intravenous placebo, the renin inhibitor remikiren, or the converting enzyme inhibitor enalaprilat followed by coinfusion of a second placebo infusion, the addition of remikiren to enalaprilat, or the addition of enalaprilat to remikiren, respectively. Systemic hemodynamics (Swan-Ganz and radial artery catheters) were measured before (rest and submaximal recumbent bicycle ergometry), during (rest), and at the end (rest and exercise) of each 45-minute single- or combination-infusion period. Placebo did not change hemodynamics or renin activity. Effective inhibition of the renin-angiotensin system by remikiren and enalaprilat was indicated by increases of plasma immunoreactive renin together with rapid and complete inhibition of renin activity after remikiren and an increase after enalaprilat (all P < or = .05). Remikiren and enalaprilat rapidly and to a similar extent reduced resting blood pressure through a reduction of systemic vascular resistance, and these changes were significantly correlated to baseline plasma renin activity. Both compounds also decreased pulmonary artery, pulmonary capillary wedge, and right atrial pressures to a similar extent (P < .05). During exercise, pulmonary capillary wedge and right atrial pressures were equally reduced and stroke volume index was increased with remikiren and enalaprilat (P < .05) for both). The combination of converting enzyme with renin inhibition or vice versa did not cause additional hemodynamic changes. Specific renin inhibition in patients with chronic heart failure produces short-term hemodynamic effects that are almost indistinguishable from those of converting enzyme inhibition. This finding and the lack of additional effects of converting enzyme inhibition added to renin inhibition suggest that nonangiotensinergic effects of converting enzyme inhibitors do not play a significant role in their short-term hemodynamic effects in patients with chronic heart failure.",1994.0,0,0
1592,7994822,"Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade.",G M London; B Pannier; A P Guerin; S J Marchais; M E Safar; J L Cuche,"We wished to assess the respective roles of the antihypertensive and blood pressure (BP)-independent effects of antihypertensive drugs on arterial hemodynamics and left ventricular hypertrophy (LVH) in end-stage renal disease (ESRD) patients. In a double-blind study, 24 ESRD patients with LVH were randomized to 12 months' administration of either the angiotensin-converting enzyme (ACE) inhibitor perindopril (n = 14) or the calcium channel blocker nitrendipine (n = 10). Repeated measurements of the following parameters were performed: BP (mercury sphygmomanometry), left ventricular mass (LVM, echocardiography), cardiac output (aortic cross-section and velocity integral), total peripheral resistance (cardiac output and mean BP), aortic and large-artery compliance (pulse wave velocity, Doppler flowmeter), and arterial wave reflections (augmentation index, applanation tonometry). Radioimmunoassay was used to determine plasma renin activity, aldosterone, and plasma catecholamine levels. Two-way (time-treatment) ANOVA for repeated measures was used for statistical analysis. Perindopril and nitrendipine induced significant and similar decreases in BP, total peripheral resistance (P < .001), aortic and arterial pulse wave velocities (P < .001), and arterial wave reflections (P < .01). At baseline, the two groups had LVH mostly due to increased LV end-diastolic diameter (LVEDD) (perindopril, 54.3 +/- 1.4 and nitrendipine, 54.3 +/ 2.4 mm) with near-normal mean LV wall thickness (perindopril, 11.4 +/- 0.3 and nitrendipine, 11.2 +/- 0.4 mm). A decrease in LVM was observed only in patients receiving perindopril (from 317 +/- 18 to 247 +/- 21 g) (time-treatment interaction, P = .036). Nitrendipine had no significant effect on LVM (314 +/- 29 versus 286 +/- 32 g). The decrease in LVM observed with perindopril was associated with a reduction in LVEDD (49.9 +/- 1.6 versus 54.3 +/- 1.4 mm after 12 months) (time-treatment interaction, P = .04), while the mean LV wall thickness was unchanged (11.4 +/- 0.3 versus 10.5 +/- 0.5 mm). Cardiac alterations were not correlated with changes in BP or with alterations in plasma renin activity or aldosterone or catecholamine levels. In ESRD patients with LVH, ACE inhibition decreases LVM independently of its antihypertensive effect and of associated alterations in arterial hemodynamics. The decrease in LVM was due primarily to a decrease in LV volume, which may have resulted in these patients from chronic volume overload.",1994.0,0,0
1593,7995270,"ACE inhibitors and their influence on inflammation, bronchial reactivity and cough.",R G Andersson; K Persson,"Orally active angiotensin converting enzyme (ACE) inhibitors have been successfully used in the treatment of congestive heart failure and hypertension. However, adverse skin reactions, such as angioneurotic oedema have been reported following such medication. Furthermore, these drugs have been associated with a persistent dry cough in subjects without previous known bronchial hyper-reactivity. There is reason to believe that an ACE inhibitor-induced cough is due to an irritant inflammatory state in the airways of susceptible individuals and that this might have pathophysiological features in common with the cough seen as an early symptom of asthma. All inflammatory responses--wheal and flare reactions, airway reactivity, and infiltration by neutrophils and eosinophils--were enhanced by ACE inhibitors in a dose-dependent manner. Other ACE inhibitors might have different proinflammatory profiles.",1994.0,0,0
1594,7995312,A comparison of lisinopril and nifedipine in the treatment of mild to moderate hypertension. A multicentre study.,B Rogstad,"Lisinopril has been compared with slow-release nifedipine in a 16-week double-blind, randomized, parallel-group study involving 102 patients with mild to moderate hypertension. Sitting systolic and diastolic blood pressures were reduced 6 and 5 mmHg more by lisinopril than by nifedipine over 12 weeks monotherapy. After 12 weeks a greater proportion of patients taking lisinopril was controlled (sitting diastolic blood pressure below 95 mm Hg) than in those taking nifedipine. As a result, 17% of those taking lisinopril and 38% of those taking nifedipine required additional therapy with hydrochlorothiazide. The addition of hydrochlorothiazide resulted in similar response rates in the lisinopril and nifedipine groups (89% and 75% respectively). The rate of reporting of adverse events considered to be drug-related and the rate of withdrawals were similar for both treatments. Cough was more often reported with lisinopril and headache, sweating, and hot flushes with nifedipine. We conclude that once-daily titrated doses of lisinopril produced better control of blood pressure than twice-daily titrated doses of nifedipine.",1994.0,0,0
1595,8004831,Clinical and histopathologic associations with impaired renal function in IgA nephropathy. Mayo Nephrology Collaborative Group.,J V Donadio; E J Bergstralh; K P Offord; K E Holley; D C Spencer,"A multicenter, double-blind, placebo-controlled, randomized trial of fish oil in proteinuric patients with IgA nephropathy is being conducted by the Mayo Nephrology Collaborative Group. We completed enrollment of 106 patients into the trial in December 1991. The treatment period is for two years. Hypertension is being managed in all patients with enalapril maleate (Vasotec). We evaluated the associations between a variety of clinical and renal morphologic features and renal function at the entry of all enrolled patients. Among 78 males and 28 females [age(mean +/- SD) 36 +/- 14 years], older age at treatment randomization, hypertension, at disease discovery as well as at study entry, increased fractional excretion of albumin, increased serum triglyceride levels, and more severe tubulointerstitial, vascular, and combined glomerular and tubulointerstitial histologic lesions were all univariately associated (p < or = 0.01) with poorer renal function measured by reciprocal serum creatinine and creatinine clearance levels. In a multiple regression analysis used to predict baseline reciprocal creatinine, the best final model (R2 = 0.48) included male sex (p < .001), hypertension at treatment randomization (p = .001), decreased peripheral blood erythrocytes (p = .001), increased tubulointerstitial score (p = .004), and increased fractional excretion of albumin (p = .025) as independent predictors of decreased kidney function. These associations are similar to those seen in the high-risk subset of patients with IgA nephropathy who develop end-stage renal disease. In the eventual outcome analysis of the clinical trial, we will examine the effects of treatment on the two potentially modifiable risk factors, hypertension and proteinuria, on renal function.",1994.0,0,0
1596,8005124,Comparison of two methods of determining renal perfusion with and without captopril pretreatment in groups of patients with left ventricular dysfunction.,J G Motwani; M K Fenwick; A D Struthers,"Methods of effective renal plasma flow measurement by 125I-orthoiodohippurate elimination and para-aminohippurate clearance were compared with and without captopril pretreatment in 10 chronic heart failure patients and in 20 patients after transmural myocardial infarction. In the chronic heart failure group measurements of effective renal plasma flow by the two techniques were strongly correlated (r = 0.92, P < 0.00001), as was the captopril-mediated change in effective renal plasma flow by the two methods (r = 0.85, P = 0.002). However, in absolute terms para-aminohippurate clearance significantly exceeded 125I-orthoiodohippurate clearance by a mean (+/- SD) of 24.8 +/- 43.7 ml.min-1 (P < 0.05) so that only using the former technique was a significant increment in renal perfusion observed in response to converting enzyme inhibition. In the post-myocardial infarction group, correlations between the two methods were variable and much poorer than in the chronic heart failure group (r = 0.54, P = 0.01 and r = 0.74, P = 0.002 on consecutive days). Furthermore, captopril-mediated increments in effective renal plasma flow by the two techniques were unrelated (r = -0.19, P = 0.59). In this group 125I-orthoiodohippurate elimination significantly exceeded para-aminohippurate clearance (P < 0.05). This reversed association and the weaker relationships between methods in post-infarction as compared to chronic heart failure patients may be related to interference by thrombolytic or aspirin treatments.",1994.0,0,0
1597,8005126,Can anaerobic threshold be used as an end-point for therapeutic trials in heart failure? Lessons from a multicentre randomized placebo-controlled trial. The VO2 French Study Group.,A Cohen-Solal; J F Aupetit; P Gueret; H Kolsky; F Zannad,"Anaerobic threshold (AT), proposed as a non-invasive index of exercise tolerance, independent of patient motivation, is considered more reliable than exercise duration in assessing the effect of drug therapy in chronic heart failure (CHF). However, inter-observer variation in patients may be more difficult than in normal subjects. In a multicentre study, 85 patients from 10 centres performed a total of 331 bicycle maximal tests (ramp protocols, 10 watts.min-1) with respiratory gas analysis by different systems. A central committee reviewed all the tests. Percentages of AT determination ranged from 34% to 71% depending on the method used. Apart from the respiratory exchange ratio (RER) method, which yielded the lowest rate of determination: 34%, and the crossing point (when RER = 1), which yielded the highest rate, 71%, other methods of determination, such as carbon dioxide (42%), minute ventilation (52%) or ventilatory equivalents plotted vs time (57%), did not differ in the rate of AT determination. Thus, even among trained physicians, AT determination was not reliable. The crossing point may nevertheless be a valuable index from a pragmatic standpoint, although it occurs after the actual AT. Peak oxygen uptake should remain the main end-point in assessment of exercise capacity.",1994.0,0,0
1598,8005128,Effects of ramipril on the neurohormonal response to exercise in patients with mild or moderate congestive heart failure.,A Sigurdsson; K Swedberg; B Ullman,"Static measurements of plasma neurohormones at rest may not be adequate to detect alterations in cardiovascular control mechanisms in congestive heart failure (CHF). Therefore, it is of interest to study neurohormonal activation during different physiological conditions. Plasma neurohormones were measured in 54 patients on diuretic therapy for mild or moderate CHF. Samples were taken at rest and immediately after maximal bicycle exercise, before and after 12 weeks of treatment with ramipril or placebo. There was a strong correlation between the plasma levels of each hormone before and after exercise. An inverse correlation existed at baseline between exercise duration and angiotensin II levels after maximal exercise (r = -0.30, P = 0.03), but not at rest. Plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and noradrenaline were increased after maximal exercise compared to rest. Plasma angiotensin converting enzyme activity and ANP were reduced by ramipril compared to placebo, both at rest and after exercise, but levels of angiotensin II, aldosterone and nordrenaline were not significantly affected. Thus, exercise consistently activates neurohormonal systems in patients with CHF. Patients with the lowest exercise duration had the highest angiotensin II levels after exercise. Measurements of plasma neurohormones after maximal exercise provide limited additional value to measurements at rest.",1994.0,0,0
1599,8005182,Central effects of repeated administration of atenolol and captopril in healthy volunteers.,D G McDevitt; D Currie; A N Nicholson; N A Wright; M B Zetlein,"The central effects of atenolol (50 mg tds) and captopril (50 mg tds) ingested for a period of seven days were studied in ten healthy volunteers. A placebo and two active control drugs, methyldopa (250 mg tds) and oxazepam (10 mg), were included in the design. Oxazepam was ingested on the seventh day only, with a placebo being taken on the preceding six days. On the seventh day, central effects of the drugs were tested at 10.00-11.00 h (session 1), immediately before the subjects' last dose of each drug and at 2.5-3.5 h after the final dose of each drug (1330-1430 h, session 2). Performance was assessed using digit symbol substitution, continuous attention, letter cancellation, choice reaction time, finger tapping, immediate and short-term memory, critical flicker fusion and two flash fusion. Subjects assessed their mood and well-being on a series of 12 visual analogue scales. Recordings of the EEG and body sway were carried out. Neither atenolol nor captopril altered performance at any of the skills tested. There were no effects on subjectively assessed alertness or mood with captopril, while atenolol significantly increased wakefulness in session 2 and when the two sessions were meaned. Similarly, captopril did not modify body sway, while with atenolol there was a significant decrease in activity in the frequency range 1.0-2.75 Hz from session 1 to session 2.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1600,8006284,"Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction.",R A Wright; A D Flapan; K G Alberti; C A Ludlam; K A Fox,"This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction. Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease. In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity. Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02). Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.",1994.0,0,0
1601,8006914,Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group.,D Canter; G J Frank; L E Knapp; M Phelps; M Quade; M Texter,"A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril) in combination with the diuretic hydrochlorothiazide (HCTZ) to assess the additive effects of the combination versus monotherapy, to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ. Following a two to four week placebo-baseline period, 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were randomised to an eight week double-blind phase with one of 16 parallel treatments: placebo, one of three doses of quinapril monotherapy, one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ. Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg (n = 458). Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ. The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril. At 40 mg quinapril, the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril. Thus, the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ.",1994.0,0,0
1602,8008712,Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers.,K K Chan; A Buch; R D Glazer; V A John; W H Barr,"The absorption of benazepril-HCl (BZPH), an orally active angiotensin-converting enzyme (ACE) inhibitor, in various regions of the gastrointestinal (GI) tract was investigated using an intestinal intubation technique. Thirteen subjects completed this single-dose, three-phase sequential crossover study. The drug (20 mg) was administered either as a 4-hr colonic infusion (COLON) or as a small intestinal infusion (SI) in the first two phases and as an oral bolus solution (ORAL) in the third phase, with a 2-week washout between each treatment. Serial plasma and urine samples were collected for up to 4 days after dosing. BZPH and its active metabolite benazeprilat (BZPL) were determined using a gas chromatography/mass spectrometry method. BZPH was absorbed rapidly into the bloodstream (Tmax = 0.5 hr after ORAL). Absorption was also rapid for SI, with a postinfusion half-life (0.57 hr) nearly identical to that for ORAL (0.59 hr). The absorption rate after COLON was much slower (lower Cmax and longer Tmax) compared to that after SI, and the apparent half-life (1.7 hr) was prolonged. SI delivered 90%, whereas COLON delivered 23%, of the drug into the systematic circulation as compared to ORAL. BZPL was rapidly formed upon drug absorption. The metabolite-to-drug AUC ratios were comparable for SI and ORAL (8.9 vs 9.7), indicating that first-pass metabolism of BZPH was neither saturable nor input rate dependent. The metabolite-to-drug AUC ratio was reduced for COLON (5.0), indicating that the mechanism of absorption of BZPH in the colon may be different than that after SI and ORAL. Urinary recovery data were consistent with plasma data.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1603,8017381,"Abdominal pain, angioedema, and angiotensin-converting enzyme inhibitors.",F A Farraye; M A Peppercorn,,1994.0,0,0
1604,8021054,"Acute cardiovascular effects of the concurrent administration of enalapril, prazosin or amlodipine in healthy Nigerians.",A A Ajayi; M A Raji,"The acute circulatory effects of the combination of prazosin 1 mg, enalapril 10 mg or amlodipine 5 mg were evaluated and compared in a placebo controlled, randomised, double blind, latin-square, cross-over study in 8 normotensive healthy Nigerians. Supine and erect blood pressure were reduced by the active treatment combinations (F = 8.8, P = 0.0006, analysis of variance). In all, the onset of blood pressure fall was within 2 h, with a peak reduction at 4-6 h and persisting for at least 12 h. The combination of converting enzyme inhibitor and alpha blocker, however, caused a significantly greater hypotensive action than the other combinations (P < 0.05, analysis of variance). There was a modest reflex tachycardia in the erect position on all treatments (P = 0.008). Cardiac autonomic reflexes or left ventricular echocardiographic indices were unaffected by the drug combinations. The haemodynamic effect of enalapril plus prazosin combination, which separately cause little hypotensive effect in Africans, may reflect an important pharmacodynamic interaction between alpha 1 and angiotensin II vascular receptors. All combinations lower blood pressure and warrant further study in Nigerian hypertensives. However, the enalapril plus prazosin combination caused the greatest blood pressure fall, and caution is indicated during their concurrent use, owing to enhanced first dose hypotension.",1994.0,0,0
1605,8025983,Ventricular arrhythmias in the acute and chronic phases after acute myocardial infarction. Effect of intervention with captopril.,P Søgaard; C O Gøtzsche; J Ravkilde; A Nørgaard; K Thygesen,"Ventricular arrhythmias (VAs) are independent predictors of mortality in survivors of myocardial infarction (MI), and they are more likely to be induced in dilated hearts with increased wall stress. Angiotensin-converting enzyme (ACE) inhibitors have been shown to prevent progressive dilation of the left ventricle after MI. The effects of captopril were evaluated in 58 patients with left ventricular (LV) dysfunction after MI. Patients were randomized on day 7 to either placebo or captopril (50 mg daily) in a double-blind parallel study over a period of 6 months. Patients were followed up by means of ambulatory ECG monitoring and echocardiography. There was a significant increase in VA in the placebo group (P < .05) in contrast to a significant decrease in the captopril group (P < .05). As a consequence, there was a significant between-group difference after 6 months (P < .05). Furthermore, the number of patients without VA at baseline who presented with this at the completion of the study was 6% in the captopril group versus 38% in the placebo group (P < .05). At baseline as well as at the termination of the study, LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) were significantly increased among patients with VA (P < .01). On day 180, both myocardial ischemia and an increase in the LVEDVI were independent predictors of VA; however, progressive dilation of the left ventricle was confined to the placebo patients with significant increases in the LVEDVI compared with the captopril group: 17% versus 0%, respectively (P < .01). Furthermore, the duration of ambulatory ST-segment depression was significantly longer in this group compared with the captopril group (P < .01). Dilation of the left ventricle and myocardial ischemia predict VA during both the acute and chronic phases after MI. In post-MI patients with LV dysfunction, captopril has a beneficial effect on both the number of complex VAs as well as the number of patients who develop VA during the chronic phase. This is in all probability mediated through effects on both LV remodeling, LV function, and myocardial ischemia in patients who are exposed to an increased risk of undergoing progressive dilation of the left ventricle.",1994.0,0,0
1606,8025984,Effects of converting enzyme inhibition on heart period variability in patients with acute myocardial infarction.,D Bonaduce; F Marciano; M Petretta; M L Migaux; G Morgano; V Bianchi; L Salemme; G Valva; M Condorelli,"Heart period variability provides useful prognostic information on autonomic cardiac control, and a strong association has been demonstrated after myocardial infarction (MI) between cardiac mortality, sudden death, and reduced total power, ultralow-frequency (ULF) power, and very-low-frequency (VLF) power. Converting enzyme inhibitors are widely used in MI patients, but their influence on heart period variability remains to be defined. Time- and frequency-domain measures of heart period variability were calculated from 24-hour Holter monitoring in 40 patients with a first uncomplicated MI. After baseline examination between 48 and 72 hours after symptom onset, patients were randomly assigned to placebo or captopril administration, and on the third day, 24-hour Holter monitoring was repeated. No changes in time and frequency domain were detectable after placebo. After captopril, the SD of all normal RR (NN) intervals (SDNN) increased from 90 +/- 29 to 105 +/- 30 milliseconds (P < .01); the SD of the average NN intervals for all 5-minute segments (SDANN index) and the mean of the SDs of all NN intervals for all 5-minute segments (SDNN index) also increased from 74 +/- 24 to 90 +/- 26 milliseconds (P < .01) and from 45 +/- 17 to 49 +/- 15 milliseconds (P < .05), respectively. The root mean square successive difference (r-MSSD) and the percent of differences between adjacent NN intervals > 50 milliseconds (pNN50) remained unchanged. In regard to frequency-domain measures, after captopril, total power (ln unit) increased from 8.28 +/- 0.42 to 8.47 +/- 0.30 (P < .01); considering the frequency bands, a significant increase was observed in ULF (P < .01), VLF (P < .05), and low-frequency (LF) power (P < .05), whereas high-frequency (HF) power remained unchanged. This study supports the hypothesis that the renin-angiotensin system modulates the amplitude of ULF and VLF power. Furthermore, it demonstrates that in MI patients, converting enzyme inhibition favorably modifies measures of heart period variability strongly associated with a poor prognosis.",1994.0,0,0
1607,8026000,Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition.,J M Good; A J Brady; F H Noormohamed; C M Oakley; J G Cleland,"Contrary to expectation, most studies have demonstrated that initiation of an angiotensin-converting enzyme (ACE) inhibitor in conventional doses in patients with heart failure reduces the diuretic efficacy of furosemide. Recently, it has been suggested that single low doses (1 mg) but not high doses (25 mg) of captopril enhance furosemide-induced diuresis. It is not known whether the interaction between diuretics and ACE inhibitors are altered during long-term dosing. Eight patients with heart failure treated with diuretics and ACE inhibitors for at least 3 months were studied. All patients were established on captopril 12.5 mg three times daily for 2 weeks before the study. Sodium intake was fixed before the study, and usual medication was withheld on study days. Intravenous furosemide was given on each of 2 study days to maintain a moderate, constant diuresis. Renal plasma flow and glomerular filtration rate (GFR) were determined using clearance techniques, and urine was collected hourly over 4 hours. Captopril 12.5 mg or placebo was given in a randomized, single-blind fashion at the end of the first hour. Compared with placebo, captopril reduced plasma concentrations of angiotensin II (23 +/- 18 versus 4 +/- 3 pg/ml 1 hour after dosing, P < .02) and systolic (131 +/- 31 versus 122 +/- 29 mm Hg, P < .01) and diastolic (74 +/- 15 versus 67 +/- 13 mm Hg, P < .05) blood pressures. GFR fell (55 +/- 24 versus 51 +/- 22 mL/min, P < .02) and effective renal plasma flow rose during the first (198 +/- 76 versus 231 +/- 49 mL/min) and second hours after dosing (185 +/- 69 versus 247 +/- 74 mL/min, P < .02). Similarly, urine volumes, in response to furosemide, increased after captopril (238 +/- 90 versus 283 +/- 111 mL, P < .05, and 245 +/- 78 versus 311 +/- 92 mL, P < .01, 1 and 2 hours after dosing). Urinary electrolyte concentrations fell, but total urinary sodium (22 +/- 7 versus 28 +/- 12 mmol/hr, P < .01) and chloride (20 +/- 6 versus 25 +/- 11 mmol/hr, P < .05) excretion increased in the 2 hours after dosing, as did fractional excretion of sodium (urinary sodium/urinary creatinine) (61 +/- 27 versus 75 +/- 36 mmol/mumol, P < .01). Intense although transient ACE inhibition with captopril enhances the diuretic effects of furosemide during long-term ACE inhibition.",1994.0,0,0
1608,8026195,"Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.",R Pacher; S Globits; M Wutte; S Rödler; G Heinz; G Kreiner; S Radosztics; R Berger; I Presch; H Weber,"To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. Prospective, placebo-controlled, randomized, single-blind study. Intensive care unit at a university hospital. Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.",1994.0,0,0
1609,8031212,Minocycline pneumonitis and eosinophilia. A report on eight patients.,O Sitbon; N Bidel; C Dussopt; R Azarian; M L Braud; F Lebargy; T Fourme; F de Blay; F Piard; P Camus,"We identified eight patients (six women and two men) who had pulmonary infiltrates during treatment with minocycline hydrochloride between 1989 and 1992 in French referral centers for drug-induced pulmonary diseases. Clinical files, chest roentgenograms, computed tomographic scans, pulmonary function, and bronchoalveolar lavage data were reviewed. Minocycline treatment was given for acne (n = 4), genital infection (n = 3), and Lyme disease (n = 1). The duration of treatment averaged 13 +/- 5 days (mean +/- SE); the total dose, 2060 +/- 540 mg. Patients presented with dyspnea (n = 8), fever (n = 7), dry cough (n = 5), hemoptysis (n = 1), chest pain (n = 2), fatigue (n = 3), and rash (n = 3). Chest roentgenograms showed bilateral infiltrates in all cases. Pulmonary function was measured in five patients; four had airflow obstruction and two had mild restriction. Blood gas tests demonstrated hypoxemia in seven patients (58 +/- 3 mmHg). Seven patients had blood eosinophilia (1.76 +/- 0.2 x 10(9)/L). Bronchoalveolar lavage (performed in seven patients) showed an increased proportion of eosinophils (0.30 +/- 0.07). The Cd4+/CD8+ ratio was determined in four cases and was low in three. Transbronchial lung biopsy, performed in two patients, showed interstitial pneumonitis in both patients, with marked infiltration by eosinophils in one patient. The outcome was favorable in all patients. Because of severe symptoms, steroid therapy was required in three patients. Rechallenge was not attempted. We conclude that minocycline can induce the syndrome of pulmonary infiltrates and eosinophilia, that presenting symptoms may be severe and may culminate in transient respiratory failure, and that the disease has a favorable prognosis.",1994.0,0,0
1610,8031548,Effects of antihypertensive medications on quality of life in elderly hypertensive women.,S H Croog; M F Elias; T Colton; R M Baume; S R Leiblum; C D Jenkins; H M Perry; W D Hall,"The impact of antihypertensive medications on the quality of life of elderly hypertensive women has rarely been systematically evaluated in large clinical trials using drugs from the new generations of pharmaceutic preparations. We carried out a multicenter, randomized double-blind clinical trial with 309 hypertensive women aged 60 to 80 years to assess effects of atenolol, enalapril, and isradipine on measures of quality of life over a 22-week period. The patients had mild to moderate hypertension. Hydrochlorothiazide was added to treatment if monotherapy was inadequate in lowering blood pressure. At the conclusion of the trial the three drug groups did not differ in degree of reduction of diastolic blood pressure or in supplementation with hydrochlorothiazide. Over the 22-week trial, linear trend analysis showed no differences between the treatment groups in change from baseline on quality of life measures of well-being, physical status, emotional status, cognitive functioning, and social role participation. Regarding each of 33 physical side effects over the 22 weeks, we found no general difference between atenolol, enalapril, and isradipine groups on measures of change in distress over symptoms except for enalapril patients who worsened in distress over cough (P = .001) and atenolol patients who worsened in distress over dry mouth (P = .014). Centering on three medications that are relatively new additions to the armamentarium for blood pressure control, the findings underline the increasing opportunities for the physician to select drugs that can control blood pressure while maintaining the quality of life of elderly hypertensive women.",1994.0,0,0
1611,8031555,Effectiveness of blood pressure control with once daily administration of enalapril and perindopril.,A Anderson; O Morgan; T Morgan,"Ten patients who had their blood pressure controlled with enalapril (10 mg, n = 4; 20 mg, n = 6) and 10 control subjects on perindopril (4 mg, n = 6; 8 mg, n = 4) entered a double-blind crossover study. They received placebo or the active drug 1 week apart and had their blood pressure measured at 0, 2, 3, 4, and 24 h. Then they crossed over to the other angiotensin-converting enzyme inhibitors (4 mg perindopril congruent to 10 mg enalapril) and the double-blind study was repeated. Blood pressure control 2 to 4 h after drug administration was similar with both drugs (perindopril = 150 +/- 2/80 +/- 1; enalapril = 150 +/- 2/81 +/- 1). Twenty-four h after administration of perindopril blood pressure was lower than on enalapril (perindopril = 154 +/- 3/85 +/- 2; enalapril = 159 +/- 3/89 +/- 2). Enalapril, 2 to 4 h after administration, caused a greater decrease than placebo, whereas the change with perindopril did not differ from placebo. Twenty-four hours after receiving the active drug the blood pressure of subjects on perindopril did not differ from the peak effect when corrected for placebo and circadian variation, whereas the blood pressure on enalapril was higher. This study indicates that perindopril in the doses used has a longer duration of action than enalapril and is more suited to once daily use.",1994.0,0,0
1612,8031705,"A long-term, double-blind, comparative study on quality of life during treatment with amlodipine or enalapril in mild or moderate hypertensive patients: a multicentre study.",P Omvik; E Thaulow; O B Herland; I Eide; R Midha; R R Turner,"The efficacy, tolerability and impact on quality of life of amlodipine and enalapril were compared in a multicentre, double-blind, general practice study in 461 mild and moderate hypertensives over a 50-week active treatment period. Amlodipine (5-10 mg, once daily) and enalapril (10-40 mg, once daily) were found to be similarly effective in lowering blood pressure while not adversely affecting quality-of-life parameters. However, 20% of the enalapril group compared with 11% of the amlodipine group required the addition of hydrochlorothiazide for blood pressure control (P < 0.01). Diastolic blood pressure was normalised or reduced by 10 mmHg in 204 (90%) patients on amlodipine and in 190 (85%) patients on enalapril. Side-effects were, in general, mild or of little clinical significance. The major side-effects recorded were class-typical of ACE inhibitors and calcium antagonists, namely cough (enalapril) and oedema (amlodipine), respectively. Tolerability was very good, with only 17 patients (8 amlodipine, 4%; 9 enalapril, 4%) being withdrawn from the study due to side-effects definitely related to treatment. Amlodipine monotherapy produced a slightly beneficial effect on blood lipid concentration, and both drugs reduced the calculated 10-year risk of coronary heart disease. It was concluded that the calcium antagonist amlodipine compared favourably with the ACE inhibitor enalapril in terms of antihypertensive efficacy, tolerability and impact on quality of life.",1994.0,0,0
1613,8037104,Tolerability of enalapril initiation by patients with left ventricular dysfunction: results of the medication challenge phase of the Studies of Left Ventricular Dysfunction.,J B Kostis; B J Shelton; S Yusuf; M B Weiss; R J Capone; C J Pepine; G Gosselin; F Delahaye; J L Probstfield; L Cahill,"Although converting-enzyme inhibitors are useful for the treatment of congestive heart failure (CHF), there are concerns about adverse reactions especially on initiation of therapy. In the Studies of Left Ventricular Dysfunction, enalapril, 2.5 mg twice per day was given on an open-label outpatient basis for 7 days (mean 6.1, range 2 to 7, and median 7) as a prerandomization drug challenge to 7487 patients with left ventricular dysfunction (ejection fraction < or = 0.35). Four hundred forty-four (5.93%) patients reported side effects, including symptoms attributed to hypotension (in 166 patients [2.2%]). The majority (346 [77.9%] of 444 and 129 [77.7%] of 166 with symptoms attributed to hypotension) of patients who reported side effects were willing to participate in the study and to continue receiving enalapril. Thus only 98 (1.3%) of 7487 patients (0.5% because of symptoms attributed to hypotension) were not willing to continue because of side effects. Women and patients of CHF class III or IV were more likely to report side effects. In conclusion, enalapril is well tolerated by patients with left ventricular dysfunction; treatment can be initiated on an outpatient basis in the majority of patients.",1994.0,0,0
1614,8037993,Lack of effect of nitrates on exercise tolerance in patients with mild to moderate heart failure caused by coronary disease already treated with captopril.,S Wieshammer; M Hetzel; J Hetzel; M Kochs; V Hombach,"To test the hypothesis that the addition of nitrates improves exercise tolerance in patients with heart failure caused by coronary artery disease already treated with an angiotensin converting enzyme inhibitor and diuretics. Randomised, double blind, placebo controlled, 16 week treatment periods. Outpatient clinic at a university hospital. 54 patients with previous myocardial infarction, symptoms of mild to moderate heart failure, left ventricular ejection fraction below 40%, no exercise-induced angina or electrocardiographic signs of ischaemia. Four patients in the nitrate group (n = 24) and one patient of the placebo group (n = 25) were withdrawn from the study. After the patients had been on constant doses of captopril and diuretics for at least 2 weeks, they were randomised to receive a target dose of 40 mg isosorbide dinitrate twice daily or placebo in addition to the continuation of captopril and diuretics. Bicycle exercise tests with measurement of gas exchange were carried out before randomisation and after 1, 6, 12, and 16 weeks of the double blind treatment. The change in peak oxygen uptake from control to week 16 was prospectively defined as the main outcome measure. The increase in peak oxygen uptake from before randomisation tended to be greater in the placebo group (before randomisation 17.4 (3.4) ml/min/kg) than in the nitrate group (before randomisation 17.1 (3.5) ml/min/kg) after 12 weeks (mean increase 1.1 (2.7) v 0.0 (2.7) ml/min/kg, p < 0.12) and 16 weeks (1.7 (3.0) v 0.3 (2.6) ml/min/kg, p < 0.14) of treatment. The addition of nitrates to a baseline treatment consisting of captopril and diuretics did not improve exercise tolerance.",1993.0,0,0
1615,8039405,"Survival of myocardial infarction long-term evaluation (SMILE) study: rationale, design, organization, and outcome definitions.",E Ambrosioni; C Borghi; B Magnani,"The rationale, design, organization, and outcome definitions of the Survival of Myocardial Infarction Long-term Evaluation (SMILE) study are described in detail. Recruitment of a total of 1500 patients (750 per treatment group) has been planned for this multicenter, double-masked, randomized, placebo-controlled trial investigating the effects of oral treatment with zofenopril calcium (7.5-30 mg twice a day) on the combined short-term total mortality and occurrence of severe refractory congestive heart failure in patients with acute anterior myocardial infarction (AMI). Secondary outcomes of the study include recurrent myocardial infarction, angina, and progression of congestive heart failure, as well as long-term mortality. Patients are initially treated in hospital within 24 hr from the onset of symptoms of AMI and their active follow-up is continued for 6 weeks. In addition, the patients will be passively followed for 12 months from the index AMI to assess vital status and the occurrence of congestive heart failure. The trial data are analyzed on an intention-to-treat basis. An international independent policy and safety monitoring board is acting as the overall supervisory body and is responsible for the ethical conduct of the trial. A scientific committee is responsible for the scientific aspects of the trial and for the regular review of the progress of the study.",1994.0,0,1
1616,8044157,Quality of life among patients post-myocardial infarction at baseline in the Survival and Ventricular Enlargement (SAVE) trial.,L Gorkin; M J Follick; E Geltman; P Hamm; J Sollano; S Sylvia; K Jacobson; M J Jacobson; B S Cochrane; B Sussex,"A quality of life ancillary study was incorporated into the Survival and Ventricular Enlargement (SAVE) trial of captopril versus placebo among patients who survived an acute myocardial infarction with compromised ventricular functioning, but no overt heart failure. Assessments included patient symptoms, health perceptions, emotional, cognitive, social and sexual levels of functioning, as well as potential covariates, such as life events and social support. The purpose of this study was to evaluate the psychometric properties of the quality of life measures in the SAVE at baseline, and provide a pre-randomization profile of the SAVE patients. One hundred and eighty-four patients participated in this aspect of the trial. Reliability alpha coefficients were adequate or better for all questionnaires, except for life events and sexual activities. Consistent with prior studies, the quality of life parameters were uncorrelated with ventricular ejection fraction. Despite experiencing a recent myocardial infarction with compromised ventricular functioning, patients at baseline generally neither appeared depressed nor focused on symptoms. The baseline findings support the inclusion of the quality of life ancillary study in the overall SAVE trial because of the independent contribution likely to be achieved in terms of evaluating both disease progression and treatment efficacy.",1994.0,0,1
1617,8049587,Pharmacologic treatment of heart failure with standard drugs.,B Pitt,"During 1993 the indications for the use of angiotensin-converting enzyme (ACE) inhibitors were expanded to include patients with left ventricular dysfunction and acute myocardial infarction. The role and use of ACE inhibitors in patients with chronic systolic ventricular dysfunction, established in earlier trials, has been further clarified. Increasing attention is being focused on ACE inhibitors, specifically the mechanisms by which they improve mortality, their side effects, and the possibility of further increasing their use by avoiding renal dysfunction and first-dose hypotension. Although most of the interest has centered on ACE inhibitors, the importance of diuretics and their use in combination with ACE inhibitors is being clarified. Most important has been the demonstration over the past year of the effectiveness of digoxin in preventing cardiac deterioration in patients with systolic left ventricular dysfunction and sinus rhythm. The increased understanding of the renin-angiotensin-aldosterone system, its modification by ACE inhibitors, and the interaction of ACE inhibition with other drugs provides the basis for a further improvement in morbidity and mortality in patients with heart failure.",1994.0,0,0
1618,8052354,Henoch-Schoenlein purpura and angiotensin-converting enzyme inhibitors.,J Neumann; K Andrassy; I Walter-Sack; P A Berg,,1994.0,0,0
1619,8053053,Efficacy of captopril on posttransplant erythrocytosis. Long-term follow-up.,J V Torregrosa; J M Campistol; M Montesinos; A G Rogada; F Oppenheimer; J Andreu,"Posttransplant erythrocytosis (PTE) represents a common complication in allograft recipients with normal renal function. Although the pathogenesis is not completely known, an alteration in the regulation of erythropoietin production by native kidneys or by renal allograft have been implicated as the main causes. Traditional therapies include repeated phlebotomies, bilateral native nephrectomies, and anticoagulant therapy. Recently, theophylline has been proposed as an effective therapy, although without general acceptance. Also, angiotensin-converting enzyme inhibitors have been involved in the development of anemia in chronic renal failure and dialysis patients. The aim of the present study was to demonstrate the efficacy of captopril on long-term treatment of PTE. Nineteen renal allograft recipients affected with severe PTE were included in the study. All patients had their native kidneys and none had a renal tumor or hydronephrosis. Restrictive criteria for PTE were applied to all patients and other causes of erythrocytosis were rationally excluded. Captopril was administered at a dose of 25 mg/24 hr (12.5 mg b.i.d.) during 12 months and no change on the initial dose was made during follow-up. After 3 months of captopril therapy and during the study period, significant reductions in hematocrit (P < 0.001), hemoglobin (P < 0.001), and RBC count (P < 0.001) were obtained in all patients. Erythropoietin levels decreased significantly during the study period, although the values were within the normal range of our laboratory. Captopril was well tolerated and only 1 patient had to be withdrawn from the drug because of dry cough. The present study has shown that captopril, at a low dose, represents a safe and effective therapy for PTE, without remarkable side effects or graft dysfunction. Long-term treatment with captopril in PTE did not induce anemia.",1994.0,0,0
1620,8053578,Influence of chronic angiotensin-converting enzyme inhibition on anesthetic induction.,P Coriat; C Richer; T Douraki; C Gomez; K Hendricks; J F Giudicelli; P Viars,"Several cases of hypotension have been reported in patients who received angiotensin-converting enzyme inhibitors (ACEIs) before a surgical procedure, suggesting that interactions between ACEIs and anesthesia may be neither beneficial nor predictable. To determine if continuation of ACEI therapy until the morning of surgery leads to an unacceptable decrease in blood pressure on induction, we investigated 51 vascular surgical patients that were chronically treated for hypertension with either captopril or enalapril. After randomization, ACEI therapy was either continued until the morning of surgery or stopped at the time of the preanesthetic visit, at least 12 h (captopril) or 24 h (enalapril) before surgery. Each patient received a standardized anesthetic induction. If systolic blood pressure (monitored using a radial artery cannula) decreased to less than 90 mmHg in response to induction, ephedrine was administered. A marked decrease in plasma converting-enzyme activity was found in patients who received enalapril until the morning of the surgical procedure, and 100% of them required ephedrine after induction. In patients who received their usual dose of captopril on the morning of surgery, plasma converting-enzyme activity was reduced to a lesser extent (when compared with patients who received enalapril). Finally, in the patients in whom ACEI therapy, either enalapril or captopril, was stopped of the evening before surgery, the incidence of induction-induced hypotension was significantly less when enalapril or captopril therapy has been discontinued. These data indicate that in hypertensive patients chronically treated with ACEIs, maintenance of therapy until the day of surgery may increase the probability of hypotension at induction.",1994.0,0,0
1621,8055999,"Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.",M Flather; A Pipilis; R Collins; A Budaj; A Hargreaves; T Kolettis; A Jacob; T Millane; L Fitzgerald; K Cedro,"The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)",1994.0,1,1
1622,8059025,Acute tubular necrosis in kidney transplant patients treated with enalapril.,T M Garcia; J A da Costa; R S Costa; A S Ferraz,"We report two cases of acute renal failure in renal transplant patients using cyclosporine-A (CsA) after the introduction of angiotensin-converting enzyme inhibitor (ACEI) to control arterial hypertension. They had no renal artery stenosis or acute rejection. Both patients presented severe acute tubular necrosis (ATN), which subsided after discontinuation of the ACEI. Synergistic toxic effect of ACEI and CsA on the renal tubules might explain ATN in these two cases.",1994.0,0,0
1623,8059624,Hypertension: current management strategies.,J Sutherland; C Castle; R Friedman,"Hypertension affects 50 million persons in the United States and is the most common reason for office visits and prescriptions. This report reviews the epidemiology, diagnosis, and treatment of this condition and provides special attention to concomitant risk factors and issues of adherence. A literature search was performed using MEDLINE files dating back to 1986. The key words were ""hypertension,"" ""antihypertensive agents,"" ""patient compliance,"" ""cardiovascular risk factors,"" ""isolated systolic hypertension,"" and ""JNC."" Additional references were accessed by cross-referencing the bibliographies of the articles obtained in this search. Effective therapeutic pharmacologic and nonpharmacologic management of hypertension, including stage 1 as reclassified by the Fifth Report of the Joint National Committee (JNC-V), can greatly reduce mortality for patients. Despite extensive national efforts, 35 percent of hypertensive patients remain unknown, and only 7 percent have their hypertension adequately controlled. Any additional cardiovascular risk factors compound the risk of adverse outcome and can be adversely affected by treatment. JNC-V recommendations regarding equally effective pharmacologic agents are flexible but controversial. The favorable cardioprotective effects of angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, and alpha-beta-blockers often make them a more appropriate choice than diuretics or beta-blockers. Practical techniques for improving patient adherence to treatment regimens are also important and should begin when the diagnosis of hypertension is made.",1994.0,0,0
1624,8059778,ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group.,A Overlack; M Adamczak; W Bachmann; G Bönner; R G Bretzel; R Derichs; W Krone; R M Lederle; H J Reimann; H Zschiedrich,"Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated. In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks. Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection). This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.",1994.0,0,0
1625,8060578,Nifedipine versus captopril in the management of moderate hypertension in black patients.,J Skoularigis; L Eitzman; J Davis; V Strugo; P Sareli,"The efficacy of nifedipine (20 to 40 mg twice daily) and captopril (25 to 50 mg twice daily) was assessed during a 12-week single-blind randomized trial in 41 moderately hypertensive black patients (mean 24-h diastolic blood pressure [BP] > or = 90 mm Hg and < 115 mm Hg). Nifedipine and captopril were administered as monotherapy in increasing dosage while a diuretic was added after 8 weeks in patients who failed to reach the target BP (24-h mean diastolic BP < 90 mm Hg) on monotherapy. After 8 weeks of monotherapy, the mean 24-h ambulatory BP was reduced from 156 +/- 12/101 +/- 5 to 128 +/- 11/84 +/- 7 mm Hg (P < .0001) in the nifedipine group while it remained essentially unchanged (156 +/- 15/101 +/- 7 to 158 +/- 17/102 +/- 9) in the captopril group. Left ventricular (LV) mass index was also reduced significantly (P < .05) in the nifedipine group, while cardiac index and fractional shortening changed marginally. The addition of diuretic in the captopril group (16/21 patients) resulted in a significant fall in BP to 123 +/- 11/81 +/- 7. Only 2/20 patients in the nifedipine group required the addition of diuretic. The overall incidence of side effects was similar with both treatments but the addition of diuretic in the captopril group was followed by adverse changes in serum sodium (P < .01), urea (P < .05), and creatinine (P < .01) levels.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1626,8061842,24-hour ambulatory blood pressure monitoring and spirapril in mild to severe essential hypertension: a randomized dose comparison.,G Vreugdenhil; G A van Montfrans; M C Jacobs; J H de Bruijn; D P Veerman; P N van Es; B Mellein; C Guitard; T Thien; P W de Leeuw,"This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and < 120 mmHg] were randomized to receive spirapril at either 3 mg or 12 mg once daily for 8 weeks. At the end of active treatment and using the standard mercury sphygmomanometer, the number of responders (sitting DBP < 90 mmHg, but decrease > or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of spirapril, and 9 of 24 taking 12 mg of spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1627,8061845,"Single daily administration of spirapril in the treatment of essential hypertension. A multicentre double-blind comparison of 1, 6, 12 and 24 mg of spirapril once daily.",K Hayduk; F Schardt; B Sierakowski; G Weidinger; D Welzel,"A total of 171 male and female patients with mild-to-moderate hypertension [diastolic blood pressure (DBP) 100-115 mmHg] entered this randomized, double-blind, multicentre study. A 3-week placebo run-in period was followed by a 5-week active-treatment period during which patients received either 1, 6, 12 or 24 mg of spirpril once daily. Predose sitting blood pressure was taken in the morning by sphygmomanometer as well as by an automatic device (Tonoprint). Spirapril in doses of 6, 12 or 24 mg once daily significantly and similarly lowered systolic blood pressure (SBP) and DBP compared with 1 mg once daily. The rates of blood pressure normalization (DBP < or = 90 mmHg) were 12.5%, 37.5%, 30.8% and 28.9% with 1, 6, 12 and 24 mg, respectively. The percentage of patients experiencing a DBP reduction of at least 10 mmHg was 25.0%, 56.3%, 48.7% and 52.6% and 1, 6, 12 and 24 mg of spirapril, respectively. No serious or severe adverse events related or uncertain if related to the study medication were observed. The effective 6-mg dose was as well tolerated as the inefficacious 1-mg dose. In conclusion, in patients with mild-to-moderate essential hypertension, 6 mg of spirapril once daily is an efficacious and safe antihypertensive therapy with a favourable benefit-risk profile.",1994.0,0,0
1628,8061847,Spirapril in chronic renal failure.,G Stein; B Sierakowski; U Jansa; C C Haufe,"In a single-blind trial with a 2-week placebo run-in phase and a 4-week active-treatment period, spirapril at 6 mg once daily was administered to 49 consecutive hypertensive patients (34 men and 15 women). All had pretreatment diastolic blood pressures (DBP) of 95-115 mmHg and varying degrees of renal impairment. At the end of the placebo run-in and at the end of active treatment, renal function was assessed using the following procedures: technetium 99m-DTPA clearance [for glomerular filtration rate (GFR)]; radioiodine (131I)-labelled sodium iodohippurate (Hippuran) clearance [for renal plasma flow (RPF)]; creatinine clearance (Clcr). No statistically significant differences were found in GFR or Clcr during spirapril treatment. In renally impaired patients, RPF remained virtually unchanged whereas, in patients with normal Clcr, there was an increase of around 10% during active treatment. At the end of the study, 48% of the patients with renal failure achieved normalization of DBP (< or = 90 mmHg) and/or a DBP reduction of > or = 10 mmHg; the corresponding rate for patients with normal renal function was 31%. In conclusion, in patients with mild-to-moderate essential hypertension and varying degrees of renal impairment, spirapril at 6 mg once daily is an efficacious and well tolerated antihypertensive therapy.",1994.0,0,0
1629,8061848,"Placebo-controlled crossover comparison of spirapril at 3, 6, 12 and 24 mg once daily in mild to severe essential hypertension.",C Guitard; P Sassano; C Tzincoca; J Duchiez; M E Safar,"In a randomized, double-blind, crossover study, 20 patients with mild to severe essential hypertension received 3 weeks of treatment with each of four dosages of spirapril (3, 6, 12 and 24 mg once daily) or placebo. Standing and supine blood pressures were measured by use of both an automatic oscillometric instrument (Dinamap) and a mercury sphygmomanometer over a 24-hour period. Spirapril at 6, 12 and 24 mg once daily produced similar reductions in systolic and diastolic blood pressure. At most time points, there was a statistically significant difference between the reductions with spirapril compared with placebo. Spirapril at 3 mg once daily was less effective than the higher dosages, producing a lower mean blood pressure reduction and a shorter duration of antihypertensive action, mainly as regards systolic pressure. Spirapril was well tolerated and no patients withdrew from the study because of adverse effects. These data suggest that, although all four evaluated spirapril dosages effectively lowered supine and standing blood pressure in patients with mild to severe hypertension, the blood pressure-lowering effect of the 3 mg/day regimen was less than optimal. There were only minor variations in efficacy between dosages > or = to 6 mg/day, which may be attributable to the variability of blood pressure. Further investigations of larger numbers of patients are required to verify these results.",1994.0,0,0
1630,8061849,Changes in left ventricular dimensions and haemodynamics during antihypertensive treatment with spirapril for 36 months.,J E Otterstad; G Froeland,"To assess the long-term course of regression of left ventricular hypertrophy (LVH) and haemodynamic changes during spirapril treatment, 11 male hypertensive patients with a left ventricular mass (LVM) > 240 g and a mean age of 48 (range 41-60) years were followed-up with echo-Doppler examinations for 36 months. The initial spirapril dose was 6 or 12 mg once daily, which was titrated to a minimum of 3 mg and a maximum of 24 mg to keep diastolic blood pressure (DBP) < or = to 95 mmHg. Patient compliance based on tablet counts was 98% (range 95-100%). The mean spirapril dose was 9 +/- 6 mg at 3 months, 9 +/- 6 mg at 12 months, and 15 +/- 9 mg at 36 months. Blood pressure was reduced from 161 +/- 20/107 +/- 6 mmHg at baseline to 137 +/- 11/89 +/- 6 mmHg at 3 months (p < 0.001), 141 +/- 20/89 +/- 4 mmHg at 12 months and 135 +/- 11/87 +/- 6 mmHg at 36 months. The respective values for LVM at baseline and at 3, 12 and 36 months were 340 +/- 71 g, 305 +/- 61 g (p < 0.05 vs baseline), 303 +/- 88 g and 298 +/- 94 g. Cardiac output did not change whereas systemic arteriolar resistance (SAR) was significantly reduced after 3 and 36 months (p < 0.01). Thus, the regression of LVH with spirapril was 10% of LVM at 3 months, 11% at 12 months, and 12% at 36 months. These changes were mainly related to a reduction of LV posterior wall thickness and SAR.",1994.0,0,0
1631,8061851,Angiotensin-converting enzyme inhibition with spirapril in patients with coronary artery disease.,P Thürmann; N Rietbrock,"In a randomized double-blind, placebo-controlled, crossover trial, the potential anti-ischaemic action of the angiotensin-converting enzyme (ACE) inhibitor spirapril was studied in 19 patients with coronary artery disease (CAD) and reproducible exercise-induced ST-segment depression, but without hypertension or congestive heart failure. Measurements of blood pressure and heart rate as well as exercise-testing were performed after 2 weeks of treatment each with placebo and spirapril. Anginal attacks and consumption of short-acting nitrates were recorded in the patients' diaries. Resting blood pressure was not significantly reduced (143 +/- 20/89 +/- 10 mmHg vs 138 +/- 17/87 +/- 10 mmHg). The exercise-induced ST-segment depression, the main criterion for anti-ischaemic effect, was 2.17 +/- 1.72 mm after placebo and not significantly affected by spirapril (2.03 +/- 1.47 mm) despite a significant reduction in blood pressure x heart rate product at maximum workload (213 +/- 45.4 vs 197.5 +/- 36.8; p < 0.05). The number of anginal attacks per week and nitrate consumption remained virtually unchanged. A significant reduction of exercise-induced ischaemia in normotensive patients with CAD was not demonstrated with spirapril.",1994.0,0,0
1632,8061852,A multicentre multidose study of the efficacy and safety of spirapril in mild-to-moderate essential hypertension. UK Study Group of Spirapril in Hypertension.,G J Fairhurst,"This was a randomized double-blind parallel-group study of 283 patients who had mild-to-moderate [diastolic blood pressure (DBP) > 100 mmHg and < or = 115 mmHg] hypertension. After a 3 (or 4)-week placebo wash-out period followed by 6 weeks of active treatment with spirapril at either 3, 6, 12 or 24 mg once daily (or placebo), DBP decreased by approximately 10 mmHg in the (pooled) spirapril-treated patients compared with approximately 5 mmHg with placebo. There were statistically significant differences between all active-treatment groups (except the 24-mg dose group) and placebo, but not among the spirapril groups at the end of the +24-hour dosing interval. Reported adverse events were mostly not study drug-related and were similar to those with placebo except for headache, which was more frequent with spirapril than placebo (5.8% vs 1.7%, respectively). Similarly, the number and severity of the changes in laboratory variables did not differ between placebo vs spirapril, and none of these changes were dose-related. In conclusion, the studied dosages of spirapril were equally effective in reducing DBP, and the overall good decrease in blood pressure at the end of the dosing interval indicates that once-daily administration is effective in patients with mild-to-moderate hypertension.",1994.0,0,0
1633,8061853,"Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension.",C Guitard; V Alvisi; E Maibach; J Franck; G Cocco; G Boxho; B Mellein; R Waite,"In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1634,8061856,Regression of left ventricular hypertrophy by spirapril.,H Eichstädt; B Sierakowski; H Eskötter; M Cordes; D Kreuz,,1994.0,0,0
1635,8062609,Effects of long-term enalapril treatment on persistent micro-albuminuria in well-controlled hypertensive and normotensive NIDDM patients.,T Sano; T Kawamura; H Matsumae; H Sasaki; M Nakayama; T Hara; S Matsuo; N Hotta; N Sakamoto,"To determine whether long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor has a beneficial effect on the urinary microalbumin excretion and renal function in non-insulin-dependent diabetes mellitus (NIDDM) patients, enalapril (5 mg/day) was administered for 48 months. -Fifty-two patients with NIDDM who had persistent microalbuminuria in the range of 20-300 mg/24 h, serum creatinine < 106.1 microM (1.2 mg/dl), supine systolic blood pressure (BP) < 150 mmHg, supine diastolic BP < 90 mmHg, and HbA1c < 10% were divided into four groups. Twenty-six patients with normotension were divided at random into two groups; one group received enalapril (5 mg/day) (NE group), the other did not receive enalapril (NC group). In the same way, 26 other patients who were already well-controlled with nifedipine (30 mg/day) over a long-term period (4-6 years) were divided at random into two groups; one received enalapril (5 mg/day) (HE group), the other did not receive enalapril (HC group). After 48 months, urinary albumin excretion (UAE) was markedly reduced in group NE from 102.4 x/divided by 1.3 to 55.5 x/divided by 1.3 mg/24 h (P < 0.005), whereas no significant change occurred in group NC. In the well-controlled hypertensive groups, a significant reduction in UAE occurred in group HE (P < 0.05), whereas no significant change occurred in group HC. No changes in creatinine clearance, BP, or blood glucose control were seen during the study. Treatment with enalapril for 48 months may have a beneficial effect on the decline of microalbumin excretion in NIDDM patients.",1994.0,0,0
1636,8062610,Variability of urinary albumin excretion in patients with microalbuminuria.,G Phillipou; P J Phillips,"To estimate the within-person variability (SDi) for the overnight urinary albumin excretion rate (AER) in diabetic patients with persistent microalbuminuria. Thirteen normotensive diabetic patients in stable medical control, with normal renal function and without any associated cardiovascular or other clinical disorders, collected overnight urines at monthly intervals during one year. AER was determined by radioimmunoassay. Analysis of individual series of AER showed a significant trend (P < or = 0.01) in three cases. The remaining patients (eight men, two women; seven with insulin-dependent diabetes mellitus) had a median mean AER 102 micrograms/min (range 30-238 micrograms/min). Because the individual mean AERs were significantly associated with their respective SDis, the data was loge transformed. LogeSDi was estimated as 0.420, and its 90% probability range (0.353-0.490) was calculated using the bootstrap method. The high within-person variance for AER means that only people with an initial AER in the range of 53-76 micrograms/min have a high probability (P > or = 0.95) of being classified as microalbuminuric (20-200 micrograms/min) on a subsequent specimen. However, subjects with an initial AER > or = 53 or > or = 80 micrograms/min have a 95 and 99% probability of persistent microalbuminuria. The large variability of AER limits its potential as a serial marker to detect any gradual deterioration of established renal dysfunction.",1994.0,0,0
1637,8064166,Blood pressure effects of acute intravenous renin or oral angiotensin converting enzyme inhibition in essential hypertension.,M Azizi; T T Guyene; G Chatellier; J Ménard,"To assess the participation of the renin-angiotensin system in the blood pressure regulation of essential hypertensive patients through acute specific renin inhibition. Fifty-three consecutive untreated hypertensive patients (mean +/- SD age 55 +/- 10 years, 42 male) were investigated on their usual sodium diet in a 3-h protocol. The first 11 patients did not receive any drug, the following 20 patients ingested a single oral dose of captopril (1 mg/kg) and the last 22 patients received a renin inhibitor infusion (remikiren; 1 mg/kg over 60 min). The maximum diastolic blood pressure fall was comparable in the two treated groups. Diastolic blood pressure changes analysed as area under the curve were similar for both drugs (overall F1,40 = 1.26, P = 0.27). Even though the baseline renin levels were within the narrow range 5-80 pg/ml, the diastolic blood pressure fall analysed as area under the curve from time 32 min to time 60 min was significantly correlated with the baseline active renin level in both groups (remikiren r = 0.44, P < 0.05; captopril r = 0.47, P < 0.05). The plasma active renin levels were significantly increased at 30, 90 and 120 min in both groups, and the maximum active renin levels were significantly correlated with the baseline active renin level (remikiren r = 0.62, P < 0.01; captopril r = 0.66, P < 0.01). The plasma prorenin levels did not change. This study suggests that acute renin inhibition and acute angiotensin converting enzyme inhibition similarly decrease the blood pressure and increase the plasma active renin levels. Acute blockade of the renin-angiotensin system at its initial step by a renin inhibitor can therefore be used to investigate the renin dependence of the blood pressure in essential hypertension.",1994.0,0,0
1638,8064788,"Clinical pharmacology of converting enzyme inhibitors, calcium channel blockers and diuretics.",A R Sinaiko,"The predominant trend in pediatric antihypertensive management is towards increasing reliance on angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers because of their general effectiveness, low incidence of adverse reactions and potential specific benefit in patients with renal disease. The common aetiological relationship between renal disease and elevated BP also is the reason that diuretic therapy continues to be included in many treatment regimens. A number of ACE inhibitors are available for clinical use, although only captopril has been subjected to any meaningful degree of investigation in children. Initial doses of captopril are 0.5 mg/kg in children > 6 months of age and 0.01-0.1 mg/kg in neonates, because of an apparent increased antihypertensive effect and duration of action in this age group. Side-effects are few and the major adverse effect is a reduction in glomerular filtration in patients with bilateral renal artery stenosis. The calcium channel blockers reduce cytosolic calcium concentration and are particularly effective in patients with volume dependent forms of hypertension. The pharmacokinetic properties of these drugs are similar with drug clearance by hepatic metabolism. In particular, nifedipine has a rapid onset of action and is widely used to treat hypertensive emergencies. Although it has been used sublingually, the effectiveness of the drug is due to absorption from the gastrointestinal tract. Few side-effects from these drugs have been reported in children. Heart rate and cardiac output increase but return to pretreatment levels within a few weeks. As is the case with the ACE inhibitors, calcium channel blockers appear to have a positive effect on renal function.",1994.0,0,0
1639,8070610,Impact of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.,F S Nielsen; P Rossing; M A Gall; P Skøtt; U M Smidt; H H Parving,"Diabetic nephropathy is characterized by hypertension and a relentless decline in kidney function. Angiotensin-converting enzyme inhibitors have been claimed to preserve kidney function better than an equal blood pressure (BP) reduction with conventional antihypertensive treatment (renoprotection). We compared the effect on kidney function of lisinopril (10-20 mg/day) and atenolol (50-100 mg/day) in hypertensive NIDDM patients (mean age 60 +/- 8 years) with diabetic nephropathy. Forty-three (21 lisinopril and 22 atenolol) patients were enrolled in a 1-year randomized double-blind parallel study. Eight patients dropped out, and the results for the remaining 35 patients (16 lisinopril and 19 atenolol) are presented. Diuretics were required in 10 of 16 lisinopril patients and 12 of 19 atenolol patients. The following variables were measured: 24-hour ambulatory BP (Takeda TM2420), albuminuria (enzyme-linked immunosorbent assay), fractional albumin clearance, and glomerular filtration rate (GFR) ([51Cr]EDTA technique). The average reduction in mean arterial BP during the 12 months was identical in the two groups 12 +/- 2 vs. 11 +/- 1 mmHg in the lisinopril and atenolol group, respectively. Albuminuria was on average reduced 45% in the lisinopril group vs. 12% in the atenolol group (P < 0.01), and fractional albumin clearance was on average reduced 49% in the lisinopril group vs. 1% in the atenolol group (P < 0.05). GFR declined identically in the two groups 11.7 +/- 2.3 vs. 11.6 +/- 2.3 ml.min-1.year-1 in the lisinopril and atenolol groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1640,8074019,"First-dose effects of enalapril 2.5 mg and captopril 6.25 mg in patients with heart failure: a double-blind, randomized, multicenter study. The Enalapril-Captopril Investigators.",R M Lang; R DiBianco; G T Broderick; S S Gottlieb; J Kostis; P A Lyle; L Makris; S I Rajfer; E J Rucinska,"Significant decreases in blood pressure (BP) may occur when administration of angiotensin-converting enzyme (ACE) inhibitors is initiated for the treatment of heart failure. The purpose of this study was to compare the safety and tolerability of recommended initial doses of the longer-acting ACE inhibitor enalapril (ENAL) with those of the shorter-acting captopril (CAP) in patients with heart failure who were treated concomitantly with digitalis and diuretic agents. We evaluated BP, serum ACE activity, and clinical status when a low, first dose of ENAL (2.5 mg, n = 59) or CAP (6.25 mg, n = 58) was administered in a double-blind, randomized, and parallel fashion to 117 patients with mild to moderate heart failure. BP and serum ACE activity were measured at 30 min and hourly for 8 hours after drug administration. BP decreases were similar for both groups (mean supine BP -6.2/-4.8 mm Hg for ENAL vs -8.3/-6.4 mm Hg for CAP; mean standing BP -9.2/-5.6 mm Hg for ENAL vs -10.0/-4.7 mm Hg for CAP). Although the maximum mean decrease in BP occurred at hours 4 and 5 in the ENAL group and hours 1 and 2 in the CAP group, considerable between-group overlap was observed for individual patients. Decreases in mean serum ACE activity occurred earlier and were of shorter duration in the CAP group. ENAL significantly inhibited serum ACE activity to a greater extent than did CAP at all time points except the 1st hour. Administration of a first dose of ENAL, 2.5 mg or CAP, 6.25 mg to patients with heart failure was well tolerated.",1994.0,0,1
1641,8074020,Comparison of the hemodynamic responses to molsidomine and isosorbide dinitrate in congestive heart failure.,P Unger; J L Vachiery; D de Cannière; M Staroukine; G Berkenboom,"To evaluate the mechanisms involved in nitrate tolerance, we randomized 23 patients with congestive heart failure resulting from coronary artery disease to an isosorbide dinitrate or a molsidomine infusion. The drugs were titrated to decrease pulmonary capillary wedge pressure by > or = 30% or > or = 10 mm Hg. Then isosorbide dinitrate, molsidomine, or placebo was infused in a double-blind randomized manner for 24 hours. In all patients, treatment with enalapril was begun > or = 48 hours before the beginning of the protocol and was continued throughout the study to avoid renin-angiotensin activation. The pulmonary capillary wedge pressure remained significantly decreased at 24 hours during molsidomine infusion only. No significant increase in catecholamines occurred. Because molsidomine differs from organic nitrates by its property of directly stimulating guanylate cyclase without depending on thiol group availability, these results suggest that impaired biotransformation of nitrates is involved in tolerance induced by high doses of isosorbide dinitrate in congestive heart failure.",1994.0,0,0
1642,8088918,Effect of captopril and enalapril on endothelial function in hypertensive patients.,M A Creager; M A Roddy,"Endothelium-dependent vasodilation is impaired in patients with essential hypertension. The objective of this study was to determine whether long-term treatment with angiotensin-converting enzyme inhibitors improves endothelium-dependent vasodilation in forearm resistance vessels of patients with hypertension. Furthermore, since tissue thiols may be relevant to nitric oxide-mediated vasodilation, we queried whether an angiotensin-converting enzyme inhibitor with a sulfhydryl group preferentially augments endothelium-dependent vasodilation in these individuals. The study included 24 patients with essential hypertension (mean age, 45 +/- 2 years) and 20 normotensive subjects (mean age, 47 +/- 1 years). Methacholine chloride (0.3 to 10 micrograms/min) was infused via the brachial artery to assess endothelium-dependent vasodilation in forearm resistance vessels. Nitroglycerin (1 to 30 micrograms/min) was administered to evaluate endothelium-independent vasodilation. Forearm blood flow was determined by venous occlusion strain-gauge plethysmography. Forearm vascular function studies were performed in hypertensive patients before and 7 to 8 weeks after randomization to either captopril or enalapril, angiotensin-converting enzyme inhibitors with and without a sulfhydryl moiety, respectively. Normotensive subjects were studied on only one occasion. Before treatment, the forearm vasodilative response to methacholine was attenuated in hypertensive compared with normotensive subjects (P < .01). The effects of nitroglycerin on forearm blood flow did not differ significantly between the two groups. Both captopril and enalapril reduced mean blood pressure in the hypertensive subjects (12 +/- 2 versus 15 +/- 3 mm Hg, respectively; P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1643,8089635,Angiotensin converting enzyme inhibitor and chronic renal failure.,V Sitprija; D Lumlertgul,"To evaluate the renal protection of enalapril a study was made in 37 patients with chronic renal failure and hypertension. Sixteen patients had diabetic nephropathy with the serum creatinine ranging from 2.0 to 4.0 mg/dl. Twenty-one patients had non-diabetic chronic renal failure with serum creatinine from 2.2 to 6.3 mg/dl. Of 16 patients with diabetic nephropathy, 6 served as control and 10 received enalapril. Nine patients in the non-diabetic chronic renal failure group served as controls, while 12 were given enalapril. The control patients received alpha methyldopa (500 mg/day) for blood pressure control. In the studied patients enalapril was given at the dose of 5-10 mg/day. Over a period of 2 yrs, enalapril attenuated progression of renal failure in patients with diabetic nephropathy at the serum creatinine level from 2 to 2.9 mg/dl (creatinine clearance 21.5-38.4 ml/min) when compared with control patients. At the serum creatinine of 3 to 4 mg/dl progression of renal failure did not differ from control patients. In non-diabetic renal failure progression of renal failure was delayed in patients with serum creatinine level ranging from 2.2 to 5 mg/dl (creatinine clearance 18-42 ml/min); patients with serum creatinine level ranging from 5.5 to 6.3 mg/dl had deterioration of renal function as control patients. Proteinuria was decreased in all patients on enalapril. Thus, for preventing progression of renal failure, enalapril should be given in chronic renal failure with milder degree of renal function impairment; in diabetic nephropathy it should be started earlier at the lower serum creatinine level than in non-diabetic chronic renal failure, yet with comparable creatinine clearance.",1993.0,0,0
1644,8107938,Acute transplant artery thrombosis induced by angiotensin-converting inhibitor in a patient with renovascular hypertension.,B Dussol; F Nicolino; P Brunet; F Leonetti; S Siles; Y Berland,Acute renal failure due to angiotensin-converting enzyme inhibitors (ACEI) usually results from a marked fall in renal perfusion pressure in patients with renovascular disease. We report herein one case of acute kidney transplant artery thrombosis in a patient with renovascular hypertension. The thrombosis occurred immediately after a single dose of ACEI for evaluation of a renal transplant artery stenosis by renal scintigraphy. The dramatic fall of arterial pressure observed in our patient probably played an important role in the thrombosis. The risk of the administration of a single dose of ACEI coupled with renal scintigraphy in diagnosing renovascular hypertension is stressed.,1994.0,0,0
1645,8109551,Effects of benazepril on stress testing blood pressure in essential hypertension.,C Cardillo; N Mores; M Motolese; G Folli,"The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1646,8110005,Efficacy and dosage of enalapril in congenital and acquired heart disease.,A M Leversha; N J Wilson; P M Clarkson; A L Calder; M C Ramage; J M Neutze,"In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril. Renal failure in eight patients was related to young age, low weight, and left-to-right shunt group. Three patients died in congestive heart failure with renal failure. Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.",1994.0,0,0
1647,8111799,Quinapril in the treatment of hypertension in primary care centers.,L Alcocer; G Novoa; D Sotres,"A multicenter, open, prospective study was carried out to establish the efficacy and safety of quinapril 10.0, 20.0, or 40.0 mg, or 20 mg plus 12.5 mg hydrochlorothiazide (HCTZ) given once daily in 256 patients with mild-to-moderate essential hypertension treated in primary care units in Mexico. The study consisted of a 4-week placebo washout period, followed by 12 weeks of active treatment. Quinapril doses were titrated upward at 4-week intervals to three dosage levels. Patients who did not respond to 20-mg doses were randomly assigned to receive 40 mg quinapril daily or 20 mg quinapril plus 12.5 mg HCTZ daily until the end of the study. Quinapril was useful as monotherapy in 78% of the 256 patients (92.9% of patients who completed the study were evaluable): 73.3% of patients required only 10 mg, and their average blood pressure was similar to that of patients who required doses of greater than 10 mg. Only 12.2% of responsive patients required either 40 mg of quinapril or 20 mg of quinapril plus HCTZ 12.5 mg. Quinapril was equally effective and safe in elderly patients (> 60 years old) and in obese and nonobese patients. A low incidence of adverse effects in our patients confirms quinapril's safety, and no adverse changes were observed in laboratory tests.",1993.0,0,0
1648,8111807,Efficacy and safety of enalapril versus extended-release nifedipine for the treatment of mild-to-moderate essential hypertension: a multicenter 22-week study. Multicenter Cooperative Study Group.,A S Leon,"The antihypertensive effects and tolerability of single daily doses of enalapril and extended-release nifedipine (nifedipine-ER) were compared in an open-label, randomized, parallel-group, 22-week treatment study involving 230 men and women (mean age, 55 years). Following a 3-week washout period, mean +/- SD blood pressure levels were 153 +/- 17/99 +/- 4 mmHg in the enalapril group (n = 117) and 157 +/- 17/100 +/- 5 mmHg in the nifedipine-ER group (n = 113). Beginning at 5 mg once daily for enalapril and 30 mg once daily for nifedipine-ER, the dosage was titrated every 4 weeks for 16 weeks, up to a maximum of 40 mg for enalapril and 120 mg for nifedipine-ER. The treatment goal (satisfactory response) was to lower trough sitting diastolic blood pressure to < 90 mmHg or by at least 10 mmHg to a level of < 100 mmHg. At a mean daily dose of 16 mg of enalapril and 57 mg of nifedipine-ER, more than three quarters of each treatment group achieved a satisfactory response. The mean reductions in trough sitting blood pressure levels at the end of 22 weeks of treatment were 15/11 mmHg for enalapril and 21/13 mmHg for nifedipine-ER. The difference between treatments was significant only for the change in systolic blood pressure (P < 0.05). However, enalapril was better tolerated than nifedipine-ER. The numbers of patients with adverse experiences and withdrawals from the study because of an adverse experience were significantly lower for enalapril than for nifedipine-ER (P < 0.05). The incidence of abnormal laboratory findings was small and considered of no clinical importance in either group. These data suggest that enalapril and nifedipine-ER had approximately equal efficacy as once-daily antihypertensive treatments, but enalapril was better tolerated.",1993.0,0,0
1649,8112060,Delayed hypersensitivity drug reactions diagnosed by patch testing.,J M Calkin; H I Maibach,"Drug reactions are a common problem in hospital inpatients and outpatients. Oral or parenteral drug challenges are valuable diagnostic aids, but time consuming. We review attempts to diagnose delayed hypersensitivity drug eruptions by patch testing. We review control data, and offer an operational definition that might make for greater acceptance of the rôle of diagnostic patch testing in this entity.",1993.0,0,0
1650,8112372,The pharmacokinetics and pharmacodynamics of fosinopril in haemodialysis patients.,T W Gehr; D A Sica; D M Grasela; K L Duchin,"The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium (a new angiotensin-converting enzyme (ACE) inhibitor), were investigated in six haemodialysis patients. Intravenous 14C-fosinoprilat (7.5 mg), oral 14C-fosinopril sodium (10 mg) and oral fosinopril sodium (10 mg) were administered in an open-label, randomized study. Mean maximum concentration (Cmax), clearance (CL), volume of distribution at steady-state (Vss), mean residence time (MRTiv), and t1/2 values after IV administration of 14C-fosinoprilat were 2,042 micrograms.ml-1, 11.3 ml.min-1, 11.0 l, 16.3 h and 28.3 h, respectively. Following oral administration of 14C-fosinopril, mean Cmax, time to maximum plasma concentration (tmax), and fosinoprilat bioavailability values were 197 ng.ml-1, 5.2 h and 29.2%. Para-hydroxy fosinoprilat and fosinoprilat glucuronide comprised approximately 15% and 2% of radioactivity recovered in faeces. Four hours of haemodialysis only cleared approximately 1.5% of the administered dose. The maximum effect (Emax) model was fitted to the percentage inhibition of serum ACE activity vs. fosinoprilat concentration data in three patients. Emax ranged from 95.3 to 102.5%, and IC50 (the fosinoprilat concentration required to produce 50% of Emax) ranged from 2.6 to 4.2 ng.ml-1. Pharmacokinetic variables of the patients were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dosing following dialysis are unnecessary.",1993.0,0,0
1651,8112904,The effect of early converting enzyme inhibition on neurohumoral activation in acute myocardial infarction.,T Omland; T Aarsland; A Aakvaag; K Dickstein,"The effect of early converting enzyme inhibition with enalapril on the extent of neurohumoral activation in acute myocardial infarction was evaluated in a randomized, placebo-controlled double blind fashion. Plasma levels of atrial natriuretic factor and noradrenaline on day 1, i.e. prior to randomization (n = 99), and on days 3 (n = 145) and 30 (n = 69) following myocardial infarction were determined. Enalapril did not significantly affect neurohumoral activation on day 3 (enalapril vs. placebo (mean (S.E.M.); atrial natriuretic factor: 35.3 (3.0) vs. 37.2 (2.9) pmol/l; noradrenaline: 2.82 (0.20) vs. 3.70 (1.02) nmol/l) or at 1 month (atrial natriuretic factor: 33.1 (3.0) vs. 32.4 (3.9) pmol/l; noradrenaline: 2.77 (0.25) vs. 2.82 (0.28) nmol/l). However, in myocardial infarction patients developing heart failure, a significant attenuation of the day 3 atrial natriuretic factor, but not of the noradrenaline response, was seen (atrial natriuretic factor: 47.0 (7.7) vs. 59.0 (6.4) pmol/l, P < 0.05; noradrenaline: 3.37 (0.42) vs. 6.59 (3.26) nmol/l, P = ns). In conclusion, enalapril did not significantly reduce neurohumoral activation in acute myocardial infarction, possibly because the activation in most patients is modest and confined to the early convalescent phase. However, in patients with myocardial infarction and heart failure enalapril therapy was associated with a reduction in early plasma atrial natriuretic factor levels, compatible with decreased cardiac filling pressures.",1993.0,0,0
1652,8113548,Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina.,J C Kaski; G Rosano; S Gavrielides; L Chen,"This study was conducted to test the hypothesis that angiotensin-converting enzyme inhibition may lessen myocardial ischemia in patients with microvascular angina. Patients with syndrome X (angina pectoris, positive findings on exercise testing and normal coronary arteriogram) have a reduced coronary vasodilator reserve (""microvascular angina"") and may show an increased sympathetic drive. Angiotensin-converting enzyme inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Ten patients (seven women and three men, mean age [+/- SD] 53 +/- 6 years) with syndrome X and a reduced coronary flow reserve underwent a randomized, single-blind, crossover, placebo-controlled study of the effects of the angiotensin-converting enzyme inhibitor enalapril on angina and exercise-induced ST segment depression. Assessment was by symptom-limited treadmill exercise testing after 2 weeks of treatment with 10 mg/day of enalapril and after 2 weeks of placebo administration. All patients had positive findings on exercise testing (> or = 1 mm ST segment depression and angina) while taking placebo, whereas six patients had a positive test result (four with angina) during enalapril therapy. Total exercise duration and time to 1 mm of ST segment depression were prolonged by enalapril over those obtained with placebo (mean 779 +/- 141 vs. 690 +/- 148 s, p = 0.006 and 690 +/- 204 vs. 485 +/- 241 s, p = 0.007, respectively). The magnitude of ST segment depression was also less with enalapril than with placebo (mean 1.1 +/- 0.4 vs. 1.5 +/- 0.2 mm, p = 0.004). Heart rate and blood pressure at peak exercise and at 1 mm of ST depression were not significantly different during placebo and enalapril treatment. Angiotensin-converting enzyme inhibition lessens exercise-induced ischemia in patients with syndrome X and microvascular angina, probably by a direct modulation of coronary microvascular tone, which results in an increased myocardial oxygen supply.",1994.0,0,0
1653,8114057,"Influence of benazepril and captopril on blood pressure, glucocorticoids and progesterone in essential hypertensives.",L I Olbinskaya; S A Golubev; T D Bolshakova,"The antihypertensive activity and the influence of adrenal cortex hormones of benazepril versus captopril were studied in 30 essential hypertensives in a double-blind, randomised, placebo-controlled trial during eight weeks of treatment. Patients started with 50 mg of captopril or 10 mg of benazepril once daily; if normotension had not been obtained after four weeks of treatment the doses were increased to 50 mg twice daily or 20 mg once daily, respectively. 11-Oxycorticosteroids and progesterone in males were measured in blood and daily urine at baseline and at the 4th and the 15th days of drug administration, as well as aldosterone in daily urine by radioimmunoassay, and compared with these data in 15 healthy subjects. Following eight weeks of treatment in 64% and 56% of patients treated with benazepril and captopril respectively, blood pressure was normalised. In the corresponding remaining 14% and 13%, diastolic blood pressure decreased by 10 mmHg and more but not below 90 mmHg. Before treatment excretion of 11-oxycorticosteroids, progesterone and aldosterone was significantly increased without changes in blood levels. After two weeks of treatment 11-oxycorticosteroids and aldosterone excretion decreased (P < 0.05) without progesterone changes, benazepril treatment being more effective in decreasing 11-oxycorticosteroids levels in blood (P < 0.05). In patients with high pretreatment levels of 11-oxycorticosteroids in urine we have noticed the highest antihypertensive effect of both drugs. The main conclusions are that both the ACE inhibitors are effective in mild to moderate essential hypertensives and might decrease glucocorticoids in urine and blood.",1993.0,0,0
1654,8114058,Frequency of cough during therapy with ACE inhibitors in Greek hypertensives.,A D Efstratopoulos; M Meikopoulos; S Voyaki,"Persistent dry cough is one of the most common side-effects during therapy with ACE inhibitors. The frequency of cough ranges widely (from 0.2% to 15%) in different series, being higher in small studies and smaller in retrospective studies with large number of patients. The aim of the present study was to evaluate the true frequency of cough induced by treatment with ACE inhibitors in Greek hypertensives and to determine various possibly correlated parameters, including sex, duration of therapy and kind and dose of ACE inhibitors. All hypertensive patients followed in our Hypertension Clinic and treated with ACE inhibitors participated in the study. A total of 228 patients, 103 males and 125 females, 24-80 years of age, were treated with ACE inhibitors for a period of 1-41 months: 121 with enalapril, 40 with captopril, 39 with lisinopril, 25 with perindopril and 3 with ramipril. During treatment with ACE inhibitors persistent dry cough occurred in 15 patients, 12 women and 3 men, giving a frequency of 6.58%. Eleven patients (4.82%) volunteered the information and three after questioning. The mean age of these 15 patients with cough was significantly higher from that of the group (n = 213) without cough (64.27 +/- 2.5 vs. 57.9 +/- 0.74 years, mean +/- SEM, P = 0.024). The 12 women with cough were significantly older than the 113 without cough (67.77 +/- 2.8 vs. 57.8 +/- 1.04 years, P = 0.032).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1655,8115879,Fulminant pancreatitis associated with lisinopril therapy.,J B Standridge,"Adding to the growing awareness of medications that can cause pancreatitis is a small but significant number of reports implicating the angiotensin converting enzyme (ACE) inhibitors. In this report, I describe the case of a patient who had no risk factors for pancreatitis and who was taking no medications known to cause pancreatitis other than lisinopril. The abruptness, severity, and fulminant course of this case of probable ACE inhibitor-induced pancreatitis are unprecedented in the medical literature. Possible mechanisms underlying the induction of pancreatitis by ACE inhibitors are discussed. The medical literature concerning pancreatitis and articles reviewing ACE inhibitors do not make note of the relationship between the two. Greater awareness of this association will promote a higher index of suspicion in appropriate clinical settings. Further reporting of cases and clinical research into the cause and prevention of drug-induced pancreatitis appears to be indicated.",1994.0,0,0
1656,8117550,Post-marketing surveillance of lisinopril in general practice in the UK.,J M Fallowfield; J Blenkinsopp; A Raza; A G Fowkes; T J Higgins; K M Bridgman,"A total of 4676 patients and 1759 patients were treated with lisinopril and nifedipine respectively in a post-marketing surveillance study conducted in general practice in the UK. Patients were followed up for 12 months. Most of the lisinopril patients had hypertension, but a small number (180) had heart failure. Most of the nifedipine patients had uncomplicated hypertension, but some (22.57%) had other cardiovascular disease with or without hypertension. Lisinopril and nifedipine were equally effective in reducing blood pressure. During the study, 1.5% of hypertensive patients assigned to lisinopril died compared with 1.8% of patients assigned to nifedipine, and 15.1% of lisinopril patients compared with 19.7% of patients in the nifedipine group withdrew because of adverse events. Cough, malaise and fatigue, nausea and vomiting were more frequent causes of withdrawal from lisinopril than nifedipine. Conversely, headaches, pallor and flushing, oedema and palpitations caused more frequent withdrawals from nifedipine. Anaemia was more often encountered on nifedipine treatment than on lisinopril. In hypertensive patients, the frequency of first-dose hypotension was similar on both treatments. Serious events occurred in 0.8% and 0.5% of patients given lisinopril and nifedipine respectively. Lisinopril was well tolerated by heart failure patients: 16 patients (8.88%) died and an incidence of 4.44% of serious adverse events was reported, a pattern to be anticipated in such patients; dizziness, giddiness, dyspnoea, cough, nausea and vomiting were the most frequent causes of withdrawal; the incidence of first-dose hypotension was low (2.22%).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1657,8117555,Sodium cromoglycate: a remedy for ACE inhibitor-induced cough.,M Hargreaves,"The beneficial effects of angiotensin converting enzyme (ACE) inhibitors may be limited by cough, for which the only consistently effective treatment is withdrawal of therapy. The effect of inhaled sodium cromoglycate (20 mg, 4 times daily) was examined in five patients who experienced cough following the introduction of an ACE inhibitor. In three patients inhaled cromoglycate suppressed the cough. Inhaled sodium cromoglycate may thus be of value in a proportion of patients with ACE inhibitor-induced cough.",1993.0,0,0
1658,8122944,Angiotensin-converting enzyme inhibitors in hypertension. A dozen years of experience.,B J Materson; R A Preston,"Introduction of the first angiotensin-converting enzyme (ACE) inhibitor, captopril, in 1981 marked a major advance in the treatment of essential hypertension. This article reviews the 12 years of clinical experience during which it and other ACE inhibitors have become recognized as first-line agents for treating hypertension. The benefits of ACE inhibition in diabetic patients are being defined. In recent years, beneficial effects on glucose handling, left-ventricular mass, quality of life, renal function, and myocardial protection have become recognized. For these reasons, and because of their excellent safety profile, ACE inhibitors are now widely used for the treatment of hypertensive patients.",1994.0,0,0
1659,8124636,"Erythema multiforme (""minus"" and ""maius"") and drug intake.",P Fabbri; E Panconesi,,1993.0,0,0
1660,8124639,Drug-induced pemphigus. I. A survey.,S Brenner; R Wolf; V Ruocco,,1993.0,0,0
1661,8124640,Drug-induced pemphigus. II. Pathomechanisms and experimental investigations.,V Ruocco; E De Angelis; M L Lombardi,,1993.0,0,0
1662,8124641,Drug-induced bullous pemphigoid.,M J Fellner,,1993.0,0,0
1663,8124643,Drug-induced linear immunoglobulin A disease.,P M Collier; F Wojnarowska,,1993.0,0,0
1664,8124645,Drug-induced blistering oral lesions.,G Laskaris; R A Satriano,,1993.0,0,0
1665,8125421,Angiotensin-converting enzyme inhibition during thrombolytic therapy in acute myocardial infarction: the Captopril and Thrombolysis Study (CATS).,J H Kingma; W H van Gilst,"The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. In the acute phase, captopril may scavenge free radicals, blunt the catecholamine response, elicit coronary vasodilation and increase prostacyclin and bradykinin levels. In the chronic phase remodelling may be attenuated. At present, a large number of controlled clinical trials mainly focussing on the effects of ACE-inhibition in the chronic phase is under way. Only few studies concentrate on the effect of acute intervention with ACE-inhibitors in ischemia-reperfusion i.e. thrombolysis in myocardial infarction. In the Captopril And Thrombolysis pilot study (CAT pilot-study) 3 mg and 6.25 mg captopril was tolerated well as adjunctive therapy to intravenous streptokinase. Decrease in mean arterial blood pressure (36 +/- 11%) after 6.25 mg was comparable to the control group (30 +/- 7%). Furthermore noradrenaline levels decreased dose dependently to 47 +/- 6 and 38 +/- 7% from baseline respectively. These results prompted a large nationwide acute intervention trial with captopril in 300 patients receiving thrombolytic therapy: the Captopril And Thrombolysis Study (CATS). The primary hypothesis of CATS supposes a very early effect of converting enzyme inhibition on evolving myocardial damage due to ischemia and the consequences of early reperfusion. This will be evaluated by serial echocardiography, Holter monitoring and neurohumoral measurements immediately upon thrombolysis and during the first year after myocardial infarction. Blinded data show a favourable blood pressure response, with systolic hypotension below 100 mm Hg occurring only in 0.2% of patients.",1993.0,0,0
1666,8125422,Experiences with ACE inhibitors early after acute myocardial infarction. Rationale and design of the German Multicenter Study on the Effects of Captopril on Cardiopulmonary Exercise parameters post myocardial infarction (ECCE).,F X Kleber; I Reindl; M Wenzel; P Rodewyk; S Beil; B Kosloswki; W Doering; G V Sabin; S Hinzmann; U J Winter,"Left ventricular damage by necrosis of myocardial tissue can lead to compromise of left ventricular function, to left ventricular volume increase and ultimately to development of heart failure. This sequence in the pathophysiology has been shown to be blunted by ACE inhibitors. Volume increase, however, can also be helpful in restoring stroke volume and ameliorate elevation of filling pressures. Furthermore, very early institution of ACE inhibition has failed to improve short-term mortality after myocardial infarction in one large trial. The aim of the ECCE trial therefore is, to investigate the early effects of the ACE inhibitor captopril on compromise of exercise capacity, thought to be a first measurable sign of developing heart failure. The ECCE trial is a randomized, seven-center investigation, studying the effects of ACE inhibition on oxygen uptake in a double blind, placebo controlled design in a group of 204 patients. Sample size was calculated on the basis of a pilot trial. The study design and first not unblinded data of 104 patients are presented. The population consists of predominantly male patients with mostly first myocardial infarction. They were admitted to hospital within five hours of onset of chest pain. End-diastolic volumes were normal, but ejection fraction was moderately compromised. ACE inhibition was started after the first day, but within 72 hours of onset of chest pain. After four and after twelve weeks, oxygen uptake was considerably below expected values and one third of the patients had severe compromise of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,1,1
1667,8125423,The Survival and Ventricular Enlargement (SAVE) study: rationale and perspective.,M A Pfeffer,"Myocardial infarction increases the risk of subsequent cardiovascular events (e.g., heart failure or another myocardial infarction) among survivors as compared with the general population. Left ventricular dysfunction is among the major risk factors for such adverse events. Although reductions in cardiovascular risk have been achieved by use of aspirin, beta-blockers (and sometimes revascularization and/or serum lipid-lowering agents), the potential of angiotensin-converting enzyme (ACE) inhibitors to improve the outcome for survivors of myocardial infarction has only recently been examined. The concept that ACE inhibition might be of benefit for these patients originated from animal studies demonstrating that long-term ACE inhibition therapy attenuated left-ventricular enlargement. After clinical confirmation of this initial finding, the Survival and Ventricular Enlargement (SAVE) trial was designed to determine whether long-term ACE inhibition therapy would reduce morbidity and mortality among survivors of myocardial infarction. The SAVE study found the following risk reductions among captopril vs placebo recipients: death (all causes) 19% (95% confidence interval, 3 to 35%; p = 0.019); cardiovascular death 21% (95% confidence interval, 5 to 35%; p = 0.014); myocardial infarction 25% (95% confidence interval, 5 to 40%; p = 0.012). To the list of proved therapies that extend survival following myocardial infarction, the physician can now add ACE inhibition with captopril for patients with left ventricular dysfunction. Survivors of myocardial infarction are at heightened risk for subsequent adverse cardiovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,1,1
1668,8125424,"Captopril versus digoxin in patients with coronary artery disease and mild heart failure. A prospective, double-blind, placebo-controlled multicenter study. The CADS Study Group.",H Just; H Drexler; S H Taylor; J Siegrist; G Schulgen; M Schumacher,"We conducted a prospective, double-blind, placebo-controlled multicenter trial in order to evaluate the long-term effects of captopril (50 mg/day), digoxin (0.25 mg/day) and placebo on quality of life, cardiovascular events, clinical symptoms and exercise tolerance in patients with documented myocardial infarction, resulting in regional wall motion abnormalities, and with mild heart failure (NYHA class II to III without treatment) and exercise not limited by angina. 222 patients were studied, 63 were randomized to captopril, 66 to digoxin, 67 to placebo. Follow-up was conducted for two years. Base line characteristics in the three treatment groups were similar. After one year of therapy, digoxin had significantly improved general well-being (p < 0.01 vs captopril), symptom score (p < 0.05 vs captopril and placebo), and vitality (p < 0.05 vs captopril). Digoxin improved NYHA class in 45% as compared to placebo (28%, p < 0.05). Worsening of angina was more frequent with captopril as compared to digoxin (p < 0.05). However, cardiovascular events during follow-up were lower in the captopril group as compared to placebo and digoxin (p < 0.01 captopril vs placebo). No differences between groups were observed in baseline and follow-up exercise tolerance between the three groups. Dizziness during upright tilt and cough were more frequent with captopril as compared to digoxin or placebo. After two years of follow-up (captopril n = 32, digoxin n = 29, placebo n = 27) general well-being was improved with both digoxin and captopril (p < 0.004 and p < 0.03 vs placebo).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,1
1669,8125425,Reduced mortality and morbidity with the use of angiotensin-converting enzyme inhibitors in patients with left ventricular dysfunction and congestive heart failure.,S Yusuf,"The Studies of Left Ventricular Dysfunction (SOLVD) examined the effect of an angiotensin-converting enzyme (ACE) inhibitor, enalapril on mortality and hospitalization in 6,797 patients with low ejection fraction (EF < 0.35). Patients requiring treatment for heart failure were entered to the treatment trial (n = 2,569) while those patients not receiving pharmacological treatment for heart failure were entered in the prevention trial (n = 4,228). In the treatment trial, there was a 16% (95% confidence interval [CI], 5% to 26%) reduction in mortality with the largest reduction in deaths due to progressive heart failure (22%, 95% CI, 6 to 35%). There was also a 26% (95% CI, 18 to 34%) reduction in mortality or hospitalization for worsening heart failure. In the prevention trial there was an 8% (95% CI, -8 to 21%) reduction in mortality, 12% (95% CI, -3 to 26%) reduction in cardiovascular mortality, and a 29% (95% CI, 21 to 36%) reduction in mortality or development of heart failure. In addition, there was a 20% (95% CI, 9 to 30%) reduction in mortality or hospitalization for heart failure. There were consistent effects among subgroups defined by baseline serum sodium, vasodilator use, etiology and NYHA functional class. The effect of enalapril on mortality and hospitalization for heart failure was significantly greater for patients with the lowest ejection fraction. In both trials, there were highly significant reductions in myocardial infarction (23%, 95% CI, 11 to 34%) and hospitalizations for unstable angina (20%, 95% CI, 9 to 29%).",1993.0,0,1
1670,8129864,"Drug-induced hepatic disorders. Incidence, management and avoidance.",M Døssing; J Sonne,"Drug-induced liver injury has been associated with more than 800 different drugs, leading to hospital admission in 1 of 600 to 3500 admissions. This amounts to 2 to 3% of all hospitalisations due to adverse drug reactions, or about 3% of all jaundiced patients. The prognosis of clinically overt drug hepatotoxicity is relatively serious. The clinical picture is essentially nonspecific, with a highly variable latency period from days to years. Drug hepatotoxicity can mimic almost any kind of liver disease. A thorough drug history, a low threshold of suspicion and the exclusion of other causes of liver disease are important for the detection of drug-induced liver disorders. Treatment consists of discontinuation of suspected drug(s), acetylcysteine in the course of paracetamol (acetaminophen) toxicity, and liver transplantation in selected cases of fulminant liver failure. Guidelines regarding the use of selected drugs such as methotrexate and halothane should be followed. Potentially hepatotoxic drugs should be used cautiously in alcoholic patients with or without liver involvement. Patients with uncompensated liver disease should receive a reduced dose of drugs adjusted to the degree of liver function impairment. The general public should be warned against abuse of hepatotoxic drugs such as paracetamol and anabolic steroids.",1993.0,0,0
1671,8130100,Clinical quiz. What is the cause of anuria in this newborn infant?,B Hoppe; T Neuhaus; B Weisser; E Leumann,,1993.0,0,0
1672,8131769,The effects of early captopril treatment on left ventricular volumes and function in patients with and without depressed global ejection fraction after acute myocardial infarction.,M K Kyriakidis; P N Petropoulakis; E K Georgiou; S A Marakas; D A Michalopoulos; A A Antonopoulos; C C Proukakis; P K Toutouzas,"To determine the effects of captopril on left ventricular volumes and function in patients with and without depressed ventricular function following acute myocardial infarction (AMI) we studied 78 patients with a first Q wave AMI and no clinical evidence of heart failure. All patients underwent radionuclide ventriculography (RVG) on the 4th day after admission and were then randomly assigned to receive conventional treatment alone (36 patients, control group) or with the addition of oral captopril, 25 mg three times daily (42 patients, captopril group). RVG was repeated one month after the baseline examination. After one month the left ventricular ejection fraction (LVEF) significantly increased in the captopril group (from 43.2 +/- 1.3 to 50.9 +/- 1.6%, P < 0.001) and remained relatively unchanged in the control group (from 47 +/- 1.3 to 49.2 +/- 1.7%, P = ns). In the captopril group the subgroup of patients with a baseline LVEF < 45% demonstrated a significant decrease in end-systolic volume index (ESVI) (from 53.3 +/- 3.2 to 42.4 +/- 2.8 ml. m-2, P < 0.002) and a highly significant improvement in LVEF (from 36.3 +/- 1.3 to 49.6 +/- 1.8%, P < 0.00005). In the control group, LVEF also increased in those in whom it was < 45% (from 38 +/- 1.4 to 42 +/- 2.4%, P < 0.01), but the increase was less than that in the captopril group (P < 0.01), mainly due to an increase in end-diastolic volume index (EDVI) (from 78.2 +/- 4.6 to 84.6 +/- 12.3 ml.m-2, P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,1
1673,8131770,Effects of transdermal nitroglycerin in combination with an ACE inhibitor in patients with chronic stable angina pectoris.,M L Muiesan; E Boni; M Castellano; M Beschi; G Cefis; B Cerri; P Verdecchia; C Porcellati; G Pollavini; E Agabiti-Rosei,"We have previously shown that transdermal nitroglycerin may induce an increase in the activity of the adrenergic and the renin-angiotensin-aldosterone systems (SRAA) in patients with chronic stable angina pectoris (SA); when the activation of these systems is more pronounced, the antianginal effect of this drug seems to be reduced. The aim of this study was to evaluate the antianginal efficacy of transdermal nitroglycerin administration (TTS-NG 10 mg.24 h-1) in combination with an ACE inhibitor without sulphydryl groups (BNZ, benazepril 10 mg b.i.d.) in respect to placebo, or to TTS-NG or BNZ administered as monotherapy. Twenty-four patients (21M, 3F) were admitted to this multicentre, randomized, double-blind, latin square, placebo-controlled study. Patients received all the treatments (placebo, TTS-NG, BNZ and BNZ + TTS-NG) each for one week; at the end of each week patients performed two exercise tests 2 and 22 h post-dosing. Two hours post-dosing, exercise duration at 1 mm ST depression was significantly increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05) treatments. Two hours post-dosing, exercise duration at peak exercise was also increased in respect to placebo during TTS-NG (P < 0.05) and TTS-NG + BNZ (P < 0.05); 22 h post-dosing the increase in exercise duration was significant only during TTS-NG + BNZ treatment (P < 0.05) in respect to placebo, but not during TTS-NG given alone. Rate-pressure product at 1 mm ST depression was significantly increased 2 h post-dosing during TTS-NG treatment (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1674,8132854,Organization and functioning of an adverse drug reaction clinic.,A G Recchia; N H Shear,,1994.0,0,0
1675,8136110,Albumin excretion rate and metabolic modifications in patients with essential hypertension. Effects of two angiotensin converting enzyme inhibitors.,J G Puig; F A Mateos; T H Ramos; M P Lavilla; M C Capitán; A Gil,"A prospective randomized, double-blind, double-dummy study investigated the effects of two angiotensin converting enzyme (ACE) inhibitors on urinary albumin excretion in nondiabetic patients with mild to moderate essential hypertension. At the end of a 4-week placebo run-in period, 36 patients were randomly allocated to receive a 12-week course of treatment with quinapril (10, 20, or 40 mg) once daily or captopril (25, 50, or 75 mg) twice daily. Seventeen patients in each group completed the study. The mean change in mean blood pressure for patients taking quinapril (mean dose 32 mg/24 h) was -5 mm Hg (P = .002), and for patients taking captopril (mean dose 132 mg/24 h), -9 mm Hg (P = .002). The baseline urinary albumin excretion rate in both groups was (mean +/- EEM) 57 +/- 7 micrograms/min. Fifteen patients in the quinapril group and 12 patients in the captopril group had baseline albumin excretion rates of more than 20 micrograms/min. Mean urinary albumin excretion decreased in patients treated with quinapril from 55 to 33 micrograms/min (mean decrease 22 micrograms/min, 95% confidence interval [CI], 1 to 43 micrograms/min; P = .031) and with captopril from 59 to 41 micrograms/min (mean decrease 18 micrograms/min, 95% CI, 3 to 32 micrograms/min; P = .025). No significant modifications were observed in serum lipid concentrations, serum and urinary electrolytes, and magnesium or phosphorus metabolism. Mean urinary calcium excretion decreased in the quinapril-treated group (from 219 to 188 mg/24 h; P = .023) but not in the captopril group (from 264 to 267 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1676,8136116,Membrane stretch directly activates large conductance Ca(2+)-activated K+ channels in mesenteric artery smooth muscle cells.,A M Dopico; M T Kirber; J J Singer; J V Walsh,"Large-conductance, Ca(2+)-activated K+ channels were identified in single smooth muscle cells freshly isolated from rabbit superior mesenteric artery. They typically showed a reversal potential close to 0 mV in excised, inside-out patches in symmetric 130 mmol/L [K+] with a unitary conductance of 260 pS, and increased activity at more positive potentials and/or when [Ca2+] was raised at the cytosolic surface of the membrane. Both in cell-attached and in excised, inside-out configurations, stretching the membrane patch by applying suction to the back of the patch pipette increased the activity of these channels without changing either the unitary conductance or the voltage sensitivity of the channel. Stretch activation was repeatedly seen in inside-out patches when both surfaces were bathed with a 0 Ca2+ solution containing 2 or 5 mmol/L EGTA to chelate trace amounts of Ca2+, making it highly improbable that stretch activation could be secondary to a stretch-induced flux of Ca2+. Consequently, stretch activation of large-conductance, Ca(2+)-activated K+ channels in mesenteric artery smooth muscle cells seems to be due to a direct effect of stretch on the channel itself or on some closely associated, membrane-bound entity.",2001.0,0,0
1677,8136667,"Risk of gynaecomastia associated with cimetidine, omeprazole, and other antiulcer drugs.",L A García Rodríguez; H Jick,"To study the risk of gynaecomastia associated with cimetidine, misoprostol, omeprazole and ranitidine. Open cohort study with nested case-control analysis. General practices in United Kingdom that had computerised offices, 1989-92. 81,535 men aged 25-84 years who received at least one prescription for cimetidine, misoprostol, omeprazole, or ranitidine during the study period. New occurrences of idiopathic gynaecomastia diagnosed by general practitioner. The relative risk of gynaecomastia for current users of cimetidine compared with non-users was 7.2 (95% confidence interval 4.5 to 11.3). Relative risks for misoprostol, omeprazole, and ranitidine were 2.0 (0.1 to 10.7), 0.6 (0.1 to 3.3), and 1.5 (0.8 to 2.6), respectively. Current users of cimetidine on a daily dose > or = 1000 mg had more than 40 times the risk of developing gynaecomastia than non-users. The period of highest risk was seven to 12 months after starting cimetidine treatment. Spironolactone (relative risk 9.3 (3.3 to 26.1)) and verapamil (9.7 (2.6 to 36.0)) were associated with a relative risk of gynaecomastia comparable to one for cimetidine. Use of cimetidine, but not the three other antiulcer drugs, is associated with a substantially greater risk of gynaecomastia in men. A strong dose-response relation was present among cimetidine users.",1994.0,0,0
1678,8137599,Clinical pharmacokinetics of ramipril.,S Meisel; A Shamiss; T Rosenthal,"Ramipril is a long-acting nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor introduced for clinical use about a decade ago. Ramipril is a prodrug that undergoes de-esterification in the liver to form ramiprilat, its active metabolite. Ramipril rapidly distributes to all tissues, with the liver, kidneys and lungs showing markedly higher concentrations of the drug than the blood. After absorption from the gastrointestinal tract, rapid hydrolysis of ramipril occurs in the liver. In the therapeutic concentration range, protein binding of ramipril and ramiprilat is 73 and 56%, respectively. Ramiprilat binds to ACE with high affinity at concentrations similar to that of the enzyme and establishes equilibrium slowly. Although ramipril is metabolised by hepatic and renal mechanisms to both a glucuronate conjugate and a diketopiperazine derivative, most of the drug is excreted in the urine as ramiprilat and the glucuronate conjugate of ramiprilat. Elimination from the body is characterised by a relatively rapid initial phase with a half-life of 7 hours and a late phase with a half-life of about 120 hours. No clinically significant pharmacokinetic interactions between ramipril and other drugs have been reported. The drug has been generally well tolerated with the most prevalent adverse effects being dizziness (3.4%), headache (3.2%), weakness (1.9%) and nausea (1.7%). Ramipril is an effective and well tolerated drug for the treatment of hypertension and congestive heart failure in all patients, including those with renal or hepatic dysfunction, and the elderly.",1994.0,0,0
1679,8138330,Effects of captopril on myocardial protection during cardioplegia.,P Di Pasquale; S Paterna; M Valenza; L Valdes; V Albano; G Trombino; G Vitrano; S Cannizzaro; G Licata; R Albiero,"The study aimed at checking effects exerted by captopril (C) on human myocardial ACE system as well as the role played by tissue ACE inhibition in reducing reperfusion damage. A human experimental model was used during cardioplegia due to aorto-coronary-by-pass (CABG). Fifty-four patients with coronary artery disease affecting 3 vessels having suffered from acute myocardial infarction anterior (AMI-ant), homogeneous as far as ejection fraction (35-55%), number of grafts (3), clamping time, age and sex, were randomised in a double blind experiment, and were given captopril or placebo (P). A total of 4 mg/l Captopril was mixed into the cardioplegic solution with blood according to the method of Buckberg (Buckberg GD. J Thorac Cardiovasc Surg 1987; 93: 127-139). Eight samples (blood/perfusate) were obtained from each patients and norepinephrine (NE), epinephrine (E) were assayed using an HPLC technique. Angiotensin I was assayed by RIA. CK was also assayed (units/ml). Blood/perfusate samples were taken during CABG: (1) pre-pump; (2) pump sample; (3) pump preclamping; (4) coronary sinus; (5) coronary sinus sample during reperfusion; (6) coronary sinus during warm reperfusion; (7) after clamping sample; (8) after decanulation; Captopril group (29 patients): angiotensin I: (1) 8.15; (2) 7.0; (3) 7.31; (4) 8.45; (5) 8.93; (6) 8.73; (7) 9.07; (8) 9.40; versus placebo: (1) 7.09, (2) 7.43; (3) 7.80; (4) 9.31; (5) 9.01; (6) 8.35; (7) 8.85; (8) 8.07 ng/ml, probability, not significant.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1680,8138400,One-year clinical and echocardiographic follow-up of patients with congestive cardiomyopathy treated with captopril compared to placebo.,G Keren; A Pardes; Y Eschar; B Koifman; J Scherez; I Geleranter; S Laniado,"The beneficial hemodynamic and clinical effects of angiotensin-converting enzyme (ACE) inhibition in patients with severe congestive heart failure has recently been documented in large-scale studies. This mode of therapy when added to digitalis and diuretics improves survival. To evaluate the clinical effect and the changes in cardiac dimensions of captopril compared to placebo we followed 50 patients with severe congestive heart failure over 1 year using echo-Doppler cardiography. After randomization, 25 patients were started on captopril and 25 patients on placebo. At baseline and at 6 and 12 months, each patient underwent exercise tolerance test, radionuclide angiography to estimate left and right ventricular ejection fraction, M mode and two-dimensional echocardiography and Doppler cardiography to calculate cardiac dimensions and stroke volumes. During follow-up two patients in the captopril group and four in the placebo group died. Due to clinical deterioration nine patients in the placebo group had to be started on open-label captopril. Treatment with captopril was associated with a more significant improvement in functional class and exercise duration compared to placebo. Forward stroke volume estimated from Doppler echocardiography increased significantly by captopril from 47 +/- 3 to 55 +/- 3 ml and decreased in the placebo-treated patients from 49 +/- 5 to 44 +/- 4 ml. This improvement was associated with a trend towards reduced heart rate by captopril. Left ventricular end diastolic volume tended to increase in the placebo group and did not change in the captopril group. Calculated mitral regurgitant volume at 6 and 12 months tended to be lower in the captopril-treated patients. Thus captopril therapy proved efficacious in patients with severe congestive heart failure and resulted in increased forward stroke volume; it may have a beneficial effect on cardiac dimensions and on mitral regurgitation.",1994.0,0,0
1681,8140569,[Cough caused by angiotensin converting enzyme. Reflections on the data in computerized data banks of the French system of pharmacovigilance].,S Morange-Sala; M J Jean Pastor; F Rodor; M C Galland; D Gambini; J Jouglard,,1993.0,0,0
1682,8140862,Angiotensin-converting enzyme inhibition and anaemia in renal patients.,A Korzets; D Zevin; A Chagnac; U Gafter; T Weinstein; Y Ori; J Levi,A 35-year-old renal transplant patient with stable renal function developed an unexplained anaemia. Appropriate investigations proved non-diagnostic. Only when enalapril therapy was stopped did the anaemia reverse and haemoglobin levels returned to pre-treatment levels. An association between angiotensin-converting enzyme inhibitors and anaemia in patients with renal failure is becoming more evident. A literature review of this problem and its possible pathogenesis in patients with renal failure is given.,1993.0,0,0
1683,8141183,Role of bradykinin in anaphylactoid reactions during hemodialysis with AN69 dialyzers.,R M Schaefer; E Fink; L Schaefer; R Barkhausen; P Kulzer; A Heidland,"In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme (ACE) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane. In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients, not being treated with ACE inhibitors, using AN69, cuprophane, and polysulfone membranes. Bradykinin was measured after extraction by radioimmunoassay. During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane. Blood samples were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer (baseline 40 +/- 3 vs. 4,900 +/- 130 fmol/ml after 5 min). Even though none of the patients received ACE inhibitors, there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer. When these patients were treated either with cuprophane or with polysulfone dialyzers, no significant bradykinin formation was detected, nor were there any adverse events. Taken together, these findings show that anaphylactoid reactions with the AN69 membrane are due to excessive bradykinin generation which even may occur in the absence of ACE inhibitors.",1993.0,0,0
1684,8143294,Converting enzyme inhibitors in cardiovascular therapy: current status and future potential.,T Unger; P Gohlke,,1994.0,0,0
1685,8146829,CART and logistic regression analyses of risk factors for first dose hypotension by an ACE-inhibitor.,J Hasford; H Ansari; K Lehmann,"Angiotensin converting enzyme inhibitors (ACEI) are established drugs for the treatment of congestive heart failure. Cases of symptomatic hypotension, especially on the first day of treatment, have been reported occasionally. The database we analysed consisted of 1,177 patients, mean age approximately 70 yrs, with congestive heart failure NYHA functional class II or III. These patients were treated and observed prospectively according to a uniform protocol, starting therapy with 2.5 mg enalapril and measuring blood pressure at hourly intervals for eight hours thereafter. 94.6% of the patients experienced no symptomatic hypotension, 4.75% moderate symptoms (e.g. dizziness, headache) and 0.59% severe symptoms (e.g. fainting, collapse, renal failure). For the analyses of risk factors a large number of baseline variables were analysed univariately to select those significant for inclusion in a multivariate stepwise logistic regression. Alternatively the CART-(classification and regression tree) technique was used. Both techniques showed diastolic blood pressure < or = 70 mmHg to be the single most significant risk factor. CART-analyses showed also pretreatment with nitrates and systolic blood pressure < or = 120 mmHg to be of prognostic relevance. Thus CART is a valuable complement when looking for prognostic factors.",1993.0,0,0
1686,8147677,Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group.,S G Chrysant,"To test the antihypertensive and metabolic effects of lisinopril, 10 mg/d (L); hydrochlorothiazide, 12.5 and 25 mg/d (H12.5 and H25); and its combination with lisinopril (L/H12.5 and L/H25) against placebo in patients with mild to moderate (stage I and stage II) hypertension. Multicenter, double-blind, placebo-controlled outpatient study of 12 weeks' duration. After 4 weeks of single-blind placebo treatment, 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were randomized into the study--467 patients completed it (placebo, 71; L, 80; H12.5, 79; H25, 77; L/H12.5, 79; and L/H25, 81). The patients were seen in the clinic every 2 weeks, where measurements of their sitting and upright blood pressure and heart rate were taken 24 +/- 2 hours after drug administration. Complete blood cell counts with differential cell counts, blood chemistry studies, urinalyses, and electrocardiograms were done at baseline and during the study. Roentgenograms were done once at baseline. Compared with placebo, all drug regimens decreased sitting and upright blood pressure (P < .001) and had no effect on sitting and upright heart rate. The greatest effect was obtained with the combinations of L/H12.5 and L/H25. There was no difference between L/H12.5 and L/H25 or between H12.5 and H25. There were no serious clinical side effects except cough, which was slightly higher with L, L/H12.5, and L/H25. The only metabolic side effects were in serum potassium level, which was lower with H25 (P < .01), and serum glucose level, which was higher with H25 and L/H25 (P < .01). The data suggest that (1) monotherapy of hypertension with L, H12.5, H25, L/H12.5, and L/H25 was effective and well tolerated; (2) the best results were achieved with L/H12.5 and L/H25; (3) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects.",1994.0,0,0
1687,8149523,Plasma endothelin determination as a prognostic indicator of 1-year mortality after acute myocardial infarction.,T Omland; R T Lie; A Aakvaag; T Aarsland; K Dickstein,"Plasma endothelin concentrations are increased in the acute phase of myocardial infarction and in chronic heart failure. Since endothelin may contribute to hemodynamic deterioration by potent vasoconstrictory and cardiotoxic actions, increased plasma levels may be associated with an unfavorable prognosis after myocardial infarction. We tested the hypothesis that plasma endothelin determination in the subacute phase of myocardial infarction is related to subsequent survival and assessed whether plasma endothelin measurements provide additional prognostic information to that obtained from clinical and biochemical variables previously known to be associated with high mortality. Plasma endothelin determination was obtained from 142 patients (average age +/- SD, 67.8 +/- 10.1 years) on day 3 after documented myocardial infarction and was related to 1-year mortality. Sixteen patients died during the follow-up period. In a univariate Cox proportional-hazards model, day 3 plasma endothelin concentrations were significantly related to mortality (P < .0001). Patient age, previous treatment for systemic hypertension, presence of clinical heart failure, and plasma atrial natriuretic factor levels were all related to mortality in univariate analysis but provided no additional prognostic information to that obtained from endothelin determination in a multivariate model. Plasma endothelin concentrations are strongly related to outcome after myocardial infarction and provide prognostic information independent of clinical and biochemical variables previously associated with a poor prognosis.",1994.0,0,0
1688,8151606,Effect of sodium restriction and fish oil supplementation on BP and thrombotic risk factors in patients treated with ACE inhibitors.,P R Howe; Y K Lungershausen; L Cobiac; G Dandy; P J Nestel,"Effects of dietary sodium restriction combined with fish oil supplementation on BP and related risk factors were assessed in hypertensives treated with angiotensin converting enzyme (ACE) inhibitors. After a four week run-in phase, a six week intervention trial was conducted in which four matched groups of 14 patients, taking either captopril or enalapril, were assigned to one of four dietary treatments: low sodium (80 mmol/day) with fish oil (5 g of omega-3 fatty acids per day); normal sodium (150 mmol/day) with fish oil; low sodium with olive oil; normal sodium with olive oil. All subjects adopted a low sodium diet and adjustments of nutrient intake were made by double-blind administration of sodium and oils in supplementary tablets and capsules. BP fell in all treatment groups during intervention. However, the reduction of SBP was 4.2 mmHg greater in subjects on a low sodium intake than in those taking normal sodium. There were no differences in BP between those taking olive oil and those taking fish oil but plasma triglycerides and serum thromboxane production were reduced by 27% and 51%, respectively in the latter. Thus the antihypertensive effect of ACE inhibitors can be augmented by sodium restriction alone but supplementing the diet with fish oil may yield additional cardiovascular benefits.",1994.0,0,0
1689,8155084,LDL-apheresis and concomitant ACE-inhibitor therapy.,H Sinzinger; J Bednar; S Granegger; I Blazek; B A Peskar,,1994.0,0,0
1690,8157946,Structural adaptation of the heart in borderline hypertensives in response to blood pressure lowering with captopril.,R J Henderson; R W Cranswick; S N Hunyor,"To determine whether treatment of borderline hypertension reverses the cardiac 'amplifier' effect associated with increased left ventricular mass. Randomized, double-blind, placebo-controlled trial involving treatment for 6 months. Ambulant outpatients in a teaching hospital. Recruited by local doctor referral or worksite screening. Average of two readings of entry blood pressures taken 1 week apart 140-160 mmHg (systolic) or 90-95 mmHg diastolic, or both. Twenty-six previously untreated males, mean +/- SD age 33 +/- 9.2 years with mean +/- SD blood pressure 138 +/- 7.4/90 +/- 7.0 mmHg entered and completed the study. Twelve subjects received captopril, average dose 72 mg/day for 24 weeks, the remainder receiving placebo. Echocardiographic left ventricular dimensions, mass and transmitral Doppler flow, as well as office, ambulatory and exercise blood pressure. In the captopril group blood pressure was reduced significantly. Left ventricular mass decreased significantly from 205 to 195 g at 8 weeks and to 202 g at 24 weeks, returning to 232 g 4 weeks after treatment. Interventricular septum thickness fell significantly at 24 weeks. Doppler parameters did not alter. Baseline 8-h ambulatory blood pressure did not change with treatment. The reduction in peak exercise systolic blood pressure in the captopril group was not different from the change in the placebo group. Blood pressure can be effectively lowered using captopril in young subjects with borderline hypertension. Treatment is well tolerated and leads to regression of left ventricular wall thickness and mass, suggesting that treatment of blood pressure elevations may be advisable at lower levels than currently recommended.",1994.0,0,0
1691,8158592,Coroner's cases of death due to errors in prescribing or giving medicines or to adverse drug reactions: Birmingham 1986-1991.,R E Ferner; R M Whittington,"The records for Coroner's Inquests in one district during a 6 year period were examined retrospectively to establish the number and nature of deaths which were due to errors in the prescription or administration of medicines, and those due to adverse drug reactions. The district has a population of 1.19 million (1991), and a total of 3277 inquests were opened during the period 1986-1991. Ten of the deaths were identified as due to errors of prescribing or giving drugs. During the same period, 36 deaths were caused by adverse drug reactions. These 46 deaths made up approximately one in 2000 of all deaths during the study period. About a fifth of deaths related to prescribing and administering drugs are due to errors and may be more easily preventable than deaths due to adverse reactions.",1994.0,0,0
1692,8162243,Effects of angiotensin-converting enzyme inhibitor therapy on presence of late potentials detected using signal-averaged electrocardiography in patients with congestive heart failure.,J L Vacek; L R Handlin; C J Beaufort; C A Koenig,"Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve the mortality rate in patients with congestive heart failure. The exact mechanism of this effect is uncertain. Signal-averaged electrocardiography has been used to evaluate the presence of late potentials as a marker for sudden cardiac death. We examined prospectively the effects of ACE inhibitor therapy on signal-averaged ECGs and ventricular arrhythmia frequency in 20 patients with moderate to severe left ventricular dysfunction and symptomatic congestive heart failure. A signal-averaged ECG and 24 h Holter monitor were performed immediately before and both 1 week and 6 weeks after captopril initiation. The mean dose of captopril at 6 weeks was 38 +/- 31 mg. The patients (19 men and one woman, mean age 63 +/- 12 years) had a baseline ejection fraction of 22 +/- 7% and mean functional class of 2.6 +/- 0.5. The cause of congestive heart failure was coronary artery disease in 18 patients, idiopathic cardiomyopathy in one, and valvular disease in one. All three signal-averaged ECG time-domain parameters tended to improve over the course of the study (study 1, 2, 3: QRS duration (ms) = 108 +/- 11, 106 +/- 12, 105 +/- 11; low-amplitude signal duration (ms) = 30 +/- 8, 31 +/- 10, 28 +/- 10; root mean voltage (microV) = 33 +/- 20, 37 +/- 24, 40 +/- 2, respectively). These changes were not statistically significant, although the improvement in QRS duration was nearly so with P = 0.06. The occurrence and complexity of ventricular ectopy did not appear to be consistently altered. ACE inhibitor therapy with captopril did not appear to alter ventricular ectopy over the course of this study. However, the trends toward improvement of signal-averaged ECG parameters deserve further evaluation in a larger and longer-term study.",1993.0,0,0
1693,8169014,Three cases of pemphigus vegetans: induction by enalapril--association with internal malignancy.,M T Bastiaens; N V Zwan; G L Verschueren; T J Stoof; C Nieboer,"Pemphigus vegetans, a rare form of pemphigus vulgaris, consists of vegetating plaques localized to flexural areas. Two types, the Neumann and the Hallopeau type, are recognized with their own characteristics. Three patients with pemphigus vegetans were examined, two with Hallopeau type and one with Neumann type. The microscopic and immunofluorescence findings were recorded. Two remarkable features were present. In one case pemphigus vegetans was possibly induced by the use of enalapril. Only in three previous cases has enalapril been described in relation to pemphigus. A second case was associated with a malignant lung tumor, a phenomenon which could not be traced in the literature. Two types of pemphigus vegetans must be distinguished. Induction of pemphigus (also vegetans) is an accepted side effect of captopril. The effect of enalapril on pemphigus is still in debate. To the best of our knowledge, this is the first time that a patient with pemphigus vegetans and a simultaneously occurring internal malignancy is described.",1994.0,0,0
1694,8173699,Differential effects of ACE inhibitors and vasodilators on renal function curve in patients with primary hypertension.,D Fliser; R Nowack; G Wolf; E Ritz,"In experimental studies differential effects of antihypertensive agents on the renal function curve have been observed: in SHR captopril lowered the slope of the renal function curve, i.e. blood pressure (BP) became salt sensitive, whereas hydralazine shifted the curve without changing its slope. To evaluate whether ACE inhibitors and vasodilators have different effects on salt sensitivity of BP in humans, we compared the effect of the ACE inhibitor cilazapril and the vasodilator dihydralazine on the renal function curve in a randomized prospective single blind cross-over study. Nine patients (1 f, 8 m, mean age 41 +/- 4 y) with mild to moderate primary hypertension were put on low (20 mmol/d) and on high salt diet (200 mmol/d). Drugs were given in random low salt+cilazapril, high salt+cilazapril; low salt+dihydralazine, high salt+dihydralazine; or in reverse order. All antihypertensive interventions lowered BP, but the averaged posttreatment MAP was significantly (p < 0.02) lower with cilazapril on low salt intake (83.6 +/- 2.8 mmHg) than with all of the following: cilazapril on high salt intake (86.4 +/- 2.9 mmHg), dihydralazine on low (91.6 +/- 3.2 mmHg) and high salt (90.1 +/- 3.3 mmHg) intake. Probably as a result of sympathetic activation, average daily heart rate was higher after dihydralazine on low (72.9 +/- 2.9 b/min) and high salt intake (72.4 +/- 2.8 b/min) than after cilazapril on either salt intake (68.7 +/- 3.1 and 62.7 +/- 3.2 b/min). The results document that BP reduction after acute ACE inhibition is a function of salt intake, i.e. with ACE inhibitor therapy, BP is ""salt sensitive"". In contrast, vasodilators of the dihydralazine type have similar antihypertensive effects on low and high salt intake. To the extent that the findings of this short-term study can be extrapolated to long-term effects they suggest that intrarenal mechanisms, i.e. resetting of the pressure-natriuresis relationship, are involved in the long-term antihypertensive action of ACE inhibitors.",1993.0,0,0
1695,8173700,A comparison of spirapril and isradipine in patients with diabetic nephropathy and hypertension.,K Nørgaard; T Jensen; P Christensen; B Feldt-Rasmussen,"The effects of spirapril and isradipine on blood pressure, urinary albumin excretion and sodium-volume homeostasis in hypertensive insulin-dependent diabetic patients with nephropathy were assessed. Fifteen Type 1 diabetic patients aged 28-53 years with a diabetes duration of 19-37 years were studied. All had hypertension and diabetic nephropathy with a urinary albumin excretion of more than 300 mg/24 h. After a single blind placebo treatment period of 4 weeks the patients were randomly assigned to treatment with the calcium antagonist isradipine SRO 5 mg once daily or the ACE inhibitor spirapril 6 mg once daily for 6 months in a double-blind design. Isradipine lowered ambulatory systolic blood pressure from 152 +/- 12 to 141 +/- 11 mmHg (p < 0.05) and ambulatory diastolic pressure from 91 +/- 9 to 86 +/- 8 mmHg (p < 0.05). The blood pressure lowering effect of spirapril was similar: 156 +/- 13 vs 143 +/- 11 mmHg (p < 0.01) and 90 +/- 4 vs 84 +/- 4 mmHg (p < 0.05). The fractional albumin clearance was unchanged on isradipine but decreased after 6 months treatment with spirapril with on average 20% (p < 0.05). Total body exchangeable sodium decreased on spirapril treatment: 2994 +/- 296 vs 2636 +/- 194 meq/1.73 m2 (p < 0.05) and extracellular volume tended to do so (p = 0.12). On isradipine treatment these parameters remained unchanged. In conclusion both isradipine and spirapril lowered blood pressure in patients with diabetic nephropathy. Only the ACE inhibitor had demonstrable beneficial effects on urinary albumin excretion rate and the sodium-volume expansion seen in these patients.",1993.0,0,0
1696,8174380,Reduction of proteinuria and changes of renal function in patients with glomerulonephritis and mild renal insufficiency. Short- versus long-acting angiotensin-converting enzyme inhibitors.,C M Erley; S Wolf; E Komini; T Nicaeus; N Braun; T Risler,,1994.0,0,0
1697,8175218,Does captopril treatment before thrombolysis in acute myocardial infarction attenuate reperfusion damage? Short-term and long-term effects.,P Di Pasquale; S Paterna; S Cannizzaro; V Bucca,"Several experimental studies carried out on animals and on isolated heart preparations show that captopril can reduce post-ischemic reperfusion injury. Our study was aimed at investigating the effects of captopril before thrombolysis in acute myocardial infarction (AMI) and included 259 patients, hospitalized within 4 h of the onset of symptoms. Patients were randomly subdivided into two groups: the first group (131 patients, Group A, pretreatment) received 6.25 mg captopril orally about 15 min before i.v. administration of urokinase (2 million), the second group (128 patients, Group B, late-treatment), received captopril about 3 days after thrombolytic treatment. Captopril doses were later increased in both groups according to blood pressure. All patients were subdivided according to the localization of infarction. Anterior AMI was shown by 166 patients (84 from Group A and 82 from Group B); 93 patients showed inferior AMI (47 from Group A and 46 from Group B). Ventricular hyperkinetic arrhythmias (VHAs) due to reperfusion were evaluated during the first 2 h. VHAs occurred in 11.9% of patients with anterior AMI in Group A vs. 37.8% in Group B (P < 0.001). CK peak normalization time in the group with anterior AMI was achieved after 58 +/- 2 h in Group A vs. 71 +/- 2 h in Group B (P < 0.001). CK peak was 1719 +/- 152 in Group A vs. 2184 +/- 164 U/l in Group B, (P < 0.039). Late arrhythmias, higher than Lown's Class 2 were found to occur in 15.4% of patients with anterior AMI of Group A vs. 31.7% in Group B (P < 0.022), at predischarge Holter test.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1698,8178391,Surgery and percutaneous angioplasty in the management of renovascular hypertension.,J A Libertino; C F Beckmann,"Unfortunately, no randomized trials have compared PTRA for renovascular hypertension with surgical or medical treatment. PTRA appears to be a safe and relatively simple procedure with complication rates lower than those of operation. The outcome of renal angioplasty depends on the type of stenosis. In all published series, the cure rates for fibromuscular disease are significantly higher than for atherosclerotic disease, and PTRA appears to be the procedure of choice in the treatment of hypertension in patients with fibromuscular disease. The role of renal angioplasty in patients with renovascular hypertension due to atherosclerotic diseases is uncertain. Most large published series describing the success of angioplasty in patients with atherosclerotic lesions have been highly selective, primarily including patients with focal stenotic lesions. Despite this selectivity, the cure rate has been only 19%. In completely unselected patients, atherosclerotic lesions are associated with a very high rate of technical failure, possibly as high as 60%. From the data available, focal isolated stenotic lesions of the renal artery due to atherosclerotic disease can be treated with a reasonable rate of success. The success rate in patients with bilateral disease, osteal stenosis, or total occlusion of the renal arteries appears to be very limited. In these patients, angioplasty should be attempted only when a surgical contraindication exists.",1994.0,0,0
1699,8179979,Problems solved and lives saved? Chronic heart failure.,J McMurray; M Francis,"Chronic heart failure (CHF) is common, disabling and deadly. Recent studies show that ACE inhibitors reduce morbidity and mortality in all grades of CHF and may even delay or prevent the onset of overt CHF in patients with asymptomatic left ventricular dysfunction. In this review, guidelines are given for how to use these drugs both in hospital and in general practice. New evidence on the benefits of digoxin is also considered, and the management of concomitant problems such as angina and arrhythmias in patients with CHF is discussed.",1994.0,0,0
1700,8180725,Hypocaloric diet and antihypertensive drug treatment. A randomized controlled clinical trial.,B Darné; M Nivarong; A Tugayé; M Safar; P F Plouin; M T Guillanneuf; J Cubeau; B Pannier; F Péquignot; F Cambien,"To compare the amount of drug quantified by a score needed to control blood pressure in two groups of overweight hypertensive patients, receiving or not receiving a hypocaloric diet. Randomized controlled clinical trial. Two hospital outpatient hypertension clinics. Fifty-four subjects with a DBP between 95 and 110 mmHg and a weight > or = 110% of the ideal weight. Allocation to either drug treatment (DT) or hypocaloric diet (HD). In the HD group, after 2 months, an antihypertensive drug was administered to the subjects with a DBP > or = 90 mmHg, following the same scheme protocol as in the DT group. Subjects were followed during 10 months by a clinician only in the DT group and by a clinician and a dietician in the HD group. Score of treatment: hydrochlorothiazide 25 mg [score = 1] with, as needed to obtain a DBP < 90 mmHg, the addiction of enalapril 10 mg [score = 2], 20 mg [score = 3], and nifedipine 40 mg [score = 4]. At the end of the trial, 5 subjects were lost to follow-up in the HD group and 1 in the DT group (p > 0.05). Mean weight loss was 5.9 kg (sd = 1.2) in the HD and 2.3 kg (sd = 0.7) in the DT group (p = 0.02). Mean decrease in DBP was 18 mmHg (sd = 7) and 15 mmHg (sd = 8) in HD and DT groups respectively (p = 0.36). Mean DBP was 84 mmHg (sd = 7.8) in the HD group and 85 mmHg (sd = 7.2) in the DT group. In the HD group, 8 (38.1%) subjects had a DBP < 90 mmHg without any drug treatment. The mean drug treatment score was 0.86 (sd = 0.91) in the HD and 1.52 (0.70) in the DT group (p = 0.01). This study shows that in overweight hypertensives, the quantity of drug needed to achieve an acceptable level of BP is nearly reduced by 50% when an efficient hypocaloric diet is prescribed simultaneously.",1993.0,0,0
1701,8180726,"STOP-Hypertension 2: a prospective intervention trial of ""newer"" versus ""older"" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension.",B Dahlöf; L Hansson; L H Lindholm; B Scherstén; P O Wester; T Ekbom; T Hedner; U de Faire,"It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p < 0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure is > or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.",1993.0,0,0
1702,8181019,Blockade of the renin-angiotensin system. Effect on mortality in patients with left ventricular systolic dysfunction.,B Pitt,"Blockade of the renin-angiotensin-aldosterone system (RAAS) has been shown to be effective in reducing morbidity and mortality in patients with symptomatic left ventricular dysfunction. Angiotensin converting enzyme inhibitors (ACE-I) should be administered to all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. Although ACE-Is are effective, there is reason to believe that further blockade of the RAAS by aldosterone antagonists and/or alternative means of blocking the RAAS by use of renin inhibitors or angiotensin II receptor blocking agents may have an important role in the future. The finding in the SOLVD and SAVE trials that ACE-Is are effective in reducing recurrent ischemic events in patients with left ventricular dysfunction also holds great promise for the future, not only for patients with left ventricular dysfunction but also as a possible secondary prevention of ischemic heart disease in patients without left ventricular dysfunction.",1994.0,0,0
1703,8181027,Nitrates in heart failure.,U Elkayam,"Organic nitrates have been used widely in the treatment of chronic congestive heart failure. These drugs have been shown to have beneficial hemodynamic effects both at rest and during dynamic and isometric exercise. In combination with hydralazine, nitrates have been shown to improve exercise tolerance, enhance left ventricular ejection fraction, and prolong survival. The potential limitations of nitrate therapy are related to dose-related nitrate resistance and the development of nitrate tolerance. More information is needed regarding the usefulness of nitrate therapy without hydralazine and the additional benefits of these drugs in patients already treated with angiotensin converting enzyme inhibitors.",1994.0,0,0
1704,8181115,N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction.,C Hall; J L Rouleau; L Moyè; J de Champlain; D Bichet; M Klein; B Sussex; M Packer; J Rouleau; M O Arnold,"Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure. Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly. To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF. The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure.",1994.0,0,0
1705,8184809,Effects of early administration of enalapril on radionuclide left ventricular ejection fraction and plasma N-terminal atrial natriuretic peptide after acute myocardial infarction.,R V Kettunen; O Vuolteenaho; O Ukkola; M Lilja; A Jounela; Y A Kesäniemi; J Leppäluoto; J Heikkilä,"The effects of enalapril therapy on radionuclide ejection fraction and plasma N-terminal atrial natriuretic peptide were investigated in a randomized, double-blind, placebo-controlled study of 52 patients with acute myocardial infarction. The medication was begun intravenously within 24 hours of the onset of symptoms. At discharge and the end point of 6 months, the radiographic size of the heart was significantly smaller in patients receiving (n = 28) than in those not receiving (n = 24) enalapril therapy (p < 0.03 vs < 0.01). However, left ventricular ejection fraction decreased simultaneously from 50 +/- 10% to 47 +/- 11% in patients treated with enalapril, whereas it increased from 48 +/- 13% to 50 +/- 14% in control patients (p < 0.05 for the difference of the changes). The decrease in ejection fraction was most marked in the infarct-related region of the left ventricle (p < 0.01). During the in-hospital period, plasma N-terminal atrial natriuretic peptide was decreased in patients treated with enalapril, whereas it was increased in those treated with placebo with complicated acute myocardial infarction (p < 0.05). During the following 6 months, the differences remained insignificant. Early administration of enalapril significantly attenuated heart enlargement after myocardial infarction and probably improved hemodynamics during the acute phase of complicated infarction. The decrease in ejection fraction during recovery indicates an impairment of systolic function. The decrease in infarct-related regional ejection fraction suggests that the impairment may be due to poor healing of the infarction scar.",1994.0,0,0
1706,8184813,Discontinuation of chronic diuretic therapy in stable congestive heart failure secondary to coronary artery disease or to idiopathic dilated cardiomyopathy.,W C Grinstead; M J Francis; G F Marks; C B Tawa; W A Zoghbi; J B Young,"To assess the feasibility of diuretic discontinuation in patients with stable congestive heart failure (CHF) and to identify risk factors for subsequent development of congestion, a prospective, 12-week clinical trial of unmasked diuretic withdrawal was conducted with continuation of background CHF therapy and double-blind randomization to placebo or lisinopril. Forty-one patients with a history of CHF and continuous diuretic use for > or = 3 months had all diuretic therapy discontinued, and therapy with lisinopril 5 mg (target 20 mg)/day (n = 20) or placebo (n = 21) begun the next day. A diuretic was restarted if new or worsening CHF symptoms and signs developed. Twelve patients (29%) did not require diuretic reinitiation at any time during follow-up, whereas 29 (71%) restarted diuretic therapy after a median of 15 days (range 2 to 42). Fourteen patients taking lisinopril and 15 taking placebo required diuretic drugs (p = NS). The baseline daily furosemide dose of > 40 mg, a left ventricular ejection fraction < or = 0.27, and history of systemic hypertension were independently predictive of early diuretic reinitiation by Cox proportional-hazards analysis. The probability of remaining diuretic-free after 6 weeks was 71% if none of these criteria were present. This trial demonstrates the feasibility of discontinuing diuretic drugs in certain patients with stable CHF and predicts those patients likely to require reinitiation of therapy. Diuretic withdrawal may be warranted when the furosemide dose is < or = 40 mg/day, left ventricular ejection fraction is > 0.27 and when no history of systemic hypertension is present.",1994.0,0,0
1707,8184862,Comparison of single dose nifedipine and captopril for chronic severe mitral regurgitation.,C Röthlisberger; P Sareli; T Wisenbaugh,,1994.0,0,0
1708,8187120,Exercise capacity in patients with left ventricular dysfunction following acute myocardial infarction: relation to systolic and diastolic function and intervention with captopril.,P Søgaard; C O Gøtzsche; J Ravkilde; A Nørgaard; K Thygesen,Patients with acute or chronic heart disease may have limited exercise capacity if they have reduced left ventricular function. Indexes of reduced left ventricular function during exercise are a predictor of subsequent survival although left ventricular ejection fraction is a poor predictor of physical endurance. We evaluated the effect of captopril on physical endurance in 48 males with left ventricular dysfunction following myocardial infarction. On the 7th day following myocardial infarction patients were randomized to either captopril 50 mg daily or corresponding placebo. Patients were followed up by means of serial echocardiography and exercise stress testing for a period of 180 days. Exercise capacity was significantly improved in the captopril group. Changes in exercise capacity were significantly correlated to changes in left ventricular (LV) volumes and compliance. The beneficial effect of captopril on exercise capacity was probably mediated via improvement in LV performance and compliance.,1994.0,0,0
1709,8187316,"Plasma corticotrophin releasing hormone, vasopressin, ACTH and cortisol responses to acute myocardial infarction.",R A Donald; I G Crozier; S G Foy; A M Richards; J H Livesey; M J Ellis; L Mattioli; H Ikram,"We assessed the magnitude and duration of the response of hypothalamic-pituitary-adrenal hormones to the stress of myocardial infarction, in the presence and absence of angiotensin converting enzyme inhibitors. In particular, we wished to analyse the interrelationships between peripheral plasma levels of corticotrophin releasing hormone (CRH), vasopressin (AVP) and adrenocorticotrophin (ACTH), and also between ACTH and cortisol, during a prolonged medical stress. All hormones were measured within 6 hours of the onset of an acute myocardial infarction. Patients were randomly allocated to three different study groups according to a double blind procedure. Group 1 (10 patients) received placebo treatment, Group 2 (13 patients) received a maintenance dose of captopril 25 mg three times daily, Group 3 (11 patients) received enalapril 5 mg three times daily. Peptide hormones were measured by radioimmunoassay, and cortisol by ELISA. Reference ranges for all hormones were obtained from 40 or more volunteers from the electoral roll. At the start of the study, mean +/- SEM plasma AVP (27.9 +/- 4.6 pmol/l) was significantly (P < 0.001) raised above the mean for the reference range (1.82 +/- 0.09 pmol/l), and 12 patients had values > 50 pmol/l. Mean plasma cortisol (960 +/- 89.6 nmol/l) was also raised above the reference range mean (554 +/- 28 nmol/l, P < 0.001), as was mean plasma CRH (4.97 +/- 0.5 pmol/l, reference mean 1.52 +/- 0.09 pmol/l, P < 0.001). By contrast, mean ACTH (3.88 +/- 0.66 pmol/l) was significantly less than the reference mean (10.7 +/- 0.7 pmol/l, P < 0.001). During the 72-hour observation period there was a highly significant fall (P < 0.001) in plasma CRH, AVP and cortisol. By contrast, plasma ACTH rose, and the change with time of ACTH was significantly different from the fall in plasma CRH, AVP or cortisol (P < 0.001 for each comparison). No significant differences in plasma CRH, AVP, ACTH or cortisol responses to placebo, captopril or enalapril were observed. Within 6 hours of a myocardial infarction, mean plasma CRH, AVP and cortisol values were very significantly raised above mean control values, while ACTH was very significantly reduced. During the 3 days following an acute myocardial infarction, plasma CRH, AVP and cortisol fell substantially, and this pattern was not influenced by angiotensin converting enzyme inhibitors. By contrast, plasma ACTH showed a significant increase with time. This suggests that the usual relationships between CRH, AVP and ACTH, and between ACTH and cortisol are disturbed in patients admitted to hospital with myocardial infarction. Maximum levels of AVP observed in 12 patients exceeded 50 pmol/l, which may be sufficiently high to interfere with tissue perfusion. It is postulated that V1 AVP receptor antagonists may have a therapeutic application in limiting infarct size.",1994.0,0,1
1710,8187356,Effect of enalapril on the microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.,A Chagnac; A Korzets; D Zevin; T Wender; G Carmon; J Hirsh; U Gafter; J Levi,"The transcapillary escape rate of albumin (TERalb) is often elevated in patients with diabetic microangiopathy. The objective of this study was to examine the effect of enalapril on the TERalb of diabetic patients with albuminuria and normal or mildly elevated blood pressure. Seventeen diabetic patients with diabetic retinopathy, albuminuria, a diastolic blood pressure below 100 mmHg and increased TERalb participated in the study. Blood pressure and TERalb were measured before and after 14 days of therapy with enalapril, 20 mg daily for 14 days. Systolic and diastolic blood pressure fell from 168 +/- 6 to 155 +/- 6 (p < 0.001) and from 87 +/- 2 to 81 +/- 2 mmHg (p < 0.005) respectively. Mean arterial pressure declined from 114 +/- 3 to 105 +/- 3 mmHg (p < 0.0001). The elevated TERalb decreased from 9.5 +/- 0.5 to 7.2 +/- 0.5%/hr (p < 0.005). In the hypertensive subset, systolic, diastolic and mean arterial pressure decreased significantly by 15, 7 and 10 mmHg (p < 0.005, p < 0.005 and p < 0.005 respectively); TERalb decreased from 9.5 +/- 0.6 to 7.3 +/- 0.6 (p < 0.03). In the normotensive subset, arterial pressure remained unchanged and TERalb decreased from 9.0 +/- 0.8 to 6.8 +/- 1.0%/hr (p < 0.03). Plasma fructosamine decreased from 373 +/- 23 to 347 +/- 20 (p < 0.05) in the hypertensive group and remained unchanged in the normotensive patients. No correlation could be demonstrated between variation in TERalb and changes in blood pressure. In conclusion, enalapril decreases microvascular albumin leakage in patients with diabetic microangiopathy and normal or mildly elevated blood pressure.",1994.0,0,0
1711,8187369,The plasma concentration of N-terminal proatrial natriuretic factor ANF(1-98) is related to prognosis in severe heart failure.,C Hall; J Kjekshus; P Eneroth; S Snapinn,"Due to its longer halflife, the N-terminal of ANF prohormone, ANF(1-98), has plasma concentrations that exceed those of ANF itself by a factor of 10 or more. It is also less prone to rapid changes secondary to hemodynamic alterations. To evaluate the prognostic significance of ANF(1-98) plasma levels in severe heart failure (NYHA IV), the peptide was measured by radioimmunoassay in plasma samples from patients randomized to additional treatment with enalapril (n = 78) or placebo (n = 61) (CONSENSUS study). In the placebo group there was a positive relation between mortality after 6 months and baseline ANF(1-98) level. Because of a reduced mortality, especially among patients with high ANF(1-98) levels, there was no such relation in the patients treated with enalapril. For both groups there was a positive relationship between increase in ANF(1-98) after 6 weeks of treatment and mortality, while a decrease signaled a favorable prognosis. It is concluded that the magnitude and changes of plasma ANF(1-98) provide information on prognosis and therapeutic effects with respect to mortality in patients with severe heart failure. Plasma ANF(1-98) may serve as a useful clinical biochemical parameter in the treatment of heart failure.",1994.0,0,0
1712,8193732,Comparison of felodipine and enalapril monotherapy in essential hypertension.,R W Watts; A Dufek; L M Wing,"This study compared the efficacy and tolerability of monotherapy with felodipine and enalapril in patients with essential hypertension using a double-blind randomised crossover design. Thirty-five subjects (22 male, 13 female--ages: median 48 years, range 31-69 years) entered the randomised phases of the study and 32 subjects completed the study. Following a 4-week run-in placebo phase, the treatments were felodipine (""Plendil ER"") 5-20 mg and enalapril 5-20 mg orally once daily for 8 weeks, each with matching placebos. Dose titration was at 2 and/or 4 weeks in each phase. Number of subjects with each different end-of-phase dose were for felodipine: 5 mg--8, 10 mg--11, 20 mg--13 and enalapril: 5 mg--6, 10 mg--9, 20 mg--17. Predose supine blood pressure (mean +/- SEM) was reduced in both active treatment phases compared with the run-in phase (159 + 2/101 +/- 1), but there was no significant difference in blood pressure between the active phases: felodipine 143 +/- 2/90 +/- 1 and enalapril 146 +/- 2/92 +/- 1. The most common adverse effects were for felodipine: headache, flushing, ankle swelling; and for enalapril: cough. Felodipine and enalapril as once daily monotherapy are thus of similar antihypertensive efficacy but with predictably different adverse effect profiles.",1993.0,0,0
1713,8196289,Is the antiproteinuric effect of ACE inhibition mediated by interference in the renin-angiotensin system?,R T Gansevoort; D de Zeeuw; P E de Jong,"Angiotensin converting enzyme (ACE) inhibition causes specific renal effects, such as a rise in effective renal plasma flow, a fall in filtration fraction and a lowering of proteinuria. The mechanism of these renal effects is still debated. Recent animal studies suggest that non-angiotensin (Ang) II related actions of ACE inhibition, such as bradykinin accumulation, may have a role. We therefore investigated the effects of specific intervention in the renin-angiotensin system with the Ang II receptor antagonist losartan, and compared these effects to those obtained with ACE inhibition, as this comparison might resolve the question whether or not the effects of ACE inhibition are Ang II related. The effects of losartan and enalapril were studied in eleven patients with non-diabetic proteinuria and hypertension. The protocol consisted of seven periods, each lasting one month, in which patients received once daily placebo, 50 mg losartan, 100 mg losartan, placebo, 10 mg enalapril, 20 mg enalapril, and placebo, respectively. At the end of each study period proteinuria, blood pressure, and renal function were determined. On both doses of losartan and enalapril proteinuria and blood pressure fell, whereas ERPF increased and GFR remained stable. The fall in urinary protein excretion was similar for both drugs: 46.3% (28.3% to 63.1%) on 100 mg losartan versus 51.6% (37.0% to 69.2%) on 20 mg enalapril (expressed as Wilcoxon-based estimated median with 95% CI).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1714,8198036,Effectiveness of enalapril in combination with low-dose hydrochlorothiazide versus enalapril alone for mild to moderate systemic hypertension in black patients.,S J Middlemost; R Tager; J Davis; P Sareli,"The importance of concomitant low-dose hydrochlorothiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic parameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 +/- 17 versus 102 +/- 23 g/m2, and 24-hour ambulatory BP measured 120 +/- 8/75 +/- 6 versus 155 +/- 12/100 +/- 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 +/- 15/100 +/- 7 mm Hg to 148 +/- 19/96 +/- 11 mm Hg after treatment (p < 0.05 for systolic BP); systolic BP load (70% to 59%, p < 0.05), and diastolic BP load (67% to 60%, p = NS) decreased. Baseline BP decreased from 157 +/- 9/101 +/- 6 to 132 +/- 13/86 +/- 8 mm Hg (p < 0.0001); systolic BP load (64% to 29%, p < 0.0001), and diastolic BP load (64% to 33%, p < 0.0001) decreased in group 2. Exercise systolic BP was attenuated (p = 0.007, group 2; p = NS, group 1) and duration increased (p = NS) only in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1715,8198936,Dose finding studies with imidapril--a new ACE inhibitor.,M J Vandenburg; E M Mackay; I Dews; T Pullan; S Brugier,"1. We describe an approach involving a smaller, shorter study, leading onto a longer, larger study in which the antihypertensive effects of ascending doses of imidapril, a new ACE inhibitor, were investigated. Both studies were planned prospectively, assuming a clinically useful fall in BP to be 8 mm Hg (s.d. = 9). The studies included patients with mild to moderate essential hypertension (baseline sitting diastolic blood pressure (SDBP) 95-115 mm Hg). After a placebo run-in of 2-3 weeks patients received either placebo or imidapril 2.5, 5, 10 or 20 mg in the 2 week study (n = 91) or imidapril 5, 10, 20 or 40 mg in the 4 week study (n = 162). 2. The overall mean baseline SDBP was 103.4 mm Hg (s.d. 0.62) in the initial study and 101.5 mm Hg (s.d. 0.41) in the 4 week study. 3. Compared with placebo, imidapril 10, 20 and 40 mg significantly reduced SDBP. There was no significant difference between these doses, suggesting that 10 mg achieved maximal ACE inhibition in most patients. The 2.5 mg dose showed no significant effect. The 5 mg dose gave an intermediate effect. In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups, and was not worrying.",1994.0,0,0
1716,8199724,Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension.,L M Wing; A E Russell; A L Tonkin; R W Watts; A J Bune; M J West; J P Chalmers,"Using a randomised double-blind crossover design with Latin square allocation of treatments in 20 subjects (7 male, 13 female-ages: 61-87 years) with systolic hypertension, we investigated the efficacy and tolerability of once daily felodipine (extended release) 5-20 mg, enalapril 5-20 mg and their combination compared with placebo in four treatment phases each of 6 weeks duration. During each phase, doses were titrated to achieve a predose clinic supine systolic blood pressure of 140 mmHg or to a predetermined maximum dose. In both the felodipine and combination phases, predose supine and standing systolic and diastolic pressures were significantly reduced compared with the placebo phase (decrease in supine pressure: -13/-5 and -18/-7, respectively). Only predose supine diastolic pressure was significantly reduced (-3 mmHg) compared to placebo in the enalapril phase. In combination the effects of the two drugs on predose blood pressure were additive. There was a 40-60% increase in reported symptoms in the felodipine and combination phases compared with the placebo and enalapril phases. Thus, in elderly subjects with systolic hypertension, felodipine effectively reduces blood pressure throughout the dose interval but with vasodilator adverse effects. In contrast, enalapril is well tolerated but is less effective in reducing blood pressure throughout the whole dose interval.",1994.0,0,0
1717,8203335,"Comparison of enalapril versus captopril on left ventricular function and survival three months after acute myocardial infarction (the ""PRACTICAL"" study).",S G Foy; I G Crozier; J G Turner; A M Richards; C M Frampton; M G Nicholls; H Ikram,"Left ventricular (LV) function and survival can be improved with captopril when initiated later than 24 hours after acute myocardial infarction. Animal studies suggest additional benefits may be obtained with earlier initiation of angiotensin-converting enzyme (ACE) inhibitors. The effects on LV function of captopril and enalapril initiated within 24 hours of myocardial infarction were studied. Two hundred twenty-five patients with acute myocardial infarction were enrolled within 24 hours of the onset of chest pain. They were randomized to receive either captopril 25 mg three times daily, enalapril 5 mg three times daily, or placebo. LV ejection fraction (EF) and volumes were measured by radionuclide ventriculography at baseline during treatment and at 3 months after a 3-day withdrawal from therapy. The ACE inhibitor group had a significant increase in EF (45 +/- 1 to 47 +/- 1%; p = 0.005) and significantly attenuated LV dilatation compared with results in the placebo group (175 +/- 6 to 189 +/- 7 ml in the placebo group vs 168 +/- 4 to 172 +/- 4 ml in the ACE inhibitor group; p = 0.051 for LV end-diastolic volume; and 99 +/- 6 to 108 +/- 7 ml in the placebo group vs 94 +/- 3 to 94 +/- 4 ml; p = 0.026 for LV end-systolic volume). The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction and were comparable in both the captopril and enalapril groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,1,1
1718,8203337,"Determinants of the initial effects of captopril on blood pressure, glomerular filtration rate, and natriuresis in mild-to-moderate chronic congestive heart failure secondary to coronary artery disease.",J G Motwani; M K Fenwick; J J Morton; A D Struthers,"Whereas angiotensin-converting enzyme inhibitors are now indicated for all grades of chronic heart failure, the 2 adverse effects that limit use of these drugs are systemic hypotension and renal dysfunction. The recognized clinical correlates such as hyponatremia and high diuretic dose, which predict occurrence of these adverse effects in severe chronic congestive heart failure (CHF), are rarely evident in patients with mild-to-moderate CHF. Accordingly, we studied 36 patients with stable, moderate CHF in a double-blind, placebo-controlled, crossover fashion to evaluate by multiple discriminate regression analysis the pathophysiologic determinants of changes in blood pressure, glomerular filtration rate, and urinary sodium excretion after initial converting enzyme inhibition with captopril 25 mg. A captopril-mediated decrease in mean arterial pressure was predicted by 3 factors (r2 = 0.74): the decrease in serum angiotensin II (F ratio = 10.3, p < 0.01), the decrease in plasma norepinephrine (F = 8, p = 0.02), and, inversely by pretreatment mean arterial pressure (F = 5.6, p = 0.04), patients with higher initial values exhibiting greater decreases in response to captopril. A captopril-mediated decline in glomerular filtration rate, determined by radioisotope elimination, was also predicted by 3 factors (r2 = 0.67): a decrease in renal plasma flow (F = 48.6, p < 0.01), low pretreatment glomerular filtration rate (F = 11.1, p < 0.01), and low absolute post-treatment serum angiotensin II (F = 5, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1719,8205297,Does the combination of ACE inhibitor and calcium antagonist control hypertension and improve quality of life? The LOMIR-MCT-IL study experience.,M Amir; N Cristal; D Bar-On; A Loidl,"The LOMIR-MCT-IL study was designed to investigate the effects of different antihypertensive drugs on the quality of life (QoL) of men with mild-to-moderate hypertension. This report focuses on the subgroup of patients treated with the combination of the angiotensin converting enzyme (ACE) inhibitor captopril and the calcium antagonist isradipine. The LOMIR-MCT-IL was a double-blind multicenter, placebo-controlled, one-year follow-up study in which 368 hypertensive men, aged 40-65 years, were randomly allocated to receive either isradipine, methyldopa or placebo at three titration levels. If diastolic blood pressure (DBP) remained > 90 mmHg, captopril was added openly. The QoL evaluation introduced a qualitative self-structured subjective measure in addition to prestructured quantitative measures. The quality of life was assessed at baseline, after 6 months and at the end of the study. Methyldopa normalized DBP in 50% of patients when given as monotherapy and an additional 34% with the addition of captopril (84% total). With placebo, 36% normalized DBP and another 39% on addition of captopril (75% total) and, with isradipine, 64% normalized DBP and an additional 26% with added captopril (90% total). Assessment of QoL showed that both the placebo and the isradipine+captopril groups showed significant improvement in semantic memory after antihypertensive treatment. The isradipine+captopril group showed a clear tendency towards lower depression scores, better quality of sleep, better subjective evaluation of QoL and a more positive evaluation of personal life events in comparison to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1720,8205299,Concomitant administration of isradipine and spirapril prevents reduction of renal function induced by acute administration of spirapril in patients with reduced renal function.,C Wittenberg; A Erman; J Shohat; G Boner,"Angiotensin-converting enzyme (ACE) inhibitors may cause a further decrease in renal function in patients who already have renal failure. The acute effects of the ACE inhibitor spirapril on renal function were investigated in 10 patients with mild-to-moderate renal failure (serum creatinine of 1.5-2.5 mg/dl). Acute oral administration of spirapril at 6 mg resulted in decreases in inulin clearance (from 53.7 +/- 12.8 to 44.6 +/- 8.8 ml/min; p < 0.02; n = 5) and in PAH clearances (from 215 +/- 141.9 to 184 +/- 37.8 ml/min; p < 0.006; n = 5). However, when the acute administration of 6 mg of spirapril was given concomitantly with isradipine at 5 mg, there were no changes in these renal function parameters.",1994.0,0,0
1721,8205314,A comparison of isradipine and felodipine in Australian patients with hypertension: focus on ankle oedema. The Physician's Study Group.,J J Hammond; S A Cutler,"The aim of this study was to compare the tolerability and efficacy of isradipine and felodipine in the treatment of mild-moderate hypertension. After a 4 week placebo period, 143 patients entered a randomized, double-blind, multicentre study of 12 weeks duration. Patients received either isradipine (n = 72) or felodipine (n = 71) 2.5 mg twice daily. Doubling of this dose and the addition of enalapril (2.5 mg once daily) was permitted if DBP was > 90 mmHg at weeks 4 and 8, respectively. Isradipine monotherapy reduced BP from 165/104 +/- 13/6 mmHg at baseline to 149/91 +/- 14/10 mmHg at week 8 (p < 0.001), while felodipine alone reduced BP from 171/104 +/- 17/6 at baseline to 151/92 +/- 19/9 (p < 0.001). Following the addition of enalapril to 35% of patients in the isradipine group BP was further reduced to 144/88 +/- 13/8 mmHg at week 12 (p < 0.001). The addition of enalapril to 24% of the felodipine group further reduced BP to 150/92 +/- 19/9 mmHg at week 12 (p < 0.001). No differences in BP were found between the 2 groups while on monotherapy. However, the isradipine group had a significantly lower DBP than the felodipine group at the conclusion of the study (p = 0.008; 95% CI 0.7 to 6.9 mmHg). Similar incidences of headache, flushing, dizziness and tachycardia were reported in both groups. However, the incidence of ankle oedema was significantly lower in the isradipine group (p = 0.028). Overall, ankle oedema was reported more often by female patients and was not associated with an increase in weight.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1722,8205743,Response of plasma neuropeptide Y and noradrenaline to dynamic exercise and ramipril treatment in patients with congestive heart failure.,B Ullman; K Lindvall; J M Lundberg; A Sigurdsson; K Swedberg,"Forty-two patients with congestive heart failure were studied in order to clarify whether the plasma level of neuropeptide Y-like immunoreactivity (NPY-LI) rises in parallel with plasma noradrenaline (NA) during physical exercise in congestive heart failure (CHF). All patients were studied in a randomized placebo-controlled trial with the ACE-inhibitor ramipril during 12 weeks to determine whether ACE-inhibition alters the response of plasma NPY-LI to exercise. The patients were treated with diuretics and had stable congestive heart failure (NYHA classes II-III). Plasma NPY-LI was 50 +/- 5 pmol l-1 (mean +/- standard error of the mean) at rest and 60 +/- 6 pmol l-1 at the end of exercise at baseline (P < 0.01). The corresponding values for plasma NA were 2.8 +/- 0.2 nmol l-1 and 15.3 +/- 1.2 nmol l-1 (P < 0.001). Before ACE-inhibition, there was a correlation between high NPY-LI and NA values after exercise. After treatment with ramipril or placebo for 12 weeks, there was no difference in plasma NPY-LI and NA at rest or after exercise between the two treatment groups. The maximal exercise time was unchanged. It is concluded that plasma NPY-LI and NA were elevated at rest in CHF. The additional rise of plasma NPY-LI and NA after exercise was attenuated in CHF compared to healthy individuals. ACE-inhibition with ramipril did not alter plasma NPY-LI or NA at rest or after exercise compared to placebo.",1994.0,0,0
1723,8207741,Perindopril plus nifedipine versus perindopril plus hydrochlorothiazide in mild to severe hypertension: a double-blind multicentre study. The Multicentre Study Group on Treatment Association with Perindopril.,P Letellier; A Overlack; E Agnes; P Desche,"Thiazide diuretics are considered as the choice drug to combine with ACE inhibitors for the treatment of hypertension. However, there is much evidence showing that the combination of ACE inhibitors with a calcium channel blocker is effective and safe. We compared the safety and efficacy of perindopril 8 mg once daily plus nifedipine SR 10 mg twice daily with perindopril 8 mg once daily plus hydrochlorothiazide (HCTZ) 12.5 mg once daily in a two phase three month study. After a one month placebo run-in period, patients whose DBP averaged 95-125 mmHg received perindopril 4 mg once daily for the first open phase (n = 524). After one month those whose DBP remained > 90 mmHg were prescribed perindopril 8 mg once daily for a second month. Among them, those whose DBP were still > 90 mmHg entered the second phase for one month, in a double-blind fashion. Fifty-three patients received HCTZ (BP: 161.2/99.2 +/- 2.0/0.9 mmHg), 57 received nifedipine (BP: 161.4/98.7 +/- 2.2/0.7 mmHg). Five patients withdrew due to side-effects, three patients in the perindopril plus nifedipine group and two in the perindopril plus HCTZ group. After one month there was a significant drop in BP (P < 0.01) in both groups: perindopril plus HCTZ (-13.9/-11.9 mmHg) and perindopril plus nifedipine (-12.1/-10.8 mmHg). Heart rate was not significantly modified: perindopril plus HCTZ (-1.30 beats/min), perindopril plus nifedipine (+0.54 beats/min). There were no significant difference between the two combinations for BP reduction and heart rate. The incidence of adverse experiences was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1724,8208641,ACE inhibition versus calcium antagonism in the treatment of mild to moderate hypertension: a multicentre study. Ireland-Netherlands Lisinopril-Nifedipine Study Group.,W Hart; R J Clarke,"The efficacy of lisinopril 10-40 mg once daily was compared with that of nifedipine tablets 20-40 mg twice daily in a multicentre double-blind randomized parallel group study of 16 weeks duration involving 127 patients with mild to moderate hypertension. The groups randomized to lisinopril or to nifedipine were not significantly different with respect to any demographic variable. An analysis of the pooled data from all centres demonstrated a significantly greater fall in both lying and standing systolic blood pressure (SBP) on lisinopril than on nifedipine treatment (difference between treatments 7.70 +/- 3.34 mmHg; P = 0.02 and 10.2 +/- 3.30 mmHg; P = 0.003 for lying and standing SBP, respectively). However, this difference may be accounted for by the slightly higher mean SBP in the lisinopril treatment groups compared with the nifedipine group at the end of the placebo run-in period. Both treatments lowered lying and standing diastolic blood pressures (DBP) to the same extent and the response rates to the two treatments were the same. The effects of the two drugs on heart rate were indistinguishable from each other. There were six lisinopril and 12 nifedipine-treated patients withdrawn during randomized treatment (P = 0.22). Nineteen per cent of lisinopril patients reported an adverse event compared with 36% of nifedipine patients. The relative risk of an adverse event on lisinopril compared with nifedipine was 0.42 (confidence limits 1.027-0.172) a difference which approached statistical significance (P = 0.0573). Lisinopril produced a greater reduction in both lying and standing SBP than nifedipine and both were associated with equivalent reductions in DBP. Lisinopril may be better tolerate than nifedipine.",1993.0,0,0
1725,8208656,Sublingual captopril in hypertensive urgencies.,A Misra; P Jain; R B Reddy,,1993.0,0,0
1726,8247194,"Comparison of sublingual captopril, nifedipine and prazosin in hypertensive emergencies during hemodialysis.",S G Wu; S L Lin; W Y Shiao; H W Huang; C F Lin; Y H Yang,"Hypertensive emergencies in hemodialysis require immediate therapy, usually by parenteral drug administration; however, sublingual medications may have potential in this special condition. Sublingual captopril (25 mg), nifedipine (10 mg) and prazosin (2 mg) were prescribed to determine the effectiveness and safety of each medication in the treatment of hypertensive emergencies during hemodialysis. Blood pressure and heart rate were measured continuously up to 120 min postdose. The response rates were 83% for captopril, 90% for nifedipine and 11% for prazosin. The significant hypotensive effects of both sublingual captopril and nifedipine occurred at 10 min and continued up to 120 min. The reduction of systolic blood pressure occurred earlier in nifedipine than captopril (10 vs. 15 min). No significant difference in heart rate between them was noted. There were no side effects in the captopril group but flushing, tachycardia and headache were observed in 4 patients of the nifedipine group. We concluded that sublingual captopril and nifedipine were effective but captopril seemed to have less side effects than nifedipine and may be an excellent alternative to sublingual nifedipine in the urgent treatment of hypertensive emergencies in hemodialysis. Prazosin was not recommended because of its low response rate.",1993.0,0,0
1727,8247909,The use of angiotensin-converting enzyme inhibitors after acute myocardial infarction.,I V Mehra; M D Wilson,"During and immediately after myocardial infarction (MI), many interrelated and complex processes manifest the body's attempt to minimize damage and compensate for lost cardiac function. Although these compensatory responses may provide some short-term restoration of function, their long-term consequences actually may increase morbidity and mortality. Several agents have established roles in the treatment of these patients, whereas others, including the angiotensin-converting enzyme (ACE) inhibitors, have yet to be investigated thoroughly. Results of two trials investigating the role of ACE inhibition after MI seem to provide sufficient data to warrant the use of these drugs in certain patient populations. These results are promising, but further investigation is necessary to answer key questions arising from these trials.",1993.0,0,0
1728,8249842,Usefulness of piretanide plus ramipril for systemic hypertension: a multicenter trial.,V Homuth; H D Faulhaber; U Loose; K Löffler; F C Luft,"To test the dose responses of piretanide, ramipril, and their combination in patients with essential hypertension, a prospective, randomized, double-blind, placebo-controlled trial was conducted in 480 patients. Twelve separate groups were studied: placebo, piretanide 3 mg, piretanide 6 mg, ramipril 2.5 mg, ramipril 5 mg, ramipril 10 mg, and their combinations, as single daily morning doses. Patients were randomized after a 2-week run-in period without drugs; treatment was given for 6 weeks. A dose response compared with placebo was found for both drugs; the combination was more effective than either drug alone. Piretanide 6 mg, combined with ramipril 5 mg, provided optimal blood pressure reduction. Self-reported adverse effects of both drugs and their combinations did not exceed those reported for placebo. A surface analysis suggested that piretanide primarily reduced systolic blood pressure, whereas ramipril was more effective in reducing diastolic blood pressure. The data attest to a combined efficacy of piretanide and ramipril in decreasing arterial blood pressure.",1993.0,0,0
1729,8252860,Treatment of idiopathic glomerulonephritis in the elderly. Personal data.,G Splendiani; S Costanzi; A Sturniolo; S Passalacqua; P Fulignati; G Piccinni; F Federico; C Chiarelli,,1993.0,0,0
1730,8252957,Modification of exercise performance by sharp reduction of blood pressure. A study in patients with uncomplicated hypertension.,P G Agostoni; E Doria; M Alimento; S Riva; M Muratori; G Tamborini,"We evaluated exercise performance in 14 patients with uncomplicated essential hypertension 1 h after the administration of a single dose of placebo, nifedipine (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at the same time of day following a randomized, double-blind protocol. Mean resting blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/- 4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4, respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen consumption at VAT was reduced by nifedipine and propranolol but unaffected by captopril. The effects on exercise capacity of blood pressure reduction in hypertensive patients are dependent on the drug utilized and are not related to the amount of blood pressure reduction. The lowered oxygen consumption at VAT observed with nifedipine and propranolol, and not with captopril, might be due to an excessive downward shift of the muscle perfusion pressure--oxygen consumption relationship which might take place during exercise.",1993.0,0,0
1731,8255797,Captopril-induced bone marrow suppression in two cardiac patients with trisomy 21.,M M Gleason; J S Roloff; S E Cyran; H S Weber; B G Baylen; J L Myers,"Neutropenia is an infrequent complication following administration of the angiotensin-converting enzyme (ACE) inhibitor, captopril. Most reports have been in adult patients, with rare reports in the pediatric population. We report two cases of neutropenia following captopril use in cardiac patients with trisomy 21. As this was not seen in patients without Down's syndrome, we postulate that patients with trisomy 21 have bone marrow which is ""at risk"" for suppression, and, thus warrant close evaluation while on such medications.",1993.0,0,0
1732,8257959,Decision analysis applied to the selection of angiotensin-converting enzyme inhibitors.,B Santos Ramos; M J Piña Vera; E Carvajal Gragera; M Atienza Fernández,"Decision analysis is applied to the group of angiotensin-converting enzyme inhibitors, in order to select those which should be included in the hospital formulary and to establish a research method which allows the reproduction of the process with new, related drugs. Captopril, enalapril and lisinopril were the alternatives considered. Evaluation criteria were efficacy, clinical experience, safety, dosage interval, hepatic bioactivation, interactions, dosage forms and cost. A relative weight was assigned through a survey among the hospital's staff. Each alternative was evaluated in relation to all criteria. Sensitivity analysis was applied to validate the method. Enalapril obtained the highest score, followed by lisinopril and captopril. The sensitivity analysis confirms this result. Enalapril is selected for the hospital formulary due to its higher score, although the differences between the three are very small.",1993.0,0,0
1733,8258676,Improved baroreflex sensitivity in elderly hypertensives on lisinopril is not explained by blood pressure reduction alone.,B M Egan; M J Fleissner; K Stepniakowski; J M Neahring; K B Sagar; T J Ebert,"The major goals of this study were to determine whether lisinopril and nifedipine lowered blood pressure and improved carotid baroreflexes in older hypertensives. The effects of lisinopril at 10-40 mg/day versus nifedipine gastrointestinal therapeutic system (GITS) at 30-90 mg/day on blood pressure and baroreflex sensitivity were studied after 3 weeks each on (1) single-blind placebo, (2) double-blind assignment to either lisinopril or nifedipine, (3) single-blind placebo, and (4) crossover to double-blind lisinopril or nifedipine. Measurements at the end of the four phases included 24-h blood pressure using the Accutracker, laboratory hemodynamics with the Dinamap and impedance cardiography, baroreflex sensitivity with the pneumatic neck chamber, and plasma samples for neurohumoral and metabolic activity. Thirteen patients aged 55 years or older (mean +/- SEM 65 +/- 1 years) with mild-to-moderate hypertension completed the study. The primary data for analysis across the four study phases included ambulatory blood pressure values, laboratory hemodynamics, and baroreflex sensitivity. Compared with the preceding placebo, lisinopril and nifedipine lowered 24-h blood pressure significantly. In the laboratory, the effects of both compounds on blood pressure, cardiac output, calculated total systemic resistance, and the stroke volume-pulse pressure relationship, an index of arterial compliance, were similar. Lisinopril was associated with a relative increase in the standing systolic blood pressure compared with nifedipine (P < 0.05). This coincided with an enhanced heart-rate (R-R interval) response to neck pressure, which also decreased carotid transmural pressure, with lisinopril versus nifedipine (P < 0.05). Lisinopril and nifedipine were both effective as monotherapy for controlling blood pressure in these elderly patients. Despite similar effects on blood pressure and systemic hemodynamics, baroreflex sensitivity in response to a reduction in carotid transmural pressure was greater with lisinopril than with nifedipine.",1993.0,0,0
1734,8261491,Left ventricular mass regression and diastolic function improvement in mild and moderate hypertensive patients treated with lisinopril.,R J Esper; O H Burrieza; J L Cacharrón; G Fábregues; H P Baglivo,"Thirty patients (18 male), mean age 49.5 +/- 6.3 years, were treated with lisinopril 10-40 mg once daily for 16 weeks. The effect of treatment on left ventricular mass and improvement in left ventricular diastolic function (measured by echo-Doppler) was assessed. Blood pressure changes were measured conventionally in the clinic and by ambulatory blood pressure monitoring. Clinic blood pressure decreased from 168.3 +/- 13.8/105.5 +/- 5.4 mm Hg to 137.5 +/- 4.1/88.8 +/- 4.1 mm Hg (p < 0.005 for both systolic and diastolic blood pressures), and the heart rate from 75.2 +/- 3.7 to 74.4 +/- 7.6 beats per minute (NS). The frequency of ambulatory systolic blood pressure values > 140 mm Hg decreased in percentage from 63.3 +/- 12.8 to 29.9 +/- 9.1% (p < 0.005) and the frequency of ambulatory diastolic blood pressure values > 90 mm Hg decreased in percentage from 61.1 +/- 12.8 to 28.6 +/- 7.5% (p < 0.005). Septal and left ventricular posterior wall thickness decreased from 11.2 +/- 0.9 to 10.3 +/- 0.6 mm and from 10.9 +/- 0.9 to 10.1 +/- 0.6 mm, respectively (both p < 0.005). Left ventricular diastolic diameter and the shortening fraction did not change significantly. Left ventricular mass, calculated from left ventricular wall thickness and diastolic diameter, decreased from 132.6 +/- 11.5 to 119.9 +/- 6.3 g/m2 (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
1735,8265877,Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced cough.,M Cazzola; M G Matera; G Liccardi; F De Prisco; G D'Amato; F Rossi,"Preliminary reports suggest that some pharmacologic agents may be effective in ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and, perhaps, allowing continuing use of ACE inhibitors in patients for whom this class of medication is important. We examined the effect of a once-a-day theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of the cough reflex to capsaicin in 10 hypertensive patients who had developed cough during treatment with an ACE inhibitor. Theophylline did not induce bronchodilation but induced complete remission of clinical symptoms in 8 and attenuated the capsaicin-induced cough number in 7 subjects when compared with placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced cough.",1993.0,0,0
1736,8269207,Early reocclusion after successful thrombolysis is related to lesion length and roughness.,N B de Cesare; S G Ellis; P R Williamson; S F Deboe; B Pitt; G B Mancini,"Reocclusion is a significant problem after thrombolysis. Results of previous studies conflict regarding the association of various features of postlytic lesions that might predict reocclusion. A computer-assisted algorithm was therefore used to quantitatively measure edge roughness in the 90-minute postlysis angiogram of 84 patients receiving recombinant tissue plasminogen activator within 6 hours of chest pain. Twenty-five patients had reocclusion, and 59 did not. The baseline angiogram showed no differences between these two groups with respect to minimal dimensions or relative percentage of stenosis. Length was greater in the reocclusion group (12.2 +/- 5.0 vs 10.0 +/- 4.2 mm, P < 0.05). Three of four roughness indices based on curvature analysis indicated greater roughness in those patients with reocclusion. These differences were largely due to the increased length of these lesions. The scaled edge-length ratio, an index of roughness that is independent of length, was, however, significantly greater in the reocclusion group (1.15 +/- 0.10 vs 1.09 +/- 0.08, P < 0.006). Multiple regression analysis showed that lesion length, the scaled edge-length ratio, and the number of features (invaginations and evaginations) per cm correlated independently with the risk for reocclusion. The length and roughness of postlytic residual lesions are determinants of reocclusion.",1993.0,0,0
1737,8269447,Large prospective study of ramipril in patients with hypertension. CARE Investigators.,N M Kaplan; L E Sproul; W S Mulcahy,"The results of controlled trials demonstrate that ramipril lowers blood pressure in hypertensive patients, has a long duration of action suitable for once-daily administration in most patients, and is well tolerated. To assess the efficacy and safety of ramipril in a large cross-section of patients, we conducted a multicenter, open-label, prospective study, in which 591 men or women with essential hypertension (diastolic blood pressure > or = 95 and < or = 114 mmHg) received ramipril on a regimen of 1.25 to 10 mg once daily for 8 weeks. Forty-one percent of the patients required 2.5 mg and 81% required < or = 5 mg once daily at study completion. Compared with baseline, ramipril reduced mean systolic/diastolic blood pressure by 19.9/14.7 mmHg (P < 0.001/P < 0.001). Ramipril reduced diastolic blood pressure to < or = 90 mmHg or by at least 10 mmHg in 84.1% of the patients. Response rates were similar regardless of age, gender, and race. No patient stopped ramipril because of an adverse event or experienced an unexpected adverse event. In our real-world study, low-dose ramipril given once daily controlled blood pressure in most patients and was well tolerated.",1993.0,0,0
1738,8269792,Improved insulin action and glycemic control after long-term angiotensin-converting enzyme inhibition in subjects with arterial hypertension and type II diabetes.,E Torlone; M Britta; A M Rambotti; G Perriello; F Santeusanio; P Brunetti; G B Bolli,"To determine the long-term effects of the angiotensin-converting enzyme inhibitor captopril on insulin sensitivity in subjects with type II diabetes and arterial hypertension. The chronic effects of angiotensin-converting enzyme inhibition on insulin-sensitive individuals are presently controversial. Sixteen subjects, with type II diabetes (on diet and/or diet plus oral hypoglycemic agents) and arterial hypertension, were studied. During a 1-mo run-in period no antihypertensive drugs were administered, but oral hypoglycemic agents were continued in subjects already in therapy. The subjects were then randomly assigned to two 3-mo treatment periods, with either captopril or placebo (single blind, cross-over design). At the end of each treatment period, insulin sensitivity was assessed by means of a euglycemic-hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1 mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3-3H]glucose (for calculation of hepatic glucose output and peripheral glucose utilization, rates of glucose disappearance), and indirect calorimetry (for calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid oxidation). The percentage of HbA1c was measured to assess long-term glycemic control. Comparing data at the end of placebo and captopril treatment, captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3 mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in hyperglycemic conditions (total amount of insulin infused and time of insulin infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58 +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater insulin sensitivity in euglycemic conditions at liver level (hepatic glucose output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp), muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1 mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately 29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/- 0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2 vs. 7.3 +/- 0.2%, P < 0.05). Long-term captopril administration in type II diabetic subjects improves insulin sensitivity in the postprandial state, not in the fasting state, and improves glycemic control.",1993.0,0,0
1739,8273728,Therapeutic effects of captopril on ischemia and dysfunction of the left ventricle after Q-wave and non-Q-wave myocardial infarction.,P Søgaard; A Nøgaard; C O Gøtzsche; J Ravkilde; K Thygesen,"Treatment with angiotensin-converting enzyme inhibitors has a beneficial effect on myocardial ischemia and left ventricular dysfunction after myocardial infarction. The effect of captopril on myocardial ischemia was evaluated in 58 patients with left ventricular dysfunction (ejection fraction < 45%) after Q-wave or non-Q-wave myocardial infarction in a placebo-controlled, parallel, double-blind study. Patients were randomized on day 7 to either placebo or captopril (50 mg daily) and monitoring for a period of 180 days by serial echocardiography and ambulatory ST-segment monitoring. There was a significant effect of captopril on the duration of ambulatory ST depression during the 180 days: The values per day were reduced from 28 +/- 5 min at baseline to 2 +/- 1 min on day 180 in the Q-wave group (p < 0.01) and from 39 +/- 10 min at baseline to 6 +/- 1 min on day 180 in the non-Q-wave group (p < 0.05). In the placebo group the duration of ST depression on day 180 were 21 +/- 8 min in the Q-wave group and 22 +/- 7 min in the non-Q-wave group, thus being significantly higher as compared with the corresponding captopril groups (p < 0.01 and p < 0.05, respectively). In the placebo Q-wave group there was a significant increase in left ventricular end-diastolic volume index from 74 +/- 3.5 to 89 +/- 4.5 ml/m2 (p < 0.01) during the study period, which was in contrast to unchanged values of 75.5 +/- 3.0 and 75.0 +/- 3.5 ml/m2 (not significant [NS]) in the captopril Q-wave group.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1740,8276048,Acute haemodynamic effects and pharmacokinetics of ramipril in patients with heart failure. A placebo controlled three-dose study.,B Beermann; O Nyquist; C Höglund; K A Jacobsson; U Näslund; M Jensen-Urstad,"The aim of the present study was primarily to evaluate the haemodynamic effects of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat. Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12 patients with heart failure (NYHA III) in a double-blind randomised, parallel study. Haemodynamics were monitored for 24 h and blood was sampled and urine collected for up to 96 h. In the placebo-treated group the cardiac index (CI) was significantly increased (15.8%) and right atrial pressure decreased (26.6%). Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril 5 mg had pronounced and sustained effects on pulmonary artery pressure, which fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; -59.1%); systemic vascular resistance was also decreased 21%. A significant effect on CI was only seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was 73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat of 4.7 ng.ml-1. The degree of inhibition declined with a half life of about 75 h. There was a significant relation between the degree of ACE-inhibition and change in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the form of ramiprilat and inactive metabolites.",1993.0,0,0
1741,8278939,Effect of tensiomin in ischaemic dilatative cardiomyopathy.,G Buzási; F Endresz; S Karády; E Böszörményi,"The effect of the angiotensin-converting enzyme inhibitor, Tensiomin, has been examined in patients suffering from ischaemic dilatative cardiomyopathy who had become unresponsive to combined vasodilatator--diuretic--digitalis therapy. The results were evaluated according to the changes in NYHA classes and echocardiographic parameters. Significant improvement was observed in response to Tensiomin in 38 of the 52 patients (73%). On the basis of the results the use of captopril (Tensiomin) is highly recommended for the treatment of ischaemic dilatative cardiomyopathy.",1993.0,0,0
1742,8280816,Review article: drug-induced hepatotoxicity.,W M Lee,"The liver is central to the metabolic disposition of virtually all drugs and xenobiotics (foreign substances). For the most part, this process is accomplished without injury to the liver itself or to other organs. A few compounds such as acetaminophen, CCl4 and the toxin responsible for mushroom poisoning are toxic themselves or produce metabolites which cause liver injury in a uniform, dose-dependent fashion. However, most agents form a sufficiently toxic byproduct and cause liver injury only quite rarely, under special circumstances. Generation of a toxic metabolite within the hepatocyte may produce direct cell injury with disruption of intracellular function, or may cause indirect injury by immune-mediated membrane damage. Factors promoting the accumulation of toxins include genetic enzyme variants which allow greater formation of the harmful metabolite, induction of an isozyme species which produces more than the usual quantity of the toxin, interference with regular (non-toxic) metabolic pathways by substrate competition for enzyme, or depletion of required detoxifying substrates. The following review will provide clinical examples of some of these well-known metabolic reactions, discuss some new issues in drug-induced hepatotoxicity, such as use of combination agents and complex multiple drug regimens, alternative health strategies (vitamins and herbal remedies) as well as the widespread use of cocaine. The overall message is that, as new compounds are issued, new opportunities for drug-induced hepatotoxicity arise. Until extensive experience with any new compound has evolved, it is best to maintain a healthy paranoia concerning the newer drugs--there are very few totally safe agents.",1993.0,0,0
1743,8281528,Effects of nitrendipine and lisinopril on blood pressure and sodium excretion in ciclosporin-associated hypertension after heart transplantation.,A Hartmann; G Schwietzer; D Stratmann; M Kaltenbach; G Kober,"Hypertension associated with ciclosporin A may be mediated by sodium and volume retention. Therefore, the effects of an antihypertensive therapy (6 weeks) with nitrendipine (10-20 mg twice daily) or lisinopril (10-20 mg once daily) on office blood pressure, 24-hour ambulatory blood pressure, and left ventricular function were evaluated in a randomised, double-blind cross-over trial in patients after heart transplantation. Nitrendipine and lisinopril were equally effective in lowering office and ambulatory systolic and diastolic blood pressures. After an acute sodium load (210 mval/2 h i.v.), sodium excretion was significantly increased during therapy with lisinopril but only slightly during nitrendipine, indicating that angiotensin-converting enzyme inhibition may improve the sodium-retaining state of heart transplant recipients associated with ciclosporin A.",1993.0,0,0
1744,8281530,Glucose and lipid metabolism in essential hypertension: effects of diuretics and ACE-inhibitors.,R De Cesaris; G Ranieri; V Filitti; A Andriani; G Lamontanara,"Various aspects of carbohydrate and lipid metabolism were studied in two groups of patients with mild hypertension before and after 6 months' treatment with either lisinopril (n = 10) or hydrochlorothiazide (n = 10). A significant reduction of arterial blood pressure was seen after both treatment regimens. Circulating plasma glucose, insulin, C-peptide and triglyceride concentrations were measured at hourly intervals from 8.00 a.m. to 5.00 p.m. in patients on an isocaloric diet (35 cal/kg/day). Plasma glucose concentrations remained unchanged, while insulin and C-peptide concentrations were higher in association with hydrochlorothiazide treatment. Conversely, lisinopril-treated patients had lower C-peptide concentrations after treatment. The changes in daylong plasma glucose and insulin-stimulated glucose uptake increased after hydrochlorothiazide treatment and decreased following lisinopril. Lastly, plasma cholesterol concentrations did not change after lisinopril therapy, whereas plasma high density cholesterol decreased as a result of hydrochlorothiazide treatment.",1993.0,0,0
1745,8281674,Angiotensin-converting enzyme inhibition with fosinopril sodium in the prevention of restenosis after coronary angioplasty.,W Desmet; M Vrolix; I De Scheerder; J Van Lierde; J L Willems; J Piessens,"Several angiotensin-converting enzyme inhibitors have antiproliferative effects in a rat model after carotid artery balloon injury. We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of fosinopril, a novel angiotensin-converting enzyme inhibitor, in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily for 6 months. In addition, all patients received aspirin. Coronary angiograms before PTCA and immediately after PTCA as well as at 6-month follow-up were quantitatively analyzed. A total of 509 patients were recruited. The final per-protocol population consisted of 153 fosinopril-treated and 151 placebo-treated patients. Restenosis rates according to the National Heart, Lung, and Blood Institute criterion 4 (loss of > or = 50% of the initial gain [primary end point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively (not significant). The respective mean differences in minimal coronary luminal diameter between post-PTCA and follow-up angiograms were -0.59 +/- 0.71 mm and -0.51 +/- 0.67 mm (not significant). Clinical events during the 6-month follow-up period, analyzed on an on-treatment basis, were ranked according to the most serious event. The respective numbers in the fosinopril and the control groups were for death, 0 and 0; myocardial infarction, 0 and 0; coronary artery bypass graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia necessitating early repeat coronary angiography and managed medically, 6 and 7; and none of the above, 111 and 106. All these differences were significant. Administration of fosinopril in a dose of 40 mg daily during 6 months after PTCA does not prevent restenosis and has no effect on overall clinical outcome.",1994.0,0,0
1746,8281697,Quantitative two-dimensional echocardiographic measurements are major predictors of adverse cardiovascular events after acute myocardial infarction. The protective effects of captopril.,M St John Sutton; M A Pfeffer; T Plappert; J L Rouleau; L A Moyé; G R Dagenais; G A Lamas; M Klein; B Sussex; S Goldman,"Left ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome. Two-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitalization or open-label angiotensin-converting enzyme inhibitor therapy, and recurrent infarction were determined over a follow-up period averaging 3.0 +/- 0.6 years. Irrespective of treatment assignment, baseline left ventricular systolic area and percent change in area were strong predictors of cardiovascular mortality and adverse cardiovascular events. At 1 year, left ventricular end-diastolic and end-systolic areas were larger in the placebo than in the captopril group (P = .038, P = .015, respectively), and percent change in cavity area was greater in the captopril group (P = .005). One hundred eleven of the 420 1-year survivors with 1-year echo measurements (26.4%) experienced a major adverse cardiovascular event, and these patients had more than a threefold greater increase in left ventricular cavity areas than those with an uncomplicated course. Sixty-nine patients with adverse cardiovascular events were in the placebo group compared with 42 patients in the captopril-treated group (a risk reduction of 35%, P = .010). Two-dimensional echocardiography provides important and independent prognostic information in patients after infarction. Left ventricular enlargement and function after infarction are associated with the development of adverse cardiac events. Attenuation of ventricular enlargement with captopril in these patients was associated with a reduction in adverse events. This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome.",1994.0,0,0
1747,8282330,Responses to converting enzyme and renin inhibition. Role of angiotensin II in humans.,N D Fisher; D Allan; I Kifor; C L Gaboury; G H Williams; T J Moore; N K Hollenberg,"We compared the renal vascular responses to angiotensin converting enzyme inhibition and renin inhibition to assess the influence of angiotensin II (Ang II). We examined the renal and endocrine responses to the renin inhibitor enalkiren, to captopril, and to placebo in nine healthy and nine hypertensive men on a 10-mmol sodium diet. Ang II was infused to assess effects of the agents on renal and adrenal responsiveness to Ang II. Plasma Ang II concentration was suppressed similarly with enalkiren and captopril--an identical level of blockade was achieved. Although renal plasma flow was stable during placebo, a substantial rise was seen with both enalkiren (+133 +/- 26 mL/min per 1.73 m2) and captopril (+99.4 +/- 22.6). There was remarkable intrasubject concordance between the renal plasma flow responses to renin inhibition and converting enzyme inhibition (r = .90, P < .004). The vasodilator response to both agents correlated inversely with the fall in renal plasma flow induced by Ang II alone (r = -.66, P < .05). Both agents significantly enhanced the renal vascular response to Ang II (P = .01), and, furthermore, the renal vasodilator response to captopril predicted the potentiation of the renal plasma flow response to Ang II after either agent (enalkiren: r = .91, P < .001; captopril: r = .56, P < .05). Concordance of the maximal renal plasma flow response to the two agents appeared in the hypertensive men as well. Our results indicate that the acute renal response to captopril largely reflects a reduction in Ang II formation.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1748,8287564,The effects of drugs on endocrine function.,M P Vanderpump; W M Tunbridge,,1993.0,0,0
1749,8287657,Non-angiotensin effects of angiotensin-converting enzyme inhibitors.,W Sunman; P S Sever,,1993.0,0,0
1750,8290016,"Anaphylactoid reactions, angiotensin-converting enzyme inhibitors and extracorporeal hemotherapy.",A Schwarzbeck; K W Wittenmeier; U Hällfritzsch,,1993.0,0,0
1751,8290406,A risk-benefit analysis for the treatment of hypertension.,C J Bulpitt,,1993.0,0,0
1752,8292465,The incidence of first-dose hypotension with quinapril in patients with mild to moderate hypertension.,D Maclean; S M Maton; A J Bibby; Z Eminton,"A total of 2242 patients with mild to moderate hypertension (diastolic pressure 95-120 mmHg) were randomised on a double-blind basis to receive a single dose of placebo, 5 mg quinapril or 10 mg quinapril. Patients were identified who: (a) met the blood pressure (BP) criteria for first-dose hypotension (sitting or standing systolic BP < 100 mmHg, or a fall in systolic BP > or = 20 mmHg on standing); (b) had symptoms suggestive of hypotension; and (c) met the BP criteria and had symptoms. In all three classifications there were no statistically significant differences between the incidences in placebo and combined active treatment groups, or between those in the two quinapril groups. No associated serious adverse events were reported. In the low-risk population studied, it would appear that the incidence of first-dose hypotension with quinapril is similar to placebo and is not dose-related.",1993.0,0,0
1753,8294693,"Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: the Studies of Left Ventricular Dysfunction. The SOLVD Investigators.",W J Rogers; D E Johnstone; S Yusuf; D H Weiner; P Gallagher; V A Bittner; S Ahn; E Schron; S A Shumaker; L T Sheffield,"This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo. Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure. A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction < or = 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560). Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire. Modest benefits in quality of life for > or = 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.",1994.0,0,0
1754,8295285,Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group.,G Viberti; C E Mogensen; L C Groop; J F Pauls,"To study the effect of angiotensin converting enzyme inhibition on the rate of progression to clinical proteinuria and the rate of change of albumin excretion rates in patients with insulin-dependent diabetes mellitus and persistent microalbuminuria. Randomized, double-blind, placebo-controlled clinical trial of 2 years' duration at 12 hospital-based diabetes centers. Ninety-two patients with insulin-dependent diabetes mellitus and persistent microalbuminuria but no hypertension. The patients were randomly allocated in blocks of two to receive either captopril, 50 mg, or placebo twice per day. Albumin excretion rate, blood pressure, glycosylated hemoglobin level, and fructosamine level every 3 months; urinary urea nitrogen excretion every 6 months; and glomerular filtration rate every 12 months. Twelve patients receiving placebo and four receiving captopril progressed to clinical proteinuria, defined as an albumin excretion rate persistently greater than 200 micrograms/min and at least a 30% increase from baseline (P = .05). The probability of progression to clinical proteinuria was significantly reduced by captopril therapy (P = .03 by log-rank test). Albumin excretion rate rose from a geometric mean (95% confidence interval) of 52 (39 to 68) to 76 (47 to 122) micrograms/min in the placebo group but fell from 52 (41 to 65) to 41 (28 to 60) micrograms/min in the captopril group, a significant difference (P < .01). Mean blood pressure was similar at baseline in the two groups and remained unchanged in the placebo group but fell significantly, by 3 to 7 mm Hg, in the captopril group. Glycosylated hemoglobin levels and glomerular filtration rate remained stable in the two groups. Captopril therapy significantly impeded progression to clinical proteinuria and prevented the increase in albumin excretion rate in nonhypertensive patients with insulin-dependent diabetes mellitus and persistent microalbuminuria.",1994.0,0,1
1755,8297690,Angiotensin converting enzyme inhibition in chronic stable angina: effects on myocardial ischaemia and comparison with nifedipine.,H Ikram; C J Low; T M Shirlaw; S G Foy; I G Crozier; A M Richards; N S Khurmi; R J Horsburgh,"To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease. Placebo controlled, double blind, latin square design. Regional cardiology service for a mixed urban and rural population. 40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial. Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks. Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0.05). Benazepril, an angiotensin converting enzyme inhibitor, had a modest anti-ischaemic effect in effort angina, but this effect was not as pronounced as with nifedipine. The anti-ischaemic action was more noticeable in asymptomatic ischaemia during daily activity, whereas nifedipine had little effect on this aspect of myocardial ischaemia. The combination of benazepril and nifedipine reduced ischaemia of daily activity.",1994.0,0,0
1756,8298346,"Dyspnoea, asthma, and bronchospasm in relation to treatment with angiotensin converting enzyme inhibitors.",H Lunde; T Hedner; O Samuelsson; J Lötvall; L Andrén; L Lindholm; B E Wiholm,"To evaluate the occurrence of asthma and dyspnoea precipitated or worsened by angiotensin converting enzyme inhibitors. Summary of reports of adverse respiratory reaction in relation to treatment with angiotensin converting enzyme inhibitors that were submitted to Swedish Adverse Drug Reactions Advisory Committee and to World Health Organisation's international drug information system until 1992. Sales of angiotensin converting enzyme inhibitors in Sweden were also summarised. Patients receiving angiotensin converting enzyme inhibitors who reported adverse respiratory reactions. Clinical characteristics of adverse reactions of asthma, bronchospasm, and dyspnoea. In Sweden 424 adverse respiratory reactions were reported, of which most (374) were coughing. However, 36 patients had adverse drug reactions diagnosed as asthma, bronchospasm, or dyspnoea. In 33 of these cases the indication for treatment with angiotensin converting enzyme inhibitors was hypertension, in only three heart failure. The respiratory symptoms occurred in about half of the patients within the first two weeks of treatment, and about one third needed hospitalisation or drug treatment. Dyspnoea symptoms occurred in conjunction with other symptoms from the airways or skin in 23 out of the 36 cases. In the WHO database there were 318 reports of asthma or bronchospasm, 516 reports of dyspnoea, and 7260 reports of cough in relation to 11 different angiotensin converting enzyme inhibitors. Symptoms of airway obstruction in relation to treatment with angiotensin converting enzyme inhibitors seem to be a rare but potentially serious reaction generally occurring within the first few weeks of treatment.",1994.0,0,0
1757,8299854,Ketanserin alone and in combination with enalapril in the treatment of essential hypertension: assessment of the haemodynamic effects.,O de Divitiis; M Galderisi; A Celentano; P Tammaro; M Garofalo; V Palmieri; M Crivaro; G Assogna; C Zanna,"The antihypertensive and haemodynamic efficacies of ketanserin and ketanserin plus enalapril were compared. The monotherapy phase of the study involved the oral administration of 40 mg ketanserin twice daily or 20 mg enalapril once daily for 12 weeks to 25 hypertensive patients. Systolic and diastolic blood pressures were significantly reduced by both drugs. Left ventricular function both at rest and during effort improved significantly with either drug. This was due to a reduction of end-systolic volume; end-diastolic volume decreased only with the use of enalapril. Combination therapy, involving 16 patients and both drugs given at the original dosage schedule for 12 weeks, resulted in further reductions in systolic and diastolic blood pressures, and an improvement in left ventricular function; indices of diastolic function were not modified. In conclusion, ketanserin and enalapril showed comparable antihypertensive and haemodynamic activities. A combination of ketanserin and enalapril increased the favourable characteristics of both drugs.",1993.0,0,0
1758,8300456,Effect of vasodilator therapy on mortality in chronic congestive heart failure.,J C Ghose; S Chakraborty; M Mondal; B Bhandari,"We compared the effects of Hydralazine and Isosorbide dinitrate (ISDN) with those of an angiotensin-converting-enzyme inhibitor, captopril on mortality in patients with chronic congestive heart failure (NYHA class III and IV). Patients receiving conventional treatment with digoxin and diuretics were randomly assigned to receive either placebo (n = 51), hydralazine-ISDN. (n = 50) or captopril (n = 52) in a double blind trial. At the end of 6 months there were 14 deaths in the placebo group (27.4%) as compared with 11 deaths in the hydralazine-ISDN group (22%)--a mortality reduction of 20% (P > 0.05) and 10 deaths in the captopril group (19.2%)--a mortality reduction of 30% (p > 0.05). At the end of one year, mortality was 50%, 42% and 30% in the placebo, hydralazine-ISDN and captopril groups respectively with a mortality reduction of 16% in the hydralazine-ISDN group (p > 0.05) and 40% in the captopril group (p < 0.05) compared to the placebo group. The mortality reduction was mainly due to reduction in deaths attributed to progressive heart failure. The data suggests that the addition of captopril to conventional treatment significantly reduces mortality in patients with severe congestive heart failure. Hydralazine-isorobide dinitrate also reduced mortality but statistically this was not significant.",1993.0,0,0
1759,8300885,Angiotensin II receptor blockade: an innovative approach to cardiovascular pharmacotherapy.,R T Eberhardt; R M Kevak; P M Kang; W H Frishman,"Through the multiple actions of angiotensin II (AII), the renin-angiotensin system (RAS) participates in cardiovascular homeostasis. Angiotensin II acts by binding to specific membrane-bound receptors, which are coupled to one of several signal transduction pathways. These AII receptors exhibit heterogeneity, represented by AT1 and AT2 receptor subtypes. The AT1 receptor mediates the major cardiovascular action of the RAS. This receptor has been cloned from multiple species, disclosing features consistent with a transmembrane, G-protein-linked receptor. Further AII receptor heterogeneity is evident by the cloning of isotypes of the AT1 receptor. Blocking the interaction of AII with its receptor is the most direct site to inhibit the actions of the RAS. Many AII receptor antagonists, including peptide analogs of AII and antibodies directed against AII, possess unfavorable properties that have limited their clinical utility. The discovery and further development of imidazole compounds with AII antagonist properties and favorable characteristics, however, has promise for clinical utility. The leader in this field is a selective AT1 receptor antagonist losartan (previously known as DuP 753 or MK-954). Losartan was demonstrated to be an effective antagonist of many AII-induced actions and an effective antihypertensive agent in many animal models of hypertension (HTN). Losartan also demonstrated secondary benefits in preventing stroke, treating congestive heart failure (CHF), and delaying the progression of renal disease in animal models. Clinical studies confirm the AII antagonist action of losartan and suggest that losartan will be effective in the treatment of essential HTN. AII antagonism is likely to provide useful treatment in essential HTN and CHF, conditions in which the RAS is known to play a major role. The utility of AII antagonism may extend beyond that of HTN and CHF, as suggested by the potential usefulness of angiotensin-converting enzyme (ACE) inhibition in the treatment or prevention of many other diseases. The key advantage AII antagonists provide over ACE inhibitors is that they may avoid unwanted side effects, related to bradykinin potentiation with the latter drugs. The AII antagonists will help determine the role of the RAS in physiologic regulation and in the pathophysiology of various disease states.",1993.0,0,0
1760,8300997,Risk for drug-induced malnutrition is unchecked in elderly patients in nursing homes.,R N Varma,,1994.0,0,0
1761,8304355,"Lupus and antiphospholipid antibody syndrome: either, neither, or both.",M D Lockshin,,1994.0,0,0
1762,8304366,"Efficacy and safety of atenolol, enalapril, and isradipine in elderly hypertensive women.",H M Perry; W D Hall; J R Benz; D W Bartels; J B Kostis; R R Townsend; D L Due; A Peng; M Sirgo,"This trial was designed to evaluate the efficacy and safety of three different classes of antihypertensive agents in elderly women. The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of titration, and 16 weeks of maintenance. White women between 60 and 80 years old with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated with placebo were evaluated by history, physical examination, laboratory studies, and quality-of-life interview. After double-blind randomization with low-dose atenolol, enalapril, or isradipine, the dose was increased stepwise and hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and greater than 10 mm Hg below baseline). During maintenance, patients not at goal were ""stepped up,"" and patients with uncontrolled DBP at maximum dosage were removed from the study. The pretreatment (baseline) blood pressure of the 315 randomized participants averaged 161/100 mm Hg; 92% had been treated previously for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed alcohol. For 245 patients completing the trial, the average decrease in blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal. Of the 70 patients who did not complete the trial, 42 left because of symptoms and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes in symptoms or blood chemistries were noted. Symptom frequency differed little among the three dosage levels, becoming maximal by the second visit at the same dosage level. All three drugs lowered DBP comparably, and none produced alarming effects. Thirteen percent of patients left the study because of symptoms.",2001.0,0,0
1763,8305640,Effect of low-dose aspirin on thromboxane production and the antihypertensive effect of captopril.,S R Smith; T M Coffman; L P Svetkey,"Some of the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors occur through nonangiotensin II-mediated mechanisms. One of these is through decreased kinin degradation, leading to enhanced production of vasodilator arachidonic acid metabolites. It was reasoned that if ACE inhibition also leads to an increase in the production of the potent vasoconstrictor thromboxane A2, then maneuvers that selectively inhibit thromboxane production without reducing prostaglandins (PG) E2 + PGI2 might enhance the antihypertensive effect of ACE inhibition. This double-blinded, randomized, crossover study was therefore undertaken to determine: (1) if captopril increases platelet and/or renal thromboxane production; and (2) if low-dose aspirin enhances the antihypertensive effect of captopril. Patients with mild essential hypertension and no other significant medical problems were studied. In a double-blinded, random order, patients took captopril alone (25 mg every 12 h) for 2 wk and captopril plus aspirin (75 mg/day) for another 2 wk. Active treatment periods were preceded by 2 wk of single-blind placebo. Fifteen patients with a mean age of 53 yr and an average mean arterial pressure (MAP) of 114 +/- 8 (+/- SD) mm Hg were studied. Serum thromboxane B2 was higher (P < 0.05) during treatment with captopril/placebo (600 +/- 46 (+/- SE) pg/mL) than during the two washout periods combined (420 +/- 57 and 553 +/- 78) and was lowest (P < 0.0005) during treatment with captopril/aspirin (302 +/- 36). Captopril treatment significantly increased the urinary excretion of PGE2 (P = 0.038). Captopril/placebo significantly lowered MAP (P < 0.05) to 105.0 +/- 3.7 mm Hg compared with the washout period. However, the addition of aspirin to captopril caused no additional lowering of MAP (105.2 +/- 2.8 mm Hg). It was concluded that treatment with captopril does increase platelet thromboxane production. However, lowering platelet thromboxane with low doses of aspirin may not enhance the antihypertensive effect of captopril.",1993.0,0,0
1764,8305779,Acute pancreatitis associated with the use of lisinopril.,J Maliekal; C F Drake,"To report a case of acute pancreatitis associated with lisinopril use. A 67-year-old man with no past history of pancreatitis or its associated risk factors developed acute pancreatitis after taking lisinopril for two years. To date, the use of angiotensin-converting enzyme (ACE) inhibitors and development of pancreatitis has been described in the literature with captopril, enalapril maleate, and one case temporally related to lisinopril use. The use of ACE inhibitors as first-line agents in controlling hypertension and congestive heart failure has increased. In addition to monitoring for efficacy and commonly reported adverse effects, clinicians need to be aware that acute pancreatitis may occur with all ACE inhibitors.",1993.0,0,0
1765,8305794,Drug-induced lupus-like reaction and captopril.,M Pelayo; V Vargas; A Gonzales; A Vallano; R Esteban; J Guardia,,1993.0,0,0
1766,8307623,Hypertension in the spontaneously hypertensive rat and the sex chromosomes.,M Vincent; M A Kaiser; V Orea; D Lodwick; N J Samani,"We investigated the involvement of loci on the sex chromosomes in the hypertension of the spontaneously hypertensive rat (SHR) by studying male F1 and F2 generation rats derived from reciprocal crosses of SHR with Wistar-Kyoto (WKY) rats (cross 1: WKY female x SHR male; cross 2: SHR female x WKY male). At 16 weeks of age there was no significant difference in the blood pressures of F1 animals derived from the two crosses. Similarly, in the F2 generation there was no significant difference in either indirect blood pressures measured at 12, 16, or 20 weeks of age or in direct systolic and diastolic blood pressures measured at 25 weeks of age between animals derived from the two crosses maintained on a normal salt diet. In a second study, cohorts of F2 rats from the two crosses were given 1% salt in their drinking water for 10 weeks from 16 weeks of age with indirect blood pressure measurements at 16 (presalt), 18, and 20 weeks and direct blood pressure measurements at 26 weeks. Although overall these animals had significantly higher blood pressures at both 20 and 26 weeks than animals of the first study, again there was no difference in blood pressures of animals derived from the two crosses, apart from a marginally significantly higher blood pressure at 18 weeks in animals from cross 1 (with SHR grandfather). The findings indicate that the sex chromosomes of the SHR and WKY rat used in these crosses do not contain loci where alleles differentially influence blood pressure under the genetic milieu provided by the cross.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
1767,8312677,A double-blind randomised comparison of perindopril and ketanserin in the treatment of hypertension in elderly diabetic patients.,J Woo; K S Woo; K H Or; C S Cockram; M G Nicholls,"A double-blind, randomised study of the antihypertensive efficacy of perindopril and ketanserin in 44 elderly noninsulin-dependent diabetic patients aged > or = 60 years was conducted. Blood pressure, blood biochemical and haematological parameters, plasma vasoactive hormones, urinary volume, electrolytes and microalbumin were measured at baseline, after a 4-week placebo period, and at intervals during 8 weeks of treatment with active drug. Electrocardiogram and echocardiogram data were also obtained. Dosages of perindopril used were 2 mg once daily for 4 weeks doubling to 4 mg once daily if a target blood pressure of < or = 160/90 mm Hg was not reached. Dosages of ketanserin were 40 mg twice daily increasing to 80 mg twice daily. Both drugs caused a small but statistically insignificant reduction in blood pressure. Although the response rates (supine systolic blood pressure reduction of > 10 mm Hg) were 54% for perindopril and 45% for ketanserin, target blood pressure (supine blood pressure 160/90 mm Hg) was reached in only 21% of perindopril and 20% of ketanserin recipients. Plasma creatinine and 24-hour urine sodium excretion increased in patients receiving ketanserin therapy. Glycaemic indices and the lipid profile did not change in either group, except for a reduction in plasma triglycerides in the ketanserin group. No changes in urinary microalbumin, electrocardiogram, or echocardiographic cardiac parameters were observed. It is concluded that in the present study neither drug provoked a significant blood pressure lowering effect and that serum creatinine increased in the ketanserin group.",1993.0,0,0
1768,8314271,Sublingual nifedipine and captopril in hypertensive urgencies and emergencies.,V N Dadkar; N D Karnik; M Izar; S R Sharma; Y P Gandhi; N M Narawane; S S Vyawahare; S Sudhakar; A G Gore; N M Kapadia,"Fifty two patients of severe hypertension, diastolic blood pressure > or = 115 mmHg, with or without acute complications, were treated with sublingual nifedipine 10 mg or sublingual captopril 25 mg in a randomized prospective in patient study with careful clinical monitoring. Both the drugs were safe and effective in rapidly lowering blood pressure. Nifedipine appeared to be superior to captopril with earlier onset of action, greater magnitude of response and longer duration of action. No significant side effects were observed in either of the two groups.",1993.0,0,0
1769,8520076,Water handling in patients receiving haloperidol decanoate.,J M Rider; T F Mauger; J P Jameson; D D Notman,"To determine whether water handling in patients receiving haloperidol decanoate (HD) was impaired. Prospective, controlled trial of water handling in patients without symptomatic hyponatremia receiving HD. Eligibility for study inclusion required that patients had received HD for at least 4 months, were not taking any medication reported to cause inappropriate antidiuretic hormone secretion or hyponatremia (excluding haloperidol), and would agree to participate in the study. An age- and gender-matched healthy control subject was enrolled for each study patient. Baseline laboratory values were obtained within 48 hours prior to the standard water-loading test to screen for abnormalities in electrolytes, kidney function, and liver function. A 20-mL/kg water-load test was administered to each patient. Urine volume and osmolality were measured every hour for 4 hours. A community mental health (CMH) outpatient psychiatric facility for the patients receiving HD and Saint Mary's Health Services for the controls. Fifteen patients receiving HD from the CMH facility and 15 age- and gender-matched control subjects were enrolled. Impaired water handling was defined as a failure to dilute urine to less than 100 mmol/kg or a failure to excrete more than 65% of a water load in 4 hours. Five patients receiving HD were excluded because of protocol refusal or violation. Five of 10 evaluable patients receiving HD had abnormal water handling. Two of these could not lower their urine osmolality to less than 100 mmol/kg, 2 could not excrete more than 65% of the water load, and 1 did not meet either criteria. None of the healthy volunteers had abnormal free water handling. The difference between the study patients and the control subjects was statistically significant (p = 0.0097). Fifty percent of our study patients receiving HD had abnormal free water handling. This finding, combined with our clinical observations of symptomatic hyponatremia in other patients receiving the drug, suggests the need to investigate the incidence of hyponatremia and to design a useful screening tool to identify patients at risk. In the meantime, clinicians should be aware of the potential for impaired water handling in patients receiving HD.",1995.0,0,0
1770,8521771,Nifedipine gastrointestinal therapeutic system (GITS). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in hypertension and angina pectoris.,R N Brogden; D McTavish,"Nifedipine 'gastrointestinal therapeutic system' (GITS) is a recently developed formulation that slowly releases the drug into the intestinal tract over a 24-hour period. When administered once daily, it is of similar efficacy to sustained release formulations of felodipine, verapamil, and diltiazem and at least as effective as standard formulations of lisinopril and enalapril, and long-acting propranolol and atenolol in the treatment of patients with mild to moderate essential hypertension. Substitution of nifedipine GITS for conventional formulations of nifedipine, diltiazem or verapamil, maintained adequate control of anginal symptoms in patients with stable angina pectoris. Nifedipine GITS appears to maintain quality of life and is apparently better tolerated than those formulations of nifedipine which require 2 or 3 times daily administration in both elderly and younger patients. In addition, it has minimal effect on lipid and glucose metabolism and reverses left ventricular hypertrophy, and is thus suitable for treatment of the majority of patients with mild to moderate hypertension or angina pectoris.",1995.0,0,0
1771,8522408,Captopril does not affect plasma endothelin-1 during thrombolysis and reperfusion.,P Di Pasquale; S Paterna; G Parrinello; V Bucca; S Cannizzaro; F Pipitone; G Maringhini; S Scalzo; G Licata,"Studies showed that endothelin-1 (ET-1) was increased in the acute myocardial infarction (AMI). Experimental studies reported that captopril was able to reduce ET-1 secretion, and that ET-1 was increased during reperfusion. This study was aimed to verify if captopril was able to reduce plasma ET-1 during thrombolysis in AMI. Seventy-three patients, hospitalized for suspected AMI within 4 h from the onset of symptoms suitable for thrombolysis (1st episode), Killip class 1-2, were randomized (double blind) into two groups: group 1 (37 pts), 8 F/29 M, received captopril, 6.25 mg, orally 15 min before thrombolysis. Group 2: (36 pts) 8 F/28 M, received placebo before thrombolysis. All patients met the reperfusion criteria. Plasma ET-1 were checked on admission, at 1 h and at 2 h, after starting thrombolysis. Group 1 contained ten unstable angina, 17 anterior and ten inferior AMIs. Group 2 contained ten unstable angina, 16 anterior and ten inferior AMIs. Mean concentrations of ET-1: Unstable angina: group 1, basal--4.56, at 1 h--4.47, 2 h--5.89 pg/ml; group 2: basal--4.17, at 1 h--4.59, 2 h--5.24 pg/ml. Inferior AMI: group 1: basal--6.87, 1 h--7.75, 2 h--8.47; group 2: basal--6.34, 1 h--6.68, 2 h--7.98 pg/ml. Anterior AMI: group 1: basal--7.17, 1 h--7.93, 2 h--10.76 pg/ml (between basal and 2-h samples P < 0.05); group 2: basal--7.46, 1 h--7.51, 2 h--10.74 pg/ml. Differences between the two groups were not significant. Our data suggest that captopril does not affect plasma ET-1 during thrombolysis.",1995.0,0,0
1772,8522409,Left ventricular volume in thrombolysed patients with acute anterior myocardial infarction: the effect of captopril and xamoterol.,K H Darasz; J Bayliss; S R Underwood; J Keegan; P A Poole-Wilson; G C Sutton,"We measured left ventricular volume in 70 asymptomatic patients after first Q-wave anterior myocardial infarction in order to determine whether ventricular dilatation occurs and whether there is evidence for its attenuation or prevention by treatment with captopril or xamoterol--PRevention Of VEntricular Dilatation?: the PROVED? study. 77% of patients received thrombolytic treatment. Patients were randomised a mean of 11 days after infarction to receive either captopril 25 mg three times daily, xamoterol 200 mg twice daily or matching placebo. After 6 months of treatment, 6 patients from the placebo group (n = 24), 1 from the captopril group (n = 23) and 3 from the xamoterol group (n = 23) had been withdrawn from the study because of clinical complications. Left ventricular volume was measured using magnetic resonance imaging, before randomisation and after 6 months of treatment. Changes in left ventricular end-diastolic and end-systolic volume after 6 months of treatment were defined prospectively as the primary endpoints. Mean initial end-diastolic volume index was 85 (S.D. 19) ml/m2, mean end-systolic volume index was 45 (S.D. 18) ml/m2, and mean ejection fraction was 48 (S.D. 11)% for the whole group. There was no significant change in left ventricular volume index in the placebo or either treatment group after 6 months of treatment. Only minimal left ventricular dilatation was evident at 11 days. No further increase in left ventricular volume occurred after six months and there was no additional benefit from treatment with either captopril or xamoterol.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1773,8522630,Management of hypertensive urgencies and emergencies.,W Abdelwahab; W Frishman; A Landau,"Hypertensive emergency is a condition in which there is elevation of both systolic and diastolic blood pressure with the presence of acute target organ disease. Hypertensive urgency is a condition where the blood pressure is elevated (diastolic > 120 mmHg) with the absence of acute target organ disease. Hypertensive emergencies are best managed with parenteral drugs and careful intraarterial blood pressure monitoring. Hydralazine has been widely used in treatment of hypertension in eclampsia and preeclampsia, and its safety has been demonstrated in these patients. Sodium nitroprusside (SNP) has the most reliable antihypertensive activity, which begins immediately after its administration and ends when the infusion is stopped. As with diazoxide, it should be used with caution in patients with impaired cerebral flow. SNP is the preferred drug in obtaining controlled hypotension in patients undergoing neurovascular surgery. Intravenous nitroglycerin is useful in patients prone to myocardial ischemia, but should be avoided in patients with increased intracranial pressure. Esmolol is effective in controlling both supraventricular tachyarrhythmias and severe hypertension. Its short onset of duration of action make it useful in the emergent setting, but because of its negative inotropic effect its use should be avoided in patients with low cardiac output. Verapamil should not be used in patients with preexisting conduction abnormalities. Nicardipine is a potent arteriolar vasodilator without a significant direct depressant effect on myocardium. As with other afterload reducing agents, it should not be used in patients with severe aortic stenosis. Because angiotensin-converting enzyme (ACE) inhibitors generally cause cerebral vasodilatation, enalaprilat may be particularly beneficial for patients who are at high risk of developing cerebral hypotensive episodes secondary to impaired cerebral circulation. Fenoldopam, a selective post-synaptic dopaminergic receptor (DA1) has been shown to be effective in treating severe hypertension with a lower incidence of side effects than SNP. Hypertensive urgencies can usually be managed with oral agents. Oral nifedipine, captopril, clonidine, labetalol, prazosin, and nimodipine have all been shown to be effective in these situations.",1995.0,0,0
1774,8522636,Moexipril in the treatment of mild to moderate essential hypertension: comparison with sustained-release verapamil.,D R Abernethy; A A Fox; M Stimpel,"To compare and contrast the antihypertensive efficacy of an angiotensin-converting enzyme (ACE) inhibitor to a calcium antagonist, 88 and 90 patients with essential hypertension were randomly assigned to receive moexipril and verapamil, respectively. At the end of the first 6 weeks of active therapy, sitting diastolic blood pressure decreased by 11 mmHg in patients receiving moexipril and by 9 mmHg in patients receiving verapamil. The 24-week treatment period was completed by 72 patients who received moexipril and 71 patients who received verapamil. Mean decreases in sitting diastolic blood pressure of 10 mmHg and 11 mmHg were observed in the respective intent-to-treat moexipril and verapamil groups. At doses of 7.5 mg and 15 mg once daily, moexipril had an antihypertensive effect comparable to that of sustained-release verapamil at doses of 180 mg and 240 mg once daily.",1995.0,0,1
1775,8522669,Enalaprilat controls postoperative hypertension while maintaining cardiac function and systemic oxygenation after neurosurgery.,H Tohmo; M Karanko,"The efficacy of intravenous enalaprilat in lowering postoperative hypertension. Prospective, randomized, controlled, single blind trial. Surgical ICT in a university hospital (tertiary care center). 18 neurosurgical patients subjected to the extirpation of a supratentorial intracerebral tumour were studied after detection of postoperative hypertension. This was defined as a constant elevation of systolic arterial pressure over 160 mmHg or diastolic arterial pressure over 95 mmHg. Enalaprilat 0.015 mg kg-1 was injected within 5 min to 9 patients. Central haemodynamics and systemic oxygenation were assessed at baseline before enalaprilat injection, and repeatedly during four hours after the injection. The statistical analysis was performed with analysis of variance for repeated measurements. As compared to control patients, the blood pressure lowering effect of enalaprilat became evident within 15 min and lasted for over four hours (p = 0.008). It was mainly due to the reduced systemic vascular resistance. Enalaprilat also induced a small decline in myocardial perfusion pressure. Cardiac performance, preload, heart rate and systemic oxygenation were not affected by enalaprilat. We found intravenous enalaprilat effective and safe in lowering postoperative hypertension following neurosurgery as assessed by it's effects on central haemodynamics and systemic oxygenation.",1995.0,0,0
1776,8522681,"Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty of occluded versus nonoccluded coronary arteries. Results from the Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MARCATOR).",P B Berger; D R Holmes; E M Ohman; M A O'Hanesian; J G Murphy; R S Schwartz; P W Serruys; D P Faxon,"This study sought to compare the frequency of restenosis, reocclusion and adverse cardiovascular events after angioplasty of occluded versus nonoccluded coronary arteries. Angioplasty of chronically occluded coronary arteries is believed to be associated with a higher frequency of restenosis and reocclusion than angioplasty of subtotal stenoses. Whether this leads to adverse cardiovascular events is unknown. The Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Restenosis (MARCATOR) was a placebo-controlled trial with angiographic follow-up to determine the effect of the angiotensin-converting enzyme inhibitor cilazapril on the frequency of restenosis. In this trial, restenosis was defined as 1) angiographic reduction of minimal lumen diameter > or = 0.72 mm between angioplasty and the follow-up visit; and 2) > 50% diameter stenosis on the follow-up angiogram. We identified 139 patients with successful angioplasty of a coronary occlusion (Group 1) and compared the frequency of restenosis, reocclusion and adverse cardiovascular events with that in 1,295 patients with successful angioplasty of a subtotal stenosis (Group 2). Restenosis occurred in 36 patients with occluded arteries (29%) versus 264 with nonoccluded arteries (23%, p = 0.177) by definition 1 and in 62 patients with occluded arteries (49%) versus 478 with nonoccluded arteries (42%, p = 0.119) by definition 2. Occlusion was present in 24 Group 1 patients (19%) compared with 74 Group 2 patients (7%) (p < 0.001). During the 6 month follow-up period, two Group 1 patients (1.4%) and six Group 2 patients (0.5%) died; no Group 1 patients and 10 Group 2 patients (0.8%) developed severe congestive heart failure; nonfatal myocardial infarction occurred in 4 Group 1 patients (2.9%) and 31 Group 2 patients (2.4%); repeat coronary angioplasty or bypass surgery was performed in 29 Group 1 patients (21%) and 232 Group 2 patients (18%); and angina was present in 18 Group 1 and 163 Group 2 patients (13% for both). Eighty-six Group 1 patients (62%) and 853 Group 2 patients (66%) remained free of these adverse events during the 6-month follow-up period (p = 0.513). The frequency of restenosis was slightly but not significantly greater after successful angioplasty of an occluded artery than after angioplasty of a subtotal stenosis. Although reocclusion was more frequent, occurring in 19% of patients, the net clinical benefit of angioplasty in such patients was similar to that in patients with subtotal stenoses over the 6-month follow-up period.",2001.0,0,0
1777,8523379,Comparison of amlodipine and quinapril on ambulatory blood pressure and platelet function in hypertension.,Y A Ding; S M Chang; T C Chou,"The effect of calcium channel blocker (CCB), amlodipine (5-10 mg/day) and angiotensin-converting enzyme (ACE) inhibitor, quinapril (10-40 mg/day) on ambulatory blood pressure (ABP), rheological and platelet function in hypertension were compared in this randomised double-blind placebo-controlled cross-over study. This study was preceded by 4 weeks placebo run-in period and the total duration of the study was 28 weeks. Casual and 24 h ABP, plasma renin activity (PRA) and plasma aldosterone (PA) concentration as well as metabolic and platelet function were determined before and at the end of each drug therapy. A total of 27 patients completed this study. Casual BP was significantly reduced after amlodipine or quinapril treatment, but there was no change in heart rate. Regarding the 24 h ABP, amlodipine produced a fall from 145 +/- 8/94 +/- 7 to 130 +/- 13/85 +/- 10 mm Hg (P < 0.001 for both SBP and DBP). Quinapril also caused a reduction from 144 +/- 10/94 +/- 7 to 134 +/- 12/88 +/- 8 mm Hg (P < 0.001 for both SBP and DBP). Neither amlodipine nor quinapril produce any significant change in heart rate. The level of 6-keto-prostaglandin Fl alpha (6-Keto-PGFl alpha) was increased from 36.8 +/- 4.4 to 45.1 +/- 2.5 pg/ml (P < 0.05) and no significant change of thromboxane B2(TXB2) was noted after amlodipine treatment. PRA was increased from 1.24 +/- 0.31 to 1.62 +/- 0.41 ng/ml/h (P < 0.05) after quinapril treatment. Other biochemical parameters were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1778,8535985,Advantages and disadvantages of combining sedative agents.,D P Stoltzfus,One advantage of combination sedative therapy is the use of small doses of agents from different drug classes to treat concomitant behavioral problems. The simultaneous use of multiple sedative agents results in the need for new clinical decisions regarding the administration of and weaning from the pharmacologic effects of these drugs. This article reviews the current status of research regarding combination sedative therapy.,1995.0,0,0
1779,8538349,Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy.,G G van Essen; P L Rensma; D de Zeeuw; W J Sluiter; H Scheffer; A J Apperloo; P E de Jong,"Polymorphism in the gene for angiotensin-converting enzyme (ACE), especially the DD genotype, is associated with risk for cardiovascular disease. Glomerulosclerosis has similarities to atherosclerosis, and we looked at ACE gene polymorphism in patients with kidney disease who were in a trial of long-term therapy with an ACE inhibitor or a beta-blocker. 81 patients with non-diabetic renal disease had been entered into a randomised comparison of oral atenolol or enalapril to prevent progressive decline in renal function. The dose was titrated to a goal diastolic blood pressure of 10 mm Hg below baseline and/or below 95 mm Hg. The mean (SE) age was 50 (1) years, and the group included 49 men. Their renal function had been monitored over 3-4 years. We have looked at their ACE genotype, which we assessed with PCR. 27 patients had the II genotype, 37 were ID, and 17 were DD. 11 patients were lost to follow-up over 1-3 years. The decline of glomerular filtration rate over the years was significantly steeper in the DD group than in the ID and the II groups (p = 0.02; means -3.79, -1.37, and -1.12 mL/min per year, respectively). The DD patients treated with enalapril fared as equally a bad course as the DD patients treated with atenolol. Neither drug lowered the degree of proteinuria in the DD group. Our data show that patients with the DD genotype are resistant to commonly advocated renoprotective therapy.",1996.0,0,0
1780,8541002,Effect of low-dose ramipril on microalbuminuria in normotensive or mild hypertensive non-insulin-dependent diabetic patients. North-East Italy Microalbuminuria Study Group.,R Trevisan; A Tiengo,"Microalbuminuria predicts early mortality and renal disease in non-insulin-dependent diabetic patients. In insulin-dependent diabetic patients, angiotensin converting enzyme inhibition decreases microalbuminuria and retards the progression of renal disease. The aim of this study was to evaluate the effect of low dose ramipril on albumin excretion rate (AER) and blood pressure in non-insulin-dependent diabetic patients with persistent microalbuminuria (AER > 20 < 200 micrograms/min) and normal blood pressure or mild hypertension. The study was a randomized, double-blind, placebo-controlled clinical trial of 6 months duration at 14 hospital-based diabetes centers in northeastern Italy. Blood pressure, plasma glucose, and body weight were determined every month; AER, serum creatinine, glycosylated hemoglobin, and plasma lipids at baseline, after 1 month, and at the end of the study. Of 122 non-insulin-dependent diabetic patients randomly allocated in blocks of four to receive either ramipril (1.25 mg/day) or placebo, 108 (54 in the ramipril group and 54 in the placebo group) completed the study. At baseline, age, duration of diabetes, body mass index, and glycosylated hemoglobin were similar in the two groups and remained unchanged throughout the study. In the placebo group, AER rose from a baseline median of 65 micrograms/min (range 53 to 76, 95% confidence Interval) to 72 micrograms/min (57 to 87) and to 83 micrograms/min (62 to 104) after 1 and 6 months, respectively, but fell from 62 micrograms/min (48 to 76) to 45 micrograms/min (33 to 57) and to 53 micrograms/min (38 to 69), respectively, in the ramipril group, a significant difference between the groups (P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1781,8541006,The effect of enalapril on mortal and morbid events in patients with hypertension and left ventricular dysfunction.,J B Kostis,"The objective of this study was to examine the effect of enalapril on morbid and mortal events in patients with left ventricular dysfunction and hypertension using a retrospective analysis of patients with systolic left ventricular dysfunction (ejection fraction < or = 0.35) who participated in the Studies of Left Ventricular Dysfunction (SOLVD). Among the 6797 patients who were randomized to enalapril or placebo, 2652 had history of hypertension, 1508 had systolic blood pressure (SBP) > or = 140 mm Hg, and 985 had diastolic blood pressure (DBP) > or = 90 mm Hg. During average follow-up of 40 months, the rate of hospitalization for congestive heart failure was lower in the enalapril group than the placebo group among patients with history of hypertension (20.6% v 28.3%, P < .001, relative risk [RR] 0.664), and among those with elevated DBP (16.5% v 26.0%, P < .001, RR = 0.574), or SBP (19.5% v 27.7%, P < .001, RR = 0.647) at baseline. These risk ratios were similar to those observed in patients without history of hypertension (RR = 0.647). Also, the decreased rates of mortality, myocardial infarction, stroke, and unstable angina observed in SOLVD were seen, with similar relative risks, in patients with (RR = 0.927, 0.836, 0.979, 0.900, respectively) and without (RR = 0.866, 0.729, 0.775 and 0.743) history of hypertension as well in those with elevated SBP (RR = 0.841, 0.806, 0.707, 0.867) or DBP (RR = 0.791, 0.889, 0.755, 0.872) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1782,8542050,"Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension.",S G Chrysant; T Fagan; R Glazer; A Kriegman,"To assess the efficacy and safety of several combinations of benazepril, an angiotensin-converting enzyme inhibitor, and hydrochlorothiazide, as compared with placebo, in the treatment of patients with essential hypertension. A 6-week, randomized, double-blind, parallel study conducted at 24 centers. A placebo run-in period of 1 to 4 weeks preceded the double-blind phase. Male and female outpatients, aged 18 years and older, were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase. Among the 334 patients who entered the double-blind phase, 17% were aged 65 years or older and 26% were black. Eleven patients withdrew because of adverse experiences, including two patients receiving placebo. Patients received placebo; benazepril, 20 mg; hydrochlorothiazide, 25 mg; or combination therapy with benazepril/hydrochlorothiazide, 5/6.25 mg, 10/12.5 mg, 20/25 mg, 20/6.25 mg, or 5/25 mg, once daily for 6 weeks. The mean change from baseline in sitting diastolic blood pressure at end point (last postrandomization measurement carried forward) in the double-blind phase. Combination therapy with benazepril/hydrochlorothiazide, 20/25 mg, was compared with benazepril, 20 mg alone, and hydrochlorothiazide, 25 mg alone. Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated. Compared with placebo, all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point. In the benazepril/hydrochlorothiazide, 20/25 mg, group, the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups (benazepril, 20 mg, P < or = .05; hydrochlorothiazide, 25 mg, P < or = .001) alone. All therapies were generally well tolerated. Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy. Benazepril in combination with hydrochlorothiazide, including a low-dose combination of 5/6.25 mg, is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension.",1996.0,0,0
1783,8542529,Exercise guidelines for patients with high blood pressure: an update.,L S Pescatello; T Buckley,,1995.0,0,0
1784,8542882,Should ACE inhibitors be administered to all patients after acute myocardial infarction? A (cautious) negative response.,D G Julian,,1995.0,0,0
1785,8545563,Stress reactivity in responder and non-responder hypertensives treated with verapamil and enalapril.,P Nazzaro; M Manzari; M Merlo; R Triggiani; A M Scarano; A Lasciarrea; N Marella; A Pirrelli,"Hypertension was found to be associated with sympathetic overdrive but it is still debated if the antihypertensive agents can differently affect the stress response in hypertensive subjects. Through a psychophysiological study, we evaluated the effect of verapamil (V) and enalapril (E), both as monotherapy and association. Office BP was successfully reduced (< 145/90 mmHg) in 11 patients treated with V (V-Resp) and in 10 patients treated with E (E-Resp). Both the drugs were prescribed in 9 patients (V+E) who did not sufficiently lower their blood pressure (N-Resp) with monotherapy. Patients performed three stressors (color word stroop, cold pressor and handgrip). Extracardiovascular and hemodynamic functions were measured during baseline, stress and recovery periods. The response was evaluated adding the changes occurred in every phase of the psychophysiological session. This was performed before run-in and after any modification of the therapeutic intervention. The emotional arousal (phrontalis muscular contraction, skin conductance, peripheral temperature) was reduced when BP was normal. No change in BP reactivity was found. HR response decreased in V-Resp and cardiac output increased in E-Resp while the vascular reaction was restrained in E-Resp and V-Resp. This was reduced also in N-Resp when they assumed V+E and normalized their arterial pressure. The findings indicate that the sympathetic reactivity may be modified by the therapy. In particular, verapamil restrained the cardiac stress response without lowering the cardiac output and was advantageously associated with enalapril to control the psychophysiological response in more resistant hypertensive patients.",1995.0,0,0
1786,8546135,Decrease of exercise-induced microalbuminuria in patients with type I diabetes by means of an angiotensin-converting enzyme inhibitor.,F Inserra; H Daccordi; J L Ippolito; L Romano; H Zelechower; L Ferder,"Taking into account both the importance of microalbuminuria (MA) as a predictive parameter of clinical nephropathy in diabetic patients and the efficiency of exertion to show and/or to increase MA in both diabetic patients and normal individuals, we studied 37 type I diabetic patients divided into two groups: group A, with no MA at rest (n = 19), and group B, with MA at rest (n = 18). Group C comprised 10 healthy volunteers as controls. Changes of basal MA during exercise and postexercise were studied in all three groups. Normotensive patients with no metabolic disorders, normal renal function, and no proteinuria underwent an ergometric test up to 600 kg. This test was repeated after the administration of 20 mg enalapril in a single daily dose for 60 days. Body weight, systolic and diastolic arterial pressure, creatinine, and creatinine clearance were determined and showed no significant variations either between groups or with treatment. Microalbuminuria was studied in the three groups with and without administration of enalapril throughout the 2 months of the study. Determinations were performed under conditions of rest, exercise, and postexercise. Mean baseline MA values +/- SEM were as follows: at rest, 5.22 +/- 0.49, 58.36 +/- 13.24, and 4.73 +/- 0.45 micrograms/min for groups A, B, and C, respectively; with exercise, 15.19 +/- 4.43, 74.70 +/- 14.89, and 16.76 +/- 4.62 micrograms/min for groups A, B, and C, respectively; and postexercise, 32.04 +/- 6.64, 253.15 +/- 63.88, and 9.23 +/- 3.25 micrograms/min, respectively. The geometric means of the baseline to posttreatment MA ratio were as follows: at rest, 0.95, 1.59 (P < 0.01), and 1.03 for groups A, B, and C, respectively; with exercise, 1.53 (P < 0.01), 1.91 (P < 0.01), and 1.69 for groups A, B, and C, respectively; and postexercise, 2.94 (P < 0.01), 3.24 (P < 0.01), and 1.03 for groups A, B, and C, respectively. In conclusion, in the early diagnostic suspicion of diabetic nephropathy, the screening of postexercise MA during an ergometric test could be of help. Treatment with enalapril decreased MA in diabetic groups A (no MA at rest) and B (MA at rest) during exercise and postexercise, and also decreased MA in group B while at rest.",1996.0,0,0
1787,8546174,Quiz of the month.,S H Norris,,1995.0,0,0
1788,8546341,Power spectral analysis of heart rate in elderly hypertensive subjects with or without silent coronary disease.,G Piccirillo; F L Fimognari; E Santagada; M R Munizzi; E Viola; G Monteforte; C Bucca; M Durante; C Di Gioacchino; S Tarantini; A Lo Verde; M Cacciafesta; V Marigliano,"Much evidence indicates an involvement of the sympathetic nervous system in the genesis of silent myocardial ischemia. The authors assessed autonomic system activity by power spectrum analysis of heart rate variability in 21 elderly hypertensive men with and without angiographically confirmed coronary artery disease and compared the results with those from an age-matched control group. In the analysis an autoregressive algorithm was used to determine the power spectrum from an electrocardiographic recording of 512 consecutive RR intervals. The autonomic nervous system induces two distinct sinusoids: a low-frequency signal attributable to sympathetic activity and a high-frequency vagal response. In the hypertensive patients with coronary disease the authors also evaluated sympathetic activation after double-blind, placebo-controlled administration of metoprolol (100 mg/day), followed by amlodipine (10 mg/day), quinapril (20 mg/day), and amlodipine (5 mg/day) plus quinapril (10 mg/day).",1996.0,0,0
1789,8549868,Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients.,M Velussi; E Brocco; F Frigato; M Zolli; B Muollo; M Maioli; A Carraro; G Tonolo; P Fresu; A M Cernigoi; P Fioretto; R Nosadini,"Contrasting information has been reported concerning the course of renal function in NIDDM with hypertension alone or in association with renal damage. The aim of the present study was to elucidate the course of the glomerular filtration rate (GFR) in hypertensive NIDDM patients during antihypertensive therapy. Furthermore, we compared the effects of ACE inhibitors (cilazapril, Inibace, Roche, Milan, Italy) and Ca(2+)-channel blockers (amlodipine, Norvasc, Pfizer, Rome, Italy). Of the hypertensive NIDDM patients attending the outpatient's clinic of the internal medicine departments of the University of Padova and Sassari, 44 participated in the present study. Of these patients, 26 were normoalbuminuric and 18 microalbuminuric. They were randomly treated with either cilazapril or amlodipine. The target of antihypertensive treatment was a value < 140 mmHg for systolic and 85 mmHg for diastolic blood pressure (BP). Microalbuminuria was defined as an albumin excretion rate (AER) between 20 and 200 micrograms/min. GFR was measured by plasma clearance of 51Cr-labeled EDTA at baseline and every 6-12 months during a 3-year follow-up interval. A significant decrease was observed in the values of GFR, AER, and systolic and diastolic BP in normoalbuminuric and microalbuminuric patients during antihypertensive therapy. The GFR fall in the overall population of NIDDM patients was significantly and inversely related to the decrease of mean BP (diastolic + 1/3 pulse pressure) (r = -0.80, P < 0.0001) but not to that of HbA1c, triglycerides, and BMI. The GFR decline (mean +/- SE) per year in the normoalbuminuric patient was 2.03 +/- 0.66 ml.min-1 x 1.73 m-2 (95% CI 0.92-3.17) during cilazapril and 2.01 +/- 0.71 ml.min-1 x 1.73 m-2 (95% CI 0.82-3.11) during amlodipine therapy. The GFR decline per year in the microalbuminuric patient was 2.15 +/- 0.69 ml.min-1 x 1.73 m-2 (95% CI 0.86-3.89) during cilazapril and 2.33 +/- 0.83 ml.min-1 x 1.73 m-2 per year (95% CI 1.03-3.67) during amlodipine therapy. Cilazapril and amlodipine lowered AER to a similar extent in normoalbuminuric and microalbuminuric patients. No significant changes were observed concerning other clinical and biochemical features between the two antihypertensive therapies and particularly HbA1c, BMI, triglycerides, and cholesterol plasma values. These results support the tenet that arterial hypertension plays a pivotal role in contributing to renal damage in NIDDM, even when AER is normal. However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy.",1996.0,0,0
1790,8551488,"'Captopril test', with blood pressure and peripheral renin as response variables in hypertensive patients with suspected renal artery stenosis.",G Schreij; P N van Es; P M Schiffers; A T Lavrijssen; P W de Leeuw,"In forty six hypertensive patients in whom a high level of clinical suspicion for renovascular hypertension was present on the basis of clinical clues, a captopril test was performed with either 25 mg of captopril or placebo on 2 separate days to determine prospectively the value of the captopril test. Blood pressure (BP) and peripheral renin were used as response variables. All patients had discontinued their anti-hypertensive medication and were not salt depleted. In all patients selective renal angiography was performed irrespective of the results of the captopril test. Twenty patients proved to have uni- or bilateral renal artery stenosis (RAS) giving a prevalence of 43%. After the placebo and after captopril there were no significant changes (absolute or proportional) in BP values between patients with essential hypertension or RAS, either for all measurements or if only the fall in BP was taken into account. The receiver operator characteristic curves of both baseline and post-captopril peripheral renin levels indicate that the captopril test does not discriminate appropriately between patients with essential hypertension and RAS. Therefore, we would not advise the use of the captopril test as a screening test for RAS in hypertensive patients in whom a high level of clinical suspicion for RAS is already present.",1995.0,0,0
1791,8554206,"United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus.",R Turner; C Cull; R Holman,"To report the progress (after 9-year follow-up) of a study designed to determine whether improved glucose control in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM) is effective in reducing the incidence of clinical complications. A multicenter, randomized, controlled trial of different therapies for NIDDM. After initial diet therapy, 4209 asymptomatic patients who remained hyperglycemic (fasting plasma glucose levels, 6.0 to 15.0 mmol/L) were assigned to either a conventional therapy policy, primarily with diet alone, or to an intensive therapy policy, aiming for fasting plasma glucose levels of less than 6.0 mmol/L, with assignment to primary therapy with sulfonylurea or insulin (which increased insulin supply) or metformin (which enhanced insulin sensitivity). All three modes of pharmacologic therapy in the intensively treated group-sulfonylurea, insulin, and metformin-had similar efficacy in reducing the fasting plasma glucose and glycated hemoglobin levels. Over 9 years, patients assigned to intensive therapy with sulfonylurea or insulin had lower fasting plasma glucose levels (median, 7.3 and 9.0 mmol/L, respectively) than patients assigned to conventional therapy. Regardless of the assigned therapy, however, the fasting plasma glucose and hemoglobin A1c levels increased, and maintaining near-normal glycemia was, in general, not feasible. Even insulin therapy did not achieve the therapeutic goal of near-normal glycemia because of the difficulty in treating marked hyperglycemia and the risk for hypoglycemic episodes. Nine years after the diagnosis of diabetes, 29% of the patients had had a diabetes-related clinical end point, 20% had had a macrovascular complication, and 9% had had a microvascular complication. A report will be published in 1998 after a median duration from randomization of 11 years (range, 6 to 20 years) with an 81% power at a 1% level of significance of detecting whether the obtained improvement in glucose control causes a 15% decrease or increase in the incidence of major complications and whether any specific therapy is advantageous or disadvantageous.",1996.0,0,0
1792,8557903,Six-month effects of early treatment with lisinopril and transdermal glyceryl trinitrate singly and together withdrawn six weeks after acute myocardial infarction: the GISSI-3 trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.,,"This 6-month follow-up analysis sought to assess whether the early reduction of mortality obtained with a 6-week treatment course of lisinopril or glyceryl trinitrate, or both, in unselected patients with acute myocardial infarction outlasts therapy and is still present after 6 months. The primary outcome of the 6-month follow-up was the combined end point of mortality and severe left ventricular dysfunction. The assumption was that the early benefit on remodeling processes may be maintained over a longer period of time, even in the absence of treatment. A total of 19,394 patients with acute myocardial infarction were randomized within 24 h of onset of symptoms to a 6-week treatment course of oral lisinopril or open control and, according to a 2 x 2 factorial design, to glyceryl trinitrate or open control. Randomized treatments were stopped after 6 weeks in the absence of specific indications, and the patients were followed up for 6 months. At 6 months, among patients randomized to lisinopril, 18.1% died or developed severe ventricular dysfunction versus 19.3% of those randomized to no lisinopril (2p = 0.03). No difference was found between patients with and without glyceryl trinitrate therapy (18.4% vs. 18.9%, 2p = 0.39). Although the systematic administration of glyceryl trinitrate started early and continued for 6 weeks after acute myocardial infarction does not yield evidence of benefit, early treatment with lisinopril appears to improve prognosis. This effect seems to carry over the first 6 months from randomization, even after treatment withdrawal.",1996.0,1,1
1793,8557961,The influence of perindopril and the diuretic combination amiloride+hydrochlorothiazide on the vessel wall properties of large arteries in hypertensive patients.,M J Kool; F A Lustermans; J G Breed; H A Struyker Boudier; A P Hoeks; R S Reneman; L M Van Bortel,"To compare the cardiovascular effects of 6 months of treatment with the angiotensin converting enzyme inhibitor perindopril and with the diuretic combination amiloride+hydrochlorothiazide, and to study possible persistence of observed treatment effects after discontinuation of antihypertensive therapy. A placebo run-in period preceded a 6-month active-treatment phase in 41 patients with essential hypertension, according to a double-blind, randomized, parallel-group design. Patients received either 4 mg perindopril or 2.5/25 mg amiloride+hydrochlorothiazide once a day. Patients were then studied for a 3-month single-blind placebo run-out period. After 6 months of treatment, systolic blood pressure was reduced significantly by perindopril (supine by 11%, sitting by 10%) and by amiloride+hydrochlorothiazide (supine by 8%, sitting by 12%). Diastolic blood pressure was also decreased significantly by perindopril (supine by 8%, sitting by 11%) and by amiloride+hydrochlorothiazide (supine by 4%, sitting by 9%). Mean arterial pressure decreased significantly during treatment with perindopril (by 9%) and with amiloride+hydrochlorothiazide (by 6%). Cardiac index increased with perindopril (by 6%), because of an increased stroke index (by 5%), but amiloride+hydrochlorothiazide did not change cardiac function. Systemic vascular resistance index decreased significantly more with perindopril (by 14%) than with amiloride+hydrochlorothiazide (by 8%). The distensibility of the common carotid artery was significantly enhanced by perindopril (by 16%), but not changed by amiloride+hydrochlorothiazide (1% difference). The difference between perindopril and amiloride+hydrochlorothiazide for carotid distensibility was statistically significant. The compliance of the common carotid artery tended to be increased more by perindopril (by 7%) than by amiloride+hydrochlorothiazide, which induced a 5% decrease in carotid compliance. After withdrawal of therapy, for both drugs, all treatment-induced changes were reversed to pretreatment values within 7 weeks. The distensibility of the elastic common carotid artery was increased by perindopril, but not by amiloride+hydrochlorothiazide. Large-artery properties of the muscular arteries and systemic vascular resistance improved with both drugs, but in general the changes were more pronounced with perindopril than with amiloride+hydrochlorothiazide. The present results indicate a more pronounced effect of perindopril at both macro- and microcirculatory levels, which will consequently lead to a larger decrease in cardiac afterload. After discontinuation of therapy all parameters returned to baseline values within 7 weeks.",1995.0,0,0
1794,8557971,Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients.,J Polónia; I Boaventura; G Gama; I Camões; F Bernardo; P Andrade; J P Nunes; F Brandão; M Cerqueira-Gomes,"To evaluate the influence of non-steroidal anti-inflammatory drugs (NSAIDs; aspirin and indomethacin) on the renal and antihypertensive effects of enalapril and nifedipine gastrointestinal therapeutic system (GITS) in patients with essential hypertension. In a crossover study, 18 patients on an unrestricted-salt diet were randomly assigned to receive either enalapril (20-40 mg/day) or nifedipine-GITS (30-60 mg/day) for 4-8 weeks, followed by aspirin (100 mg/day for 2 weeks) and then indomethacin (75 mg/day for 1 week). Blood pressure was measured by 24h ambulatory monitoring. Enalapril and nifedipine-GITS significantly reduced blood pressure compared with placebo. Aspirin did not alter the antihypertensive effect of either drug. Indomethacin attenuated (by 45%) the antihypertensive effect of enalapril throughout the 24h period of evaluation, but did not interfere with the effect of nifedipine. Furthermore, indomethacin significantly reduced the fractional excretion of sodium and plasma levels of prostaglandins in a similar way when added to either the enalapril or the nifedipine regimen. Vasodilatory prostaglandins are probably involved in the antihypertensive effects of enalapril but not of nifedipine, and this interaction seems to be independent of any indomethacin-induced decrease in renal sodium excretion. Nifedipine may be an appropriate drug to treat hypertensive patients requiring concomitant therapy with NSAID.",1995.0,0,0
1795,8562296,High prevalence of persistent cough with angiotensin converting enzyme inhibitors in Chinese.,K S Woo; M G Nicholls,"1. Angiotensin converting enzyme (ACE) inhibitors are in common use for the treatment of hypertension and heart failure. Whereas they are, in general, well tolerated, a dry cough can develop which, on occasion, requires termination of therapy. The reported prevalence of cough with ACE inhibitor therapy has varied from 0.2 to 25%, depending upon methods of data collection, analysis and symptom reporting. 2. To evaluate the prevalence of cough in Chinese patients receiving ACE inhibitors, interviews were carried out in 191 patients in Hong Kong who were taking therapy which included captopril or enalapril for hypertension or heart failure, and 382 patients matched for sex and age receiving alternative medications which excluded an ACE inhibitor (controls). Patients and controls were interviewed in a blinded manner by the same interviewer using a common adverse-effect questionnaire. 3. Persistent cough was reported in 44% of patients taking an ACE inhibitor (46% of those receiving captopril and 41.8% of patients taking enalapril), and in 11.1% of the controls (P < 0.001). The prevalence of other adverse reactions was similar, with no significant difference between the two treatment groups. The complication of cough was not related significantly to age, sex, underlying disease, drug dosage or smoking status. 4. This study indicates that cough is a common side effect of treatment with ACE inhibitors in Hong Kong Chinese, although in most patients cessation of therapy is not required. Whether Chinese are particularly susceptible to ACE-inhibitor cough requires a formal prospective study comparing Chinese and non-Chinese patients.",1995.0,0,0
1796,8565028,Isradipine versus captopril in patients with essential hypertension.,A J Manolis; I Gavras; M Pieprzak; H Gavras,"We conducted a double-blind, crossover study comparing the antihypertensive effects of isradipine versus captopril in patients with essential hypertension. Seventeen patients (8 men, 9 women; 6 whites, 11 blacks) completed both phases of the study, which consisted of two 5-week treatment periods separated by 2 weeks of placebo treatment. Each drug was randomly allocated to half the patients as the first drug and half as the second drug they received. Ambulatory blood pressure (BP) monitoring was carried out on the day before treatment and the last day of each active treatment. Both drugs were effective and well tolerated but isradipine was more effective overall than captopril in lowering BP (9.4% vs 3.9%, respectively; P < 0.02). Black patients had significantly higher BP at baseline than white patients; furthermore, black patients responded better to isradipine than to captopril. White patients had a smaller decrease in blood pressure with both drugs than did black patients, but white patients still attained a lower diastolic BP with captopril than did black patients (88 +/- 2 mm Hg vs 96 +/- 9 mm Hg; P < 0.01). There was no correlation between the pretreatment plasma levels of pressor hormones (plasma renin activity, catecholamines, and arginine vasopressin) and the magnitude of BP response to either drug, but the decrease in BP in response to captopril correlated significantly with the increase in plasma renin activity during treatment (r = -.84; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
1797,8565612,Generalized pustular eruption associated with converting enzyme inhibitor therapy.,J Carroll; M Thaler; E Grossman; A Alder; H Trau; T Rosenthal,"A 67-year-old man presented with a high fever and a generalized rash. His extended hospital stay was characterized by fever with repeated staphylococcal bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and uclers. Examination of skin and lymph node biopsy specimens showed findings consistent with mycosis fungoides. The patient unexpectedly recovered on discontinuation of captopril. A positive macrophage inhibiting factor response for both captopril and enalapril indicated that the non-sulfhydryl moiety was the antigenic stimulant for the lesion resembling mycosis fungoides.",1995.0,0,0
1798,8569365,Treatment with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy.,B V Jensen; S L Nielsen; T Skovsgaard,"Anthracycline chemotherapy in cancer can cause severe, frequently fatal congestive heart failure (CHF), the first-line treatment for which is diuretics and digoxin. We have studied the use of an angiotensin-converting-enzyme (ACE) inhibitor added as a third agent. In an observational study in hospital and as outpatients, 92 patients with advanced breast cancer were treated with epirubicin at a cumulative dose of 360 to 1000 mg/m2 (median 1000). Of 85 evaluable, nine developed life-threatening CHF at 1.5 to 13 months after ending epirubicin. Left ventricular ejection fraction (LVEF) decreased from normal to 18 to 35%. All received frusemide and digoxin, and then, after transient clinical relief, enalapril or ramipril (initially 1.25 mg orally daily, increasing to 10-15 mg after 4-6 weeks). Eight of the nine patients deteriorated while on digoxin/diuretic. Within 3 months of starting the ACE inhibitor in these patients, LVEF had increased to normal or near normal. Only one patient died in heart failure. Follow-up ranged from 11 to 42 months (median 26). The ACE inhibitor was well-tolerated, with no first-dose hypotension, except for one patient who discontinued treatment after 6 months because of persistent cough. Two others discontinued treatment with their ACE inhibitor after 22 and 28 months because they felt well. Survival in the nine patients was similar to that of those who did not develop CHF. Our experience suggests that treatment of anthracycline-induced CHF with an ACE inhibitor should start soon after clinical improvement on digoxin/diuretic regardless of the severity of symptoms rather than waiting for clinical deterioration.",1996.0,0,0
1799,8569962,Severe reduction of renal function in hypertensives and/or diabetics induced by angiotensin-converting enzyme inhibitors.,L Gotloib; S Jaichenko; R Fudin; A Shostok,,1995.0,0,0
1800,8570428,Age and carotid artery occlusive disease are important determinants of cerebral blood flow changes after antihypertensive therapy.,S C Fagan; S R Levine; J R Ewing; N M Ramadan; K M Welch,"To determine the short-term effects of antihypertensive therapy on cerebral blood flow (CBF). Prospective, observational study. A university-affiliated teaching hospital. Twenty-four patients (age range 53-85 yrs) with chronic hypertension, nine of whom had carotid artery occlusive disease (CAOD). The CBF (xenon-133 inhalation technique) and blood pressure were measured before and at 60 minutes after administration of antihypertensive therapy. Age was inversely related to the change in CBF in patients with CAOD (p < 0.01). In all patients, the change in CBF after taking antihypertensive drugs was significantly inversely associated with baseline CBF (p < 0.01). Changes in regional CBF, measured by asymmetry scores, were significantly greater in patients with CAOD than in those without CAOD (p < 0.05). Elderly patients with occlusive extracranial cerebrovascular disease are at risk of drug-induced changes in both mean and regional CBF, and may benefit from a CBF assessment before being prescribed antihypertensive therapy.",1995.0,0,0
1801,8571750,Risk factors and differential antihypertensive therapies.,I Os,"A less pronounced reduction in the incidence of coronary heart disease than in cerebrovascular events has been observed during antihypertensive therapy. Hypertension may not be the dominant risk factor for coronary heart disease as it is for cerebrovascular disease, and metabolic factors gain more importance. The reason for the differential effect of antihypertensive therapy could partly be explained by the adverse metabolic effects of some antihypertensive drugs which may thus attenuate the beneficial effects. When decision is made concerning antihypertensive treatment, it is imperative to assess the overall cardiovascular risk of the patient and take into account the possible impact on these factors of the different antihypertensive drugs.",1995.0,0,0
1802,8572838,Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study.,M Ravid; R Lang; R Rachmani; M Lishner,"Diabetic nephropathy is the leading cause of end-stage renal disease in developed countries. Duration of diabetes, blood pressure values, and metabolic status are the major determinants of the course of nephropathy, and microalbuminuria is the hallmark of its onset. Angiotensin-converting enzyme inhibitors offer important renoprotection to hypertensive and normotensive patients with insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus. Our study extends previous observations for duration and the effect of angiotensin-converting enzyme inhibition on advanced nephropathy. Double-blinded (first phase) and open (second phase) randomized controlled study of 7 years. Ninety-four normotensive patients with non-insulin-dependent diabetes mellitus whose serum creatinine levels were lower than 123.76 mumol/L (1.4 mg/dL) and who had microalbuminuria (30 to 300 mg/24 h) were given enalapril maleate, 10 mg/d, or placebo, for 5 years. For 2 more years they were followed up openly and given the choice to receive enalapril or no treatment. In the enalapril-treated patients, albuminuria remained stable for 7 years. An increase from (mean +/- SD) 123 +/- 58 to 310 +/- 167 mg/24 h occurred in the untreated group after 5 years, and a further increase to (mean +/- SD) 393 +/- 223 mg/24 h occurred after 7 years. Reciprocal creatinine was unchanged in treated patients for 7 years; in the untreated patients, the mean decline was 13% at 5 years and 16% at 7 years. Treatment with enalapril resulted in an absolute risk reduction of 42% for nephropathy to develop during 7 years (95% confidence interval, 15% to 69%; P < .001, Student's t test). Glycosylated hemoglobin and body mass index remained unchanged. Angiotensin-converting enzyme inhibition offers long-term protection against the development of nephropathy in normotensive patients with noninsulin-dependent diabetes mellitus who have microalbuminuria, and it stabilizes renal function in previously untreated patients with impaired renal function. Discontinuation of treatment results in renewed progression of nephropathy.",1996.0,0,1
1803,8575234,Effect of perindopril and metoprolol on left ventricular hypertrophy and performance in essential hypertension.,Y Hui; Z Dai; X Chen; W Wang,"The effects of perindopril and metoprolol on left ventricular hypertrophy (LVH) and function were studied in 47 essential hypertensive patients with LVH. Previous antihypertensive drugs were discontinued for at least 2 weeks, after which patients were randomly divided into 2 groups. 25 subjects were treated with perindopril 4 to 8 mg once daily in the morning (Group A) and 22 subjects with metoprolol 25 to 62.5 mg twice daily (Group B). The subjects were evaluated before and after 4 and 8 weeks of treatment by use of echocardiography. Before treatment LV mass indexes (LVMI) of two groups were respectively 143.2 +/- 21.3 g/m2 and 140.6 +/- 23.7 g/m2 (P > 0.05). In Group A, reduction of LVMI occurred after 4 weeks of treatment, and more pronounced after 8 weeks (from 143.2 +/- 21.3 g/m2 to 126.6 +/- 15.3 g/m2, P < 0.001), whereas reduction of LVMI occurred only after 8 weeks in Group B (from 140.6 +/- 23.7 g/m2 to 133.4 +/- 13.2 g/m2, P < 0.001). In addition, there was a significant (P < 0.05) difference in LVMI between the two groups after 8 weeks. LV systolic function remained unchanged, whereas E/A increased significantly (P < 0.001) in two groups after 8 weeks. In conclusion, antihypertensive treatment with perindopril and metoprolol induced a significant regression of LVH associated with improvement in LV diastolic performance. Perindopril, compared with metoprolol, was more effective in reversing LVH.",1995.0,0,0
1804,8576893,Results of combination anti-hypertensive therapy after failure of each of the components. Department of Veterans Affairs Cooperative Study Group on Anti-hypertensive Agents.,B J Materson; D J Reda; W C Cushman; W G Henderson,"We randomised ambulatory men with diastolic blood pressure (BP) 95-109 mmHg without anti-hypertensive medication to single drug treatment with either hydrochlorothiazide 12.5-50 mg/day, atenolol 25-100 mg/day, captopril 25-100 mg/day, clonidine 0.2-0.6 mg/day, diltiazem-SR 120-360 mg/day, prazosin 4-20 mg/day or placebo in a double-blind prospective trial. The assigned drug was titrated to a goal BP of < 90 mm Hg. Patients not achieving goal BP were rerandomised to an alternative single active drug. Non-responders to the second drug received the first drug in combination with the second. Of the 102 non-responders to both drugs who qualified for the combination, 59 (57.8%) responded. The combination pairs that included a diuretic achieved diastolic goal BP in 69% and < 140 mm Hg systolic in 77% compared with 51% and 46%, respectively, for those combinations without a diuretic (P = 0.067; P = 0.002). Six of the eight terminations due to adverse drug reactions were in combinations containing prazosin; three of these six were hypotensive reactions. We conclude that two single drugs of insufficient efficacy to control BP individually have a high probability of achieving goal BP when combined, especially if the combination contains a diuretic.",1995.0,0,0
1805,8579032,Adverse effects of enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). SOLVD Investigators.,J B Kostis; B Shelton; G Gosselin; C Goulet; W B Hood; R M Kohn; S H Kubo; E Schron; M B Weiss; P W Willis; J B Young; J Probstfield,"In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction < or = 0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p < 0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p < 0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients.",2001.0,1,1
1806,8582461,Chronopharmacology of enalapril in hypertensive patients.,K Sunaga; A Fujimura; T Shiga; A Ebihara,"The pharmacokinetics and pharmacodynamics of enalapril, an angiotensin converting enzyme inhibitor, are reported to vary with the time of administration. The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin (BK), substance P and prostaglandin E2 (PGE2), which are likely to be involved in the mechanism of enalapril-induced cough, might also be affected by its time of administration. Enalapril 5 mg or placebo was given orally at 10:00 h (day trial) or 22:00 h (night trial) to 12 patients with essential hypertension. Serum concentrations of total drug (enalapril + enalaprilat, its active metabolite) during the day and night trials did not differ significantly at any time. However, serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial. Blood pressure 24 h after administration of enalapril was reduced at 22:00 h, but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h, but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough. However, no such increase in plasma BK or subsequent adverse effect were recorded in the night trial. Plasma substance P and PGE2 did not change significantly following enalapril administration either in the day or night trial. The results suggest that the response of BK to enalapril is affected by the time of administration. In patients who complain of cough during treatment with enalapril during the daytime, this adverse effect might be diminished or eliminated by a switch to night-time administration.",1995.0,0,0
1807,8583465,Anti-hypertensive effects of intravenous compared with oral captopril.,J J Sramek; J J Brennan; D R Much; K Duchin; A Luna; N R Cutler,"Twenty mild to moderate hypertensive subjects (11 men, 9 women, mean age 54.3 years, range 39-65 years) were studied to determine whether an intravenous form of captopril could be as safe and efficacious as an oral form and to estimate the time course of anti-hypertensive action over a wide dose range (100-fold) of i.v. doses versus oral captopril and placebo. Each subject demonstrated supine diastolic blood pressure (DBP) < or = 90 mm Hg following prospective ACE inhibitor monotherapy, with return of supine DBP to within 95-110 mm Hg 4 weeks after ACE inhibitor discontinuation. These subjects were then admitted to an inpatient unit for six 24 h periods; an initial acclimation period followed by five single doses of i.v. captopril (1.25, 12.5 and 125 mg) or placebo given as a 20 min infusion and oral captopril (25 mg) or placebo in a double-blind, double-dummy crossover study. Each dose was separated by 48 h. All 20 patients completed the study with no clinically significant adverse events. Captopril at doses of 125 mg i.v., 12.5 mg i.v. and 25 mg orally produced similar BP reductions over the 12 h postdose interval, and were more effective in lowering BP than intravenous captopril 1.25 mg or placebo. The 125 mg intravenous captopril dose was no more effective overall in BP reduction than the 12.5 mg i.v. and 25 mg oral doses and was associated with a greater incidence of adverse events. Treatment with 12.5 mg i.v. captopril is safe and comparable to 25 mg oral therapy.",1995.0,0,0
1808,8583466,Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension.,W B White; M Stimpel,"The purpose of this study was to evaluate the long-term safety and efficacy of moexipril, a non-sulphydryl angiotensin converting enzyme inhibitor, alone or in combination with hydrochlorothiazide in older patients with hypertension. One hundred and seventy two hypertensive men and women, 65-80 years old, with seated DBP between 95 and 114 mm Hg were studied. The study was a 2 year, multicentre (12 centres), open-label protocol of moexipril monotherapy or combination therapy (with hydrochlorothiazide). Blood pressure, pulse rate, weight, adverse effects and laboratory studies were assessed following moexipril at 7.5 or 15 mg once daily or 7.5 or 15 mg daily in combination with 25 mg of hydrochlorothiazide if the seated DBP remained > or = 90 mm Hg on moexipril monotherapy. The primary measure of efficacy was a change from baseline in seated DBP. Secondary outcome measures included changes in seated DBP, pulse rate, laboratory parameters and adverse side-effects. Following 1 year of therapy in 135 patients, the BP fell 16/14 mm Hg among patients receiving moexipril monotherapy and 27/17 mm Hg for those receiving combined therapy compared with baseline (P < 0.001 for both). After 2 years of treatment, reductions were similar in 120 patients. Nineteen patients (11%) were prematurely withdrawn from the study because of inadequate therapeutic response and 28 (16%) because of adverse experiences. There were no significant changes in pulse rate or postural reductions in BP on either moexipril monotherapy or combination treatment. Three adverse side-effects occurred at a frequency exceeding 2% that were possibly or probably attributable to moexipril or combination therapy: hypotension (2%), dizziness (6%) and increased cough (12%). There were no clinically relevant mean group changes from baseline laboratory values in the treatment groups. In conclusion, these long-term data demonstrate that moexipril, either alone or in combination with hydrochlorothiazide, has long-term anti-hypertensive efficacy and is generally well tolerated in elderly patients with hypertension.",1995.0,0,0
1809,8586009,Effects of enalapril and nitrendipine on the excretion of epidermal growth factor and albumin in hypertensive NIDDM patients.,Z Josefsberg; S A Ross; A Lev-Ran; D L Hwang,"To compare the effect of the antihypertensive drugs nitrendipine and enalapril on the excretion of epidermal growth factor (EGF) and albumin in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) subjects. After a 4-week washout period, mildly hypertensive (systolic blood pressure [sBP] > or = 140 mmHg and/or diastolic blood pressure [dBP] > or = 90 mmHg) NIDDM patients with albuminuria (15-200 micrograms/min) were randomized into an 8-month-long therapy with either nitrendipine (n = 11) or enalapril (n = 10). Blood pressure, EGF, and microalbumin excretion were measured at baseline and throughout the treatment period. A significant fall in sBP was noticed in the enalapril group and in dBP in the nitrendipine group. In the enalapril group, EGF excretion progressively increased from 188 to 214 nmol/mmol creatinine after 6 weeks and to 274 after 8 months of therapy (P = 0.03). There was a significant fall in albumin excretion while patients were on enalapril, but in the nitrendipine group, neither albuminuria nor EGF excretion changed significantly. There was no correlation of improved EGF excretion with a decrease in albuminuria or BP. The angiotensin-converting enzyme inhibitor enalapril has been effective in decreasing albumin and increasing EGF excretion. Measurement of urinary EGF may provide a new valuable index of renal function.",1995.0,0,0
1810,8586803,Mechanisms responsible for sustained hypotension after captopril treatment.,D G Chen; X Q Jin; H J Wang; S C Chen,"To investigate new aspects of the relationship between sustained reduction of blood pressure and alteration of cardiovascular structure and function after cessation of early captopril treatment. Spontaneously hypertensive rats (SHR) were given captopril 20 mg/kg per day (n = 13) or 100 mg/kg per day (n = 12) from the intra-uterine period to age 16 weeks and then the treatment was stopped. Age-matched untreated SHR (n = 16) and Wistar-Kyoto (WKY) rats (n = 17) served as controls. The experiments were carried out at 40 weeks. Withdrawal of captopril treatment resulted in a rapid rebound of SBP to a level close to that of untreated SHR in the low-dose group, whereas a persistently lower SBP was maintained in the high-dose group. Both doses of captopril treatment completely prevented wall hypertrophy either of arteriolar resistance vessels or of muscular vessels. Captopril decreased left ventricular mass:body weight ratio dose-dependently. High-dose captopril improved the resting and stress systolic and diastolic function. Thoracic angiotensin converting enzyme levels were dose-dependently reduced by captopril treatment. The curves of perfusion pressure response to incremental doses of phenylephrine shifted to the right in both captopril treatment groups compared with those of the control SHR. Addition of L-NAME and L-arginine to the perfusate augmented or attenuated the vasoconstrictor activity in all of the rats, whereas high-dose captopril totally restored the abnormal hypersensitivity to L-NAME and caused less attenuation in response to L-arginine in the control SHR. The persistent lower blood pressure caused by early captopril treatment was ascribed mainly to its sustained normalization of structure and function of resistance vessels, which may be partly mediated by the improvement of endothelial cell function. The persistent reduction of angiotensin converting enzyme activity in blood vessel wall attenuated left ventricular hypertrophy, and the improvement of cardiac systolic and diastolic function may also contribute to the sustained hypotensive effect.",1995.0,0,0
1811,8586825,A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice. The OCAPI Study Group. Optimiser le Choix d'un Anti-hypertenseur de Première Intention.,J P Boissel; J P Collet; L Lion; T Ducruet; P Moleur; J Luciani; H Milon; O Madonna; J Gillet; P Gerini,"To assess the equivalence of four antihypertensive treatments in patients with mild-to- moderate hypertension, and to compare the effects of those drugs on the subjective quality of life and clinical safety. 653 patients aged > or = 18 years with untreated hypertension were randomly allocated to receive a combination of two diuretics (altizide and spironolactone), a beta-blocker (bisoprolol), a calcium antagonist (verapamil), or an angiotensin converting enzyme (ACE) inhibitor (enalapril). Follow-up lasted for 1 year. A composite outcome of the following measures was used to define success: attendance at the 12-month visit; at least nine supine DBP measurements during the study; and median supine DBP < 90 mmHg and a reduction of at least 10 mmHg compared with the baseline value. Failure was defined as one or more of those criteria not being fulfilled. Equivalence was concluded if the 95% confidence interval for the success rates differed between two groups by less than +/- 10%. Clinical safety and subjective quality of life were also assessed. No statistically significant differences in the change in DBP or systolic blood pressure were observed between the groups. The success rates were 43.9, 42.0, 32.5 and 43.9% in diuretic, beta-blocker, calcium antagonist and ACE inhibitor groups, respectively. Equivalence between the treatments could not be concluded, although analysis with a larger equivalence interval showed that some comparisons indicated equivalence. Significant improvement in satisfaction was observed for certain items for subjective quality of life at 1 month in the calcium antagonist treatment group, and significant differences in the responses to the clinical safety questionnaire were observed after 1-month follow-up in calcium antagonist and beta-blocker groups. Differences were no longer significant after 9 months. These results do not provide evidence on the basis of efficacy of blood pressure lowering or ability to increase short-term (1-year) safety and quality of life favouring any particular treatment among the studied drugs for newly diagnosed patients with mild-to-moderate hypertension.",1995.0,0,0
1812,8587636,Inflammatory peptides at the beginning of hemodialysis in asymptomatic patients treated or not with angiotensin I-converting inhibitors.,F Marceau; S Brochu; I Pelletier; G Drapeau; A Adam; M Lebel,,1995.0,0,0
1813,8588063,Serum sodium stabilizing effect of enalapril after standard water load in a patient with a history of self-induced water intoxication.,C S Sebastian; D Sinha; N K Gulati,"1. A 21 day prospective placebo controlled double blind cross over trial of enalapril was studied in a normonatremic patient with a known history of SIWI. 2. At the end of each prophylactic treatment, the patient was challenged with a water load of 20 ml/kg. 3. The mean serum sodium of 140.111 mmol/L on prophylactic enalapril was significantly higher than the 137.6 mmol/L on placebo (p = 0.0015). 4. After a water load, the mean serum sodium on enalapril was 137.6 mmol/L, compared to 133.833 mmol/L (p = 0.0015) on placebo.",1995.0,0,0
1814,8590792,Hypertension and non-insulin-dependent diabetes. A comparison between an angiotensin-converting enzyme inhibitor and a calcium antagonist.,G Crepaldi; A Carraro; E Brocco; L Adezati; D Andreani; G Bompiani; P Brunetti; D Fedele; R Giorgino; G Giustina,"The effects of the angiotensin-converting enzyme lisinopril were compared with those of the calcium antagonist nifedipine in 162 non-insulin-dependent diabetic hypertensive patients for a 24-week period. In 83 and 79 patients, respectively, lisinopril and slow-release nifedipine produced similar reductions in blood pressure (systolic/diastolic: -16/-13 mmHg supine and -14/-11 mmHg standing after lisinopril; -15/-12 mmHg supine and -14/-11 mmHg standing nifedipine). Fasting and post-prandial plasma glucose, glycosylated haemoglobin and plasma lipids appeared to be unaffected by either agent. Also, 28% of the patients on lisinopril and 30% of those on nifedipine presented microalbuminuria. Both drugs induced a reduction in the albumin excretion rate (AER). The geometric mean x:tolerance factor of the reduction in AER among the 23 microalbuminuric patients on lisinopril (-10.0 x:1.3 micrograms/min) was greater, though not significantly so, than that observed in the 26 on nifedipine (-0.9 x 1.2 micrograms/min). Moreover, lisinopril appeared to be better tolerated than nifedipine in our study population. Microalbuminuria is an important risk factor for cardiovascular mortality in non-insulin-dependent diabetic patients as well as in the general population. To what extent a reduction in the AER could ameliorate diabetic patients is, at present, unknown. Finally, both lisinopril and nifedipine showed a similar antihypertensive effect in these patients which was not associated with significant differences in plasma glucose, insulin or lipid concentrations. The clinical consequences of the insignificant differences in AER remain unclear.",1995.0,0,0
1815,8595643,Efficacy and tolerability of losartan versus enalapril alone or in combination with hydrochlorothiazide in patients with essential hypertension.,R Townsend; B Haggert; C Liss; J M Edelman,"The antihypertensive effects and the tolerability of losartan and enalapril given alone or in combination with hydrochlorothiazide (HCTZ) were compared in a multicenter, double-blind, randomized, parallel-group, 16-week clinical trial. The study consisted of a 4-week placebo washout phase and a 12-week active treatment phase. Patients with mild-to-moderate, uncomplicated essential hypertension were considered for participation in the study. To enter the treatment phase of the study, a mean sitting diastolic blood pressure (SiDBP) > or = 95 and < or = 115 mm Hg was required. Patients received either 50-mg losartan once daily or 5-mg enalapril once daily at randomization. The dose of enalapril could be titrated to 10 mg after 4 weeks and 25 mg of HCTZ could be added after 8 weeks, based on measurements of SiDBP at clinic visits. The dose of losartan remained at 50 mg; 12.5 mg of HCTZ could be added after 8 weeks. Changes in the treatment regimen at each step were required if SiDBP remained > or = mm Hg. Doses of the diuretic were chosen based on commercially available forms of the test agents in combination with HCTZ. Trough blood pressure, heart rate, and safety parameters were measured at 4-week intervals during the treatment phase of the study. Significant reductions in mean SiDBP and mean sitting systolic blood pressure (SiSBP) were achieved at all time points (4, 8, and 12 weeks) with both treatments. No significant differences between treatment groups for mean changes in SiDBP or SiSBP were observed overall. At study end, patients receiving the losartan regimen had a mean reduction in SiDBP of 10.3 mm Hg, whereas patients in the enalapril regimen had a mean reduction of 9.8 mm Hg. Likewise, the percentage of patients reaching goal blood pressure reduction was not significantly different between groups. The mean reduction in SiDBP-- but not SiSBP--in black patients was slightly greater in the losartan group than in the enalapril group (SiDBP, 10.0 mm Hg losartan vs 8.0 mm Hg enalapril; P = 0.02). Similarly, losartan patients aged 65 years and older had a slightly greater decrease in SiDBP than comparable enalapril patients (12.7 mm Hg vs 8.7 mm Hg; P = 0.03). The importance of these differences between subgroups must be clarified by additional studies. Overall, both treatments were well tolerated. A regimen of losartan alone or in combination with HCTZ was effective in treating patients with essential hypertension and was comparable to a regimen of enalapril alone or in combination with HCTZ. However, treatment with losartan was associated with a lower incidence of cough.",1995.0,0,0
1816,8596594,Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.,G Maschio; D Alberti; G Janin; F Locatelli; J F Mann; M Motolese; C Ponticelli; E Ritz; P Zucchelli,"Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases. In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-line serum creatine concentration or the need for dialysis. At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group. Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.",1996.0,0,0
1817,8597776,How adverse drug reactions can play a role in innovative drug research.,F Rikken; R Vos,"We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.",1995.0,0,0
1818,8600607,"A comparison of the metabolic effects of captopril and atenolol on glucose, insulin and lipoproteins in patients with mild-to-moderate essential hypertension.",F J Maritz; H F Weich; H S Schoeman,"The metabolic effects of captopril 25 mg twice daily and atenolol 50 mg daily on glucose, insulin and lipids were compared in 83 otherwise healthy mild-to-moderate hypertensive between the ages of 25 and 60 years in a randomised double-blind trial. Hourly glucose and insulin levels were measured during a 2-hour 75 g oral glucose tolerance test at baseline and after 12 weeks of treatment. Lipid profiles including total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, HDL2, HDL3, triglycerides, apoprotein (Apo)A1, ApoB, and Apo(a) were obtained before and after the treatment period. Blood pressure decreased significantly and equivalently in both treatment groups. The glucose and insulin levels and glucose x insulin product at 2 hours after the glucose load increased after 12 weeks of treatment with atenolol compared with the baseline values, but these parameters all decreased after the treatment period with captopril compared with their baseline values. These results indicate an improvement in insulin sensitivity with captopril and a deterioration with atenolol. HDL-cholesterol and HDL3 decreased in the atenolol group but increased in the captopril group. We conclude that captopril has more favourable effects than atenolol on glucose, insulin and lipid metabolism in the treatment of mild-to-moderate hypertension.",1995.0,0,0
1819,8605634,"The HOPE (Heart Outcomes Prevention Evaluation) Study: the design of a large, simple randomized trial of an angiotensin-converting enzyme inhibitor (ramipril) and vitamin E in patients at high risk of cardiovascular events. The HOPE study investigators.",,"To describe the design of the HOPE (Heart Outcomes Prevention Evaluation) study. Description of the key design features of HOPE, a large, simple randomized trial of two widely applicable treatments--ramipril, an angiotensin-converting enzyme inhibitor; and vitamin E, a naturally occurring antioxidant vitamin--in the prevention of myocardial infarction, stroke or cardiovascular death. Two-hundred and sixty-seven hospitals, physician offices and clinics in Canada, the United States, Mexico, Europe and South America. Over 9000 women and men aged 55 years and above at high risk for cardiovascular events such as myocardial infarction and stroke were recruited over 18 months. A 2X2 factorial design with ramipril and vitamin E with follow-up for up to four years. HOPE will be one of the largest trials of two new interventions to prevent myocardial infarction, stroke or cardiovascular death in high risk patients. The results of HOPE will have direct public health impact and are likely to be readily incorporated into clinical practice. Key design features of HOPE are inclusion of individuals at high risk of cardiovascular disease, inclusion of a substantial proportion of patients with diabetes (36%) and women (27%), and detailed substudies to provide data on mechanisms of benefit.",1996.0,0,0
1820,8606276,"Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT)",P Carson; G Johnson; R Fletcher; J Cohn,"This analysis sought to evaluate the clinical characteristics and outcome in heart failure with mild systolic dysfunction. Although heart failure with mild systolic dysfunction occurs commonly, this is an understudied area because clinical trials have usually excluded patients with ejection fraction >35%. The 422 patients with left ventricular ejection fraction </=35% were compared with 172 with a left ventricular ejection fraction >35% in the Vasodilator in Heart Failure Trial (V-HeFT I), whereas in V-HeFT-II 554 patients with a left ventricular ejection fraction </=35% were compared with 218 patients with a left ventricular ejection fraction >35% for mortality and clinical care. For a left ventricular ejection fraction >35%, treatment with hydralazine/isosorbide dinitrate was compared with prazosin and placebo therapy in V-HeFT I, and hydralazine/isosorbide dinitrate was compared with enalapril in V-HeFT II for mortality, clinical course and change in physiologic variables: ejection fraction, plasma norepinephrine levels, ventricular tachycardia and echocardiographic variables. In both studies, patients with a left ventricular ejection fraction >35% differed principally in hypertensive history, higher functional capacity and radiographic and echocardiographic cardiac dimension from patients with a left ventricular ejection fraction </=35%, and plasma norepinephrine levels differed in V-HeFT II (p < 0.01). Patients with a left ventricular ejection fraction >35% had a lower cumulative mortality than those with a left ventricular ejection fraction </=35% (p < 0.0001) and less frequent hospital admissions for heart failure (p < 0.014, V-HeFT I; p < 0.005, V-HeFT II). Although cumulative mortality and morbidity did not differ between treatment groups in V-HeFT I, enalapril decreased overall mortality versus hydralazine/isosorbide dinitrate (p < 0.035) in V-HeFT II. For physiologic variables in V-HeFT II, enalapril decreased ventricular tachycardia at follow-up (p < 0.05). In V-HeFT, heart failure with mild systolic dysfunction was associated with different characteristics and a more favorable prognosis than heart failure with more severe systolic dysfunction. Enalapril decreased overall mortality and sudden death compared with hydralazine/isosorbide dinitrate. Prospective trials are needed to address therapy for heart failure with mild systolic dysfunction.",1996.0,0,0
1821,8606538,Comparative effects of diltiazem and lisinopril on left ventricular structure and filling in mild-to-moderate hypertension.,J T van Leeuwen; A J Smit; J F May; B S ten Berge; H P Hamer; T K Havinga; F H Schuurman; E van der Veru; K I Lie; H Wesseling,"The comparative effects on echocardiographically determined left ventricular (LV) mass and pulsed Doppler derived indexes of LV diastolic filling were studied in previously untreated hypertensive patients after 6 months of treatment with diltiazem 300 mg once daily (o.d.) (n = 16), and lisinopril 20 mg o.d. (n = 20). LV mass index decreased in the lisinopril group (from 98 to 96 g/m2; mean difference after 6 months of treatment with diltiazem-lisinopril was 13.7 g/m2 [95% confidence interval (CI) 0.8 to 26.6, p < 0.05]. In both groups diastolic filling parameters improved, but there was no statistically significant difference between the groups. Both treatment regimens showed a similar decrease in office and maximal exercise systolic blood pressure (SPB). Ambulatory daytime BP was lower after lisinopril treatment (from 147/96 to 126/83 mm Hg) than after diltiazem treatment (from 142/93 to 135/87 mm Hg); mean difference between diltiazem and lisinopril after 6 months of treatment was 9.7 (95% CI 3.4 to 16.0, p < 0.05)/9.4 (95% CI 2.5 to 16.3, p < 0.05) mm Hg. Nighttime BP decreased from 129/81 to 113/70 mm Hg in the lisinopril group, but not in the diltiazem group (from 125/79 to 122/77 mm Hg); mean difference between diltiazem and lisinopril after 6 months of treatment was 4.4 (95% CI - 0.2 to 8.9)/6.6 (95% CI 1.1 to 12.0) mm Hg. Changes in diastolic filling parameters were significantly correlated with changes in LV mass index in the lisinopril group, suggesting that the improvements in diastolic filling in the diltazem group may be partly due to an effect on factors other than LV mass.",1995.0,0,0
1822,8607401,Effect of quinapril or metoprolol on heart rate variability in post-myocardial infarction patients.,A G Kontopoulos; V G Athyros; A A Papageorgiou; G V Papadopoulos; M J Avramidis; H Boudoulas,"The effect of quinapril or metoprolol on heart rate variability (HRV) indexes was studied in patients who had recovered from acute myocardial infarction. Patients with stable coronary artery disease and normal volunteers were used as controls. Sixty patients with uncomplicated myocardial infarction (aged 32 to 74 years [mean 56.7]) were randomized to quinapril (n = 25), metoprolol (n = 25), and placebo (n = 10). HRV was assessed 5 days (baseline) and 35 days after the onset of acute myocardial infarction. After the baseline studies, the post-myocardial infarction patients were treated with metoprolol (50 to 100 mg/day), quinapril (5 to 10 mg/day), or placebo. Twenty patients with stable coronary artery disease and 20 healthy volunteers, age- and sex-matched to myocardial infarction patients, were used as controls. Compared with placebo, quinapril and metoprolol increased HRV indexes significantly 35 days after the onset of myocardial infarction. HRV indexes were not statistically different between the 2 treatment groups. At baseline and after therapy, HRV was similar in patients with anterior or inferior wall myocardial infarction. HRV 35 days after the onset of myocardial infarction was not different from HRV in patients with stable coronary artery disease, but was decreased when compared with that in normal volunteers. Data suggest that quinapril has the same beneficial effect on HRV indexes as metoprolol in patients who have recovered from uncomplicated acute myocardial infarction.",1996.0,0,0
1823,8607723,Efficacy and tolerance of antihypertensive treatment in men and women with stage 1 diastolic hypertension. Results of the Treatment of Mild Hypertension Study.,C E Lewis; A Grandits; J Flack; R McDonald; P J Elmer,"To explore the sex-specific benefits and risks of treatment of stage 1 diastolic hypertension. Participants were African-American and white hypertensive men (n = 557) and women (n = 345) (age range, 45 to 69 years) with a diastolic blood pressure less than 100 mm Hg. Participants were randomized to treatment with placebo, chlorthalidone (15 mg/d), acebutolol hydrochloride (400 mg/d), doxazosin mesylate (2 mg/d), amlodipine besylate (5 mg/d), or enalapril maleate (5 mg/d); all were given nutritional-hygienic intervention. After 4 years, women who were randomized to lifestyle intervention only were less likely to be receiving step 1 therapy alone (placebo) than men who were randomized to placebo therapy (46% vs 66%, respectively, P < .01). There were significantly greater decreases in the mean systolic blood pressure in both men and women who were assigned to treatment with active drugs compared with those participants who were receiving placebo therapy; differences among treatments with active drugs were similar between men and women. Men experienced larger falls in their total and low-density lipoprotein cholesterol and triglyceride levels regardless of the treatment assignment than did women; however, there were no significant sex-by-treatment interactions. Quality-of-life indexes were generally improved with active drug treatment compared with placebo therapy in both sexes; there was a sex-by-treatment interaction for the general health index. The relative risk (RR) for combined clinical events was similar in women (RR, 0.64; 95% confidence interval [CI], (0.36 to 1.16) and in men (RR, 0.67; 95% CI, 0.40 to 1.14) who were assigned to treatment with all active drugs combined, compared with those who were receiving placebo therapy. In these exploratory analyses, men and women who were assigned to treatment with active drugs experienced greater and generally similar benefits from treatment than those participants who were assigned to lifestyle intervention only.",1996.0,0,0
1824,8609320,Ongoing clinical trials of angiotensin-converting enzyme inhibitors for treatment of coronary artery disease in patients with preserved left ventricular function.,C J Pepine,"At present there is considerable activity in the area of prevention of atherosclerosis-related events using angiotensin-converting enzyme inhibitors. Large trials have demonstrated significant reduction in cardiovascular morbidity and mortality with long-term use of angiotensin-converting enzyme inhibitors in patients with left ventricular dysfunction, heart failure or acute myocardial infarction. Reductions in acute ischemic events (e.g., myocardial infarction, unstable angina and need for early revascularization) were independent of ejection fraction and were greater than would be expected from the small reduction in blood pressure that occurred, suggesting that other patients with coronary artery disease may benefit from angiotensin-converting enzyme inhibitor therapy. This hypothesis is being tested in multiple double-blind, randomized, controlled clinical trials with durations of follow-up of 3 to 5 years that will involve approximately 30,000 patients. The trials vary with respect to patient population (e.g., normotensive vs. hypertensive, normolipidemic vs. hyperlipidemic, with vs. without diabetes mellitus), angiotensin-converting enzyme inhibitor used and outcome measures. When available, the results of these clinical trials could have very important implications for the role of long-term angiotensin-converting enzyme inhibitor therapy for preventing or delaying the development of atherosclerosis-related ischemic events.",1996.0,0,0
1825,8610874,Hypotension resistant to therapy with alpha receptor agonists complicating cardiopulmonary bypass: lithium as a potential cause.,D E Berkowitz; C Richardson; D A Elliott; J B Leslie; D A Schwinn,,1996.0,0,0
1826,8612440,Effect of chronic intermittent intravenous insulin therapy on antihypertensive medication requirements in IDDM subjects with hypertension and nephropathy.,T T Aoki; E O Grecu; J J Prendergast; M A Arcangeli; R Meisenheimer,"The prevalence of systemic hypertension is increased in patients with diabetes. In this prospective, randomized, crossover clinical trial, we assessed antihypertensive effects of chronic intermittent intravenous insulin therapy (CIIIT) on insulin-dependent diabetes mellitus (IDDM) subjects with hypertension and nephropathy by monitoring the amount of antihypertensive medication (AHM) required to maintain blood pressure (BP) < or = 140/90 mmHg. After a stabilization period, 26 hypertensive IDDM subjects were randomly assigned to a control or treatment phase for 3 months and then crossed over into the opposite phase for another 3 months. Addition of CIIIT during the treatment phase was the only procedural difference between the control and treatment phases. The AHM dosage requirements for maintenance of the baseline BP levels decreased significantly (46%; P < 0.0001) and linearly over time (P < 0.0058) during the treatment phase, while remaining essentially unchanged during the control phase. Our data suggest that CIIIT markedly improves BP control, as evidenced by the significantly reduced AHM dosage requirements in subjects with IDDM and hypertension, possibly through an improvement in vascular reactivity.",1995.0,0,0
1827,8612477,Guidelines for the drug treatment of hypertensive crises.,M M Hirschl,"Hypertensive crises are a group of clinicopathological entities in which rapid reduction of hypertension is necessary to prevent serious end-organ damage. The diagnosis and treatment plan depends on the identification of specific end-organ dysfunction. The goal of treatment is to limit the progression of end-organ damage in patients with hypertensive crises. Several potent antihypertensive drugs, such as sodium nitroprusside, labetalol and urapidil, are available to produce an immediate fall in blood pressure. The choice of the drug should be made on the basis of its pharmacodynamic properties, clinical effects, advantages and contraindications. Additionally, rapid reduction of blood pressure carries a considerable risk, if it is performed in an uncontrolled manner, leading to further end-organ damage. The aim of the treatment is not just to reduce blood pressure, but to do so with minimal adverse effects while preserving organ function.",1995.0,0,0
1828,8615323,"Angiotensin-converting enzyme inhibition, autonomic activity, and hemodynamics in patients with heart failure who perform isometric exercise.",R Willenbrock; C Ozcelik; K J Osterziel; R Dietz,"Effects of angiotensin-converting enzyme inhibition (ACEI) on autonomic responses and hemodynamics in patients with congestive heart failure (CHF) subjected to isometric exercise have not been studied. We tested whether acute ACEI might influence the effects of isometric exercise in patients with CHF. In the first part of the study we showed that isometric exercise increased blood pressure in the control group and in the CHF group, whereas cardiac output increased only in the control group. Stroke volume remained unchanged in the control group, whereas it decreased significantly in CHF group. We next analyzed the effect of acute ACEI (5 mg ramipril) on the decrease in cardiac output during isometric stress in patients with CHF. During isometric exercise mean blood pressure and heart rate increased similarly in both groups. However, cardiac output decreased during placebo by -0.48 +/- 0.12 L/min (p < 0.01) but not during ACEI. Spectral analysis of blood pressure showed an increase (p < 0.01) in the high-frequency parasympathetic component from 7.3% +/- 3.6% to 18.1% +/- 9.5% after ACEI. norepinephrine plasma levels increased after isometric stress in the placebo group, whereas other hormones did not change. ACEI prevented the norepinephrine increase after isometric stress. Thus the decrease in cardiac output during isometric exercise in patients with CHF was prevented by acute ACEI. The effect of ACE inhibition may be related to reduced sympathetic activity.",1996.0,0,0
1829,8621193,Improvement of coronary flow reserve after long-term therapy with enalapril.,W Motz; B E Strauer,"To date, no clinical study shows an improvement in coronary flow reserve due to long-term antihypertensive therapy. in view of the contribution of the renin-angiotensin system to the process of hypertensive remodeling of the heart and coronary circulation, angiotensin-converting enzyme (ACE) inhibitors might act as cardioreparative drugs in arterial hypertension. Accordingly, our objective in this investigation was to examine under clinical conditions to what extent long-term antihypertensive treatment with an angiotensin-converting enzyme inhibitor improved the diminished coronary flow reserve in hypertensive patients with microvascular angina pectoris. For the purpose of comparison, we also treated a normotensive control group of 6 patients with hypertrophic nonobstructive cardiomyopathy. Fifteen hypertensive individuals (10 men, 5 women; age, 58 +/- 6 years) were treated with enalapril (10 to 20 mg/d; mean, 16.7 +/- 4.9 mg/d) for 11 to 13 months. At the end of the treatment period, systolic pressure decreased from 178 +/- 14 to 137 +/- 12 mm Hg and diastolic pressure from 102 +/- 11 to 86 +/- 4 mm Hg under ambulatory conditions. Left ventricular muscle mass index decreased by 8%, from 149 +/- 32 to 137 +/- 28 g/m2 (P < .05). Maximal coronary blood flow after dipyridamole was increased by 43%, from 181 +/- 69 to 258 +/- 116 mL/min per 100 g (P < .001), and minimal coronary vascular resistance was diminished by 29%, from 0.66 +/- 0.23 to 0.47 +/- 0.24 mm Hg x min x 100g x mL-1 (P < .001) after enalapril treatment. Consequently, the calculated coronary reserve increased from 2.2 +/- 0.6 to 3.3 +/- 1.2 (P < .001). After enalapril therapy, the functional class of angina pectoris according to the Canadian classification system had changed from 2.5 +/- 0.6 to 1.5 +/- 0.6 (P < .01). The maximal working capacity had increased from 23.775 +/- 3.970 to 26.255 +/- 4.598 J (mean +/- SE, P < .05). The maximal ST-segment depression at maximal work-load was reduced from 0.18 +/- 0.02 to 0.06 +/- 0.02 (mean +/- SE, (P < .01). In summary, long-term therapy with the angiotensin-converting enzyme inhibitor enalapril must be considered a cardioreparative treatment with respect to the coronary microcirculation in hypertensive heart disease.",1996.0,0,0
1830,8622245,Long-term effects on plasma lipids of diet and drugs to treat hypertension. Treatment of Mild Hypertension Study (TOMHS) Research Group.,R H Grimm; J M Flack; G A Grandits; P J Elmer; J D Neaton; J A Cutler; C Lewis; R McDonald; J Schoenberger; J Stamler,"- To compare long-term plasma lipid changes among 6 antihypertensive treatment interventions for stage I (mild) hypertension. - Multicenter, randomized, double-blind, parallel-group clinical trial. - Four academic clinical research units in the United States. - A total of 902 men and women, aged 45 to 69 years, with stage I diastolic hypertension (diastolic blood pressure <100 mm Hg), recruited from 11914 persons screened in their communities. - Participants were randomized to 1 of 6 treatment groups: (1) placebo, (2) beta-blocker (acebutolol), (3) calcium antagonist (amlodipine), (4) diuretic (chlorthalidone), (5) alpha1-antagonist (doxazosin), and (6) angiotensin-converting enzyme inhibitor (enalapril). All groups received intensive lifestyle counseling to achieve weight loss, dietary sodium and alcohol reduction, and increased physical activity. - Changes in plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides from baseline to annual visits through 4 years. - Mean changes in all plasma lipids were favorable in all groups. The degree of weight loss with fat-modified diet and exercise was significantly related to favorable lipid changes. Significant differences (P<.01) among groups for average changes during follow-up in each lipid were observed. Decreases in plasma total cholesterol and LDL cholesterol were greater with doxazosin and acebutolol (for plasma total cholesterol, 0.36 and 0.30 mmol/L [13.8 and 11.7 mg/dL], respectively), less with chlorthalidone and placebo (0.12 and 0.13 mmol/L [4.5 and 5.1 mg/dL], respectively). Decreases in triglycerides were greater with doxazosin and enalapril, least with acebutolol. Increases in HDL cholesterol were greater with enalapril and doxazosin, least with acebutolol. Significant relative increases in plasma total cholesterol with chlorthalidone compared with placebo at 12 months were no longer present at 24 months and beyond, when mean plasma total cholesterol for the chlorthalidone group fell below baseline. Analyses of participants continuing to receive chlorthalidone throughout the 4 years of follow-up indicated this was not due solely to an increasing percentage of participants changing or discontinuing use of medication during follow-up. - Weight loss with a fat-modified diet plus increased exercise produces favorable long-term effects on blood pressure and all plasma lipid fractions of adults with stage I hypertension; blood pressure reduction is enhanced to a similar degree by addition of a drug from any one of 5 classes of antihypertensive medication. These drugs differ quantitatively in influencing the degree of long-term favorable effects on blood lipids obtained with nutritional-hygienic treatment.",2001.0,0,0
1831,8623766,Fourier transform infrared microscopy identification of crystal deposits in tissues: clinical importance in various pathologies.,L Estepa-Maurice; C Hennequin; C Marfisi; C Bader; B Lacour; M Daudon,"The presence of crystal deposits in tissues is associated with various pathologies. Sometimes their identification is useful for understanding the etiology or the mechanism of the disorder. The authors applied Fourier transform infrared microscopy (FTIRM) to the molecular characterization of crystal deposits in tissue and compared the results with those provided by histologic studies using polarized light microscope and histochemical reactions. Twenty-five biopsies were investigated. In 10 cases, the results were in good agreement. In 15 cases only FTIRM could precisely identify the crystals. In three cases, this technique allowed to characterize dihydroxyadenine crystals revealing an adenine phosphoribosyltransferase deficiency previously undiagnosed in patients presenting severe chronic renal failure. In three cases, crystal deposition was related to drug therapy. In other cases, crystal identification was useful to understand the mechanism of the pathology responsible for tissue damage and crystal deposition.",1996.0,0,0
1832,8626878,"Comparison of amlodipine and benazepril monotherapy to amlodipine plus benazepril in patients with systemic hypertension: a randomized, double-blind, placebo-controlled, parallel-group study. The Benazepril/Amlodipine Study Group.",W H Frishman; C V RAM; F G McMahon; S G Chrysant; A Graff; J W Kupiec; H Hsu,"A single-blind, run-in, randomized, double-blind, parallel-group, placebo-controlled comparison trial was conducted to assess the safety and efficacy of low-dose amlodipine 2.5 mg daily, low-dose benazepril 10 mg daily, and the combination of the two drugs at the same doses used once daily in patients (n = 401) with mild to moderate (stages I and II) systemic hypertension. Both monotherapy regimens were shown to significantly reduce both systolic and diastolic blood pressure compared with baseline placebo values, and the combination regimen was shown to be superior in lowering systolic and diastolic blood pressure when compared with either of the monotherapy regimens. The combination therapy also resulted in a greater percentage of patients having successful clinical response in mean sitting diastolic blood pressure. The amlodipine and benazepril regimen was also shown to be associated with a similar incidence of adverse experiences as the active monotherapy or placebo regimens, although the group given combination therapy appeared to have a lower incidence of edema than the group given amlodipine alone. Low-dose amlodipine (2.5 mg) plus benazepril (10 mg) provides greater blood-pressure-lowering efficacy than either monotherapy, and has an excellent safety profile.",1995.0,0,0
1833,8629540,Angiotensin-II receptor antagonists: a new class of antihypertensive agents.,M R Weir,"Pharmacologic agents that attenuate the influence of the renin-angiotensin-aldosterone system are known to reduce systemic arterial blood pressure through vasodilatory action and enhanced renal clearance of sodium and water. Angiotensin-converting enzyme inhibitors are known to antagonize the renin-angiotensin-aldosterone system through their ability to inhibit conversion of angiotensin I to angiotensin II. A new class of antihypertensive agents, angiotensin-II receptor antagonists, has recently been developed. These agents specifically block the receptor for angiotensin II, thereby limiting angiotensin II-mediated vasoconstriction and reducing aldosterone secretion. These effects result in a reduction in systemic arterial blood pressure through reduced vascular tone and enhanced sodium and water clearance. Clinical trials have demonstrated the efficacy of these agents in reducing blood pressure. These new antihypertensive agents also have uricosuric actions and are well tolerated, with a low incidence of cough and angioedema, side effects that are seen with angiotensin-converting enzyme inhibitors. Clinical trials are underway to see if these drugs will be useful in the treatment of diseases other than hypertension, such as congestive heart failure and chronic renal disease.",1996.0,0,0
1834,8629588,Influence of digitalis on left ventricular functional response to exercise in congestive heart failure.,C Morisco; A Cuocolo; M Romano; A Nappi; G Iaccarino; M Volpe; M Salvatore; B Trimarco,"This was a double-blind, placebo-controlled, crossover study designed to determine the influence of digitalis treatment on left ventricular (LV) response to physical exercise in patients with congestive heart failure (CHF). In 10 patients with CHF (ejection fraction 29 +/- 2%), LV function was assessed during upright bicycle exercise using an ambulatory radionuclide detector for continuous noninvasive monitoring of cardiac function. Exercise was performed during control conditions and after a 3-week treatment with digoxin (0.25 mg/day orally) or placebo. Ten normal volunteers matched for sex and age constituted the control group. In normals, exercise ejection fraction and end-diastolic volume increased (both p <0.001), while end-systolic volume decreased progressively (p <0.001). In control conditions, patients with CHF had a sharp increase in heart rate during exercise, while ejection fraction did not change; both end-diastolic and end-systolic volumes increased significantly (both p <0.001) during exercise. During digoxin treatment, heart rate response to exercise recorded in patients with CHF was comparable to that recorded in normal subjects. In addition, a significant increase in ejection fraction during exercise was detected (P <0.001), and the increase in end-systolic volume was significantly smaller than that observed in control conditions (p <0.05). When patients received placebo, the responses of LV function to exercise were comparable to those observed in control conditions. These findings demonstrate that digitalis has a favorable influence on LV functional adaptation to exercise in CHF.",1996.0,0,0
1835,8629631,Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients.,J J Sennesael; J G Lamote; I Violet; S Tasse; D L Verbeelen,"The effects of amlodipine and perindopril on renal hemodynamics and tubular function in cyclosporine-treated hypertensive renal allograft recipients were evaluated in a randomized, double-blind crossover fashion. Ten patients were studied after a 2-week placebo run-in and, after 8 weeks of active treatment, allowing a 2-week placebo washout between treatments. At the end of each period, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured as 51Cr-EDTA and 123I-hippuran clearance, respectively, and tubular function evaluated by the lithium clearance technique was determined. Both drugs maintained GFR and ERPF and lowered mean arterial pressure (MAP, mm Hg) to a similar extent (time x treatment, P = 0.466): amlodipine from 126.9 +/- 2.5 to 115.9 +/- 2.2; perindopril from 126.9 +/- 2.5 to 117.9 +/- 3.9 (time effect of all treatments together, P = 0.003). Accordingly, renal vascular resistance (RVR, mm Hg/mL/min/1.73 m2) was equally reduced (time x treatment, P = 0.955): amlodipine from 0.36 +/- 0.03 to 0.30 +/- 0.02; perindopril from 0.36 +/- 0.03 to 0.32 +/- 0.01 (time effect all treatments together, P = 0.043). Sodium clearance and fractional excretion of sodium were not affected by either drug. Output of fluid from the proximal tubules measured as clearance of lithium (CLi, mL/min) and uric acid (CUr, mL/min) was higher after amlodipine than after perindopril (CLi 19.1 +/- 2.1 v 16.5 +/- 1.7, P =0.036 and CUr 7.0 +/- 0.6 v 5.9 +/- 0.4, P = 0.007). As a consequence, after amlodipine, distal absolute reabsorption of sodium was higher (DARNa 2.57 +/- 0.28 v 2.19 +/- 0.22 mEq/min, P = 0.027) and serum uric acid was lower (5.9 +/- 0.3 v 6.7 +/- 0.4 mg/dL, P = 0.001) in comparison with perindopril. In cyclosporine-treated renal allograft hypertensives, amlodipine and perindopril lower blood pressure equally and reduce RVR to the same extent. Overall sodium excretion is not affected by either agent. Urate clearance is higher and serum uric acid lower on amlodipine as compared with perindopril.",1996.0,0,0
1836,8631039,Lipoprotein(a) and oxygen free radicals in survivors of acute myocardial infarction: effects of captopril.,P Søgaard; I C Klausen; J Rungby; O Faergeman; K Thygesen,"Long-term treatment of survivors of an acute myocardial infarction with angiotensin-converting enzyme inhibitors has a beneficial impact on their long-term outcome. We tested the hypothesis that captopril could reductively cleave the lipoprotein(a) molecule and in addition act as a scavenger of oxygen free radicals. In a double-blind trial, 20 patients were randomized to receive either captopril 50 mg daily or corresponding placebo. patients were followed for a period of 30 days. Blood samples were drawn prior to randomization and after 30 days of treatment. Plasma concentrations of lipoprotein(a) and malondialdehyde were evaluated. Captopril treatment produced a significant reduction in plasma content of lipoprotein(a) ( < 0.05) and at day 30 the plasma content of lipoprotein(a) was also significantly lower than that in the placebo group (p < 0.05). furthermore, on day 30 plasma concentrations of malondialdehyde, an indicator of oxidative damage, were significantly lower in the captopril group when compared to baseline values and corresponding placebo group values (p < 0.05). The observed effect of captopril treatment on lipoprotein(a) and malondialdehyde might be ascribed to the sulfhydryl group in the captopril molecule.",1996.0,0,0
1837,8631045,Tolerability and efficacy of antihypertensive treatment with cilazapril in general practice.,J R Rosenthal; U Osowski,"Data on the safety, tolerability and efficacy of the new angiotensin-converting enzyme (ACE) inhibitor cilazapril were obtained in a multicenter observational study carried out in a general practice setting. A total of 33,841 hypertensive patients were prescribed cilazapril 2.5-5.0 mg per day and followed for an average of 109 days. 28,792 patients (85.1%) had a baseline diastolic blood pressure (BP) > or = 95 mm Hg. 24,649 patients received cilazapril alone. during the observation period the mean blood pressure of these patients fell from 177/105 to 148/87 mm Hg (an average drop delta of 29/18 mm Hg). The response rate (diastolic BP < or = 90 mm Hg and delta > or = 10 mm Hg) in these patients was 78.9%. Adverse events were reported by 7.3% of all patients. In all, 3.7% of patients discontinued cilazapril treatment because of side effects. The most frequently reported side effect (1.5% of cases) was the dry cough typical of ACE inhibitors. The doctors judged the efficacy of cilazapril as very good or good in 89.8% of cases and its tolerability as very good or good in 94.6%. This reflects the good compliance (regular tablet intake) of more than 90% of patients.",1996.0,0,0
1838,8631567,Effect of atrial septal defect created during balloon mitral valvuloplasty on calculation of cardiac output and mitral valve area.,A Kapoor; K M Krishnamoorthy; S Radhakrishnan; S Shrivastava,"We studied the effect of atrial septal defect (ASD), produced during transseptal puncture, on estimation of cardiac output (CO) and mitral valve area (MVA), after successful balloon mitral valvuloplasty (BMV) using the Inoue balloon in 20 patients. Oximetry run, pressure gradients, thermodilution CO and MVA were measured initially while temporarily occluding the ASD by partially inflating the Inoue balloon catheter. Measurements were repeated after withdrawing the balloon catheter into the right atrium. Post-BMV cardiac output and MVA were similar in both the situations (4.52 +/- 1.37 L/min vs 4.50 +/- 1.19 L/min; 1.89 +/- 0.4 cm2 vs 1.93 +/- 0.38 cm2 respectively, p = ns). Only 2 patients showed a step up at atrial level on oximetry (9% and 16% respectively) but did not have significantly different CO or MVA, both with ASD occluded or otherwise. We conclude that the magnitude of ASD created during BMV by Inoue balloon technique is small and does not significantly affect the estimation of CO or MVA if the septal puncture is done in the fossa ovalis area.",1996.0,0,0
1839,8634167,Lisinopril and diltiazem reduce left ventricular mass without changing blood pressure in normotensive subjects with exaggerated blood pressure response to exercise.,J Polónia; L Martins; F Macedo; D B Faria; L Simões; F Brandão; M C Gomes,"To determine whether high left ventricular mass may be reduced by antihypertensive drugs in normotensives with exaggerated blood pressure response to exercise as it occurs in hypertensive patients. Randomized, single blind, controlled parallel study evaluating the influence of placebo; lisinopril 20 mg/day, diltiazem 180 mg/d for 5-6 months on left ventricular mass (LVM), evaluated by echo and on ""casual"" and 24-h ambulatory blood pressure (24-h BP) in normotensive subjects with exaggerated blood pressure response to exercise (Group I) and in weight--and age--matched mild-moderated hypertensive patients (Group II), all with high left ventricular mass. Placebo, lisinopril and diltiazem, were administered for 5-6 months in respectively 8+9+9 subjects of Group I and 8+9+10 patients in Group II. Placebo did not change either LVM index or 24-h BP values in Group I and Group II. Diltiazem and lisinopril reduced LVM index in both Groups I and II but 24-h BP values were only reduced in Group II. Lisinopril appeared to be more potent than diltiazem on LVM regression. Slopes of LVM index regression were not different between Groups I and II for each drug. Drug-induced changes of LVM index did not correlate with blood pressure changes. Drug-induced regression of LVM may be achieved in man (Group I) without any reduction of blood pressure. This may be explained by interference with growth-promoting systems other than with cardiac unloading. Also, the similar pattern of LVM regression that was observed in both Groups I and II suggests that similar underlying mechanisms may be involved in the LVH regression in these two populations.",1996.0,0,0
1840,8636558,"Effectiveness and safety of diltiazem or lisinopril in treatment of hypertension after heart transplantation. Results of a prospective, randomized multicenter trail.",S C Brozena; M R Johnson; H Ventura; R Hobbs; L Miller; M T Olivari; B Clemson; R Bourge; R Quigg; R M Mills; D Naftel,"The purpose of this study was to determine the effectiveness and safety of diltiazem or lisinopril for treatment of hypertension after heart transplantation. Systemic hypertension is common after heart transplantation, and to date there are no randomized, prospective multicenter treatment trials. Members of the Cardiac Transplant Research Database Group developed and implemented a prospective, randomized multicenter trial of the effectiveness and safety of diltiazem or lisinopril in the treatment of hypertension in cyclosporine-treated patients after heart transplantation. One hundred sixteen patients with hypertension (blood pressure > or = 140/90 mm Hg) after heart transplantation were randomized for > or = 3 months of treatment. Of 55 diltiazem-treated patients, 21 (38%) were responders (diastolic blood pressure < 90 mm Hg), 23 (42%) were nonresponders (diastolic blood pressure > or = 90 mm Hg), and 11 (20%) were withdrawn from the study. Of 61 lisinopril-treated patients, 28 (46%) were responders, 22 (36%) were nonresponders, and 11 (18%) were withdrawn. There was no difference in baseline characteristics or percent responders between the two groups. Systolic pressure decreased from 157 +/- 2.3 to 130 +/- 2.0 mm Hg (mean +/- 1 SEM) in the diltiazem-treated responders and from 153 +/- 2.1 to 127 +/- 2.7 mm Hg in the lisinopril-treated responders (p < 0.0001). Diastolic pressure decreased from 100 +/- 0.9 to 85 +/- 1.6 mm Hg in the diltiazem-treated responders and from 100 +/- 1.0 to 84 +/- 2.0 mm Hg in the lisinopril-treated responders (p < 0.0001). There were a total of 35 reported adverse events, 22 of which led to withdrawal of the patient from the study. All drug-related side effects were considered minor and resolved with discontinuation of the drug. These results indicate that both diltiazem and lisinopril are safe for treatment of hypertension after heart transplantation, although titrated monotherapy with either drug controlled the condition in < 50% of patients.",2001.0,0,0
1841,8636587,The effects of antihypertensive treatment on cognitive function: results from the HOPE study.,J M Starr; L J Whalley; I J Deary,"Hypertension is associated with impaired cognition, but it is unclear whether this impairment is reversible. We sought to evaluate the effect of blood pressure reduction on cognition. A randomized, double-blind trial. A single center, with assessments in subjects' domiciles. Community-screened subjects more than 69 years of age who had median diastolic pressures > 99 mm Hg and systolic pressures > 159 mm Hg or diastolic > 85 mm Hg and systolic > 179 mm Hg with Mini-Mental State Examination scores of 20 to 28. Subjects had not previously received antihypertensive treatment. Captopril 12.5 mg twice daily or bendrofluazide 2.5 mg daily for 24 weeks, preceded by a 2-week placebo phase. Cognition was evaluated by a psychometric test battery comprising Immediate and Delayed Logical Memory, Paired Associates recall, Raven's Progressive Matrices, Halstead Reitan Trail Making A, and the Anomalous Sentences Repetition Test. Eighty-one subjects (28 male, 53 female) were treated (41 captopril, 40 bendrofluazide). At entry, mean age was 76.1 years (range 70-84), mean blood pressure was 191 (160-230) mm Hg systolic, 101 (88-110) mm Hg diastolic, and mean MMSE score 26.1. A total of 69 subjects completed the trial. The 25th, 50th, and 75th percentiles of the difference between pretreatment and Week 24 blood pressures wer 15 mm Hg, 35 mm Hg, and 50 mm Hg (systolic) and 5 mm Hg, 10 mm Hg, and 19 mm Hg (diastolic). There were no significant differences in any psychometric test between captopril and bendrofluazide. The 19 subjects in the quartile that lowered their diastolic blood pressure most ( > or = 19 mm Hg) had improved scores on Anomalous Sentences (P = .012) and Paired Associates (P = .044) compared to the 19 subjects in the least blood pressure responsive quartile (fall < or = 5 mm Hg)s. The treatment of hypertension is not hazardous to cognitive function in older people with pre-existing cognitive impairment. Long-term adequate blood pressure control may reverse cognitive impairment associated with pre-existing hypertension.",1996.0,0,0
1842,8637188,Ambulatory blood pressure and left ventricular changes during antihypertensive treatment: perindopril versus isradipine.,A M Grandi; M Bignotti; G Gaudio; P Zanzi; L Guasti; A Venco,"Using digitized M-mode echocardiograms and 24-h ambulatory blood pressure (BP) monitoring, we compared the effects on left ventricle (LV) and BP of 6-month treatment with a calcium antagonist or an angiotensin-converting enzyme (ACE) inhibitor in 36 hypertensive patients with LV hypertrophy (group 1, 18 subjects treated with sustained-release isradipine; group 2, 18 subjects treated with perindopril). At the basal evaluation, the two groups had comparable BP and LV parameters. After treatment, both groups showed a similar and significant reduction in 24-h, day- and night-systolic and diastolic BP (SBP, DBP). The reduction in LV mass index was greater (p < 0.01) in group 2. In group 1, percentage of decrease of LV mass correlated significantly with percentage of decrease in 24-h and daytime BP; this was not true of group 2. Together with the reduction in LV hypertrophy, there was a significant increase of peak lengthening rate of LV diameter that was greater (p < 0.01) in group 1. Both drugs can reduce LV hypertrophy and improve diastolic function. The reduction of hypertrophy induced by perindopril appears to be partly independent of BP decrease and therefore partly related to a direct action of perindopril on the myocardium.",1995.0,0,0
1843,8638865,ACE inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension.,J R Petersen; H Drabaek; G Gleerup; J Mehlsen; L J Petersen; K Winther,"The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied. Thirteen patients with mild to moderate essential hypertension completed this randomized, double-blinded, placebo-controlled, crossover study. After a three-week run-in period the patients entered three periods lasting four weeks each, wherein they were treated with placebo, spirapril, or hydrochlorothiazide. Blood pressure, hemodynamic variables (stroke volume, heart rate, cardiac output, index of contractility, and systemic vascular resistance), echocardiography (left ventricular mass), and Doppler-derived atrial to early (A/E)-ratio velocity time integrals (VTI) were measured at the end of each of the four periods. Spirapril lowered the A/E-ratio VTIs (0.57, 0.12-1.00) (P < 0.02) as compared with both placebo (0.80, 0.50-2.67) and hydrochlorothiazide (0.83, 0.44-1.25), and the drug normalized the A/E-ratio VTI in those patients with elevated values. The hemodynamic variables, left ventricular mass, and end-systolic wall stress were unchanged during all three treatments. There were no significant changes in mean blood pressure during the treatment periods. These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension. It thereby seems able to improve left ventricular diastolic function. The effect is not dependent upon changes in hemodynamic variables, blood pressure, left ventricular mass, or end-systolic wall stress.",1996.0,0,0
1844,8640969,Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.,T Omland; A Aakvaag; V V Bonarjee; K Caidahl; R T Lie; D W Nilsen; J A Sundsfjord; K Dickstein,"Elevated plasma levels of atrial natriuretic peptide (ANP) and the N-terminal fragment of the ANP prohormone (N-ANP) are associated with decreased left ventricular function and decreased long-term survival after acute myocardial infarction (AMI). Previous data suggest that plasma brain natriuretic peptide (BNP) may increase proportionally more than plasma ANP after AMI and in chronic heart failure. The diagnostic and prognostic value of plasma BNP as an indicator of left ventricular dysfunction and long-term survival after AMI, relative to that of ANP and N-ANP, remain to be established. Venous blood samples for analysis of ANP, N-ANP, and BNP were obtained on day 3 after symptom onset from 131 patients with documented AMI. Left ventricular ejection fraction was determined by echocardiography in a subsample of 79 patients. Twenty-eight cardiovascular and 3 noncardiovascular deaths occurred during the follow-up period (median, 1293 days). All three peptides proved to be powerful predictors of cardiovascular mortality by univariate Cox proportional hazards regression analyses (ANP: P < .0001; N-ANP: P = .0002; BNP: P < .0001). In a multivariate model, plasma BNP (P = .021) but not ANP (P = .638) or N-ANP (P = .782) provided additional prognostic information beyond left ventricular ejection fraction. Logistic regression analysis showed that ANP (P = .003) and N-ANP (P = .027) but not BNP (P = .14) were significantly associated with a left ventricular ejection fraction < or = 45%. These results suggest that plasma BNP determination provides important, independent prognostic information after AMI. Although plasma ANP appears to be a better predictor of left ventricular dysfunction, plasma BNP may have greater potential to complement standard prognostic indicators used in risk stratification after AMI because of its strong, independent association with long-term survival, enhanced in vitro stability, and simplicity of analysis.",1996.0,0,0
1845,8641115,"Effects of long-term enalapril treatment on persistent microalbuminuria in normotensive type 2 diabetic patients: results of a 4-year, prospective, randomized study.",T Sano; N Hotta; T Kawamura; H Matsumae; S Chaya; H Sasaki; M Nakayama; T Hara; S Matsuo; N Sakamoto,"The beneficial effect of long-term treatment with an angiotensin-converting enzyme (ACE) inhibitor on urinary microalbumin excretion (UAE) and renal function was investigated in a 4 year, randomized prospective study in normotensive patients with non-insulin-dependent (Type 2) diabetes mellitus. Sixty-two normotensive patients with Type 2 diabetes mellitus and microalbuminuria but normal renal function were randomized to receive either enalapril 5 mg day-1 or no treatment. In the enalapril-treated patients, UAE was reduced from 115.4 +/- 80.1 to 95.6 +/- 61.7 mg 24 h-1 after 12 months (p < 0.05) and to 75.3 +/- 44.8 mg 24 h-1 after 48 months (p < 0.001). In the untreated group, UAE increased slowly from 93.9 +/- 69.9 to 150.0 +/- 144.5 mg 24 h-1 after 48 months. No changes in creatinine clearance, blood pressure or HbA1C were seen in either group during the 4-year period. In normotensive Type 2 diabetic patients with early stage of diabetic microalbuminuria. This effect is long-lasting and probably independent of the antihypertensive action of the drug.",1996.0,0,1
1846,8641320,"Humoral and haemodynamic effects of idrapril calcium, the prototype of a new class of ACE-inhibitors, in essential hypertensive patients.",S Taddei; L Ghiadoni; P Mattei; I Sudano; P Duranti; S Favilla; A Virdis; A Romagnoli; M Criscuoli; A Coppini,"Idrapril is the prototype of a new class of ACE inhibitors, characterised by the presence of a hydroxdmic group. Six untreated in-patients with essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blood pressure, heart rate, plasma idrapril serum UCE, active renin and angiotensin II were measured at timed intervals for 24 hours after dosing. Plasma idrapril reached a peak after 2 hours (3.01 microgm x ml(-1)), and by 12 hours the compound had almost disappeared (67 ng x ml(-1)). Derived t1/2 was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1) x min(-1) x ml] and angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 24 hours) pg x ml(-1)]. Compared to placebo, idrapril calcium significantly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg; placebo 147/100 mmHg), and upright blood pressure starting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essential hypertension, with a hypotensive action for up to 24 h.",1995.0,0,0
1847,8641743,A diuretic is more effective than a beta-blocker in hypertensive patients not controlled on amlodipine and lisinopril.,T F Antonios; F P Cappuccio; N D Markandu; G A Sagnella; G A MacGregor,"The combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist has a synergistic effect in patients with more severe hypertension. However, when this combination fails to control blood pressure, it is not clear which drug is then additive. The aim of this work was to study in a double-blind, randomized, crossover design the effect on blood pressure of the addition of either a thiazide diuretic (bendrofluazide, 5 mg once daily) or a beta-blocker (atenolol, 100 mg once daily) or placebo each for a month in hypertensive patients who are not adequately controlled on the combined treatment of amlodipine 5 mg once daily and lisinopril 5 mg twice daily. Eighteen patients with a supine diastolic pressure of more than 90 mm Hg after at least 1 month on the combined treatment of amlodipine and lisinopril were enrolled in the study. The results show that in patients whose blood pressures are not controlled by the combination of amlodipine and lisinopril, the addition of bendrofluazide 5 mg once daily causes a significant fall in blood pressure compared with placebo and a significantly greater fall than 100 mg atenolol once daily.",1996.0,0,0
1848,8642189,Prostacyclin biosynthesis in essential hypertension before and during treatment.,J M Ritter; S E Brett; J D Woods; N Benjamin; P D Stratton; S E Barrow,"Protacyclin biosynthesis was investigated in 133 untreated newly diagnosed patients with uncomplicated essential hypertension. Urinary excretion of 6-oxo-prostaglandin F1 alpha and of 2,3-dinor-6-oxo-prostaglandin F1 alpha, stable breakdown products of prostacyclin, was measured following a 1 month run-in period. To determine whether lowering blood pressure (BP) influenced prostacyclin biosynthesis, 106 consenting patients with diastolic pressure 90-120 mm Hg were allocated randomly to treatment with bendrofluazide, metoprolol, quinapril or amlodipine in an open parallel group design. Dose was increased to reduce diastolic arterial pressure to <90 mm Hg. Terazosin was added if this target BP was not achieved, and its dose increased if necessary. Urinary excretion rates of prostaglandins were measured after 1 year in patients in whom the target diastolic pressure was achieved. Mean arterial pressure varied from 106-168 mm Hg in untreated patients and excretion of both prostacyclin-derived products varied from <5 to >350 ng/g creatinine. Arterial pressure and prostaglandin excretion were not significantly correlated. In 57 patients in whom target pressure was achieved, BP before treatment was 166 +/- 2/100 +/- 1 at baseline and 144 +/- 2/86 +/- 1 mm Hg at 1 year. Excretion rates of each prostacyclin-derived product were similar before treatment and at 1 year, with no significant differences between the drugs. These findings do not support the hypothesis that deficient prostacyclin biosynthesis contributes to the pathogenesis of essential hypertension, or that increased prostacyclin biosynthesis plays a part in the response to treatment with antihypertensive medication.",1996.0,0,0
1849,8642191,Antihypertensive effects of trandolapril and nitrendipine in the elderly: a controlled trial with special emphasis on time effect profiles.,F Zannad; L Vaur; C Dutrey-Dupagne; N Genes; P Clerson,"The aim of this double-blind randomized study was to compare the antihypertensive effects of trandolapril and nitrendipine in the elderly. After a 2-week placebo period, patients received either trandolapril 0.5 mg or nitrendipine 10 mg, once daily for 15 days. At the end of this period, according to a forced titration, the dose was increased to 2 mg of trandolapril or 20 mg of nitrendipine once daily for 2 months. Seventy-three hypertensive patients, aged 65 and over, entered the study. Demographic data and initial blood pressure (BP) level were comparable in the two groups. The antihypertensive effect, measured with a mercury sphygmomanometer, was assessed in 64 patients: SBP decreased by 18.6 +/- 12.1 mm Hg in the trandolapril (P < 0.001) and by 21.0 +/- 13.7 mm Hg in the nitrendipine group (P < 0.001); DBP decreased by 13.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and by 15.4 +/-8.2 mm Hg in the nitrendipine group (P < 0.001). No statistically significant difference was seen between the two treatment groups. A sub-group of 42 patients were evaluated by 24 h ambulatory BP monitoring. Mean 24 h ambulatory SBP/DBP decreases were 6.6 +/- 18.0/8.4 +/- 8.5 mm Hg in the trandolapril group (P < 0.001) and 5.7 +/- 11.1/7.2 +/-9.6 mm Hg in the nitrendipine group (P < 0.001). The differences between the two treatment groups were not statistically significant. The antihypertensive action of trandolapril was sustained throughout the 24 h period with a trough-to-peak ratio of 70.2% for SBP and 70.9% for DBP. Nitrendipine exerted its action mainly during the day, with a very modest antihypertensive effect during the night and early morning; its trough/peak ratio was 25.9% for SBP and 28% for DBP. The tolerance of both treatments were good; seven patients were withdrawn from the trial for adverse events (four in the nitrendipine group, three in the trandolapril group).",1996.0,0,0
1850,8644569,"Management of hypertension, Part II.",M Moser,"Although calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors are effective in lowering blood pressure, no long-term data show their effect on morbidity and mortality in hypertensive patients. They are suggested as alternative initial therapy in hypertensive patients. Short-acting calcium channel blockers are to be used with caution or not at all in the treatment of hypertension. Nonhydropyridine calcium channel blockers may reduce the incidence of second infarction but not congestive heart failure or mortality in patients with ischemic heart disease. The ACE inhibitors increase insulin sensitivity and decrease intraglomerular pressure. In combination with a diuretic, they are the preferred agents in the treatment of diabetic patients with hypertension, especially those with nephropathy. In both hypertensive and normotensive patients, ACE inhibitors reduce morbidity and mortality resulting from congestive heart failure in patients with poor left ventricular function who are also being treated with a diuretic and/or digitalis. They do not, however, reduce strokes or myocardial infarctions in hypertensive patients.",1996.0,0,0
1851,8644660,Heart rate variability in systemic hypertension.,H V Huikuri; A Ylitalo; S M Pikkujämsä; M J Ikäheimo; K E Airaksinen; A O Rantala; M Lilja; Y A Kesäniemi,"Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 +/- 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 +/- 19 vs 59 +/- 20 mss; p <0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (beta--0.20, p=0.01) and in the normotensive subjects (beta--0.28, p=0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.",1996.0,0,0
1852,8644661,Rationale and design of the third vasodilator-heart failure trial (V-HeFT III): felodipine as adjunctive therapy to enalapril and loop diuretics with or without digoxin in chronic congestive heart failure. V-HeFT III investigators.,W E Boden; S Ziesche; P E Carson; C H Conrad; D Syat; J N Cohn,"Therapy with angiotensin-converting enzyme inhibitors and nonselective vasodilators (hydralazine and isosorbide dinitrate) has become accepted treatment in patients with symptomatic, chronic congestive heart failure (CHF), and has been demonstrated in large clinical trials to ameliorate symptoms, improve exercise performance, and reduce cardiac mortality. Nevertheless, the management of patients with CHF remains a therapeutic challenge. The second Vasodilator-Heart Failure Trial (V-HeFT II) showed that the average 2-year mortality with enalapril (18%) was significantly lower than that with hydralazine-isosorbide dinitrate (25%) but, somewhat surprisingly, the nonspecific vasodilators produced significantly more improvement in exercise performance and left ventricular function. Such data suggest that improvement in symptoms, hemodynamics, and survival may not be afforded by the use of a single class of vasodilator therapy, but might be optimized by the combined use of different agents. This report describes the rationale and design of V-HeFT III, a multicenter, prospective, randomized, double-blind, placebo-controlled trial comparing the effects of chronic oral extended-release felodipine (felodipine ER) 2.5 to 5 mg twice daily, when added to a stable regimen of enalapril and loop diuretics, with or without digoxin, on exercise performance, morbidity, and mortality in patients with New York Heart Association functional class II to III CHF followed for a minimum of 12 weeks. Felodipine is a second-generation dihydropyridine calcium antagonist with a high degree of vascular selectivity which, in the doses used in this study, exerts its systemic arterial effect by decreasing peripheral vascular resistance without producing negative inotropic effects. The results of V-HeFT III may shed important light on the role of additive vasodilator therapy in the management of patients with CHF.",1996.0,0,0
1853,8645078,"Captopril-associated ""pseudocholangitis'. A case report and review of the literature.",A Nissan; R M Spira; D Seror; Z Ackerman,"Captopril, a competitive inhibitor of angiotensin-converting enzyme, is widely used in the treatment of hypertension and heart failure. Captopril is known to be associated with dermatologic, hematologic, and pulmonary adverse effects. However, hepatotoxicity is extremely rare. A patient with severe cholestatic jaundice induced by captopril is presented. On admission to the hospital, the patient was diagnosed and treated as having cholangitis. Review of the literature showed similar occurrences in other patients. Patients treated with captopril who develop ""atypical cholangitis"" should be suspected of having captopril-associated liver damage.",1996.0,0,0
1854,8651088,Effects of angiotensin-converting enzyme inhibitor alacepril in patients with stable effort angina during chronic isosorbide dinitrate treatment.,T Murohara; S Tayama; T Tabuchi; H Sumida; T Honda; K Hayasaki; H Yasue,"Nitrate tolerance has been reported to be reversed by certain types of angiotensin-converting enzyme (ACE) inhibitors. We examined whether alacepril, a new long-acting oral ACE inhibitor, has beneficial effects against exercise-induced angina in patients with stable effort angina after substantial isosorbide dinitrate (ISDN) treatment. Thirteen men with stable effort angina were treated with oral ISDN (80 mg/d) for >3 weeks. After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design. Alacepril significantly improved the exercise duration by 9.1% (p=0.03), the time to 1 mm ST-segment depression by 19% (p<0.01), and the maximal ST-segment depression by 33% (p=0.015) compared with placebo. Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo. Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients. In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment. These effects may be mediated by increased coronary blood flow.",1996.0,0,0
1855,8651094,Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure.,J Lubsen; D R Chadha; Y T Yotof; K Swedberg,"In 5 separate exercise capacity trials in similar patients with chronic congestive heart failure performed in Europe, the United States, and South Africa, 627 patients were randomized to ramipril and 428 to placebo. The dose of ramipril ranged from 1.25 to 20 mg/day. Follow-up was at 12 or 24 weeks. None of the trials were designed to assess efficacy with regard to clinical outcome. To assess in the combined experience whether there was an effect of ramipril on mortality, hospitalization, functional classification (New York Heart Association class), and exercise capacity, we pooled data from each trial and performed a mata-analysis. Of the patients randomized to ramipril and placebo, respectively, and based on intention to treat, 14 (2.2%) and 18 (3.8%) patients died (odds ratio 0.60, 95% confidence interval 0.28 to 1.29), and 59 (9.4%) and 67 (14.3%) patients died or were hospitalized (odds ratio 0.68, 95% confidence interval 0.46 to 1.00). The New York Heart Association class improved in 29% and 25% respectively, whereas 8% and 15% deteriorated (p=0.04, based on intention to treat; death and hospitalization considered as deterioration). In ranked comparisons based on intention to treat and with imputation of exercise time as 0 for patients who were unable to exercise because of death or who were hospitalized, exercise capacity was significantly improved by rampril. We concluded that rampiril is likely to have an effect on mortality, morbidity, and functional capacity in patients with chronic congestive heart failure similar to that of other angiotensin-converting enzyme inhibitors.",1996.0,0,0
1856,8656661,Effect of hydrochlorothiazide on the pharmacokinetics of enalapril in hypertensive patients with varying renal function.,A D Hersh; J G Kelly; M S Laher; M Carmody; G D Doyle,"An open, randomised, cross-over study was performed to investigate the pharmacokinetics of enalaprilat, administered as 20 mg enalapril both as monotherapy and in combination with hydrochlorothiazide (HCTZ 12.5 mg). Three groups of 6 hypertensive patients were enrolled [untreated diastolic blood pressure (DBP) 90-115 mm Hg]; normal renal function [glomerular filtration rate (GFR) > 81 ml min-1 1.73 m-2], mild renal impairment (GFR 51-80 ml min-1 1.73 m-2), and moderate renal impairment (GFR 31-50 ml min-1 1.73 m-2). The pharmacokinetics of enalaprilat and enalaprilat plus HCTZ correlated predictably with renal impairment with increased plasma concentrations and decreased urinary elimination at lower values of GFR. The coadministration of HCTZ had no significant effect on the pharmacokinetics of enalaprilat in any group. We conclude that although the pharmacokinetics of both enalaprilat and HCTZ are related to renal function, HCTZ has no significant effect on the pharmacokinetics of enalaprilat and that dosage adjustment for both regimens should be based on renal function.",1996.0,0,0
1857,8658779,"Erythropoietin, interleukin-3, interleukin-11, and GM-CSF in posttransplant erythrocytosis treated with enalapril.",R H Hu; P H Lee; C J Lee,,1996.0,0,0
1858,8658783,Preventive effect of enalapril on erythrocytosis after renal transplantation.,S R Rhee; S K Park; S K Kang; S H Kim; B H Cho; J H Kim,,1996.0,0,0
1859,8658784,Effect of captopril in the treatment of erythrocytosis after renal transplantation.,B Y Suh; J D Suh; K B Kwun,,1996.0,0,0
1860,8665975,Effects of lisinopril vs hydralazine on left ventricular hypertrophy and ambulatory blood pressure monitoring in essential hypertension.,R Fogari; A Zoppi; A Mugellini; F Tettamanti; P Lusardi; L Corradi,"In order to compare the long-term effects on ambulatory blood pressure and left ventricular hypertrophy of hydralazine and lisinopril we studied 30 patients, all males, still hypertensive (diastolic blood pressure > or = 95 mm Hg) despite combined beta-blocker/diuretic therapy and with echocardiographic evidence of left ventricular hypertrophy (left ventricular mass index > or = 1.31 g.m(-1)). They wer randomized to receive hydralazine slow release 50 mg/ chlorthalidone 12.5 mg) for 6 months. Casual blood pressure, non-invasive ambulatory blood pressure monitoring (ABPM), M-mode echocardiogram, plasma renin activity and plasma catecholamines were evaluated before the randomization and after 6 months of treatment. Both drugs significantly reduced casual as well as daytime systolic and diastolic blood pressure, without statistical differences between the two treatments. Lisinopril was significantly more effective than hydralazine in reducing night-time systolic and diastolic blood pressure. Plasma norepinephrine was significantly reduced by lisinopril and increased by hydralazine. Left ventricular mass was significantly reduced by lisinopril but not by hydralazine. The results of linear regression and multiple regression analysis suggested that the lisinopril-induced decrease in both day- and night-time blood pressure might account for the regression of left ventricular hypertrophy, whereas the lack of left ventricular hypertrophy regression during hydralazine treatment could be due mainly to the reflex sympathetic activation induced by the drug.",1995.0,0,0
1861,8673754,"Effects of lacidipine on peak oxygen consumption, neurohormones and invasive haemodynamics in patients with mild to moderate chronic heart failure.",R J de Vries; P H Dunselman; U G Chin Kon Sung; D J van Veldhuisen; H M Corbeij; W H van Gilst; K I Lie,"To evaluate the efficacy and safety of the second generation dihydropyridine calcium channel blocker lacidipine in patients with heart failure. Placebo controlled, parallel group, double blind study over 8 weeks. General community hospital in Breda, The Netherlands. A random sample was studied of 25 outpatients with symptoms of mild to moderate heart failure, despite treatment with diuretics, digoxin, and angiotensin converting enzyme inhibitors. Their mean age was 65 years, with mean left ventricular ejection fraction of 0.24 and a peak oxygen consumption of 14.4 ml/min/kg. Two patients dropped out on lacidipine, one patient on placebo. Treatment with lacidipine 4 mg once daily or placebo for eight weeks. Cardiopulmonary exercise testing, invasive haemodynamics, and plasma neurohormones. Treatment with lacidipine 4 mg once daily, as compared to placebo treatment, significantly improved peak oxygen consumption (P < 0.02), cardiac index (P < 0.01), and stroke volume (P < 0.03) paralleled by a decrease in systemic vascular resistance (P < 0.03) and arteriovenous oxygen content difference (P < 0.01). Plasma noradrenaline, plasma renin activity, and aldosterone values did not differ between lacidipine and placebo. This second generation dihydropyridine may be of value as an adjunct to standard treatment in congestive heart failure patients.",1996.0,0,0
1862,8673775,Rapid improvement of acute pulmonary edema with sublingual captopril.,R J Hamilton; W A Carter; E J Gallagher,"To test the hypothesis that sublingual captopril produces a more rapid improvement of acute pulmonary edema (APE) than does placebo, when added to a standard regimen of O2, nitrates, morphine, and furosemide. Prospective, randomized, double-blind, placebo-controlled clinical trial in an urban teaching hospital ED. Adults brought to the ED with APE were given captopril or placebo sublingually. Every 5 minutes a clinical APE distress score (APEX) was obtained. Over the first 40 minutes of treatment, the mean APEXs were significantly better for the patients given captopril [p < 0.001, F = 14.5, one-way (repeated-measures) analysis of variance (ANOVA)]. At 30 minutes, the patients given captopril had a mean APEX improvement of 43% (i.e., to 57% of initial distress); the group given the current standard regimen plus placebo improved only 25% (i.e., to 75% of initial distress; p = 0.03, multiway ANOVA). In addition, there was less respiratory failure necessitating mechanical ventilation in the captopril patients (9%) vs the placebo patients (20%), which did not achieve significance (p = 0.10, Fisher's exact test). In APE, the addition of sublingual captopril to the standard regimen of O2, nitrates, morphine, and furosemide produces more rapid clinical improvement than does the standard regimen alone.",1996.0,0,0
1863,8673930,Bradykinin-evoked sensitization of airway sensory nerves: a mechanism for ACE-inhibitor cough.,A J Fox; U G Lalloo; M G Belvisi; M Bernareggi; K F Chung; P J Barnes,"Cough accompanied by an increased sensitivity of the cough reflex is the most common symptom of inflammatory airway disease. This symptom is also frequently reported in patients receiving angiotensin-converting enzyme (ACE) inhibitors as therapy for heart failure or hypertension, although the underlying mechanism is unknown. We have investigated the possibility that the inflammatory peptide bradykinin, normally degraded by ACE, causes sensitization of airway sensory nerves and an enhancement of the cough reflex in conscious guinea pigs. Treatment of guinea pigs for two weeks with captopril led to an increased cough response to inhaled citric acid, which was prevented by concomitant treatment with the bradykinin receptor antagonist icatibant. A similar icatibant-sensitive enhancement of citric acid-evoked cough was seen in untreated animals after prior inhalation of bradykinin, although cough evoked by hypertonic saline was unaffected. In electrophysiological studies performed in vitro, responses of single vagal C fibers to capsaicin, applied to receptive fields of single-fiber units in the trachea, were also markedly increased after perfusion with bradykinin, whereas A delta fiber responses to hypertonic saline were unaffected. These results indicate that bradykinin-evoked sensitization of airway sensory nerves may underlie the pathogenesis of ACE-inhibitor cough. Bradykinin receptor antagonists may be of benefit in treating chronic cough seen with this and other inflammatory conditions.",1996.0,0,0
1864,8675251,Insulin-resistant lipolysis in abdominally obese hypertensive individuals. Role of the renin-angiotensin system.,M M Hennes; I M O'Shaughnessy; T M Kelly; P LaBelle; B M Egan; A H Kissebah,"Resistance to the capacity of insulin to suppress lipolysis may be an important link in the association between abdominal obesity and hypertension. Furthermore, a more active renin-angiotensin system in adipose tissue may contribute to insulin-resistant lipolysis in abdominally obese hypertensive subjects. We determined nonesterified fatty acid concentrations and turnover as well as lipid oxidation under basal conditions and during steady-state euglycemia with two levels of insulinemia (72 and 287 pmol/L) in lean normotensive, abdominally obese normotensive, and abdominally obese hypertensive subjects. To assess the role of the renin-angiotensin system in determining non-esterified fatty acid turnover, we repeated studies in the abdominally obese hypertensive subjects after double-blind random assignment to placebo or enalapril for 1 month each. The main findings were the following: (1) Nonesterified fatty acid flux was significantly higher in abdominally obese hypertensive subjects at both levels of insulinemia than in either abdominally obese normotensive or lean normotensive subjects and correlated significantly with both mean blood pressure and total systemic resistance during the higher level of insulinemia. (2) Enalapril significantly improved insulin-resistant lipolysis in the abdominally obese hypertensive subjects. The improvement in insulin suppressibility of nonesterified fatty acid flux at the high hormonal concentrations correlated positively with the magnitude of reduction in blood pressure. (3) Basal lipid oxidation and suppression in response to insulin were similarly impaired in both obese groups. Resistance to the antilipolytic actions of insulin is thus a characteristic feature in abdominally obese hypertensive subjects and may be linked to the elevated blood pressure in these individuals. A more active renin-angiotensin system may partly explain the insulin-resistant lipolysis in this form of hypertension.",1996.0,0,0
1865,8677862,Angiotensin-converting enzyme inhibition after myocardial infarction: the Trandolapril Cardiac Evaluation Study.,C Torp-Pedersen; L Køber; J Carlsen,"To study the importance of giving an angiotensin-converting enzyme (ACE) inhibitor to patients with reduced systolic function after an infarction, the Trandodolapril Cardiac Evaluation study was designed to include the majority of patients with echocardiographic signs of left ventricular dysfunction among consecutively screened patients with infarctions. A total of 2606 consecutive patients with left ventricular systolic dysfunction corresponding to an ejection fraction < or = 35% were identified. Of these patients, 1749 (67%) were randomly assigned to receive oral trandolapril or placebo beginning on day 3 to 7 after the infarction. The follow-up period was 2 to 4 years. Trandolapril reduced all-cause mortality, with a relative risk reduction associated with trandolapril treatment of 0.78 (p = 0.0013). Benefit was seen within 1 month of treatment. Trandolapril also reduced cardiovascular death (relative risk 0.75, p = 0.001), sudden death (relative risk 0.76, p = 0.03), and progression to severe/ resistant heart failure (relative risk 0.71, p = 0.003). Recurrent myocardial infarction (fatal or nonfatal) was not significantly reduced (relative risk 0.86, p = 0.29). More than 80% of patients in both treatment groups reached the target dose of 4 mg trandolapril or placebo at the end of dose titration. Nearly half of the patients in both treatment groups discontinued taking study medication before death or trial closure. The need for open-label ACE inhibition was the reason for discontinuation for 48 and 75 patients in the trandolapril and placebo groups, respectively. In conclusion, long-term treatment with trandolapril in patients with reduced left ventricular function shortly after myocardial infarction significantly reduced mortality and morbidity. Most patients received the target dose of 4 mg trandolapril daily. The benefit observed is likely to reflect the benefit in clinical practice because the majority of eligible patients were randomized and the difference in patients leaving the trial to receive open-label ACE inhibition was moderate.",1996.0,1,1
1866,8678058,Angiotensin-converting enzyme inhibition in nondiabetic progressive renal insufficiency: a controlled double-blind trial.,B U Ihle; J A Whitworth; S Shahinfar; A Cnaan; P S Kincaid-Smith; G J Becker,"Angiotensin-converting enzyme inhibitors delay progression of renal disease in different animal models of nephropathy. We tested this treatment modality in 70 hypertensive patients with severe renal disease of various etiologies. We report a double-blind study of the effect of 5 mg enalapril once daily compared with placebo in patients with nondiabetic severe chronic renal impairment (plasma creatinine 2.8 to 6.8 mg/dL; mean creatinine clearance 15 mL/min/1.73 m2) followed for up to 2 years. Efficacy parameters were the slopes of 51Cr-EDTA clearance, reciprocal of plasma creatinine, creatinine clearance, and the effect on urinary protein excretion. Thirty-one patients completed 2 years of treatment (12 in the enalapril group and 19 in the placebo group). Two patients died from nonrenal causes (one patient each in the enalapril and placebo groups), 16 patients commenced dialysis (seven in the enalapril group and nine in the placebo group), and eight patients were discontinued due to adverse events (five in the enalapril group and three in the placebo group). Eleven patients were discontinued because they were noncompliant, uncooperative, or moved (nine in the enalapril group and two in the placebo group). Two enalapril-treated patients were dropped from the study due to protocol deviations. Importantly, the statistical approach in this study evaluated all patients, regardless of the duration of treatment. A mixed-effects linear model and intention to treat analysis, taking into account the number of observations per patient, indicated that enalapril significantly reduced the rate of deterioration of renal disease: glomerular filtration rate (P = 0.038), reciprocal of plasma creatinine (P = 0.017), or creatinine clearance (P = 0.031). The renal protective effects of enalapril were shown to be in addition to its antihypertensive effect when blood pressure was held constant. Proteinuria was reduced by enalapril (P = 0.007) and was slightly increased in the placebo-treated patients (P = 0.051). The difference between these two groups was highly significant (P = 0.002). In conclusion, enalapril retarded the progression of chronic renal failure, as assessed by changes in glomerular filtration rate, creatinine clearance, and 1/plasma creatinine, and reduced proteinuria in patients with nondiabetic severe chronic renal insufficiency.",1996.0,0,0
1867,8680103,"Captopril, an angiotensin-converting enzyme inhibitor, induced pulmonary infiltration with eosinophilia.",K Watanabe; K Nishimura; M Shiode; M Sekiya; S Ikeda; Y Inoue; C Iwanaga,"In this study, we investigated the association between the drug-induced pulmonary infiltration with eosinophilia (PIE) syndrome in a patient with hypertension and the angiotensin-converting enzyme inhibitor (ACE-I) captopril. Although the patient developed diffuse lung field infiltrates accompanied by productive cough and striking peripheral eosinophilia, these symptoms disappeared after termination of the administration of captopril, pronase and cephalexine. Furthermore, the results of the peripheral lymphocyte stimulation test, skin patch test and provocation test under informed consent showed a positive reaction only for captopril. Therefore, this patient was diagnosed as captopril-induced PIE syndrome.",1996.0,0,0
1868,8682010,Platelet and leukocyte activation after myocardial infarction. Influence of enalapril.,C Sylvén; I Hagerman; K E Karlberg; J Chen; R Wallin; P Eneroth; K Bergström; T Saldeen,"In this double-blind placebo-controlled study with enalapril, 74 patients with acute myocardial infarction were followed at 0, 7, 30, 60 and 180 days after the event. Platelets and leukocytes were activated during the first 7 days. During the 6-month period fibrinogen, leukocytes, elastase, and B beta 30-43 remained elevated in 50, 15, 30 and 80% of the patients, respectively, but there was no detectable angiotensin converting enzyme activity in platelets. Enalapril did not modulate fibrinogen, leukocyte count or elastase, while B beta 30-43 peptide showed decreased levels, although the proportion of patients with values above the reference limit did not differ from placebo. In conclusion, in the 6-month post acute myocardial infarction period, while platelet function is activated only during the first week after acute myocardial infarction, fibrinogen and leukocyte function continue to be activated throughout the 6 months in a considerable proportion of patients. These signs may indicate an ongoing atherosclerotic process. Enalapril has no major influence on these reactivities.",1995.0,0,0
1869,8682023,Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.,L Erhardt; A MacLean; J Ilgenfritz; K Gelperin; M Blumenthal,"This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [+/-SD] 26.5% [+/-6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure: death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic. At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P = 0.101 by ANCOVA and 0.010 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P = 0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20%, of patients, P = 0.002), as were hospitalizations (3% vs 12% of patients, P = 0.002) and study discontinuations (2% vs 12% of patients, P < 0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P = 0.723). In addition, symptoms of dyspnoea (P = 0.017), fatigue (P = 0.019), and NYHA functional class (P = 0.008) improved with fosinopril relative to placebo. In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure.",1995.0,0,1
1870,8682036,Left ventricular systolic function after marked reduction of ventricular hypertrophy induced by 5 years' enalapril treatment.,J R González-Juanatey; A Pose Reino; J M García Acuña; V Castelo Fuentes; A Amaro Gendón; C Calvo Gómez; M Gil de la Peña,"To determine the effects of long-term treatment of essential hypertension with an angiotensin-converting enzyme inhibitor as regards arterial pressure at rest and during exercise, left ventricular mass and functional sequelae. Twenty-six patients with previously untreated essential hypertension took enalapril 20 mg twice daily for 5 years. Cardiovascular parameters were determined by two-dimensionally guided M-mode echocardiography in a pre-treatment placebo phase, 8 weeks and 1, 3 and 5 years after the start of therapy, and 8 weeks after drugs were discontinued. Therapy reduced resting arterial pressure from 156/105 to 128/84 mmHg (P < 0.001) and arterial pressure during exercise from 205/113 to 172/94 mmHg (P < 0.0011). After 1, 3 and 5 years' therapy, left ventricular mass index had decreased by 15, 28 and 39% respectively (P < 0.001 in each case). Eight weeks after treatment was halted, arterial pressure at rest and during exercise had returned to pre-treatment values, but decreased left ventricular mass was maintained. Left ventricular pump function had improved after 5 years' treatment, and this improvement was maintained during the 8 weeks without treatment. Significant reductions in arterial pressure at rest and during exercise were achieved by 8 weeks' treatment with enalapril and maintained during 5 years' further treatment, while a marked reduction in left ventricular mass took place progressively throughout the 5 year period. Reduction of myocardial hypertrophy by enalapril appeared to be beneficial rather than detrimental to cardiac pump performance.",1995.0,0,0
1871,8682088,"The Myocarditis Treatment Trial: design, methods and patients enrollment.",E A Hahn; V L Hartz; T E Moon; J B O'Connell; A Herskowitz; B M McManus; J W Mason,"The Myocarditis Treatment Trial was a multicentre clinical trial conducted to determine the efficacy of immunosuppressive therapy for treatment of biopsy-documented myocarditis, and to improve understanding of the immunological mechanisms in the development of myocarditis. Thirty-one centres screened 2305 patients with unexplained heart failure, and 2233 patients underwent an endomyocardial biopsy which provided adequate tissue for diagnosis. Those with a positive biopsy and a left ventricular ejection fraction (LVEF) less than 45% were randomly assigned to receive immunosuppressive therapy plus conventional drug therapy for congestive heart failure (66 patients) or conventional therapy only (45 patients) for 24 weeks. For 28 additional weeks all patients received conventional therapy only. In addition to diagnostic and clinical data, serum and myocardial tissue for immunological marker analysis and histopathologic evaluation were collected at baseline and at 12, 28 and 52 weeks after randomization. The primary analysis of efficacy was designed as a comparison of the mean increase in LVEF at week 28 between treatment limbs. Secondary objectives were to evaluate survival differences, and changes in the histopathology of the disease and immunological markers. Randomized patients were relatively young (mean age, 42.0 years +/- 13.8 standard deviation (sd) and entered the Trial with a mean LVEF percent of 24.3 +/- 10.1 sd) and mean exercise treadmill duration of 9.4 (+/- 5.3 sd) minutes. The incidence of biopsy-documented myocarditis was low (9.6%). The analyses of outcome and immunological data are reported elsewhere.",1995.0,0,0
1872,8692160,Cough induced by angiotensin-converting-enzyme inhibitors: Airway responses to inhalation of methacholine in patients who have essential hypertension.,J P Kelleher; F Elijovich; C L Laffer; M Padilla,"We investigated whether patients with cough due to angiotensin-converting-enzyme inhibitors have a common pattern of airway responses to methacholine inhalation. Studies assessing only presence or absence of hyperresponsiveness to this agent have produced conflicting results. Spirometric testing before and after methacholine was performed in 14 hypertensive patients at least two weeks after discontinuation of these inhibitors, when cough had abated or disappeared. Subjects were predominantly female (86%) nonsmokers (93%), with high prevalence of respiratory atopic illnesses (57%) probably due to ethnic background (72% Hispanic). Premethacholine spirometric values were normal. Postmethacholine bronchoconstriction of varying degrees was observed in seven patients, but reached the level of hyperresponsiveness in only one patient with asthma. The other seven subjects exhibited no bronchoconstriction. The two groups did not differ in age, concomitant illnesses (e.g., atopy) and medications, or blood pressure reduction. We conclude that airway responses to cholinergic stimulation do not exhibit a common pattern and are randomly distributed in hypertensive patients who develop cough induced by angiotensin-converting-enzyme inhibitors.",1995.0,0,0
1873,8695028,The blood pressure response to antihypertensive treatment with lisinopril or bendrofluazide is related to the calcium and magnesium contents in skeletal muscle.,A Haenni; L Lind; H Lithell,"To evaluate the association between skeletal muscle mineral balance and effect of antihypertensive treatment, 37 patients with essential hypertension, randomly treated with either lisinopril or bendrofluazide, were investigated with skeletal muscle biopsies before and after 6 months of treatment. The ratio between calcium and magnesium concentrations in skeletal muscle prior to treatment predicted the blood pressure response during active treatment (r = -0.38, P < .02). During treatment the change in blood pressure was related to the change in muscle Ca/Mg ratio (r = 0.35, P < .05), especially in the patients treated with lisinopril. Thus, an association between the calcium and magnesium balance in skeletal muscle and the blood pressure response to antihypertensive treatment was found in the present study.",1996.0,0,0
1874,8697160,Hormonal and renal differences between low dose and high dose angiotensin converting enzyme inhibitor treatment in patients with chronic heart failure.,N C Davidson; W J Coutie; D J Webb; A D Struthers,"To assess the differential effects of low dose (5 mg) and high dose (20 mg) lisinopril treatment on cardiovascular hormones, renal function, and blood pressure over 24 hours in patients with heart failure. Double-blind crossover study. Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee. 19 patients with chronic heart failure and left ventricular ejection fraction < or = 45%. Plasma concentrations of aldosterone and endothelin were lower on the 20 mg dose (plasma aldosterone mean at peak drug effect: 90.7 v 152.0 pg/ml, P < 0.001; mean at trough effect: 124.7 v 174.4 pg/ml, P < 0.01; plasma endothelin at trough effect 4.70 v 6.04 pmol/l, P = 0.03). Creatinine clearance was lower on 20 mg lisinopril (68.7 v 82.1 ml/min, P < 0.05). The area under the curve for diastolic blood pressure over 24 hours was significantly lower on 20 mg (mean difference 3.0 mm Hg, P = 0.04); for systolic blood pressure there was a similar trend (mean difference 5.7 mmHg, P = 0.05). Plasma concentrations of atrial natriuretic peptide (ANP) and B-type natriuretic peptide were similar for both doses; urinary excretion of ANP was lower on 20 mg (12.2 v 13.6 pmol, P < 0.05). These results indicate that within the usual therapeutic range, high doses of lisinopril cause greater suppression of selected cardiovascular hormones than low doses in heart failure, but are associated with lower creatinine clearance in some patients.",1996.0,0,0
1875,8697308,Effect of ramipril on insulin sensitivity in obese patients. Time-course study of glucose infusion rate during euglycaemic hyperinsulinaemic clamp.,P Valensi; E Derobert; R Genthon; J P Riou,"To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.",2000.0,0,0
1876,8698125,Polycythaemia vera: response to treatment with angiotensin-converting enzyme inhibitor.,S Nomura; T Sugihara; T Tomiyama; Y Kitano; Y Yawata; G Osawa,,1996.0,0,0
1877,8698434,Effect of 1 year of lisinopril treatment on cardiac autonomic control in hypertensive patients with left ventricular hypertrophy.,M Petretta; D Bonaduce; F Marciano; V Bianchi; G Valva; C Apicella; N de Luca; P Gisonni,"In this study we evaluated in hypertensive patients the effects of drug-induced left ventricular hypertrophy regression on cardiac autonomic control, as assessed by means of heart period variability analysis. Power spectral analysis of 24-hour electrocardiographic monitoring was performed in 30 hypertensive patients with left ventricular hypertrophy at baseline, after 1 year of lisinopril treatment, and after 1 month of drug withdrawal. At the same times, patients underwent 24-hour blood pressure monitoring, echocardiographic study, and plasma renin activity assessment. Lisinopril treatment increased plasma renin activity and reduced 24-hour systolic and diastolic pressures (from 159 +/- 14 to 121 +/- 8 and from 103 +/- 7 to 80 +/- 3 mm Hg, respectively) and left ventricular mass index (from 159 +/- 33 to 134 +/- 26 g/m2); moreover, in 12 of 30 patients, left ventricular mass normalization was achieved. Drug withdrawal was followed by an increase in blood pressure without left ventricular mass modification. In the total study population, only high-frequency power was higher after lisinopril treatment. In the subgroup of patients with left ventricular mass normalization, daytime and nighttime high-frequency powers as well as nighttime total and very-low-frequency powers were higher after 1 year of treatment than at baseline. In the remaining 18 patients, power spectral measures after treatment were slightly lower than at baseline and were even lower after drug withdrawal. Thus, in hypertensive hypertrophic patients, lisinopril treatment improves sympathovagal imbalance when left ventricular mass normalization is achieved. In patients without left ventricular mass normalization, drug withdrawal is followed by a worsening of neural cardiac control.",1996.0,0,0
1878,8698447,Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.,J A Staessen; L Thijs; L Bieniaszewski; E T O'Brien; P Palatini; C Davidson; J Dobovisek; M Jääskivi; T Laks; A Lehtonen; H Vanhanen; J Webster; R Fagard,"This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.",1996.0,0,0
1879,8701878,Benefit of converting enzyme inhibition on left ventricular volumes and ejection fraction in patients receiving beta-blockade after myocardial infarction. CONSENSUS II multiecho study group.,V V Bonarjee; S Carstensen; K Caidahl; D W Nilsen; M Edner; K Lindvall; S M Snapinn; J Berning,"Beta-blockers reduce infarct size and improve survival after acute myocardial infarction (MI). Post-MI angiotensin-converting enzyme inhibition also improves survival and may attenuate left ventricular (LV) dilatation. We evaluated the effect of early enalapril treatment on LV volumes and ejection fraction (EF) in patients on concomitant beta-blockade after MI. Intravenous enalaprilat or placebo was administered <24 hours after MI and was continued orally for 6 months. LV volumes were assessed by echocardiography 3 +/- 2 days, 1 and 6 months after MI. Change in LV diastolic volume during the first month was attenuated with enalapril (2.7 vs placebo 6.5 ml/m2 change; p < 0.05), and significantly lower LV diastolic and systolic volumes were observed with enalapril treatment compared with placebo at 1 month (enalapril 47.21 23.9 vs placebo 53.1/29.2 ml/m2; p < 0.05) and at 6 months (enalapril 47.9/24.8 vs placebo 53.8/29.6 ml/m2; p < 0.05). EF was also significantly higher 1 month after MI in these patients (enalapril 50.4% vs placebo 46.4%; p < 0.05). Our date demonstrate that early enalapril treatment attenuates LV volume expansion and maintains lower LV volumes and higher EF in patients receiving concurrent beta-blockade after MI. A possible additive effect of combined therapy should be evaluated prospectively.",1996.0,1,1
1880,8703644,Cardiorespiratory effects of continuous i.v. administration of the ACE inhibitor enalaprilat in the critically ill.,J Boldt; M Müller; M Heesen; K Härter; G Hempelmann,"1. Cardiorespiratory effects of long-term, continuous i.v. administration of the ACE inhibitor enalaprilat were studied. 2. Forty-five consecutive critically patients suffering from trauma or postoperative complications were randomly separated into three groups (15 patients in each group) receiving either 0.25 mg h-1 or 0.50 mg h-1 enalaprilat, respectively, or saline solution as placebo (= control group). The infusion was continued for 5 days. 3. Haemodynamic and respiratory parameters were intensively monitored on admission to the intensive care unit (= 'baseline' values) and daily during the next 5 days. 4. Mean arterial blood pressure (MAP) decreased significantly only in the enalaprilat-treated patients, whereas heart rate (HR) remained unchanged in these patients. 5. Pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP) were decreased by enalaprilat (0.50 mg h-1: PAP (mean +/- s.d.) decreased from 28.0 +/- 4.1 to 24.0 +/- 3.0 mm Hg) and remained significantly lower than in the control group. In the untreated control group, cardiac index (CI), oxygen consumption (VO2I) and oxygen delivery (DO2I) significantly decreased, which was blunted by enalaprilat infusion. Oxygen extraction (O2-extr) increased in both enalaprilat groups (0.25 mg h-1: from 26.1 +/- 5.5 to 30.4 +/- 4.0%; 0.50 mg h-1: 25.2 +/- 5.6 to 30.9 +/- 4.4%) and decreased in the control patients. 6. Right ventricular haemodynamics improved by enalaprilat infusion (0.50 mg h-1: RVEF increased from 40.0 +/- 3.5 to 45.5 +/- 4.0%). Lactate plasma concentrations decreased in the group with 0.50 mg h-1 enalaprilat (from 1.9 +/- 1.0 to 1.3 +/- 0.3 mg dl-1) and increased in the control patients. 7. Continuous infusion of the ACE inhibitor enalaprilat exerted beneficial cardiorespiratory effects in the critically ill. The widespread common risk of altered perfusion with decreased CI, DO2, VO2, O2-extr and increased lactate concentration was blunted by enalaprilat infusion. 8. Although 0.5 mg h-1 enalaprilat was most effective, a dose of 0.25 mg h-1 also showed beneficial haemodynamic effects in the critically ill.",1995.0,0,0
1881,8703645,"Resolution of ACE inhibitor cough: changes in subjective cough and responses to inhaled capsaicin, intradermal bradykinin and substance-P.",W W Yeo; I G Chadwick; M Kraskiewicz; P R Jackson; L E Ramsay,"1. In eight hypertensive patients with ACE inhibitor-induced cough the resolution of the cough was examined in a prospective observational study over 4 weeks duration. Resolution of cough was measured by visual analogue scales and questionnaire at baseline and days 3, 7, 14 and 28. In addition changes in cough sensitivity to inhaled capsaicin, and skin responses to bradykinin and substance-P were measured at the same time points. 2. All patients recorded significant subjective improvement in cough questionnaire scores for severity and night time waking, and by visual analogue scales for severity and frequency of cough (all P < 0.0005 for trend from day 0-28). Significant changes in subjective measures were recorded by 3 to 7 days for most measures, but further reductions were observed up to day 28 (all P < 0.01 day 28 vs day 0). 3. The sensitivity to inhaled capsaicin fell over the 28 days of study after stopping enalapril. The potency of capsaicin relative to day 0 was reduced to 0.25 (95% CI 0.07-0.87) by day 14, and to 0.20 (95% CI 0.06-0.67) by 28 days. 4. After stopping enalapril there was a highly significant reduction in wheal area produced by intradermal bradykinin, with the majority of the effect seen by day 3 (P < 0.0005). The wheal area to intradermal substance-P also declined with time after stopping enalapril, but significant changes were not observed until 14 days (P < 0.01). 5. Multiple regression analysis of the rates of decline for the subjective and objective measures of cough showed significant associations between the response to inhaled capsaicin and the VAS scores for severity of cough (P = 0.005) and frequency of cough (P = 0.011). Capsaicin response was not related significantly to the severity of cough measured by self-administered questionnaire. 6. There was a significant association between bradykinin response and VAS scores for frequency of cough (P < 0.04) and severity of cough (P < 0.05), but not with cough by questionnaire or the capsaicin response. The response to substance-P did not relate significantly to any of the measures of cough. 7. Cough caused by enalapril improved markedly by 14 days but took up to 28 days to resolve. It was associated with increased sensitivity to inhaled capsaicin which decreased over 28 days, and which paralleled changes in subjective cough scores.",1995.0,0,0
1882,8706766,"ACE-inhibitor-induced cough, an adverse drug reaction unrecognised for several years: studies in prescription-event monitoring.",K Kubota; N Kubota; G L Pearce; W H Inman,"OBJECTIVE. This study examines cough recorded in Prescription-Event Monitoring (PEM) of four ACE-inhibitors. Particular attention was paid to the study of enalapril because the drug was monitored before the causal relationship between cough and ACE-inhibitors had been widely accepted. RESULTS. Several factors which had obscured the causal relationship in the individual cases were found to be also an obstacle in PEM. For example, cough was a common and non-serious event and was under-reported in the PEM study of enalapril and the rate was not strikingly different from that recorded for other drugs. Cough induced by ACE-inhibitors has several characteristics which reduce the chance of a recognisable ""signal'. The original questionnaires returned from doctors in the PEM study of enalapril have been reexamined. The observation that the rate of cough diminished after enalapril had been stopped rather than increased after starting, provided the best evidence of causality, because this was not affected by many biases such as the publicity that had occurred prior to doctors participating in PEM completed later reports.",1996.0,0,0
1883,8706769,Haemodynamic interactions of a new calcium sensitizing drug levosimendan and captopril.,S Antila; J Eha; M Heinpalu; L Lehtonen; I Loogna; A Mesikepp; U Planken; E P Sandell,"Levosimendan in a new inodilator drug that sensitizes troponin C in heart muscle cells to calcium, thus improving contractility. In previous studies, a single 2 mg intravenous dose of levosimendan increased cardiac output (CO) in healthy volunteers by about 40% and decreased pulmonary capillary wedge pressure in heart failure patients by 40-50%. The aim of the present, double-blind study was to evaluate the safety of concomitant use of levosimendan and an ACE-inhibiting drug. The haemodynamic effects of levosimendan, given with or without captopril, were evaluated by using 2-dimensional echocardiography, repeated blood pressure measurements and by ambulatory ECG recordings. Twenty-four male patients with stable NYHA II-III heart failure (EF < 40%) after a previous myocardial infarct were given, in randomised order, a single i.v. infusion of levosimendan or placebo. The infusions were repeated after 2 weeks treatment with upto 50 mg b.i.d. of captopril. Twelve patients received levosimendan 1 mg and twelve received 2 mg. Mean CO was increased from 6.0 to 6.8 1 . min-1 in patients receiving 1 mg levosimendan compared to placebo, but only from 6.3 to 6.5 1 . min-1 in patients receiving 2 mg. The increase in CO was statistically significant when all levosimendan patients were compared to placebo. Heart rate did not change after either dose. Mean stroke volume increased significantly after 1 mg but not after 2 mg of levosimendan. The addition of captopril did not change the effects of levosimendan. No additional decrease in systolic or diastolic blood pressure was observed when levosimendan and captopril were given concomitantly. It seems that concomitant treatment with captopril does not change the haemodynamic effects of levosimendan. No adverse haemodynamic interactions were seen.",1996.0,0,0
1884,8706772,A pharmacokinetic and pharmacodynamic evaluation of buffered sublingual captopril in patients with congestive heart failure.,J C McElnay; T A al-Furaih; C M Hughes; M G Scott; D P Nicholls,"The pharmacokinetics and pharmacodynamics of buffered sublingual captopril were assessed in patients with congestive heart failure (CHF). The study was carried out in a randomised single-blind cross-over fashion (n = 6, 4 males and 2 females) and involved two study days, at least 7 days apart. Baseline measurements were carried out for plasma renin activity (PRA), blood pressure (B.P.) and heart rate (H.R.). Captopril (12.5 mg) was administered sublingually with dibasic potassium phosphate which maintained salivary pH at 7, or perorally with 100 ml of water. Further B.P., H.R. measurements and venous blood samples were taken over a 3 hour period post-drug administration. Blood samples were analysed for captopril and PRA levels. tmax after buffered sublingual administration of captopril, which ranged from 40-60 min (median = 40 min), was significantly shorter than after peroral administration (range 60-120 min, median = 90 min). Cmax was slightly greater after buffered sublingual than after peroral administration with mean values of 108.2 vs. 94.0 ng.ml-1. AUC values were similar after both routes of administration. Systolic and diastolic B.P. vs. time profiles for each administration method were significantly different i.e. sublingual administration produced an earlier reduction in B.P., however, HR did not differ significantly between the two routes. The data indicate that this novel administration method of captopril leads to an increased rate, but an unchanged extent of captopril absorption, suggesting a modest therapeutic advantage with the use of buffered sublingual captopril if a rapid reduction in blood pressure is required.",1996.0,0,0
1885,8708498,Methacholine inhalation challenge in patients with chronic cough induced by angiotensin-converting enzyme inhibitors.,S Wongtim; P Chareonlap; S Mogmued,"Angiotensin-converting enzyme inhibitors (ACEI) cause cough in some patients, but the mechanism of this side effect is not clear. Five patients (group I) who had developed chronic cough induced by ACEI were evaluated to determine the bronchial hyperreactivity (BHR) by challenge with methacholine inhalation using a reservoir method at Respiratory Unit, Chulalongkorn Hospital University. Five patients (group II) who did not experience coughing associated with ACEI were also challenged as controls. The results revealed that two patients (40%) in group I demonstrated BHR with the mean PC20 at 15 mg/ml of methacholine solution. On the other hand, none of the patients in group II disclosed BHR. We concluded that coughing during ACEI therapy may be due to an increased inflammatory state in the airway in some susceptible subjects.",1996.0,0,0
1886,8711657,Angiotensin converting enzyme (ACE) inhibitor-induced cough and substance P.,M Tomaki; M Ichinose; M Miura; Y Hirayama; N Kageyama; H Yamauchi; K Shirato,"Angiotensin converting enzyme (ACE) inhibitors cause coughing in 5-10% of patients, but the exact mechanisms of this effect are still unclear. In the airways ACE degrades substance P so the cough mechanism may be related to this peptide. Nine patients who developed a cough and five patients who did not develop a cough when taking the ACE inhibitor enalapril (2.5 or 5.0 mg/day) for hypertension were enrolled in the study. No subjects had respiratory disease and the respiratory function of all subjects was normal. One month after stopping enalapril, inhalation of hypertonic saline (4%) was performed using an ultrasonic nebuliser for 15-30 minutes to induce sputum. The concentration of substance P in the sputum sample was measured by radioimmunoassay. In four of the nine cases with a cough enalapril was given again for 1-2 weeks and the concentration of substance P in the induced sputum was again measured. One month after stopping enalapril the mean (SE) concentration of substance P in the sputum of the group with a cough was 16.6 (3.0) fmol/ml, significantly higher than that in the subjects without a cough (0.9 (0.5) fmol/ml). All four subjects in the group with a cough who were given a repeat dose of enalapril developed a cough again, but the concentrations of substance P in the induced sputum while taking enalapril (17.9 (3.2) fmol/ml) were similar to the values whilst off enalapril (20.0 (2.5) fmol/ml). The mechanisms of ACE inhibitor-induced coughing may involve substance P mediated airway priming. However, the final triggering of the ACE inhibitor-induced coughing is unlikely to be due to this peptide.",1996.0,0,0
1887,8712136,Influence of age on the prognostic importance of left ventricular dysfunction and congestive heart failure on long-term survival after acute myocardial infarction. TRACE Study Group.,L Køber; C Torp-Pedersen; M Ottesen; H Burchardt; E Korup; K Lyngborg,"The aim of this study was to assess the importance of congestive heart failure and left ventricular (LV) systolic dysfunction after an acute myocardial infarction (AIM) on long-term mortality in different age groups. A total of 7,001 consecutive enzyme-confirmed AMIs (6,676 patients) were screened for entry into the TRAndolapril Cardiac Evaluation (TRACE) study. Medical history, echocardiographic estimation of LV systolic function determined as wall motion index, infarct complications, and survival were documented for all patients. To study the importance of congestive heart failure and wall motion index independent of age, we performed Cox proportional-hazard models in 4 different age strata (< or = 55 years, 56 to 65 years, 66 to 75 years, and > 75 years). Patients in these strata had 1-year mortality rates of 5%, 11%, 21%, and 32%, respectively. Three-year mortality rates were 11%, 20%, 34%, and 55%, respectively. The risk ratios (and 95% confidence limits) associated with congestive heart failure in the same 4 age strata were 1.9 (1.3 to 2.9), 2.8 (2.1 to 3.7), 1.8 (1.5 to 2.2) and 1.8 (1.5 to 2.2), respectively. The risk ratios associated with decreasing wall motion index were 6.5 (3.6 to 11.4), 3.3 (2.3 to 4.6), 2.7 (2.2 to 3.4), and 2.1 (1.7 to 2.6), respectively. In absolute percentages, there was an excess 3-year mortality associated with congestive heart failure in the 4 age strata of 14%, 24%, 25%, and 28% respectively. The absolute excess in 3-year mortality associated with LV systolic dysfunction in the 4 age strata was 15%, 19%, 25%, and 21%, respectively. Thus, the relative importance of LV systolic dysfunction and congestive heart failure diminished with increasing age. However, the absolute excess mortality associated with congestive heart failure and LV systolic dysfunction was more pronounced in the elderly than in the young.",1996.0,0,0
1888,8714512,Angiotensin converting enzyme inhibitors: present status and future perspectives.,S Sharma; V Trehan; U Gupta,,1995.0,0,0
1889,8718563,Effect of cilazapril on hyperdipsia in hemodialyzed patients.,S Kuriyama; H Tomonari; O Sakai,"To investigate whether angiotensin-converting enzyme inhibitor (ACE-I) potentially alleviates hyperdipsia, the effect of cilazapril on dialysis-associated excessive thirst was studied by evaluating various dipsogenic parameters in patients undergoing chronic hemodialysis (HD) who manifest an excessive interdialysis body weight gain of more than 5%, and show simultaneous severe-to-moderate hyperdipsia. An initial single dose of 1 mg of cilazapril given at the end of the HD session produced a marked improvement in the interdialysis thirst scores and a simultaneous reduction in plasma angiotensin II (AII) concentration due to the inhibition of ACE activity. The interdialysis body weight gain in the cilazapril treatment period was significantly smaller than that in the nontreatment period. None of the other parameters including blood pressure, plasma osmolarity, and serum Na and K concentration were different in the treatment vs. the nontreatment period. The present data help to explain the potential pharmacological action of AII in the physiology of thirst and suggest that cilazapril may effectively alleviate dialysis-associated hyperdipsia at least on some occasions. The mechanism by which ACE-I exerts an antidipsogenic action may, in part, be accounted for by the reduction in plasma concentration of AII, as a result of the ACE inhibition.",1996.0,0,0
1890,8722432,Efficacy and safety of fosinopril/hydrochlorothiazide combinations on ambulatory blood pressure profiles in hypertension. Fosinopril/Hydrochlorothiazide Investigators.,R Guthrie; D R Reggi; M M Plesher; R K Saini; J P Battikha,"Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was used to assess the antihypertensive efficacy and safety of the angiotensin converting enzyme (ACE) inhibitor fosinopril (Fos) in combination with hydrochlorothiazide (HCTZ) in doses of 10/12.5 mg and 20/12.5 mg taken once daily versus placebo in patients with mild-to-moderate hypertension. In two methodologically identical studies, the antihypertensive effects were evaluated by 24-h ABPM and by seated office diastolic (DBP) and systolic (SBP) blood pressures. After a 4- or 5-week placebo washout, 79 patients received randomized, double-blind treatment for 8 weeks with either the Fos/HCTZ 10/12.5-mg dose combination (n = 41) or placebo (n = 38), and in the second study, 62 patients were treated with either the Fos/HCTZ 20/12.5-mg dose combination (n = 30) or placebo (n = 32). Changes from baseline in mean 24-h systolic and diastolic ABPM were significantly different from placebo for both doses (SBP/DBP with 10/12.5 mg, -18.2/ -10.1 mm Hg, P <or= .001; SBP/DBP with 20/12.5 mg, -22.9/ -11.2 mm Hg, P <or= .001); whereas ambulatory SBP and DBP in the placebo group were virtually unchanged. Although the antihypertensive effect of the higher Fos/HCTZ dose combination (20/12.5 mg) appeared greater than the lower dose (10/12.5 mg), no attempt was made to make a comparison between the two doses over these two independent studies. This difference in blood pressure lowering was not reproduced by the office blood pressure readings. Both dose combinations of Fos/HCTZ produced significantly greater reductions in the office seated DBP than placebo at all time points tested with a maximum treatment effect (drug effect - placebo effect) of -7.3 mm Hg for the 10/12.5-mg dose and -8.2 mm Hg for the 20/12.5-mg dose after 8 weeks of therapy (P <or= .01). Based on the results obtained in these trials, both dose combinations of Fos/HCTZ taken once daily were safe and effective in the management of patients with mild-to-moderate hypertension. Twenty-four-hour ABPM detected what appears to be an enhanced blood pressure reduction with the higher Fos/HCTZ dose combination (20/12.5 mg) at peak and trough, which was not reproduced by trough office blood pressure measurements, suggesting greater sensitivity of 24-h ABPM for evaluating antihypertensive effects.",1996.0,0,0
1891,8722435,"Metabolic effects of doxazosin and enalapril in hypertriglyceridemic, hypertensive men. Relationship to changes in skeletal muscle blood flow.",P E Andersson; H Lithell,"In a previous open study on the metabolic effects of doxazosin in patients with essential hypertension, subgroup analysis indicated that subjects with an accumulation of risk factors for coronary heart disease (high VLDL triglycerides, low HDL cholesterol and high fasting blood glucose) seemed to benefit most from the metabolic actions of doxazosin treatment. Those results formed the basis of this double-blind, parallel-group study undertaken to elucidate the metabolic effects of 6 months of doxazosin and enalapril treatment in patients with both essential hypertension and hypertriglyceridemia. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method. Hemodynamic evaluation included measurements of office and ambulatory blood pressure and ultrasonic measurements of femoral artery blood flow. Both drugs significantly reduced both office BP and 24-h ambulatory BP. Office systolic BP was significantly better reduced by enalapril. Doxazosin, in contrast to enalapril, significantly increased insulin sensitivity (by 21%, P = .02). It also reduced serum-triglycerides (by 23%, P = .01), VLDL triglycerides (by 30%, P = .008) and VLDL cholesterol (by 24%, P = .02). This lipid-lowering effect of doxazosin was accompanied by an increase in both plasma lipoprotein lipase activity and the elimination rate of an intravenous fat emulsion load. Neither treatment significantly increased femoral artery blood flow. It is speculated that without measurably increasing blood flow in conduit vessels such as the femoral artery, doxazosin, by capillary recruitment, may prolong the transit time for the blood over the muscle bed, which could explain the increased glucose disposal and increased lipoprotein lipase activity.",1996.0,0,0
1892,8722437,Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.,B R Davis; J A Cutler; D J Gordon; C D Furberg; J T Wright; W C Cushman; R H Grimm; J LaRosa; P K Whelton; H M Perry; M H Alderman; C E Ford; S Oparil; C Francis; M Proschan; S Pressel; H R Black; C M Hawkins,"Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving ""usual care."" ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.",2001.0,0,0
1893,8722438,Presence of cardiovascular structural changes in essential hypertensive patients with coronary microvascular disease and effects of long-term treatment.,A Virdis; L Ghiadoni; A Lucarini; V Di Legge; S Taddei; A Salvetti,"In asymptomatic essential hypertensive patients with angiographically normal coronary arteries and without left ventricular hypertrophy, dipyridamole-induced ischemic-like ST segment depression may be a marker of coronary microvascular disease. In this study we evaluated, first, whether this cardiac abnormality is linked to structural or functional vascular abnormalities, and second, the effect of antihypertensive treatment by 12-month administration of the angiotensin converting enzyme (ACE) inhibitor captopril (50 mg twice a day orally). In essential hypertensives with dipypridamole echocardiography stress test (DET) (DET+, n = 8) and without (DET-, n = 8) ST segment depression greater than 0.1 mV during intravenous dipyridamole infusion (0.84 mg/kg over 10 min), we studied the forearm blood flow (FBF, venous plethysmography, mL/100) modifications induced by intrabrachial acetylcholine (Ach) (0.15, 0.45, 1.5, 4.5, 15 micrograms/100 mL/min x 5 min each), an endothelium-dependent vasodilator, and by sodium nitroprusside (SNP) (1, 2, 4 micrograms/100 mL/min x 5 min each), a smooth muscle cell relaxant compound. Minimal forearm vascular resistances (MFVR), an index of arteriolar structural changes, were also calculated. Both Ach and SNP caused greater vasodilation in DET- as compared to DET+ while MFVRs were lower in DET- compared to DET+. After treatment, both DET+ and DET- patients showed a significant and similar reduction in blood pressure and left ventricular mass index, while vasodilation to acetylcholine and sodium nitroprusside was increased only in the DET+ group. In addition, forearm minimal vascular resistances were significantly reduced only in DET+ patients, who showed disappearance of dipyridamole-induced ischemic-like ST segment depression. In conclusion, these data confirm that essential hypertensive patients with microvascular coronary disease are characterized by the presence of structural changes in the forearm vascular bed. Our results also indicate that both cardiac and forearm vascular abnormalities can be reversed by antihypertensive treatment with an ACE inhibitor.",1996.0,0,0
1894,8723367,Acute renal failure induced by angiotensin converting enzyme inhibitor in a patient with polyarteritis nodosa.,A Y Wang; K N Lai; P K Li; C B Leung; S F Lui,"We report a patient who presented with malignant hypertension and renal failure. He was treated with lisinopril, spironolactone, and nifedipine retard for blood pressure control. Subsequent renal function showed further deterioration, but it then improved after withdrawal of the angiotensin converting enzyme inhibitor (ACE I). The diagnosis of classical polyarteritis nodosa was established with aneurysmal dilatation demonstrable in the renal vasculature. His renal impairment improved further following immunosuppressive therapy and the disease has remained inactive 4 years after first presentation. This is the first reported case of acute renal failure associated with the use of ACE I in polyarteritis nodosa.",1996.0,0,0
1895,8725589,Burning mouth syndrome.,P J Lamey,"Burning mouth syndrome is a common condition particularly affecting elderly women. Numerous precipitating factors are recognized that lead to a burning sensation in clinically normal mucosa. By taking each precipitating factor into account, a favorable treatment outcome usually can be achieved. This article highlights the significance of precipitating factors in burning mouth syndrome and suggests a treatment protocol based on current scientific evidence.",1996.0,0,0
1896,8725875,Spurious ketonuria due to captopril and other free sulfhydryl drugs.,G Csako; R J Elin,,1996.0,0,0
1897,8728305,Prediction of patient responses to antihypertensive drugs using genetic polymorphisms: investigation of renin-angiotensin system genes.,C Dudley; B Keavney; B Casadei; J Conway; R Bird; P Ratcliffe,"To investigate whether the M235T polymorphism of the angiotensinogen (AGT) gene and the insertion/deletion (I/D) polymorphism of the angiotensin-1 converting enzyme (ACE) gene predict blood pressure response to different antihypertensive agents. Sixty-three patients with untreated essential hypertension were randomly assigned in a placebo-controlled crossover comparison to atenolol 50 mg once daily, lisinopril 10 mg once daily and nifedipine SR 20 mg twice daily, and the effect on blood pressure was assessed by ambulatory blood pressure monitoring (ABPM). In a further 44 patients, placebo-controlled ABPM data were available after treatment with a single agent (atenolol 50 mg once daily in 16 cases and lisinopril 10mg once daily in 28 cases). The change in systolic and diastolic blood pressure achieved by each agent was analysed for association with genotypes at the AGT and ACE gene loci. Polymerase chain reaction (PCR) amplification of genomic DNA from each individual was used to identify the I/D polymorphism of the ACE gene. The M235T polymorphism of the AGT gene was detected by Tth111I digestion of PCR product. There was no significant association between response to any drug and either the AGT M235T or ACE I/D polymorphisms. The large variability between individuals in the observed blood pressure response to these agents cannot be attributed to the polymorphisms analysed at the ACE and AGT loci.",1996.0,0,0
1898,8728306,"Comparative effects of combination drug therapy regimens commencing with either losartan potassium, an angiotensin II receptor antagonist, or enalapril maleate for the treatment of severe hypertension.",D Ruff; L P Gazdick; R Berman; A I Goldberg; C S Sweet,"To compare the efficacy and safety of a regimen of losartan potassium (losartan) and a regimen of enalapril maleate (enalapril) in a randomized trial of patients with severe hypertension in which the initial treatments were blinded. Seventy-five patients, 23-74 years of age, with sitting diastolic blood pressure of 115-130mmHg, were enrolled in a 12-site multicenter study. The primary efficacy parameters were the change in trough systolic and diastolic blood pressure, as well as response to treatment in terms of categories of hypertensive response. A gradual reduction in mean sitting diastolic blood pressure was observed in all patients treated from week 1 to 12 (10-29mmHg for the losartan regimen and 14-32 mmHg for the enalapril regimen). At week 4, a substantial number of patients remained on monotherapy at either the initial dose or double the dose of losartan (52%) or enalapril (72%). The blood pressure curves for each treatment were parallel over time. The enalapril-based regimen elicited a statistically significantly greater reduction in blood pressure than the losartan-based regimen, although the mean differences in the blood pressure response between the two treatment groups was small. Based on sitting diastolic blood pressure < 90 mmHg or a reduction in blood pressure of at least 10 mmHg, 98% of the patients assigned to the losartan regimen and 100% of the patients assigned to the enalapril regimen had a satisfactory response with a regimen of one to three antihypertensive drugs. Headache was the most common adverse experience in both treatment groups (occurring in 22% of patients assigned to the losartan regimen and 20% of patients assigned to the enalapril regimen). In this study, the losartan-based regimen effectively lowered blood pressure, was generally well tolerated, and was generally similar to the enalapril-based regimen in the treatment of patients with severe hypertension.",1996.0,0,0
1899,8730344,Calcium channel blockers versus ACE inhibitors as antihypertensives in polycystic kidney disease.,Y Kanno; H Suzuki; H Okada; T Takenaka; T Saruta,"The effects of calcium channel blockers (CCBs) and angiotensin converting enzyme (ACE) inhibitors on blood pressure and the progression of renal dysfunction were compared in hypertensive patients with polycystic kidney disease (PKD). Twenty-six patients with PKD and hypertension who had been treated with other antihypertensive agents, such as diuretics, beta-blockers, or alpha-methyldopa, were followed up for two years, during which their blood pressure and renal function were monitored. Patients were divided into two groups classified according to the type of antihypertensive agents given. Group 1 (n = 14) received CCBs, while group 2 (n = 12) received ACE inhibitors. No significant differences were found in their blood pressure control and serum creatinine levels throughout the study. The creatinine clearances were decreased in both groups. However, the decreases in creatinine clearance were smaller (p < 0.05) in the group treated with CCBs. In addition, two patients in group 2 showed rapid increases in serum creatinine. Our data suggest that CCBs reduced blood pressure effectively and preserved renal function in PKD patients at least as well as ACE inhibitors.",1996.0,0,0
1900,8733032,Does high salt intake cause hyperfiltration in patients with essential hypertension?,F Mallamaci; D Leonardis; V Bellizzi; C Zoccali,"In animal models of salt-dependent hypertension, hyperfiltration is associated with a faster decline in renal function and there is evidence that in hypertensive man, increased creatinine clearance is a marker of early hypertensive nephropathy. We have studied the influence of salt intake on the glomerular filtration rate (GFR) (Creatinine Clearance) in 14 patients with mild hypertension. Each patient was studied in random order and according to a crossover design, at habitual salt intake, at high salt intake (ie habitual +50/100 mmol/day) and at low salt intake (habitual -50/100 mmol/day). Protein, calcium and potassium intake was fixed across the three study periods. The control group was formed by seven healthy subjects. High salt intake, caused a significant (P < 0.01) increase in 24 h mean arterial pressure (MAP) and the expected suppression in plasma renin activity (PRA) and in plasma aldosterone. Seven patients were classified as salt-sensitive. The GFR was significantly higher (P < 0.01) at high salt intake (125 +/- 10 ml/min) than at habitual (113 +/- 7 ml/min) and at low salt intake (97 +/- 6 ml/min). On aggregate urinary salt excretion was significantly related with the GFR (P < 0.01 by correlation analysis for repeated observations) and the slope of this relationship predicted that a 100 mmol/day increase in salt intake is associated with the 14.6 ml/min rise in the GFR. The relationship between GFR and 24 h urinary salt in salt sensitive patients did not differ from that in salt resistant patients. The GFR response to salt loading was largely independent of the renin-aldosterone system. No change in arterial pressure nor in GFR was observed in healthy subjects. At fixed protein intake, changes in salt intake in the physiological range are associated with important GFR variations in mild hypertensives. As long as hyperfiltration in mild hypertension is a predictor of renal function deterioration, high salt intake, independent of the effect of arterial pressure, could be a factor that contributes to nephronic obsolescence in patients with essential hypertension.",1996.0,0,0
1901,8733038,Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine.,C D Agardh; J Garcia-Puig; B Charbonnel; B Angelkort; A H Barnett,"A double-blind, randomised, parallel group, multicentre, multinational study compared the effects of 12 months' treatment with lisinopril (10-20 mg once daily) or nifedipine retard tablets (20-40 mg twice daily) in 239 males (aged 18-75 years) and 96 post-menopausal females (aged 40-75 years). They all had a history of clinically stable type II diabetes > 3 months, microalbuminuria and early diabetic nephropathy (a urinary albumin excretion (UAE) rate ranging from 20 to 300 micrograms/min) and a sitting diastolic blood pressure (DBP) 90-100 mm Hg (Korotkoff phase V) inclusive at both entry and after 3-4 weeks' placebo treatment. The aim of treatment was to achieve a reduction in sitting DBP to < 90 mm Hg 24-30 h after the last dose of lisinopril or 12-18 hours after the last dose of nifedipine and to evaluate the effect of these treatments on UAE over 12 months. The effect of the two treatments on ambulatory blood pressure (BP) was also evaluated in a subset of patients. Management of diabetes with oral hypoglycaemic drugs, diet and insulin alone or in combination was permitted. Median UAE fell on lisinopril from 65.5 (range 20-297) micrograms/min at baseline to 39.0 (2-510) micrograms/min after 12 months. On nifedipine median UAE fell from 63.0 (range 20-289) micrograms/min at baseline to 58.0 (9-1192) micrograms/min after 12 months. The estimated median difference between the effects of the two treatments was 20 micrograms/min (P = 0.0006). Over 12 months both treatments produced similar falls in sitting BP from 163 +/- 17/99 +/- 6 mm Hg (mean +/- s.d.) to 147 +/- 18/88 +/- 10 mm Hg for lisinopril and from 161 +/- 18/97 +/- 5 mm Hg to 150 +/- 18/88 +/- 9 mm Hg for nifedipine. Ambulatory BP was assessed in a subset of patients and using areas under the BP-time curve (AUC) a comparison of the effects of the two treatments showed no between-treatment differences. Creatinine clearance, glycaemic control (HbA1c) and lipid profiles did not change significantly during either treatment. Frequency of withdrawals and adverse events were similar for both treatments. We conclude that lisinopril has a significantly more beneficial effect on UAE than nifedipine despite similar effects on both BP and glycaemic control in type II diabetic patients with hypertension.",1996.0,0,0
1902,8737752,"Efficacy and safety of spirapril, a new ace-inhibitor, in elderly hypertensive patients.",I Kantola; A Terént; T Honkanen; V Järveläinen; K Ekman; M Kataja,"To compare the safety, efficacy, tolerability and duration of the antihypertensive effect of an ACE-inhibitor spirapril 3 mg or 6 mg in elderly (> or = 60 y) hypertensive patients in a multicentre, observational, double-blind randomised study. After a four-week placebo period, 39 patients were randomised to six weeks of treatment with spirapril 3 mg and 47 patients with spirapril 6 mg. In the sitting position the mean (SD) decrease in systolic blood pressure (SBP) was 12(15) mmHg (95% confidence interval 7 to 17 mmHg) and in diastolic blood pressure (DBP) 10(7) mmHg (8 to 12 mmHg) in the 3-mg group and 10(13) mmHg (6 to 14 mmHg) and 9(7) mmHg (7 to 11 mmHg), respectively, in the 6-mg group (P < 0.001 compared to placebo period in both groups). Spirapril 3 mg and 6 mg produced DBP < or = 90 mmHg or a fall > or = 10 mmHg in 53% and 51% of the patients, respectively. DBP was < or = 90 mmHg in 36% and SBP < or = 160 mmHg in 67% of the patients taking 3 mg and in 26% and 63% of the patients taking 6 mg spirapril. The most commonly reported adverse effects were cough (13-17%), dizziness, headache and insomnia. A trend to a more frequent adverse effects was observed in patients receiving spirapril 6 mg. Spirapril was both cholesterol- and glucose-neutral. According to our study, spirapril 3mg seems to be a suitable starting dose for the treatment of hypertension in the elderly patients.",1996.0,0,0
1903,8737955,"Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of spirapril in severe congestive heart failure.",E Bellissant; D Annane; E Pussard; C Thuillez; J F Giudicelli,"The effects of a single oral dose (6 mg) of the angiotensin-I converting enzyme inhibitor, spirapril, on systemic, pulmonary and regional (brachial, renal, hepato-splanchnic) hemodynamics as well as on biological parameters investigating the renin-angiotensin-aldosterone and sympathetic nervous systems were studied over a 24-hour period in eight patients with severe congestive heart failure (CHF). As compared to pretreatment values, spirapril significantly decreased mean arterial (-19%, peak effect), right atrial (-42%), mean pulmonary arterial (-38%) and pulmonary capillary wedge (-46%) pressures. Spirapril significantly decreased heart rate (-14%) and increased stroke volume index (+43%) thus resulting in a slight increase in cardiac index. All these effects were maximal between 2.5 and 4 h. Brachial artery diameter (+12%) and brachial (+41%) and renal (+36%) blood flows increased significantly whereas brachial (-41%) and renal (-36%) vascular resistances decreased significantly. All these effects were usually maximal between 1 and 2.5 h. Hepato-splanchnic hemodynamics were not drug-affected. Spirapril significantly inhibited plasma converting enzyme activity (-96% at 4 h), increased plasma renin activity (+505% at 4 h), and decreased plasma aldosterone (-46% at 24 h), norepinephrine (-31% at 24 h) and atrial natriuretic factor (-33% at 7 h). Thus, in severe CHF, acute administration of spirapril, 6 mg orally, exerts both arterial and venous vasodilating properties and improves both the systemic and regional hemodynamics and the biological status of the patients.",1996.0,0,0
1904,8738954,Evolution of pontine and extrapontine myelinolysis: clinical correlation with serial CT and MRI studies.,C J Chen; C C Huang; L S Ro,,1996.0,0,0
1905,8739919,Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group.,,"In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.",1996.0,0,0
1906,8740511,"Erythrocyte Na+, K+ and Ca2+, Mg(2+)-ATPase activities in hypertensives on angiotensin-converting enzyme inhibitors.",A Golik; J Weissgarten; S Evans; N Cohen; Z Averbukh; R Zaidenstein; D Cotariu; D Modai,"To investigate erythrocyte membrane Na+, K(+)- and Ca2+, Mg(2+)-ATPase activities in newly diagnosed hypertensive patients before and after 2, 4, and 6 months of treatment with enalapril or captopril as monotherapy. Na+, K(+)-ATPase activity (nmol ATP hydrolysed/min per mg protein) rose by 6 months of treatment in both groups when values were compared in each treated group over time (4.5 +/- 0.8 to 9.9 +/- 1.2; 4.9 +/- 0.8 to 10.5 +/- 1.7, respectively, p < 0.001 for both). When the treated groups were compared with controls at each period of time, Na+, K(+)-ATPase activity was higher at months 4 and 6 (p < 0.001) for both groups, respectively). Ca2+, Mg(2+)-ATPase activity (nmol ATP hydrolyzed/min per milligram protein) in the absence and in the presence of calmodulin increased in the enalapril (6.4 +/- 0.7 to 8.9 +/- 0.95, p < 0.05; 13.4 +/- 1.2 to 17.2 +/- 1.2, p < 0.05, respectively) and captopril (7.0 +/- 0.6 to 8.5 +/- 0.7; 14.4 +/- 1.1 to 16.0 +/- 1.0, p < 0.05, respectively) groups after 6 months of treatment compared within each treated group over time. When patient groups were compared with controls at time 0, 2, 4, and 6 months, the pump activity was higher in the treated groups at 6 months. The long-term enhancement of cell membrane Na+, K(+)-and Ca2+, Mg(2+)-ATPase activity associated with enalapril and captopril therapy may represent a specific effect of these agents or alternatively, a nonspecific outcome of blood pressure reduction.",1996.0,0,0
1907,8742566,Circulating catecholamines and metabolic effects of captopril in NIDDM patients.,G De Mattia; C Ferri; O Laurenti; M Cassone-Faldetta; A Piccoli; A Santucci,"To evaluate the effects of captopril on circulating catecholamine levels in NIDDM patients and the possible relationship between captopril-related changes in circulating catecholamine levels and insulin sensitivity. Fourteen nonobese normotensive NIDDM men (aged 44.5 +/- 5.1 years) underwent a 2-h euglycemic-hyperinsulinemic clamp (40 mU.m-2.min-1). Baseline evaluation of insulin sensitivity was followed by the random assignment of each patient to either captopril or placebo treatment, according to a crossover double-blind design. Euglycemic-hyperinsulinemic clamp studies were then repeated for all patients after both placebo and captopril treatments. Plasma norepinephrine (NE) and epinephrine (E) levels were assessed before, during, and after each clamp. Resulting data showed that plasma catecholamine levels increased during baseline euglycemic-hyperinsulinemic clamp (NE: +23.6% time 0 vs. time 120 min, P < 0.05; E: +24.8% time 0 vs. time 120 min, P < 0.05). Captopril treatment significantly increased total glucose uptake (from 19.0 +/- 9.0 to 26.8 +/- 10.1 mmol.kg-1.min-1, P < 0.05) and reduced baseline plasma NE (P < 0.001) and E (P < 0.05) levels. However, the magnitude of the NE (+25.7% time 0 vs. time 120 min, P < 0.001) and E (+27.2% time 0 vs. time 120 min, P < 0.05) increments during euglycemic hyperinsulinemia were not affected by the drug. Percentage changes in the ratio of total body glucose uptake to circulating insulin levels and corresponding decrements of baseline plasma E levels after captopril therapy were negatively correlated (r = -0.57, P < 0.05). The reduction of circulating catecholamines could contribute, at least in part, to the captopril-related amelioration of insulin sensitivity.",1996.0,0,0
1908,8746602,Trough-to-peak versus surface ratio in the assessment of antihypertensive agents. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.,L Bieniaszewski; J A Staessen; G Byttebier; P De Leeuw; T Van Hedent; R Fagard,"This study investigated whether the 'surface ratio', a novel index to characterize long-acting antihypertensive agents, would provide a more reproducible estimate of the duration of the antihypertensive effect than the more commonly used trough-to-peak ratio. In 66 hypertensive patients (diastolic pressure on conventional measurement > 95 mmHg), the ambulatory blood pressure was measured on a placebo at baseline and 2 months later, while the patients took 10 mg lisinopril once a day between 7 p.m. and 11 p.m. Diurnal treatment effect curves were obtained by subtracting the blood pressure at baseline from the corresponding value at 2 months for all time intervals considered in the analysis. In order to calculate the surface ratio, the area under the treatment effect curve was divided by the product of the maximal blood pressure lowering effect and the dosing interval (24 h). Reproducibility of the trough-to-peak and surface ratios was investigated by the Bland and Altman techniques. At 2 months, lisinopril reduced (+/- standard deviation) the 24 h pressure by 13 +/- 16 mmHg systolic and by 8 +/- 8 mmHg diastolic (p < 0.001). According to the usual approach, disregarding inter-individual variability, the trough-to-peak ratio was 0.7 for systolic and diastolic pressure. When in individual patients diurnal treatment effects curves with a 1 h resolution were investigated, the median trough-to-peak ratio was 0.30 for systolic pressure (5th-95th percentile interval [PI]: -0.51, 0.82) and 0.28 for diastolic pressure (PI: -0.37, 0.78); the corresponding values for the surface ratio were 0.33 (PI: 0.03, 0.58) and 0.30 (PI: -0.01, 0.55). In the same manner, the trough-to-peak ratios and surface ratios became larger when the individual blood pressure profiles were progressively smoothed by substituting 1 h averages by 2 h moving averages, 2 h averages, 3 h moving averages or by 3 h averages. The distributions of the trough-to-peak ratios and surface ratios were non-normal in 37 of 40 instances (p < 0.001, Shapiro-Wilk's test). Consistency was higher (p < 0.001) for the surface than for the trough-to-peak ratios. The within-subject reproducibility of the surface ratios tended to be superior to that of the corresponding trough-to-peak ratios. In conclusion, the surface ratio provides an index of the duration of action of antihypertensive agents. Moreover, in the present patients, the surface ratio tended to be characterized by a higher within-subject reproducibility than the trough-to-peak ratio.",1995.0,0,0
1909,8746603,"Combined treatment with captopril, hydrochlorothiazide and pravastatin in dyslipidemic hypertensive patients.",B Waeber; P Greminger; W Riesen; R Darioli; D Simeon-Dubach; R Wunderlin,"Hypertension and hypercholesterolemia frequently coexist, necessitating concurrent treatments for both disorders. The present study aimed at evaluating the efficacy, the safety, and the toleration of captopril, an ACE inhibitor, hydrochlorothiazide, a diuretic, and pravastatin, a HMG-CoA reductase inhibitor co-administered in hypertensive patients in general practice. The patients were followed for 16 weeks and asked to comply with a lipid lowering diet for the whole period. Captopril, 50 mg/once daily, was administered alone for the first 4 weeks. Hydrochlorothiazide, 25 mg/day, was added after 4 weeks if required. Pravastatin treatment (20 mg/day) was started at the 8th week of the study and its dose was doubled 4 weeks later if needed. A total of 603 patients with hypertension (diastolic blood pressure > or = 95 mmHg) and dyslipidemia (total cholesterol > 6.5 mmol/l) were included. The study was performed in general practice by 230 physicians. Determination of blood pressure, circulating levels of total cholesterol, HDL-cholesterol and triglycerides, and blood chemistry for safety monitoring. At the end of the trial 75.1% of patients had their diastolic blood pressure < or = 90 mmHg and 43.5% a total cholesterol level < 6.5 mmol/l. The overall incidence of adverse events was 21.7%, leading to withdrawal in 10.9% of the total number of patients. The combined treatments had no deleterious effect on safety variables. Captopril, hydrochlorothiazide and pravastatin are effective and well tolerated medications to treat dyslipidemic hypertensive patients.",1995.0,0,0
1910,8746604,Effects of cilazapril on renal haemodynamics and function in hypertensive patients: a randomised controlled study versus hydrochlorothiazide.,R Scaglione; A Ganguzza; S Corrao; R Costa; S Paternà; M G Cannavo; G Parrinello; T Di Chiara; M D D'Aubert; C Cottone,"In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.",1995.0,0,0
1911,8746605,Angiotensin converting enzyme inhibitor therapy and acute pancreatitis.,J S Madsen; I A Jacobsen,"Angiotensin converting enzyme (ACE) inhibitors are generally well tolerated. Worldwide, only few reports have been published associating pancreatitis with ACE inhibitor therapy. We report a case in whom there was no other likely explanation for the acute pancreatitis than enalapril therapy, which was temporally associated with the symptoms. Possible mechanisms underlying the induction of pancreatitis by ACE inhibitors are discussed. With the increasing use of ACE inhibitors, the incidence of rare adverse effects such as potentially lethal pancreatitis is likely to increase. Clinicians need to be aware of this association.",1995.0,0,0
1912,8750365,Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients.,M Simunic; Z Rumboldt; D Ljutic; S Sardelic,"A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9 years) with essential hypertension (average blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24-hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by approximately 15% in group B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between-group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.",1995.0,0,0
1913,8750395,Angiotensin II receptor antagonism: losartan - sites and mechanisms of action.,D J Triggle,"This review surveys the basic pharmacology of angiotensin II receptors and their antagonism; reviews the existing clinical experience with losartan, the first approved nonpeptide angiotensin II antagonist; suggests other possible clinical areas for angiotensin II receptor antagonism; and compares angiotensin-converting enzyme inhibition with angiotensin receptor antagonism.",1995.0,0,0
1914,8750405,Effects of lisinopril and bisoprolol on lipoprotein metabolism in patients with mild-to-moderate essential hypertension.,K Saku; K Liu; Y Takeda; S Jimi; K Arakawa,"The short- and long-term effects of the angiotensin-converting enzyme inhibitor lisinopril and the cardioselective beta-blocker bisoprolol on serum lipids, lipoproteins, apolipoproteins, and lipoprotein(a) (Lp[a]) levels were investigated in patients with mild-to-moderate essential hypertension. Fifty-two patients completed the 12-month, randomized, multicenter trial. After administration of lisinopril (10 to 20 mg/d; n = 24) and bisoprolol (2.5 to 10 mg/d; n = 28), systolic and diastolic blood pressures decreased significantly (P < 0.01) from baseline in both groups at 3, 6, and 12 months. The reduction in diastolic blood pressure was significantly (P < 0.05) greater in the lisinopril group than in the bisoprolol group only at 6 months. Heart rates dropped significantly in the bisoprolol group but not in the lisinopril group. No significant changes in lipids, lipoproteins, apolipoproteins, or Lp(a) levels were observed with either drug at 3, 6, or 12 months, and no significant differences were noted between the two drugs for these parameters. We conclude that lisinopril and bisoprolol are effective as antihypertensive drugs without adverse metabolic effects after short- and long-term treatment in patients with mild-to-moderate essential hypertension.",1995.0,0,0
1915,8751015,Effects of lisinopril on congestive heart failure in normotensive patients with diastolic dysfunction but intact systolic function.,C C Lang; H M McAlpine; N Kennedy; A R Rahman; B J Lipworth; A D Struthers,"This study examined the effects of lisinopril on diastolic function in 12 normotensive patients (mean age 72 years) with symptomatic congestive heart failure, intact left ventricular systolic function and abnormal diastolic function secondary to ischaemic heart disease in a placebo-controlled double blind crossover study, with each treatment dosed orally for 5 continuous weeks. Compared to placebo, lisinopril significantly decreased blood pressure, increased plasma renin activity without altering heart rate or plasma norepinephrine. There was no statistically significant improvement with lisinopril in radionuclide derived peak filling rate and time to peak filling rate, in Doppler echocardiographic measurements of the ratio of peak flow velocity in early diastole to the peak flow velocity of atrial contraction (E:A ratio) and in visual analogue scales of symptoms. Thus, although angiotension converting enzyme inhibitors may have an established role in the treatment of heart failure secondary to left ventricular systolic dysfunction, its use in patients with isolated diastolic dysfunction remains unclear.",1995.0,0,0
1916,8751016,Lisinopril is neutral to insulin sensitivity and serum lipoproteins in essential hypertensive patients.,C Thürig; L Böhlen; M Schneider; M de Courten; S G Shaw; W Riesen; P Weidmann,"To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor lisinopril on insulin sensitivity and related metabolic variables, the insulin sensitivity index (SI), determined with the Minimal Model Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure were assessed in 24 lean, non-diabetic patients with essential hypertension. Following a double-blind, randomised crossover design, these parameters were measured after a 4-week run-in period, after 8 weeks of lisinopril or placebo, and after an additional 8 weeks on placebo or lisinopril, respectively. Furthermore, the level of physical fitness was estimated using the Conconi bicycle ergometer test. SI was low in this study population (5.6 vs 13.3 x 10(-4).min-1.mU-1.l-1 in normal lean control subjects). It did not differ between the placebo run-in phase, the lisinopril phase, and the placebo crossover phase (5.8, 5.5, and 5.4 x 10(-4).min-1.mU-1.l-1, respectively). Moreover, during the administration of lisinopril, no significant changes occurred in fasting plasma insulin and glucose, areas under the glucose and insulin curves, glucose disappearance rate, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. Heart rate at rest, body weight, and anaerobic threshold remained stable throughout the study. Compliance assessed by pill-counting exceeded 90% at all visits. These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in patients with essential hypertension.",1995.0,0,0
1917,8751025,European postmarketing surveillance of ramipril in hypertension. 1. Feasibility and study cohort.,D H Lawson; K Bridgman; G H de Bock; D E Grobbee; H W Hense; P Block; K R Paterson; P Stonier,"A prospective observational cohort study of the angiotensin inhibitor, ramipril, was undertaken in four countries within the European Community-Netherlands, United Kingdom, Germany and Belgium. A total of 10,377 consecutive patients with essential hypertension were recruited to the study with the aim of follow-up for one year. Overall 37% of doctors who agreed to participate in the study actually enrolled at least one patient. One third of the doctors who enrolled patients in the study entered two thirds of patients studied. Some 15% of participating males and 27% of females were aged over 70 years. Newly diagnosed hypertensives comprised 22% of the study cohort, the proportion being highest in UK and Netherlands, whereas 53% were established hypertensives of two or more years' duration, the proportion being highest in Germany and Belgium. There were substantial differences among the participating countries in the concurrent treatment these patients were receiving for hypertension, with two or more co-therapies being most frequent in Germany and Belgium. There were also substantial differences in co-therapies for concurrent diseases among the participating countries, reflecting both standard therapeutic practices in local areas and differences in marketing of drugs in the different countries. This report describes the initial findings of this multinational study and emphasises the need to consider several major potentially confounding variables in the analysis of the outcome events both in this study and in other collaborative observational international monitoring schemes for adverse drug reactions.",1995.0,0,0
1918,8751029,"Czech and Slovak spirapril intervention study (CASSIS). A randomized, placebo and active-controlled, double-blind multicentre trial in patients with congestive heart failure.",J Widimský; H J Kremer; P Jerie; O Uhlír,"A randomized, double-blind, placebo- and active-controlled multicentre study with spirapril, a new angiotensin-converting enzyme inhibitor (ACEI), has been conducted in patients with chronic congestive heart failure (CHF) of NYHA classes II-IV. After a placebo run-in period of 1-4 weeks, patients were randomly assigned to one of five treatment groups: placebo (n = 48), spirapril 1.5 mg (n = 48), spirapril 3 mg (n = 53), spirapril 6 mg (n = 51) or enalapril 5/10 mg (n = 48). The primary objective was to assess changes in exercise tolerance, and the secondary objective was an assessment of cardiovascular signs and symptoms, quality of life, ejection fraction and chest X-ray findings. Exercise tolerance increased in all groups; however, no statistically significant differences were found between any of the groups. There was a statistically significant reduction of mortality in the pooled spirapril groups compared with placebo, and a trend for reduction of serious cardiovascular adverse events as well as duration of hospitalization. These effects and improvements in lung congestion appeared to be dose dependent. In patients with moderate to severe heart failure, the combination with first-generation calcium channel blockers had an unfavourable effect on exercise capacity and clinical parameters. Spirapril might be an effective alternative to enalapril in the treatment of patients with CHF. The role of the exercise tolerance test in establishing efficacy of ACEIs in CHF and the widespread use of nifedipine in CHF is questioned.",1995.0,0,1
1919,8752803,Which patient benefits from early angiotensin-converting enzyme inhibition after myocardial infarction? Results of one-year serial echocardiographic follow-up from the Captopril and Thrombolysis Study (CATS).,W H van Gilst; J H Kingma; K H Peels; J H Dambrink; M St John Sutton,"In this study we sought to investigate the effect of intervention with captopril within 6 h of the onset of myocardial infarction on left ventricular volume and clinical symptoms of heart failure in relation to infarct size during a 1-year follow-up period. Remodeling of the heart starts in the early phase of myocardial infarction and is associated with an adverse prognosis. Angiotensin-converting enzyme inhibition started in the subacute or late phase after myocardial infarction has been shown to improve prognosis. In the Captopril and Thrombolysis Study, 298 patients with a first anterior myocardial infarction treated with intravenous streptokinase were randomized to receive either oral captopril (25 mg three times a day) or placebo. The left ventricular volume index was assessed by two-dimensional echocardiography within 24 h, on days 3, 10 and 90 and after 1 year. A small but significant increase in left ventricular volume indexes was observed after 12 months. Using a random coefficient model, no significant treatment effect on left ventricular volumes could be detected. In contrast, when survival models were used, the occurrence of left ventricular dilation was significatnly lower in captopril-treated patients (p = 0.018). In addition, the incidence of heart failure was lower in the captopril group (p < 0.03). This effect appeared early and was most obvious in patients with a medium-sized infarct (p = 0.04) and was not present in large infarcts. Very early treatment with captopril after myocardial infarction significantly reduces the occurrence of early dilation and the progression to heart failure. These data underscore the importance of early treatment. Furthermore, patients with intermediate infarct size benefit the most from this treatment strategy.",1996.0,1,1
1920,8757368,Granulocytopenia after combined therapy with interferon and angiotensin- converting enzyme inhibitors: evidence for a synergistic hematologic toxicity.,C Jacquot; V Caudwell; X Belenfant,,1996.0,0,0
1921,8759064,Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing ENdothelial Dysfunction) Study.,G B Mancini; G C Henry; C Macaya; B J O'Neill; A L Pucillo; R G Carere; T J Wargovich; H Mudra; T F Lüscher; M I Klibaner; H E Haber; A C Uprichard; C J Pepine; B Pitt,"Angiotensin-converting enzyme (ACE) inhibitors may exert some of their benefits in the therapy of hypertension, congestive heart failure, and acute myocardial infarction by their improvement of endothelial dysfunction. TREND (Trial on Reversing ENdothelial Dysfunction) investigated whether quinapril might improve endothelial dysfunction in normotensive patients with coronary artery disease and no heart failure, cardiomyopathy, or major lipid abnormalities so that confounding variables that affect endothelial dysfunction could be minimized. Using a double-blind, randomized, placebo-controlled design, we measured the effects of quinapril (40 mg daily) on coronary artery diameter responses to acetylcholine using quantitative coronary angiography. The primary response variable was the net change in the acetylcholine-provoked constriction of target segments between the baseline (prerandomization) and 6-month follow-up angiograms. The constrictive responses to acetylcholine were comparable in the placebo (n = 54) and quinapril (n = 51) groups at baseline. After 6 months, only the quinapril group showed significant net improvement in response to incremental concentrations of acetylcholine (4.5 +/- 3.0% [mean +/- SEM] versus -0.1 +/- 2.8% at 10(-6) mol/L and 12.1 +/- 3.0% versus -0.8 +/- 2.9% at 10(-4) mol/L, quinapril versus placebo, respectively; overall P = .002). TREND shows that ACE inhibition with quinapril improved endothelial dysfunction in patients who were normotensive and who did not have severe hyperlipidemia or evidence of heart failure. These benefits of ACE inhibition are likely due to attenuation of the contractile effects and superoxide-generating effects of angiotensin II and to enhancement of endothelial cell release of nitric oxide secondary to diminished breakdown of bradykinin.",1996.0,0,0
1922,8759812,Effects of the early administration of zofenopril on onset and progression of congestive heart failure in patients with anterior wall acute myocardial infarction. The SMILE Study Investigators. Survival of Myocardial Infarction Long-term Evaluation.,C Borghi; E Ambrosioni; B Magnani,"Chronic congestive heart failure (CHF) is a common disease responsible for a high mortality and morbidity whose clinical course can be improved by angiotensin-converting-enzyme (ACE) inhibition. However, limited data are available on the effects of ACE inhibitors on the onset and progression of CHF in patients with acute myocardial infarction (AMI). The present study was performed as a substudy of the Survival of Myocardial Infarction Long-term Evaluation trial and involved 1,146 patients with anterior wall AMI not undergoing thrombolysis with the exclusion of patients with prior history or clinical signs of CHF on admission. Patients were randomly allocated to treatment with zofenopril (7.5 to 30 mg twice daily) or placebo for a cumulative period of 6 weeks. The prevalence of CHF, either mild to moderate or severe, has been the main objective and has been evaluated 6 weeks and 1 year after AMI. The overall prevalence of CHF was not reduced by zofenopril after both 6 weeks and 12 months. Conversely the prevalence of severe CHF (1.6% vs 2.6%: risk reduction 55.5%; 95% confidence interval 9 to 63; p = 0.0325) and the combined occurrence of death or severe CHF (4.8% vs 8.2%: risk reduction 59%; 95% confidence interval 11 to 71; p = 0.024) were reduced after 6 weeks of treatment with zofenopril. Moreover, the percentage of patients experiencing a deterioration to severe CHF after 1 year was significantly reduced with zofenopril (11.0% vs 24.3%; p = 0.001). In conclusion, the early administration of zofenopril to patients with AMI attenuates the progression of the clinical symptoms of CHF and its clinical consequences, suggesting that ACE inhibitors should be regarded as a suitable strategy for the prevention and treatment of CHF in patients with AMI.",1996.0,1,1
1923,8759815,Effects of enalapril on tissue factor in patients with uncomplicated acute myocardial infarction.,H Soejima; H Ogawa; H Yasue; H Suefuji; K Kaikita; I Tsuji; K Kumeda; N Aoyama,"In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated acute myocardial infarction, it was established that the baseline plasma tissue factor antigen level was significantly higher in patients with myocardial infarction than in control subjects, and enalapril therapy significantly reduced the elevated plasma tissue factor antigen level. This may be associated with the reduction in the risk of coronary thrombosis seen with the use of angiotensin-converting enzyme inhibitors.",1996.0,0,0
1924,8761842,Metabolic neutrality of perindopril: focus on insulin sensitivity in overweight patients with essential hypertension.,L Böhlen; R Bienz; M Doser; M Papiri; S Shaw; W Riesen; P Weidmann,"To assess the effects of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril on insulin sensitivity, plasma insulin, and lipoprotein metabolism in overweight hypertensive patients, we measured the insulin sensitivity index (SI, determined according to the minimal model method of Bergman), fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure (BP) in 30 overweight [mean body mass index (BMI) 30.9 kg/m2], nondiabetic patients with essential hypertension after a 4-week run-in period and after 6 weeks of perindopril (n = 20) or placebo (n = 10) administered in a double-blind fashion. Furthermore, we estimated their state of physical fitness using the Conconi bicycle ergometer test before and after perindopril or placebo administration. SI was low in our study population (3.2 vs. 13.3 10(-4) ml.microU-1.min-1 in normal lean control subjects). It did not differ between the perindopril and placebo group after the placebo run-in period (3.1 vs. 3.3 x 10(-4) ml.microU-1.min-1) and was not influenced by perindopril (3.3 x 10(-4) ml.microU-1.min-1) or placebo (3.6 x 10(-4) ml.microU-1.min-1) treatment. Moreover, no significant changes were apparent in fasting plasma insulin and glucose, the areas under the glucose and insulin curves, the glucose disappearance rates, serum total triglycerides (TG), or cholesterol or lipoprotein cholesterol fractions between run-in and active treatment phases in the perindopril or the placebo group, respectively. Heart rate (HR), body weight, and anaerobic threshold remained stable in both groups. Compliance, assessed by pill counting was > 90% in both groups at all visits. Therefore, the ACE inhibitor perindopril is neutral with regard to insulin sensitivity, plasma insulin and glucose, and lipoprotein metabolism in overweight, nondiabetic patients with essential hypertension.",1996.0,0,0
1925,8762212,Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes.,M Schneider; M Lerch; M Papiri; P Buechel; L Boehlen; S Shaw; W Risen; P Weidmann,"To investigate the metabolic, antihypertensive and albuminuria-modifying effects of a heart rate-modulating calcium antagonist-angiotensin converting enzyme inhibitor combination compared with those of a beta-blocker-low-dose diuretic combination in non-insulin-dependent diabetic hypertensives. A prospective randomized double-blind study. Twenty-four diabetics with diastolic blood pressure 90-115 mmHg without azotemia (plasma creatinine level < 150 mumol/l) were evaluated after 4 weeks receiving placebo and 12 weeks receiving treatment either with combined slow-release verapamil (retard formulation) and trandolapril (mean maintenance doses, 180 and 1.6 mg daily) or with atenolol and chlortalidone (71 and 18 mg daily). Insulin sensitivity (by the minimal model method of Bergman), additional metabolic variables, clinic blood pressure, ambulatory blood pressure profile and renal indices were assessed at the end of the placebo and active treatment phases. Compared with placebo, the two therapies produced similar decreases in mean supine clinic blood pressure [10 +/- 3 versus 11 +/- 3% (means +/- SEM)], upright clinic blood pressure (10 +/- 4 versus 11 +/- 4%) and ambulatory daytime blood pressure (9 +/- 2 versus 12 +/- 3%). However, although the verapamil-trandolapril combination was found to be metabolically neutral, the atenolol-chlortalidone combination aggravated insulin resistance [insulin sensitivity index, from (0.8 +/- 0.2) to (0.3 +/- 0.1) x 10(-4)/min per U per ml], increased the serum triglycerides level and decreased the high-density lipoprotein cholesterol and plasma potassium levels. Although both therapies tended to reduce 24 h albuminuria, this was significant for the verapamil-trandolapril treatment only. Because the effect of any antihypertensive drug, including diuretics and beta-blockers, on cardiovascular morbidity and on mortality in non-insulin-dependent diabetic patients is not known, rational treatment selection can presently be based only on surrogate end-points. Therefore, the triad of metabolic neutrality with antihypertensive and antiproteinuric efficacy supports combined verapamil-trandolapril as a potentially valuable therapy for hypertension accompanying diabetes mellitus.",1996.0,0,0
1926,8762219,"Equivalent effects of nicardipine and captopril on urinary albumin excretion of type 2, non-insulin-dependent diabetic subjects with mild to moderate hypertension.",B Bouhanick,"To test if calcium antagonists and converting enzyme inhibitors can act similarly on urinary albumin excretion of type 2, non-insulin-dependent diabetic subjects with hypertension, a 24 week, double-blind, randomized, parallel multicentre study was performed in 111 such patients allocated to nicardipine 50 mg slow release form (n = 57) or to captopril 25 mg (n = 54) twice daily. The efficacy of both drugs was similar on urinary albumin excretion (Westlake test p = 0.19). However, blood pressure was lower on nicardipine than on captopril (p < 0.05), and the antialbuminuric effect of nicardipine was related to its hypotensive effect, while this was not the case for captopril. The two drugs were tolerated equally. Thus, nicardipine and captopril for 24 weeks can be equally effective on urinary albumin excretion of type 2, non-insulin-dependent diabetic subjects with hypertension, but the mechanisms of their anti-albuminuric effects may be different.",1996.0,0,0
1927,8769587,Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial.,N O Borhani; M Mercuri; P A Borhani; V M Buckalew; M Canossa-Terris; A A Carr; T Kappagoda; M V Rocco; H W Schnaper; J R Sowers; M G Bond,"To compare the rate of progression of mean maximum intimal-medial thickness (IMT) in carotid arteries, using quantitative B-mode ultrasound imaging, during antihypertensive therapy with isradipine vs hydrochlorothiazide. Randomized, double-blind, positive-controlled trial. Nine medical center clinics. A total of 883 patients with baseline mean +/- SD systolic and diastolic blood pressure (SBP and DBP, respectively) of 149.7 +/- 16.6 and 96.5 +/- 5.1 mm Hg, age of 58.5 +/- 8.5 years, and maximum IMT of 1.17 +/- 0.20 mm. Twice daily doses of isradipine (2.5-5.0 mg) or hydrochlorothiazide (12.5-25 mg). MAIN OUTCOME MEASURE (PRIMARY END POINT): Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years. There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years (P=.68). There was a higher incidence of major vascular events (eg, myocardial infarction, stroke, congestive heart failure, angina, and sudden death) in isradipine (n=25; 5.65%) vs hydrochlorothiazide (n=14; 3.17%) (P=.07), and a significant increase in nonmajor vascular events and procedures (eg, transient ischemic attack, dysrhythmia, aortic valve replacement, and femoral popliteal bypass graft) in isradipine (n=40; 9.05%) vs hydrochlorothiazide (n=23; 5.22%) (P=.02). At 6 months, mean DBP decreased by 13.0 mm Hg in both groups, and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine (P=.002); the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine. The rate of progression of mean maximum IMT in carotid arteries, the surrogate end point in this study, did not differ between the 2 treatment groups. The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further.",1996.0,0,0
1928,8770334,The effects of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects.,R J Walker; N J Lewis-Barned; E A Edwards; M C Robertson,"There are conflicting reports about the effects of ACE inhibitors (ACEI) on insulin sensitivity and glycaemic control. Most studies have used a standard high dose of an ACEI but there have been no studies reported to establish whether any changes in glycaemic control or insulin sensitivity associated with ACEI are dose-related. To examine the effect of increasing doses of enalapril on insulin sensitivity in normotensive non-insulin dependent diabetic subjects. The effects of increasing doses of enalapril on insulin sensitivity in ten normotensive non-insulin dependent diabetic subjects were measured, using the hyperinsulinaemic isoglycaemic clamp technique. Following a baseline study, enalapril was commenced at 5 mg daily and increased to 10 mg daily then 20 mg daily at 14 day intervals. Repeat studies were undertaken after 14 days at each dosage. There was a significant dose-related reduction of systolic blood pressure with enalapril. In contrast enalapril at 5-20 mg daily produced no significant changes in insulin mediated glucose uptake (M-value) or insulin sensitivity index (ISI). These findings indicate that in this insulin resistant population of normotensive non-insulin dependent diabetics, angiotensin converting enzyme inhibition with enalapril has no significant effect on insulin mediated glucose uptake.",1995.0,0,0
1929,8772689,Prognostic significance of plasma norepinephrine in patients with asymptomatic left ventricular dysfunction. SOLVD Investigators.,C R Benedict; B Shelton; D E Johnstone; G Francis; B Greenberg; M Konstam; J L Probstfield; S Yusuf,"Elevated plasma neurohormonal levels are associated with increased mortality rates in patients with symptomatic heart failure. A previous Studies of Left Ventricular Dysfunction (SOLVD) trial suggested that neurohumoral activation precedes the development of symptoms as demonstrated by increased neurohormonal levels in patients with asymptomatic left ventricular dysfunction. However, the significance of this early neurohumoral activation is unclear. The goals of this study were to determine the prognostic significance of the plasma concentrations of plasma norepinephrine (PNE) and atrial natriuretic peptide (ANP) and the renin activity (PRA) in patients with asymptomatic left ventricular dysfunction. PNE and PRA were measured before randomization in 514 patients with left ventricular ejection fractions < or = 35% who did not require treatment for congestive heart failure and were enrolled in the SOLVD Prevention Trial. Plasma ANP levels were measured in a subset of 241 patients owing to study design. Using the Cox proportional hazards model that included left ventricular ejection fraction, New York Heart Association functional class, age, sex, treatment assignment to placebo or enalapril, and cause of heart failure, we examined whether these neurohormones predicted all-cause mortality, cardiovascular mortality, hospitalization for heart failure, development of heart failure, or development of ischemic events (myocardial infarction or unstable angina). PNE was the strongest predictor of clinical events in this patient population. PNE levels above the median of 393 pg/mL were associated with a relative risk of 2.59 (P = .002) for all-cause mortality, 2.55 (P = .003) for cardiovascular mortality, 2.55 (P = .005) for hospitalization for heart failure, 1.88 (P = .002) for development of heart failure, 1.92 (P = .001) for ischemic events, and 2.59 (P = .005) for myocardial infarction. PNE remained the most powerful predictor for all-cause mortality and ischemic events when the analysis included only the patients with histories of ischemic left ventricular dysfunction. The increases in other neurohormonal levels were not useful in predicting the subsequent development of clinical events. Increased PNE levels in patients with asymptomatic left ventricular dysfunction appear to predict all-cause and cardiovascular mortalities and development of clinical events related to the onset of heart failure or acute ischemic syndromes. Thus, measurement of PNE may be a possible early marker for assessment of disease progression in patients with left ventricular dysfunction, and modulating the release or effect of PNE may lead to improved prognosis and/or a reduction in morbidity.",1996.0,0,0
1930,8773158,Conversions from captopril to lisinopril at a dosage ratio of 5:1 result in comparable control of hypertension.,T H Gill; F Hauter; M A Pelter,"To provide clinical support that conversion from captopril to lisinopril at a daily oral dosage ratio of 5:1 maintains comparable therapeutic efficacy, and to estimate retrospectively cost savings because of conversion from captopril to lisinopril therapy at the study site and with the associated overall drug conversion program instituted by Kaiser Permanente. An open-label, randomized, prospective, parallel study was performed in 56 patients with mild-to-moderate hypertension. In a 4-week preroandomization period, oral maintenance dosages of captopril were established. Patients then were randomly assigned either to continue taking captopril or to change to lisinopril at an initial conversion ratio of captopril 5 mg to lisinopril 1 mg. Blood pressures were evaluated 2, 4, 8, and 12 weeks postrandomization. If necessary, dosages were adjusted to maintain adequate efficacy (i.e., systolic pressure < 160 mm Hg and diastolic pressure < 90 mm Hg in the prerandomization period; diastolic pressure < 90 mm Hg postrandomization). Cost savings for the study site and to the overall program with respect to conversion from captopril were defined as the difference between the estimated drug costs and the drug costs projected if the conversion had not been made. Woodland Hills Medical Center of the Southern California Region of Kaiser Permanente Medical Care Program. The main outcome measures were systolic and diastolic blood pressure. The measure for the retrospective cost savings analysis was estimated cost savings based on the number of prescriptions written for captopril and lisinopril from December 1988 through December 1993, and the average wholesale price. Members of the Kaiser Permanente Medical Care Program who were diagnosed with mild-to-moderate hypertension and whose hypertension was controlled by captopril alone. Retrospectively, mild-to-moderate hypertension would have been classified as stages 1-3, based on the current guidelines of the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The blood pressures of patients in whom captopril therapy was switched to lisinopril therapy were maintained throughout the entire study within the defined acceptable limits of control when the conversion was initiated at a daily oral dosage ratio of 5:1. The final dosage conversion ratio was not significantly different statistically from the theoretical dosage conversion ratio of 5:1. The conversion from captopril (in equally divided daily doses) to lisinopril (once daily) at a dosage ratio of 5:1 maintained comparable control of mild-to-moderate hypertension with no increase in adverse effects. In addition, the cost savings associated with an overall drug conversion program were substantial, and the conversion provided a preferred once-daily dosing regimen.",1996.0,0,0
1931,8773377,Effects of ACE inhibitor on renal anemia in predialysis patients.,S Nomura; T Sasaki; Y Kitano; G Osawa,,1996.0,0,0
1932,8775936,Applying the results of large clinical trials in the management of acute myocardial infarction.,J P Sweeney; G G Schwartz,"Mortality from acute myocardial infarction has declined in recent years, largely due to the widespread application of new pharmacologic and mechanical interventions that have been tested in large, prospective, randomized clinical trials. For practicing generalists, we review the key data from such trials that have shaped the current management of patients with acute myocardial infarction. We discuss the roles of thrombolytic therapy, coronary angioplasty, nitrates, beta- and calcium channel blockers, angiotensin-converting-enzyme inhibitors, magnesium, and antiarrhythmic and antithrombotic agents. In addition, we highlight critical unanswered questions in the management of this disorder.",1996.0,0,0
1933,8777472,Quality of life in hypertensive patients treated with either carvedilol or enalapril.,J Ostergren; L Storstein; B E Karlberg; G Tibblin,"An important aspect of antihypertensive drug treatment is quality of life (QL) which should at least not be negatively affected. In this study, the QL during treatment with carvedilol (C), a beta-blocker with vasodilating properties due to alpha-1-receptor blockade, was compared to that of enalapril (E) in patients who had responded to the treatment. Patients with mild to moderate hypertension (diastolic blood pressure 95-115 mmHg) were randomised to receive either E(n = 119) of C(n = 129) in a double-blind multicenter study. The starting doses were 12.5 (C) and 10 (E) mg with doubling of the dose if necessary at 3-week intervals. If insufficient blood pressure (BP) control was found at 50 mg C or 40 mg E, 12.5 mg of hydrochlorothiazide was added. After having reached the goal BP the patients entered a 5-months maintenance period. General well-being was evaluated by the ""Göteborg Quality of Life Questionnaire"". Equally many patients in the respective treatment groups responded at the different dose levels. Diastolic BP after 5 months in the maintenance period was similar on C and E, respectively. For most items, QL was not affected by the treatments. An increased incidence of cough was perceived in the E group (p < 0.001). None of the C treated patients reported frequent cough at the end of the study compared with 12% of E treated patients. C and E had similar BP lowering effects. Neither treatment seemed to affect the patients QL adversely. Cough, although seldom leading to withdrawal from the therapy, may be more common than is commonly recognised during treatment with ACE-inhibitors.",1996.0,0,0
1934,8781825,Captopril adjuvant therapy to beta-blockers and nitrates improves post-myocardial infarction left ventricular performance.,M Kyriakidis; A Antonopoulos; E Georgiou; P Santas; C Bakirtzis; P Toutouzas,"A growing body of data support the beneficial effects of angiotensin-converting enzyme inhibitors in the prevention of cardiac enlargement and improvement of left ventricular function in patients with acute myocardial infarction. However, very little information exists about the direct effect of increased afterload on cardiac performance in these patients and the possible favourable effects of angiotensin-converting enzyme inhibitors as adjunctive treatment to thrombolysis, beta-blockers and nitrates. We have, therefore, studied the effects of captopril as adjuvant therapy to thrombolysis, beta-blockers and nitrates (standard therapy) on left ventricular performance in 77 consecutive patients with uncomplicated Q-wave acute myocardial infarction, by the measurement of the pre-ejection period/left ventricular ejection time ratio before and after (0.25-0.50 mg) phenylephrine administration on the 4th and 30th post-infarction days. Patients were randomized on day 4 either to continue standard therapy alone (group 1, 35 patients) or to receive oral captopril therapy (12.5 mg t.i.d.) in addition to standard therapy (group 2, 42 patients) in a double-blind parallel study. Among the patients of group 1 there was a significant deterioration of left ventricular function after phenylephrine administration. This was shown by an increase of pre-ejection period/left ventricular ejection time ratio only in the subset of patients with ejection fraction < 40%, as measured by contrast ventriculography, on both the 4th and 30th post-infarction days changing from 0.435 +/- 0.070 to 0.528 +/- 0.101, P < 0.01 and from 0.404 +/- 0.098 to 0.515 +/- 0.092, P < 0.02, respectively. In contrast there were no significant changes in patients with ejection fraction > or = 40%. Among patients of group 2, phenylephrine administration induced a significant increase, only on the 4th day, in pre-ejection period/left ventricular ejection time ratio only in the subset of patients with ejection fraction < 40% changing from 0.410 +/- 0.107 to 0.535 +/- 0.102, P < 0.01. In the remaining patients with ejection fraction > or = 40% there were no significant changes on either the 4th or 30th post-infarction days. Furthermore, a significant improvement was observed after phenylephrine administration in the pre-ejection period/left ventricular ejection time ratio between the 4th and 30th post-infarction days, which changed from 0.535 +/- 0.102 on day 4 to 0.368 +/- 0.052 on day 30 (P < 0.004). Also, a four-way ANOVA detected a significant reduction of heart rate in patients with ejection fraction < 40% from day 4 to day 30. The results indicate that: (1) the response of pre-ejection period/left ventricular ejection time ratio after increasing afterload may be a useful non-invasive method for the detection of left ventricular dysfunction in myocardial infarction patients; and (2) captopril adjuvant therapy as compared to thrombolysis, beta-blockers and nitrates alone, after phenylephrine administration, improves the left ventricular performance response in asymptomatic Q-wave post-infarction patients and beneficially affects heart rate. This effect is most pronounced in patients with ejection fraction < 40% whereas those with ejection fraction > or = 40% do not obtain clear benefit.",1996.0,0,0
1935,8783591,'Hypertension resistant to two-drug treatment' is a useful criterion to select patients for angiography: the 'Dutch Renal Artery Stenosis Intervention Cooperative' (DRASTIC) study.,B C van Jaarsveld; F H Derkx; P Krijnen; H Pieterman; A J Man in't Veld; A J Woittiez; A Dees; C T Postma; M A Schalekamp,,1996.0,0,0
1936,8783779,Effect of quinapril on the albumin excretion rate in patients with mild to moderate essential hypertension. Multicenter Study Group.,P Larochelle,"In patients with essential hypertension, correlations have been reported between the albumin excretion rate (AER) and ambulatory and casual blood pressure. Microalbuminuria has been indicated as a possible predictor of cardiovascular morbidity and mortality. The objective of this trial was to evaluate the effect of quinapril, an angiotensin converting enzyme inhibitor with high tissue affinity for the enzyme, on the AER in patients with mild to moderate essential hypertension and no evidence of diabetes mellitus. In this 12 week, 24 center study, quinapril was administered to 213 patients and titrated to 10, 20, or 40 mg/day alone or 20 mg/day plus 12.5 mg/day hydrochlorothiazide. Overall, blood pressure was reduced from 155.2 +/- 18.1/101.8 +/- 6.7 mm HG (mean +/- SD) to 144.4 +/- 17.8/92.3 +/- 8.9 mm HG (P = .0001) and AER decreased from 20.6 +/- 24.3 mg/24 h to 14.5 +/- 15.4 mg/24 h (P = .0001). The BP reductions were significant in all age groups. AER at endpoint was reduced 37.5% in elderly, 29.8% in middle-aged, and 11.8% in young patients from 32.5 +/- 45.0 mg/24 h, 19.1 +/- 20.9 mg/24 h, and 16.1 +/- 16.9 mg/24 h, respectively. The AER decreased in 60% of patients who had normal AER (0 to 30 mg/24 h), in 79% of those who had microalbuminuria (30 to 300 mg/24 h), and in 90% of those who had proteinuria (> 300 mg/24 h) at baseline. Baseline log-AER correlated with SBP (P = .0126, R = 0.19) and creatinine clearance (P = .026, R = 0.17), while endpoint log-AER correlated with SBP (P = .0015, R = 0.25) and DBP (P = .03, R = 0.17). In summary, we showed, in a large group of patients with mild to moderate essential hypertension and no evidence of diabetes mellitus, that quinapril not only lowers BP significantly but also reduces microalbuminuria.",1996.0,0,0
1937,8785399,Mechanism of the antiproteinuric effect of cyclosporine in membranous nephropathy.,S Ambalavanan; J P Fauvel; R K Sibley; B D Myers,"Forty-one patients with a nephrotic syndrome and biopsy-proven membranous nephropathy were administered a 3 to 6-month course of cyclosporine (CsA;4 to 5 mg/kg per day). Differential solute clearances were used to evaluate glomerular function, before and after therapy. CsA lowered median proteinuria by 56%, from 7.3 to 3.2 g/24 h (P < 0.0001). Corresponding mean increments in serum albumin, immunoglobulin G, and oncotic pressure values were 31, 32, and 26%, respectively (all P < 0.0001). Arterial pressure, GFR, and renal plasma flow remained constant, but CsA restored the dextran-sieving curve toward normal, lowering the computed fraction of shunt-like pores by 25% (P < 0.05). In 14 instances, a cross-over design was used to randomly assign patients to 3 months of CsA versus 3 months of enalapril (10 to 30 mg daily), separated by a 1-month washout interval. Although enalapril lowered arterial pressure by 8 mm Hg (P < 0.01), it had no effect on proteinuria, plasma protein composition, filtration dynamics, or dextran sieving (all P = not significant). CsA dependence of proteinuria, indicated by relapsing nephrosis after CsA withdrawal, required additional courses of CsA to maintain proteinuria subnephrotic in most patients. In six patients with declining GFR during prolonged CsA treatment, a repeat biopsy showed more prominent immune deposits and a thicker glomerular basement membrane than at baseline. It was concluded that: (1) CsA lowers proteinuria in MN in part, by enhancing barrier size-selectivity; (2) lack of comparable efficacy of enalapril suggests that the antiproteinuric effect of CsA is related to its immuno-suppressive rather than glomerulodepressor properties; but (3) judged by repeat biopsy, CsA does not prevent continuing autoantibody formation in this disorder.",1996.0,0,0
1938,8785466,ACE inhibitors in elderly patients with hypertension. Special considerations.,M Ravid; D Ravid,"Angiotensin converting enzyme (ACE) inhibitors have emerged as the class of antihypertensive and vasodilatatory agents of first choice in the treatment of elderly patients with hypertension. Normotensive patients with congestive heart failure, post-anterior myocardial infarction, or diabetes mellitus with evidence of microangiopathy will also benefit from continuous ACE inhibition. The long term use of ACE inhibitors is associated with improved survival and reduced cardiovascular, cerebral and renal morbidity in these patients. In elderly atherosclerotic patients, these agents provide good control of systolic and diastolic blood pressure and peripheral resistance, with remarkable preservation of vital organ perfusion and infrequent adverse effects. Used as monotherapy, the effectiveness of ACE inhibitors is limited. However, there are advantages for using them in combination with other drugs, notably thiazide diuretics, nitrates and calcium antagonists. Renal function is thus preserved and left heart hypertrophy is prevented. There are no major differences between the various ACE inhibitors, and the choice of drug is largely a matter of personal preference.",1996.0,0,0
1939,8785469,The changing face of hypertension and antihypertensive agents.,M E Kitler,"In summary, much is needed to be done to foster thinking, both by patients and healthcare providers, in terms of disease risks and benefits of medical care, including those of pharmaceutical options. Healthcare professionals have been relatively ineffective patient educators, perhaps because there is still the old paternalism of 'doctor knows best'. Also, insufficient attention has been given to enhance the communication skills of healthcare professionals. Very likely, one of the reasons is the pressure to control costs which limits the time that healthcare professionals spend consulting with patients. Less than ideal compliance has even been reported in large-scale trials. For example, in the SHEP trial, a 90% compliance was reported (perhaps because of patient selection) but in the Studies of Left Ventricular Dysfunction (SOLVD), only 80% compliance was achieved. Poor adherence to long term treatment, both lifestyle modifications and pharmacological therapy, has been identified as the major reason for inadequate control of elevated BP; some sources claim that only 25% of all hypertensive patients have controlled BP. Thus planned patient education efforts should be undertaken as these can significantly improve BP control and decrease hypertension-related morbidity and mortality. To achieve this, the patient must become an active participant in the planned regimen, and not remain a passive recipient (table III).",1996.0,0,0
1940,8792950,Angiotensin II receptor antagonists: the prototype losartan.,K L Schaefer; J A Porter,"To describe a new class of antihypertensive agents, the angiotensin II receptor antagonists, with emphasis on the prototype losartan. Pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, and dosing guidelines. A MEDLINE search of English-language literature published from 1966 through 1995 was performed. In addition, Merck and Co. provided bibliographic data on file for losartan. Emphasis was placed on clinical and pharmacokinetic studies in humans. Controlled, double-blind studies were evaluated to assess the efficacy and adverse effect profile of losartan. Losartan is a nonpeptide, competitive antagonist of the type I angiotensin II receptor. In comparative clinical trials, losartan appears to have antihypertensive efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitors. Losartan is well tolerated, with an adverse effect profile similar to that of placebo and a reduced incidence of cough versus that with ACE inhibitors. A combination product consisting of losartan 50 mg and hydrochlorothiazide 12.5 mg has also received approval for the treatment of hypertension. The combination product is not indicated for initial therapy, but is recommended for patients who do not respond adequately to losartan monotherapy. The angiotensin II receptor antagonists are also being investigated for beneficial effects in patients with ventricular hypertrophy, renal disease, and heart failure. Losartan, the first angiotensin II receptor antagonist to receive approval for use in the US, appears to be an effective new antihypertensive agent with an adverse effect profile similar to that of placebo. Losartan may be an alternative for patients who cannot tolerate ACE inhibitors. However, the effect of losartan on mortality remains to be evaluated. The role of the angiotensin II receptor antagonists in areas such as ventricular hypertrophy, renal function, and heart failure has yet to be determined.",1996.0,0,0
1941,8793166,Moexipril as add-on therapy to hydrochlorothiazide in moderate to severe hypertension.,M Stimpel; B Koch; K Dickstein,"This double-blind study was conducted to investigate the efficacy, safety and tolerability of three dose levels of moexipril in comparison to placebo as add-on therapy to hydrochlorothiazide (HCTZ) in patients with moderate to severe hypertension. Two hundred patients who did not respond adequately to a 4-week monotherapy with HCTZ-sitting diastolic blood pressure between 95 and 114 mm Hg- entered the 8-week double-blind period. Patients were randomized to once daily placebo or moexipril 3.75, 7.5 or 15 mg as add-on therapy to open-label HCTZ 25 mg. At biweekly visits, blood pressure and heart rate measurements were obtained and the occurrence of adverse experiences was documented. At the 8-week endpoint, adjusted mean reductions from baseline were significantly (p = 0.003) greater in patients receiving moexipril 3.75, 7.5 and 15 mg compared to placebo (-8.4, -8.8 and -8.9 vs. -4.6 mm Hg). No significant differences between the three dose levels of moexipril could be observed. Moexipril was generally well tolerated. The most frequently reported adverse events for moexipril and placebo were headache, flu syndrome and dizziness (6, 7, 5 vs. 4, 0, 4%). The results indicate that the combination of moexipril and HCTZ is a clinically valuable combination in the treatment of patients with moderate to severe hypertension.",1996.0,0,0
1942,8793704,Effects of captopril related to increased levels of prostacyclin and angiotensin-(1-7) in essential hypertension.,M Luque; P Martin; N Martell; C Fernandez; K B Brosnihan; C M Ferrario,"To evaluate the contribution of angiotensin-(1-7) [Ang-(1-7)] and prostaglandins to the acute and long-term antihypertensive actions of captopril in mild-to-moderate essential hypertensive patients. Blood pressure, cardiac rate and the plasma concentrations of angiotensin I (Ang I), angiotensin II (Ang II), Ang-(1-7), prostaglandin E2 and 6-keto prostaglandin F1 alpha (the breakdown product of prostacyclin) were determined in the peripheral venous blood of 24 essential hypertensive subjects before and 3 h after administration of 50 mg captopril. Eleven of 24 patients completed a 6-month treatment period with captopril monotherapy (50 mg twice a day). The hemodynamic and hormonal response produced by a last 50 mg dose of captopril was determined once again in the 11 subjects who maintained blood pressure control with captopril monotherapy for 6 months. The fall in blood pressure produced 3 h after drug intake was comparable for the first and the last 50 mg captopril dose. Although the first response to captopril increased plasma levels of Ang I only, the response to the last dose of the drug (6 months after) caused significantly higher levels of Ang I and Ang-(1-7). Neither acute nor chronic therapy with captopril had a significant effect on plasma concentrations of Ang II. Although plasma levels of prostaglandin E2 and 6-keto prostaglandin F1 alpha were not modified by a first exposure to captopril, the concentrations of 6-keto prostaglandin F1 alpha but not prostaglandin E2 rose significantly in subjects treated with the inhibitor for 6 months. A negative correlation was also demonstrated between diastolic blood pressure and plasma Ang-(1-7) levels in the 11 essential hypertensive subjects in whom blood pressure was controlled with captopril monotherapy. Inhibition of angiotensin converting enzyme with captopril had a significant effect on blood pressure that was not directly accounted for by a suppression of plasma Ang II levels. Continuous therapy with captopril unmasked a contribution of Ang-(1-7) and prostacyclin to the antihypertensive actions of this drug.",1996.0,0,0
1943,8794832,Influence of isradipine and spirapril on left ventricular hypertrophy and resistance arteries.,P A Thürmann; N Stephens; A M Heagerty; P Kenedi; G Weidinger; N Rietbrock,"Left ventricular hypertrophy is a common clinical feature in hypertensive patients and may be associated with structural changes in vessel morphology. In an open prospective trial, we evaluated 14 patients with previously untreated hypertension (163 +/- 2/104 +/- 2 mm Hg) and an echocardiographically determined left ventricular mass index of 141.6 +/- 5.2 g/m2, indicating left ventricular hypertrophy. We obtained a gluteal skin biopsy sample before starting treatment to investigate subcutaneous small-artery (approximately 200 to 400 microns diameter) morphology and function. Patients then received antihypertensive treatment with a combination of spirapril (3 or 6 mg) and isradipine (2.5 or 5 mg). Echocardiographic recordings were made after 6 months and 1 year, and a final biopsy was taken after 1 year. After 1 year, blood pressure was significantly reduced to 142 +/- 3/ 90 +/- 1 mm Hg (P < .001), and left ventricular mass index decreased significantly to 105.3 +/- 5.8 g/m2 (P < .001). Baseline media-lumen ratio (7.64 +/- 0.48%) was not markedly reduced (7.21 +/- 0.55%), although a decrease occurred in 7 of 12 evaluable patients. Norepinephrine-induced vasoconstriction was markedly reduced after 1 year. In conclusion, a significant regression of left ventricular hypertrophy was obtained after 1 year of treatment with spirapril and isradipine, whereas a similar reduction in medial thickness relative to lumen diameter of subcutaneous small arteries could not be observed in all patients. Reversal of structural changes in resistance vessels may require a longer treatment period in patients with proven left ventricular hypertrophy.",1996.0,0,0
1944,8794833,Lisinopril reverses left ventricular hypertrophy through improved aortic compliance.,H Shimamoto; Y Shimamoto,"We treated with nifedipine or lisinopril 38 essential hypertensive patients with left ventricular hypertrophy. The study had a single-blind crossover design; nifedipine or lisinopril was given for the first 24 weeks, and then patients were crossed over to the other antihypertensive agent for another 24 weeks. Both nifedipine and lisinopril significantly decreased mean arterial pressure to the same extent. Although lisinopril decreased left ventricular mass index more rapidly than nifedipine, 48 weeks of antihypertensive treatment with nifedipine or lisinopril reduced the extent of left ventricular hypertrophy to the same level. Stepwise multiple linear regression analysis revealed that the reversal of left ventricular hypertrophy may be mainly due to a reduction in mean arterial pressure during the 24-week nifedipine treatment and due to an improvement of aortic compliance during the lisinopril treatment. Both nifedipine and lisinopril are effective in the reversal of hypertensive left ventricular hypertrophy; however, the agents have disparate actions on hemodynamic factors.",1996.0,0,0
1945,8797128,Fosinopril versus enalapril in the treatment of hypertension: a double-blind study in 195 patients.,L Hansson; T Forslund; C Höglund; H Istad; O Lederballe-Pedersen; A Kristinsson; E Segaard; A Svensson; M Aärynen; H Wahrenberg; G Wennersten; T Kjellström,"The new angiotensin-converting enzyme (ACE) inhibitor fosinopril was compared with the ACE inhibitor enalapril in a multicenter (n = 11), multinational (Denmark, Finland, Iceland, Norway, and Sweden), double-blind, randomized, parallel-group 24-week study in 195 patients with mild to moderate essential hypertension [supine diastolic blood pressure, (SDBP) > or = 95 to < or = 110 mm Hg]. After discontinuing all previous antihypertensive medication, patients were entered into a placebo lead-in period of 4-6 weeks, followed by 24 weeks of randomized treatment with the active compounds administered with a double-dummy technique. The dose of fosinopril was 20 mg, which could be increased to 40 mg after 8 weeks (average 25.6 mg); that of enalapril was 10 mg, which could be increased to 20 mg after 8 weeks (average 12.9 mg). Hydrochlorothiazide 12.5 mg could be added after 16 weeks and was administered to 27% of the patients in the fosinopril group and to 30% in the enalapril group. All drugs were administered once daily. Supine systolic BP (SSBP) decreased from 157 to 143 mm Hg in the fosinopril group (p < 0.01), and from 159 to 147 mm Hg in the enalapril group (p < 0.01). SSDP decreased from 100 to 89 mm Hg in the fosinopril group (p < 0.01) and from 100 to 92 mm Hg in the enalapril group (p < 0.01). Throughout the study period, fosinopril reduced SSBP and SDBP numerically more than did enalapril, by 0-3 mm Hg. Adverse events (AE) caused withdrawal of study medication in 8 patients in the fosinopril group and in 14 patients in the enalapril group (NS). The number of reported AE was not statistically different in the two groups. Inhibition of the ACE was assessed in a subgroup of patients (n = 26, 13 in each group). Fosinopril caused a greater inhibition of ACE at the doses used in the present study, which was statistically significant. Both fosinopril and enalapril caused statistically significant reductions in BP of a similar magnitude, and both agents were well tolerated. However, fosinopril was consistently numerically slightly more effective than enalapril in reducing BP. There were fewer withdrawals due to AE (NS) in the fosinopril group, and the overall recorded AE were fewer in the fosinopril group (NS).",1996.0,0,0
1946,8797135,Effects of ramipril and enalapril on cerebral blood flow in elderly patients with asymptomatic carotid artery occlusive disease.,R V Patel; N M Ramadan; S R Levine; K M Welch; S C Fagan,"We wished to determine in asymptomatic hypertensive patients with > or = 70% stenosis of an internal carotid artery the change in regional cerebral blood flow (rCBF) produced by ramipril and enalapril and to evaluate the influence of age on drug-induced changes in rCBF. In a prospective, randomized, single-blind, placebo-controlled investigation, using the 133Xenon inhalation technique, we assessed baseline rCBF in 15 patients (9 men and 6 women aged 60-79 years) after a 24-h antihypertensive drug-free period. All patients then received a single 5-mg oral dose of ramipril, enalapril, or placebo. rCBF was reassessed 2 h postdose. There was no significant change in the median rCBF in any of the three treatment groups. Neither did we observe any lateralization of BF to any specific cerebral region in any of the three groups. There were no observed or patient-reported adverse events (AE). Single 5-mg oral doses of either ramipril or enalapril did not decrease CBF significantly in asymptomatic hypertensive patients with > or = 70% stenosis of an internal carotid artery and are probably safe starting doses in such patients. In addition, this effect was not modified by age.",1996.0,0,1
1947,8800625,A risk-benefit assessment of ACE inhibitor therapy post-myocardial infarction.,C Borghi; E Ambrosioni,"The use of ACE inhibitors in patients with myocardial infarction (MI) has been the subject of several studies conducted during recent years. These studies have demonstrated the capacity of these agents to improve both survival and morbidity of patients with MI. However, the use of ACE inhibitors in patients with MI has been shown to reduce blood pressure (BP) and so could jeopardise the ischaemic myocardium. A significant reduction in systemic BP has been demonstrated by all the studies of ACE inhibitors in patients with MI, but no relationship has been found between the occurrence of hypotension and a worse clinical outcome. An increased risk of death has been observed exclusively in association with severe and sudden hypotension, the occurrence of which can be largely prevented by the administration of the ACE inhibitor according to an increasing dose-titration scheme. Conversely, a certain degree of long term BP reduction could result in some beneficial effect in patients with MI and contribute to the lower incidence of re-infarction observed in patients with acute MI undergoing long term treatment with captopril. Since the renin-angiotensin system is strictly related to kidney function, its blockade by an ACE inhibitor could result in some degree of renal dysfunction, particularly in patients with MI and impaired ventricular function. The available results from large-scale studies suggest that abnormalities in kidney function (namely an increase in serum creatinine) are observed in 0.9 to 2.4% of patients with MI who, nevertheless, experience some benefit from treatment with ACE inhibitors. Interestingly, the administration of ACE inhibitors does not seem to further compromise severely impaired renal function, and may also represent a useful tool for the treatment of patients with renal dysfunction associated with MI. The use of ACE inhibitors in patients with MI is associated with a satisfactory clinical and laboratory safety profile. The occurrence of significant adverse effects seems to be very low and mainly attributable to a rather modest prevalence of cough (2.4 to 6.8%). Discontinuation of treatment because of biochemical and haematological abnormalities has been observed in less than 1% of treated patients. Thus, the beneficial effects of ACE inhibitor treatment seem to outweigh safety concerns, thereby reinforcing the role of ACE inhibition as a suitable therapeutic strategy in the treatment of patients with MI.",1996.0,0,0
1948,8803515,"Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients.",B Persson; M Stimpel,"To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ). Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension. This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) > or = 95 mmHg were randomized to monotherapy with placebo, moexipiril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks. Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group. Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension.",1996.0,0,0
1949,8803643,"Effects of captopril and ticlopidine, alone or in combination, in hypertensive patients with intermittent claudication.",S Novo; M G Abrignani; G Pavone; M Zamueli; C Pernice; A M Geraci; B Longo; R Caruso; A Strano,"Twenty four male hypertensive patients suffering also from peripheral obstructive arterial disease were randomly subdivided in two groups and after a period of farmacological wash-out of one month Group I was treated with Captopril (C 50 mg bid) or Ticlopidine (T 250 mg bid) for three months and then with the association C plus T for three months again. After placebo administration for one month, patients were further treated with C plus T at low doses (25 mg bid and respectively 250 mg daily). In the first part of the study, patients of Group II received an inverse sequence of the drugs (before Ticlopidine 250 mg bid and then Captopril 50 bid). In both groups of patients C induced a significant decrease of blood pressure and an increase of PFWD, TWD, and WI. T did not modify blood pressure but slightly increased PFWD, TWD, and WI. The improvement was more evident during administration of C plus T, whereas placebo administration induced a trend toward baseline values. Finally, the chronic administration of C plus T for twelve months induced a further improvement of all considered parameters. In conclusion, chronic administration of C plus T may be useful in the treatment of hypertensive patients suffering from intermittent claudication, improving significantly PFWD and TWD.",1996.0,0,0
1950,8804953,Perindopril-associated pneumonitis.,A Benard; B Melloni; B Gosselin; F Bonnaud; B Wallaert,"We report two cases of perindopril-associated pneumonitis with typical drug-induced clinical features. In the first case, biopsies showed granulomatous sarcoid-like lesions; in the second, bronchial wall eosinophil infiltratf2p4was reported with increased blood eosinophil count. In these two cases, improvement was obtained by withdrawal of the drug and was completed with steroids. All other causes were ruled out. Angiotensin-converting enzyme inhibitor (ACEI)-induced pneumonitis is still rare but has to be recognized as a real side-effect.",1996.0,0,0
1951,8809376,"Safety aspects of treatment with lacidipine--a slow-onset, long-acting calcium antagonist.",L H Lindholm; P Tcherdakoff; A Zanchetti,"The aim was to review the clinical safety profile of lacidipine with the help of the rather comprehensive datafile of the manufacturer- a novel approach which may be of some value while awaiting the outcome of calcium antagonist treatment in prospective, randomised trials of cardiovascular morbidity and mortality. This paper includes data from clinical trials finished before 1 January 1995. Since 1985, 50 phase III-IV trials have been performed investigating antihypertensive efficacy in patients with hypertension; 32 were controlled trials with comparison treatment and 18 were open studies of lacidipine treatment. In all, 16,590 patients received lacidipine; 13,419 in open studies and 3171 in double blind, comparative trials. Altogether, these patients contributed 5 124 person-years (p.y.). Furthermore, active comparative treatment was given to 1810 patients and placebo to 451. Both fatal and non-fatal cardiovascular events have been estimated. Efficacy (change in blood pressure and heart rate), adverse event rates, and drop-out rates have been compared for the different treatment regimes. Also the reasons for dropping out of studies have been compared. Adverse effects were also analysed as to their time of occurrence and duration. Blood pressure was lowered by 2-6 mg lacidipine; in the controlled trials from 166/102 to 144/85 mmHg. Heart rate dropped from 75.6 to 74.1 beats per minute. The estimated event rate for a possible myocardial infarction in all studies was 5.46 per 1000 p.y. The fatal (all causes) event rate was 5.27 per 1000 p.y., and the estimated fatal cardiovascular event rate 2.93 per 1 000 p.y. In one long-term study (48 weeks) comprising 2282 patients (1658 p.y.), the observed fatal (all causes) event rate was 4.2 per 1 000 p.y. The overall incidence in the comparative studies of (one or more) adverse events was: for lacidipine 30.3%, other calcium antagonists 43.8%, diuretics 18.7%, beta-receptor blockers 48.7%, ACE inhibitors 10.4%, and placebo 15.7%. The adverse effects of lacidipine were the expected ones, e.g. headache, flushing, pedal oedema, and palpitations. When analysing the data on file for lacidipine and some comparatory drugs in almost 19000 hypertensive patients we have found lacidipine to be an effective and well tolerated drug with a reasonable adverse profile typical for a calcium antagonist of the dihydropyridine group. Our study has the obvious limitations of a retrospective analysis of data obtained from a large cohort of patients, most of whom received lacidipine for a relatively short period of time. The present results indicate a lower fatal event rate than previously reported in the actively treated hypertensives in Collins' meta-analyses, comprising ten times more person-years than our analysis. Prospective studies with lacidipine focusing on possible reductions of atherosclerosis as well as incidence of cardiovascular disease are required and are well under way.",1996.0,0,0
1952,8816722,Drug associated hepatic reactions in New Zealand: 21 years experience.,P I Pillans,"To review spontaneous reports of drug-associated adverse hepatic reactions. Reports of drug-associated adverse hepatic reactions received by the New Zealand Centre for Adverse Reactions Monitoring over the 21 year period January 1974 to December 1994 were reviewed. Subdivision into three 7 year periods was undertaken to compare patterns. Of a total of 22,455 adverse medicine reaction (AMR) reports there were 943 reports of liver injury (4.2%). Two hundred and five drugs were associated with hepatic reactions. The top 20 drugs accounted for 57% of all liver reactions. Fifty-seven percent were reported in females. Hepatotoxicity was most commonly reported among patients 50-80 years old. Liver reactions were associated with a 3.3% mortality, but were responsible for 7.4% of all fatal occurrences. There was a steady increase in the number of reports over the 21 years. Although the largest number of reports of liver injury were received between 1988 and 1994, mortality was lowest during this period. There were substantial differences in the medicines associated with hepatic reactions during each of the three periods, although erythromycin was the commonest cause throughout. Erythromycin was associated with two deaths. Halothane and perhexilene were the most frequent cause of death and were two of the most important causes of liver injury during the first and second periods. Diclofenac, Augmentin and flucloxacillin were important causes of hepatotoxicity during period 3 but were not associated with a fatal outcome. Hepatic reactions accounted for 4.2% of all adverse medicine reactions and 7.4% of all fatal occurrences. The top 20 drugs were responsible for 57% of all liver reactions. Despite a steady increase in the number of reports during the 21 years, mortality was lowest during the last 7 years. Differences in the medicines causing liver injury during the three periods influenced the number of fatalities. Erythromycin was the most commonly reported cause of hepatic reactions but was usually associated with a favourable outcome. There were no reported deaths with diclofenac, Augmentin or flucloxacillin.",1996.0,0,0
1953,8817007,Treatment of hypertensive patients according to the conventional or ambulatory pressure: a progress report on the APTH trial. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.,L Bieniaszewski; J A Staessen; J Polfliet; L Thijs; R Fagard,"The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.",1996.0,0,0
1954,8817407,Nifedipine and captopril exert divergent effects on heart rate variability in patients with acute episodes of hypertension.,R Wolk; P Kulakowski; L Ceremuzynski,"Acute changes of heart rate variability (HRV) depict alterations in autonomic influences on cardiovascular system and often precede ventricular arrhythmias. The aim of the study was to assess effects of sublingual 10 mg nifedipine (n = 15) or 25 mg captopril (n = 13) on HRV in consecutive patients admitted to hospital due to severe hypertension. HRV was calculated on-line from 300 cardiac cycles before and 60-90 min after drug administration. At baseline systolic blood pressure (SBP) was > 190 mm Hg and/or diastolic blood pressure (DBP) > 110 mm Hg. Both agents caused similar reduction of blood pressure (BP). Nifedipine reduced variance (-63 +/- 6%; P < 0.0001) and high-frequency (HF) component (-72 +/- 8%; P < 0.0001), and increased both LF/HF ratio (+870 +/- 336%; P < 0.02) and heart rate (+14 +/- 3%; P < 0.0001). Captopril exerted different effects: variance and HF component increased by +176 +/- 55%; (P < 0.007) and +126 +/- 44% (P < 0.015), respectively. LF/HF (low/high frequency) ratio decreased (-44 +/- 19%; P < 0.04) together with heart rate (-4 +/- 1%; < 0.009). It is concluded that captopril, in contrast to nifedipine, increases HRV and decreases LF/HF ratio and therefore is a better choice in hypertensive patients who might be prone to dangerous arrhythmias.",1996.0,0,0
1955,8818434,"Effect of enalapril initiated early after acute myocardial infarction on heart failure parameters, with reference to clinical class and echocardiographic determinants. CONSENSUS II Multi-Echo Study Group.",M Edner; V V Bonarjee; D W Nilsen; J Berning; S Carstensen; K Caidahl,"Although the angiotensin-converting enzyme inhibitor enalapril has recently been shown to reduce mortality and the need for hospitalization in patients with left ventricular dysfunction and congestive heart failure, this drug was found to have no significant impact on short-term mortality after acute myocardial infarction (AMI) in the CONSENSUS II trial. The effect of enalapril initiated early after AMI on clinical and echocardiographic determinants of left ventricular (LV) function was studied in a subset of patients from CONSENSUS II. Symptoms and signs of heart failure were classified as NYHA and dyspnea classes. Echocardiography included LV end-systolic volumes (ESV) and end-diastolic volumes (EDV), as well as ejection fraction (EF), wall motion index (WMI), and mitral flow indices. In all, 428 patients were included and followed for an average of 5.1 months by serial examinations, starting 2-5 days after myocardial infarction (MI) and repeated after 1 month and at the completion of the study. There was no beneficial effect of enalapril on clinically determined function. Changes (i.e., changes in NYHA class) in the functional status remained correlated with changes in echocardiographic determinants throughout the study in patients belonging to the placebo group: EDV index (r = 0.36, p = 0.002, ESV index (r = 0.49, p < 0.001), EF (r = -0.41, p < 0.001), and WMI (r = 0.29, p = 0.008). In a stepwise logistic regression model, the best baseline parameters to predict NYHA class at final visit in all patients were age (p = 0.014) and ESV index (p = 0.001). Enalapril treatment for an average period of 5.1 months following MI resulted in no clinically significant beneficial effects on NYHA and dyspnea class. Changes in clinical function class were correlated with changes in echocardiographic determinants in placebo-treated patients, but not in patients given enalapril.",1996.0,0,1
1956,8824693,Effects of acute and chronic angiotensin converting enzyme inhibition by spirapril on cardiovascular regulation in essential hypertensive patients. Assessment by spectral analysis and haemodynamic measurements.,D P Veerman; C E Douma; M C Jacobs; T Thien; G A Van Montfrans,"1. The effects of a first dose and of chronic treatment with spirapril, a novel angiotensin converting enzyme (ACE) inhibitor, on short-term blood pressure and heart rate fluctuations were assessed by fast Fourier spectral analysis. The effects on systemic haemodynamics in supine and standing position were also studied. We treated 11 patients with 3 mg and 13 patients with 12 mg spirapril for 8 weeks. 2. Overall blood pressure variability was not changed by spirapril. By spectral analysis the changes in blood pressure and heart rate variability in various frequency bands can be assessed, which may be related to changes in activity of the autonomic nervous system. The relative power in the mid-frequency band (0.08-0.12 Hz) of supine systolic pressure was 23 +/- 10% during placebo and decreased during treatment with 12 mg to 11 +/- 4% (P < 0.01 vs placebo, first dose) and to 13 +/- 6% (P < 0.01, chronic treatment). Standing systolic mid-frequency power was 38 +/- 12% during placebo and decreased to 27 +/- 9% (P < 0.01 vs placebo) after the first dose of 12 mg, but it did not decrease after chronic treatment (29 +/- 13%). Treatment with 3 mg induced no changes in mid-frequency blood pressure variability. A decrease in power of the mid-frequency band may point to a decrease in sympathetic vascular drive. The power in the high-frequency band (0.15-0.40 Hz) of heart rate did not change after treatment, suggesting that there is no change in the vagal cardiac drive. 3. Supine blood pressure decreased by a decrease in vascular resistance by 16 +/- 23% (3 mg) and 14 +/- 19% (12 mg) after 8 weeks treatment. Heart rate, stroke volume and cardiac output did not change. No orthostatic hypotension occurred after the first dose. In the 12 mg group the orthostatic induced rise in heart rate (compared with supine) increased from + 9 +/- 5 beats min-1 (placebo) to + 14 +/- 4 beats min-1 (P < 0.05) after the first dose. No changes in the orthostatic heart rate increase occurred in the 3 mg group. The orthostatic changes in stroke volume, cardiac output and vascular resistance were not influenced by spirapril. 4. In conclusion, the decrease in mid-frequency blood pressure variability may suggest an inhibitory effect of acute and chronic ACE inhibition upon sympathetic vasomotor control. Vagal activity was not influenced as high-frequency heart rate variability did not change. Acute and chronic ACE inhibition did not blunt important cardiovascular reflexes, as the haemodynamic response to orthostasis remained intact.",1996.0,0,0
1957,8827932,Hypertension update.,B N Hyman; M Moser,"Hypertension affects approximately fifty million Americans. About 80% of hypertensive patients are aware that their blood pressure is elevated. While more than 50% are on medication, only about 20% of all hypertensive adults are controlled at normotensive levels. Ophthalmologists should be aware of the seriousness of hypertension because it affects many of their patients and is a risk factor for myocardial infarction, stroke, congestive heart failure, end-stage renal disease and peripheral vascular disease. As medically trained eye specialists, ophthalmologists should be knowledgeable about and take an interest in their patients' medical problems, thus playing an integral role on the health care team. As a primary health care provider, ophthalmologists should perform in-office blood pressure monitoring.",1996.0,0,0
1958,8828013,Adverse metabolic effects of antihypertensive drugs. Implications for treatment.,H G Preuss; J F Burris,"Adverse metabolic effects have been associated with drugs used in the therapy of hypertension, especially diuretics and beta-blockers. These effects include electrolyte, glucose/insulin, lipid and uric acid disturbances. This may explain, at least in part, why early trials examining the impact of antihypertensive pharmacotherapy with diuretics and beta-blockers showed beneficial effects on coronary artery disease that fell disappointingly short of the predicted effect. Among therapeutic drugs, diuretics cause disturbances in electrolyte homeostasis, e.g. hypokalaemia, hypomagnesaemia, and hyponatraemia. In contrast, ACE inhibitors cause hyperkalaemia under certain circumstances. Both diuretics and beta-blockers, especially nonselective beta-blockers that lack intrinsic sympathomimetic capabilities, have been associated with disturbances in glucose/insulin metabolism and can cause deleterious alterations in the profile of circulating plasma lipids. Hyperuricaemia, associated with diuretic use, appears to be a problem only in those patients who are predisposed to high circulating levels of uric acid.",1996.0,0,0
1959,8835055,Zinc deficiency and taste disorders.,C A Heyneman,Elemental zinc supplementation in daily dosages of 25-100 mg po appears to be an efficacious treatment for taste dysfunction secondary to zinc depletion. Insufficient evidence is available to determine the efficacy of zinc supplementation for the treatment of hypogeusia or dysgeusia secondary to drug therapy or medical conditions that do not involve low serum zinc concentrations.,1996.0,0,0
1960,8835867,Inhibition of the renin-angiotensin-aldosterone system in heart failure: new insights from basic clinical research.,J G Cleland; K Morgan,"It is sobering to recall that, despite much basic research and many small and large clinical trials, we still do not know how angiotensin-converting enzyme inhibitors work. This is true both in terms of their fundamental mode of action at a cellular level as well as in the patient in the clinical setting. New pharmaceutical compounds such as renin inhibitors, angiotensin II receptor antagonists and aldosterone antagonists are bringing new insights not only into the importance of different components of the renin-angiotensin-aldosterone system in heart failure but also into the mode of action of angiotensin-converting enzyme inhibitors. This manuscript also provides a brief update on the organization of the renin-angiotensin-aldosterone system and other angiotensin-II-forming pathways with special relevance to heart failure. Data on the potential relevance of genetic polymorphisms of the renin-angiotensin-aldosterone system are discussed. Possibly the single most important observation in clinical cardiovascular medicine in 1995 was the reporting of a highly significant interaction between angiotensin-converting enzyme inhibitors and aspirin on mortality in patients with ventricular dysfunction with or without heart failure. This has called into question the safety of aspirin use in heart failure.",1996.0,0,0
1961,8840302,Will angiotensin II receptor antagonists be renoprotective in humans?,I Ichikawa,,1996.0,0,0
1962,8841011,Angiotensin-converting enzyme inhibition after acute myocardial infarction with special reference to the Fourth International Study of Infarct Survival (ISIS-4).,M Syed; S Borzak; S M Jafri,"Role of ACE inhibitors in the management of asymptomatic or symptomatic left ventricular (LV) dysfunction after acute myocardial infarction (AMI) is well established. More recently, large clinical trials have evaluated the use of angiotensin-converting enzyme (ACE) inhibitors early after AMI, ie, within 24 hours of symptom onset. This concept has emerged with the understanding of pathophysiological changes occurring after AMI. Neurohormonal activation and ventricular remodelling after AMI form the basis of these changes, whereas the extent of LV dysfunction remains strongly predictive of poor outcome. The large clinical trials with mortality end point have shown modest benefit with early use of ACE inhibitors in an unselected population. However, the generalized use of ACE inhibitors remains controversial because of an overall small benefit. We review the pathophysiological changes occurring after AMI, the rationale for early use of ACE inhibitors, and the data available from the large clinical trials. We recommend consideration of early ACE inhibitor in all but the lowest risk patients. Clinical features of such a low-risk population would include small and nonanterior infarctions in patients less than 65 years of age and with LV ejection fractions greater than 50%. Objective assessment of LV function is warranted during hospitalization for AMI to appropriately select patients for ACE inhibitor therapy. Dosing should be started carefully to avoid hypotension and should be titrated to the goal of doses used in the large trials. Duration of therapy in patients at high risk for death or ventricular enlargement should be indefinite. Further large-scale secondary prevention trials with long-term treatment are underway to assess the effect of ACE inhibition on coronary disease progression and reinfarction.",1996.0,0,0
1963,8850410,Sudden hyperkalemia during cardiopulmonary bypass with hypothermic cardiac arrest in an infant.,D Ivens; F Camu,,1996.0,0,0
1964,8852495,"Effect of alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists on renal function in hypertensive non-insulin-dependent diabetic patients.",M Giordano; L R Sanders; P Castellino; M L Canessa; R A DeFronzo,"In the present study we investigated the effect of a selective alpha 1-adrenergic blocker (doxazosin), an angiotensin-converting enzyme (ACE) inhibitor (captopril), and a calcium channel antagonist (nifedipine) on renal function in hypertensive non-insulin-dependent diabetic patients. 30 NIDD hypertensive patients (age = 50 +/- 3 years; BMI = 30 +/- 1 kg/m2) (mean +/- SEM) were studied before and after a 12-week period of antihypertensive treatment. Ten patients were treated with doxazosin (Cardura) (2-8 mg once daily or 8 mg b.i.d.), 9 with captopril (Capoten) (25-50 mg b.i.d.), and 11 with nifedipine (Procardia-XL) (30-60 mg once daily). Blood pressure, creatinine clearance, 24-hour urinary protein excretion, fasting plasma glucose concentration and glycosylated hemoglobin were measured before and after drug treatment. Fasting plasma glucose and glycosylated hemoglobin (HbA1c) were similar in all three groups prior to the start of antihypertensive therapy and did not change significantly from baseline in any treatment groups. In the doxazosin group creatinine clearance rose from 99 +/- 8 to 122 +/- 8 ml/1.73 m2.min (p < 0.01), while 24-hour urinary protein excretion declined from 2.66 +/- 0.05 to 1.76 +/- 0.02 mg/day/ml/1.73 m2.min (p < 0.01). In diabetics treated with captopril creatinine clearance rose from 93 +/- 6 to 109 +/- 9 ml/1.73 m2.min (p < 0.05), while the 24-hour urinary protein excretion fell from 2.70 +/- 0.05 to 2.03 +/- 0.04 mg/day/ml/1.73 m2.min (p < 0.05). In patients treated with nifedipine creatinine clearance did not change (97 +/- 6 vs. 94 +/- 7 ml/1.73 m2.min), while 24-hour urinary protein excretion decreased from 2.84 +/- 0.04 to 1.95 +/- 0.03 mg/day/ml/1.73 m2.min. Systolic and diastolic blood pressure were similar in doxazosin (150 +/- 3/95 +/- 2 mm Hg), captopril (153 +/- 3/93 +/- 1), and nifedipine (155 +/- 4/93 +/- 1) groups prior to the start of antihypertensive therapy and declined to 143 +/- 3/84 +/- 3 (doxazosin), 139 +/- 3/82 +/- 3 (captopril), and 141 +/- 3/84 +/- 1 (nifedipine) mm Hg (all p < 0.01 vs. pretreatment). In summary, both doxazosin and captopril treatment were associated with significant rises in GFR, while all three antihypertensive agents caused a significant decline in proteinuria. These results indicate that alpha-adrenergic blockers, ACE inhibitors, and calcium channel antagonists can safely and effectively be used in the clinical management of non-insulin-dependent diabetic patients with hypertension.",1996.0,0,0
1965,8852521,Drugs during pregnancy: an issue of risk classification and information to prescribers.,R Sannerstedt; P Lundborg; B R Danielsson; I Kihlström; G Alván; B Prame; E Ridley,"The Swedish system for the classification of fetal risk of drugs was the first of its kind and was implemented in 1978. Drugs for use in pregnant women are classified in 4 general categories--A to D. The US Food and Drug Administration (FDA) introduced a system in 1979 also using the letters A to D, together with an X category. However, the definitions differ considerably between the FDA system and the Swedish system, resulting in a very different allocation of drugs to the respective categories. In the Swedish system, category A includes drugs that have been extensively used and/or for which there are reliable clinical data indicating no evidence of disturbance of the reproductive process. Category B includes drugs for which data from pregnant women are insufficient for making any solid estimation of human teratogenic risk, and classification is therefore based on animal data, with allocation to 3 subgroups. For products in category C, the pharmacological action of the drug may have undesirable effects on the human fetus or newborn infant. Finally, category D contains drugs for which human data indicate an increased incidence of malformations. The categorisation statement is always followed by a short explanatory text. In contrast to the FDA system, the Swedish system has been well accepted, as judged by an interview study including 934 physicians and pharmacists. We believe that much of the American dissatisfaction may be a consequence of shortcomings in the category definitions of the FDA system. The FDA system requires an unrealistically high quality of data, e.g. the availability of controlled studies in pregnant women that fail to demonstrate a risk to the fetus are needed for a drug to be assigned to category A. Consequently, the majority of drugs on the US market are allocated to category C, interpreted as 'risk cannot be ruled out'. The distribution of drugs into the various categories is thus very different between the Swedish and FDA systems. We think that the issue of this debate reflects a fundamental problem related to public health information: how should a large, compounded, changing and difficult to evaluate databank be organised before it is made available to professionals and secondarily to lay people?",1996.0,0,0
1966,8857071,Lisinopril reduces postexercise albuminuria more effectively than atenolol in primary hypertension.,C Rangemark; H Lind; L Lindholm; T Hedner; O Samuelsson,"Physical exercise causes transient albuminuria. The mechanisms of postexercise albuminuria are not fully clarified but stimulation of the reninangiotensin system (RAS) probably plays a major role through intrarenal haemodynamic changes causing an elevated filtration pressure. In a randomised, double-blind, crossover study we compared the effects on urinary albumin excretion (UAE) of lisinopril (L) and atenolol (A) therapy, i.e. we aimed to investigate whether inhibition of the RAS or inhibition of beta1-adrenoceptor-mediated effects of the sympathetic nervous system differed with regard to changes in UAE. Sixteen patients with uncomplicated primary hypertension were studied. Four standardised bicycle ergometer exercise tests were performed, before and after each active treatment period. UAE 30 min postexercise, determined by radioimmunoassay, was significantly lowered by both treatments: -278 mu g center dot min-1 (L) and -199 mu g center dot min-1 (A). The reduction of postexercise UAE achieved by treatment with the angiotensin-converting enzyme (ACE) inhibitor (L) was significantly greater than that achieved by the beta1-selective adrenoceptor blocker treatment. Blood pressure (BP) at rest and during exercise were equally reduced by both drugs. In conclusion, this study showed that antihypertensive treatment with an ACE inhibitor was more effective in reducing exercise-induced albuminuria than a beta1-selective adrenoceptor-blocking agent with a similar degree of BP reduction in patients with uncomplicated primary hypertension. This suggests that the RAS plays a major role in postexercise albuminuria in hypertensive subjects. The clinical significance of this finding, however, remains to be clarified.",1996.0,0,0
1967,8858268,Adaptive changes in the acute haemodynamic effects of cilazapril during chronic treatment. Comparison with long-term clinical effect.,J Larsen; R Sykulski; G Jensen; L Dössegger; B Trimarco; T Moccetti; D Glogar; A Schelling; A H Bosma,"To study the adaptive changes in the acute haemodynamic response to ACE inhibition during chronic treatment in CHF. The acute and chronic effects of oral cilazapril (CLZ) treatment, an ACE-inhibitor with prolonged duration on haemodynamic measures (PCWP, PAP, RAP, CI and SVR) and clinical parameters (Quality-of-Life and NYHA class) were investigated in a double-blind, randomised, placebo-controlled trial in CHF. One hundred and thirty five patients (112 completing) in NYHA Classes II-III, on digitalis and diuretic treatment, were randomised after 2 weeks of placebo run-in, to receive either placebo or CLZ 0.5 mg, 1.0 mg or 2.5 mg daily for 12 weeks, followed by 2 week placebo wash-out. Haemodynamic studies, including exercise tests before and 3 h after medication, were performed on the first and last days of treatment. Measurements were performed at rest and at the maximum exercise level. In ACEI-naive patients oral CLZ 0.5 and 1 mg/d caused a dose dependent decrease in PCWP and diastolic PAP, and a significant reduction of SVR mg. A slight increase in CI was observed in all groups. The maximum effect was observed 3-5 h post dose. After 12 weeks of oral treatment, the acute response was similar but was attenuated relative to the first dose. Exercise tolerance improved in a dose dependent manner. The NYHA classification remained unchanged or improved in the majority of patients. Entry into the 2.5 mg group had to be terminated at an early stage due to severe adverse events observed after the first dose. During chronic treatment, the haemodynamic response to oral cilazapril was attenuated, indicating that continued clinical improvement in patients with CHF on CLZ is independent of to its acute haemodynamic effects.",1996.0,0,0
1968,8859935,Differing early blood pressure and renin-angiotensin system responses to the first dose of angiotensin-converting enzyme inhibitors in congestive heart failure.,I B Squire; R J MacFayden; J L Reid; A Devlin; K R Lees,"We previously demonstrated differing blood pressure (BP) responses to the first dose of angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure (CHF). We wished to confirm the disparate responses to the first dose of these agents, study the response to repeated dosing, and explore possible explanations (slow, tight binding, and steric hindrance) for the phenomenon. Forty-eight elderly patients (aged 51-85 years) with stable CHF were studied for 48 hours. Groups (n = 12) received one of the following: (a) perindopril 2 mg orally (p.o.) + placebo intravenously (i.v.) (day 1) and perindopril 2 mg p.o. (day 2); (b) enalapril 2.5 mg p.o. + placebo i.v. (day 1) and enalapril 2.5 mg p.o. (day 2); (c) placebo p.o. + perindopril at 0.167 mg i.v. (day 1) and perindopril 2 mg p.o. (day 2); or (d) placebo p.o. + placebo i.v. (day 1) and placebo p.o. (day 2). Supine BP was measured on day 1. On day 2, BP was recorded by ambulatory BP monitor. Blood samples were taken at baseline and at intervals during the 48-h study period for estimation of neurohumoral parameters. Inhibition of the renin-angiotensin system (RAS) was estimated by plasma ACE inhibition and also by the ratio of angiotensin II (Ang II)/Ang I + Ang II. On day I, enalapril 2.5 mg caused a greater decrease in BP than did placebo response between 6 and 9 h postdose. Perindopril 2 mg produced a profile of BP response similar to that of placebo. Ambulatory BP on day 2 was consistently lower with enalapril as compared with perindopril. Profiles of plasma ACE inhibition were similar with each active therapy. Enalapril therapy produced a greater increase in plasma renin activity (PRA) than did other treatments. There was no temporal dissociation between plasma ACE inhibition and profile of Ang peptides for any treatment. We have confirmed the disparate BP responses to perindopril and enalapril in CHF. We noted no evidence of slow, tight binding or steric hindrance to explain these differences.",1996.0,0,0
1969,8860099,Low dose of ACE-inhibitor enhances sodium excretion in volume expanded patients with borderline hypertension.,C Borghi; S Boschi; F V Costa; S Bacchelli; D Degli Esposti; V Immordino; M Piccoli; F Ambrosioni,"The purpose of the present study was to separately investigate the effects of two different dosages of captopril on pressor, vascular and humoral response to acute extracellular volume expansion in patients with borderline hypertension (BHT). Thirty-five patients were randomly allocated in two groups undergoing acute saline infusion (0.40 ml/min/kg for 45 min and 0.15 ml/min/kg for 75 min)before and after a 7-day period of treatment with either placebo or captopril at the dose of 12.5 (LD-CAP) or 50 mg (HD-CAP) twice a day. At baseline the effects of LD-CAP were limited to an increase in PRA and to a decrease in plasma aldosterone whereas HD-CAP decreased systolic and diastolic blood pressure (SBP, DBP), forearm vascular resistance (FVR) and increased venous distensibility (VV(30)) as well. After saline loading patients treated with HD-CAP showed an increase in SBP, DBP not observed in patients allocated to LD-CAP. Urinary sodium excretion in response to NaCl loading was selectively enhanced by LD-CAP (+25%) whereas HD-CAP did not (+6.3%). The present data suggest that low-doses of ACE-inhibitors acting through a selective blockade of RAA not associated with hemodynamic changes can enhance the natriuretic response to acute volume expansion in borderline hypertensives.",1996.0,0,0
1970,8861547,Fosinopril: a reappraisal of its pharmacology and therapeutic efficacy in essential hypertension.,A J Wagstaff; R Davis; D McTavish,"Fosinopril is a phosphinic acid derivative which undergoes rapid hydrolysis after oral administration to the active diacid ACE inhibitor fosinoprilat. Cardiotropic effects have been associated with the drug, and the compensatory dual elimination route of fosinopril via renal and hepatic systems offers an opportunity for ACE inhibitor treatment of hypertension in patients with renal or hepatic impairment. Comparative trials of monotherapy with fosinopril 10 to 40 mg/day have demonstrated antihypertensive efficacy equivalent to that of sustained release nifedipine 40 mg/day, hydrochlorothiazide 25 to 50 mg/day, enalapril 5 to 10 mg/day amlodipine 5 to 10 mg/day and sustained release verapamil 240 to 480 mg/day, and superior to that of isradipine 5 mg/day. The efficacy of combination therapy with fosinopril 10 to 20 mg/day and hydrochlorothiazide 12.5 mg/day was significantly superior to that of hydrochlorothiazide alone, tended to be superior to that of fosinopril 20 mg/day alone and was similar to that of sustained release nifedipine 40 mg/day alone. The combination of fosinopril/chlorthalidone 20 to 40/25 mg/day was as effective as propranolol/chlorthalidone 80 to 160/25 mg/day. The incidence of adverse effects associated with fosinopril is low, and cough may possibly occur less often with this drug than with other ACE inhibitors. Fosinopril thus offers an effective and well tolerated option for the treatment of hypertension in adult and elderly patients, including those with renal or hepatic impairment.",1996.0,0,0
1971,8862331,Visceral angioedema related to treatment with an ACE inhibitor.,R J Mullins; T M Shanahan; R T Dobson,"For more than five years, a patient suffered recurrent episodes of abdominal pain accompanied by diarrhoea, nausea and vomiting. An angiotensin converting enzyme (ACE) inhibitor causing visceral oedema was eventually implicated.",1996.0,0,0
1972,8862965,"ACE inhibitor-induced cough and bronchospasm. Incidence, mechanisms and management.",A Overlack,"A dry, tickly and often bothersome cough is the most common adverse effect of ACE inhibitors. Recent studies indicate that cough may develop in around 10% of the patients treated with ACE inhibitors. In half of these patients, the ACE inhibitor has to be discontinued. Cough has emerged as a class effect occurring with all ACE inhibitors with no clear difference between the single substances. While ACE inhibition is safe in the vast majority of patients with obstructive airways disease, asthmatic symptoms or exacerbation of asthma as well as a rise in bronchial reactivity have been occasionally reported. ACE inhibition increases the cough reflex. The mechanisms underlying ACE inhibitor-induced cough are probably linked to suppression of kininase II activity, which may be followed by an accumulation of kinins, substance P and prostaglandins. Physicians should be aware that a dry cough is the most common adverse effect of ACE inhibitors and that this symptom may occur not necessarily shortly after institution of therapy but months or even a year later. Replacement by another ACE inhibitor should not be tried, since the cough will almost always recur on rechallenge with the same or another ACE inhibitor. After withdrawal of the ACE inhibitor, which is the treatment of choice, cough will resolve usually within a few days.",1996.0,0,0
1973,8862977,Evidence of depression provoked by cardiovascular medication: a prescription sequence symmetry analysis.,J Hallas,"Many cardiovascular drugs have been implicated as causes of depression. With the exception of beta-blockers, few have been studied in formal epidemiologic designs. I present a new approach to such analyses that effectively controls for confounders that are stable over time. I analyzed the exposure histories of 11,244 incident antidepressant users, using the Odense University PharmacoEpidemiologic Database. All persons starting both beta-blockers and antidepressants during a predefined period were identified. If beta-blockers do not cause depression, this particular population should show equal numbers of persons starting either drug first. A depression-provoking effect of beta-blockers would generate an excess of persons starting beta-blockers first, that is a nonsymmetrical distribution of prescription orders. Confounders causing the two drugs to be co-prescribed would rarely be expected to affect the symmetry. The initial screening showed nonsymmetrical prescription orders for a wide range of cardiovascular drugs. After adjustment for an increasing incidence of antidepressant prescribing, I found a depression-provoking effect only for angiotensin-converting enzyme (ACE) inhibitors (rate ratio = 1.29; 95% confidence interval = 1.08-1.56) and calcium channel blockers (rate ratio = 1.31; 95% confidence interval = 1.14-1.51). This prescription sequence symmetry analysis may be useful as a screening tool.",1996.0,0,0
1974,8863541,Medical treatment of cystinuria: results of contemporary clinical practice.,G K Chow; S B Streem,"We determined the efficacy of a contemporary medical regimen for treatment of cystinuria. A total of 16 patients with cystinuria was followed for 7 to 141 months (mean 78.1). Standard therapy included hydration and alkalization. D-penicillamine or alpha-mercaptoproprionylglycine was added for failure of hydration and alkalization to prevent new stones or stone growth, or to cause dissolution. Captopril was added for failure of or intolerance to D-penicillamine or alpha-mercaptopropionylglycine. Radiography was performed every 6 to 12 months, at which time stone events were documented. During hydration and alkalization 46 stone events occurred in 8 of 9 patients (1.6 events per patient-year). With addition of thiol derivatives 7 of 9 patients experienced 24 stone events, all 6 treated with hydration, alkalization and captopril experienced 10 events, and 4 of 5 treated with alkalization, thiols and captopril experienced 8 events (0.52, 0.71 and 0.54 events per patient-year, respectively). During a total treatment time of 104.1 patient-years 88 stone events occurred in 14 of 16 patients (0.84 events per patient-year). D-penicillamine and alpha-mercaptopropionylglycine are effective in decreasing the rate of stone formation in patients in whom hydration and alkalization failed. While captopril may also be beneficial in this setting, it does not appear to be as effective as D-penicillamine or alpha-mercaptopropionylglycine, and it does not clearly add clinical benefit to those thiols. Our study demonstrates that patients with cystinuria are at high risk for recurrence when treated with any contemporary medical program. This natural history must be considered when evaluating the long-term efficacy of newer or alternative modes of medical and urological treatment.",1996.0,0,0
1975,8865265,Modulators of the renin-angiotensin-aldosterone system and cough in childhood.,P Donati-Genet; M G Bianchetti,,1996.0,0,0
1976,8866628,Effects of hydrochlorothiazide and captopril on lipoprotein lipid composition in patients with essential hypertension.,J D Bagdade; W F Buchanan; T Pollare; H Lithell,"Effective antihypertensive agents may differ in their capacity to reduce cardiovascular risk because they induce potentially atherogenic alterations in lipoprotein composition. To assess this possibility, the effects of five months' treatment with either hydrochlorothiazide (HCTZ) or the converting enzyme inhibitor captopril (CAPT) on lipoprotein lipid composition were compared in thirty normolipidaemic patients with essential hypertension (EH). The sixteen patients treated with HCTZ showed the expected directional alterations in plasma TG (+31%), HDL2-C (-16%), and CHOL (+7.6%); in contrast TG and CHOL were unchanged after captopril in fourteen patients and their HDL2-C declined (-16%). Neither drug altered lipoprotein core lipid composition, but small increases were observed in the HDL2 sphingomyelin/lecithin ratio after both agents. The plasma free (unesterified) cholesterol (FC) lecithin (L) ratio, a new index of cardiovascular risk, was abnormally increased before treatment and was not altered by either drug. These findings indicate that HCTZ and CAPT treatment have small, but demonstrable effects on lipoprotein surface lipid composition in patients with EH that are confined to the HDL2 subfraction.",1996.0,0,0
1977,8867559,"Arterial stiffness, hydrochlorothiazide and converting enzyme inhibition in essential hypertension.",A Bénétos; A Laflèche; R Asmar; S Gautier; A Safar; M E Safar,"In a randomized double blind study, the arterial changes produced either by hydrochlorothiazide plus amiloride (Group I), or by hydrochlorothiazide plus captopril (Group II) were investigated in two territories of the arterial tree, the common carotid artery and the terminal aorta. Arterial echo-tracking techniques of high resolution and applanation tonometry were used to evaluate non-invasively the indices of arterial stiffness and carotid wave reflections. In Group I and II, there was a similar significant decrease in brachial blood pressure (BP) and carotid diastolic diameter and an increase in aortic compliance and distensibility. Groups I and II differed significantly in aortic diastolic diameter which decreased in Group I but not in Group II, and in carotid wave reflections which were modified in Group II but not in Group I. Thus, captopril associated with hydrochlorothiazide resulted in a shift in the carotid arterial reflection wave from systole to diastole with no reduction in the aortic diastolic dimension. For similar BP reduction, the combination of hydrochlorothiazide and amiloride had no significant effect on the carotid reflection wave, but caused a significant reduction in the aortic diastolic diameter. These intergroup differences were related to the presence or absence of converting enzyme inhibition.",1996.0,0,0
1978,8867566,Quality of life in normotensives compared to hypertensive men treated with isradipine or methyldopa as monotherapy or in combination with captopril: the LOMIR-MCT-IL study.,Y Yodfat; D Bar-On; M Amir; N Cristal,"Quality of life (QOL) measures were assessed in a multi-center, double-blind, case-controlled trial of 1 year's duration. A total of 368 hypertensive male patients were randomly assigned to monotherapies of either isradipine, methyldopa or placebo. If normotension was not achieved, captopril was added. QOL assessments in the hypertensives and in 155 normotensives included a self-structured scale to measure the subjective perception of QOL, the severity, desirability and controllability of recent critical life events, semantic memory, physical dysfunction, sleep disorders, sexual difficulties, depression and work-related stress. The overall withdrawal rate during the trial was 19%, mainly due to lack of efficacy and adverse experiences. At baseline, and at the end of the trial, the normotensives as compared to hypertensive patients, had significantly better scores in most QOL measures. Patients treated with the combination of isradipine and captopril reported more favorable changes in the subjective measure of QOL (P < 0.03) and in semantic memory (P < 0.001) than patients treated with any of the monotherapies or with methyldopa in combination with captopril. There were no statistically significant differences among treatments for changes of other indices of QOL. In most QOL measurements, normotensives rated better then hypertensives. Patients treated on long-term therapy with the combination of isradipine and captopril showed improvement in self-structured QOL measures and semantic memory, compared to patients treated either with methyldopa or placebo.",1996.0,0,0
1979,8867568,Once-daily monotherapy with trandolapril in the treatment of hypertension.,D H Smith; J M Neutel; H R Black; J A Schoenberger; M A Weber,"Once-daily antihypertensive drugs that control blood pressure (BP) for the full 24-h dosing period, enhance patient compliance and may reduce the cardiovascular complications of hypertension which occur with increased frequency in the early morning. Since some once-daily agents are more effective than others in maintaining antihypertensive effects toward the end of the 24-h dosing interval this study was designed to evaluate the duration of antihypertensive action of trandolapril using 48 h ambulatory blood pressure monitoring (ABPM) in 41 patients with mild-to-moderate essential hypertension. Twenty-four hour ABPM was performed on two consecutive days (48 h) after a 4 week single blind placebo run-in period and repeated after an 8 week double-blind period during which 20 patients were randomized to treatment with trandolapril (2-4 mg once-daily) and 21 patients to matching placebo. During the second 48 h monitoring period, placebo rather than active medication was taken by both of the groups at the beginning of the second 24 h segment. Trandolapril reduced ambulatory systolic and diastolic BP by 9.4 and 6.2 mm Hg respectively (P < or = 0.01) during the first 24 h of the post treatment monitoring period while placebo increased the systolic and diastolic BPs in the same period by 3.8 and 2.6 mm Hg (P < 0.05). During the second monitoring period (hours 25-48), trandolapril reduced systolic and diastolic BP by 5.6 and 3.9 mm Hg while placebo increased BP by 2.3 and 1.6 mm Hg (P < 0.03). When compared to placebo by 2 h time blocks, throughout the 2 days of monitoring, trandolapril produced clinically significant decreases in systolic and diastolic BP for 30 and 28 h following dosing. This indicates that trandolapril can be considered a true once-daily antihypertensive agent.",1996.0,0,0
1980,8868976,"Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?",J Boldt; G Rothe; E Schindler; C Döll; G Görlach; G Hempelmann,"To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery. Prospective randomised controlled trial. Clinical investigation in a cardiac anaesthesia department of a university hospital. 88 consecutive patients undergoing coronary artery bypass surgery. After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass. The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days. Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml). In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury.",1996.0,0,0
1981,8869864,"Effects of two different enalapril dosages on clinical, haemodynamic and neurohumoral response of patients with severe congestive heart failure.",R Pacher; B Stanek; S Globits; R Berger; M Hülsmann; M Wutte; B Frey; M Schuller; E Hartter; E Ogris,"Angiotensin converting enzyme inhibitors improve symptoms and prolong life in congestive heart failure, but the dose in the individual patient is uncertain. A randomized, 48-week, double-blind study was performed to investigate the safety and efficacy of 'high' in comparison to continued 'low' angiotensin converting enzyme inhibitor therapy in severe heart failure. Eighty-three patients (56 +/- 1.1 years; 69 men, 14 women) in New York Heart Association functional class III/IV on digoxin, furosemide and 'low' angiotensin converting enzyme inhibitors (captopril < or = 50 mg.day-1 or enalapril < or = 10 mg.day-1) were included. After a > or = 14 day run-in on 10 mg.day-1 enalapril, digitalis and furosemide, right heart catheterization at rest and exercise was performed. All patients presented with atrial pressure > 10 mmHg and/or pulmonary artery pressure > 35 mmHg, and/or cardiac index < 2.5 l.min-1.m-2 at rest. Patients then received enalapril 5 mg twice daily (n = 42), or 20 mg twice daily (n = 41) in random order. Thus, patients randomized to low doses of enalapril actually had no change in therapy from baseline to 48 weeks. Forty-three patients (52%) completed the study, 19 patients on the low dose and 24 patients on the high dose. Both dosages equally influenced survival with 15 (18%) deaths, eight on low dose and seven on high dose. After 48 weeks, functional capacity by New York Heart Association class improved more on the high dose than on the low dose (P = 0.04). In contrast, alterations in invasive haemodynamic variables at rest and exercise as well as maximal exercise capacity were comparable in both groups. Diastolic blood pressure decreased and the change between both groups was statistically significant (P = 0.01). Changes in plasma creatinine levels did not differ between high and low dose treatment and no patients had to be withdrawn because of deterioration in kidney function. With regard to neurohumoral activity, a tendency to a discrepant response to both treatments was observed with a blunted increase in noradrenaline on high versus low enalapril dose. Thus, high-dose enalapril treatment proved superior to low dose as regards symptomatology in severe heart failure after long-term treatment, despite similar effects on haemodynamics and on maximal exercise capacity.",1996.0,0,0
1982,8872795,Assessment of drug efficacy using home self-blood pressure measurement: the SMART study. Self Measurement for the Assessment of the Response to Trandolapril.,F Zannad; L Vaur; C Dutrey-Dupagne; N Genès; G Chatellier; F Elkik; J Ménard,"The SMART study (Self Measurement for the Assessment of the Response to Trandolapril) was a large scale trial conducted by general practitioners in order to assess the informative value of home self-measured blood pressure (BP) for the evaluation of therapeutic intervention. After a 2-week wash-out period, patients with office diastolic blood pressure (DBP) between 95 and 120 mm Hg received trandolapril, 2 mg once daily for 4 weeks. Four days of self-recorded BP were performed both at the end of the wash-out period and at the end of the treatment period with an automatic printerequipped device using the oscillometric method (A&D UA 751). Every day, a series of three consecutive measurements was planned in the morning before drug intake and repeated in the evening. A total of 1710 patients (946 men, 764 women) aged 56 +/- 11 entered the study. In the 816 patients who correctly performed self-measured blood pressure (SMBP) during both periods and followed the protocol schedule, office BP (SBP/DBP) decreased from 166.4 +/- 15/101.4 +/- 6 mm Hg to 144.7 +/- 14/86.1 +/- 8 mm Hg while SMBP decreased from 153 +/- 18/94 +/- 10 mm Hg to 139 +/- 16/85 +/- 10 mm Hg. A weak correlation was found between the two methods with regard to systolic (r = 0.47, P < 0.0001) and diastolic (r = 0.36, P < 0.0001) BP lowering. Individual response to therapy varied between the two methods: 633 patients (77.6%) exhibited at least a 10 mm Hg office DBP decrease while 493 (60.4%) presented at least a 6 mm Hg self measured DBP decrease in the evening; 65% of patients were considered as responders with both methods. The 24-h therapeutic coverage was assessed by the morning to evening BP decrease ratio (M/E ratio) which represents the ratio of the trough effect to the 12-h post dosing efficacy. Both population and individual M/E ratios ranged between 73% and 86% thus confirming the long duration of action of trandolapril. (1) discrepancies between office and self-measured BP evaluation of therapeutic response have been pointed out: agreement between the two methods is obtained in only 65% of patients, mainly due to intra-individual BP variability and recording conditions; and (2) self-measured BP could be a potential tool to explore the 24-h therapeutic coverage.",1996.0,0,0
1983,8872973,Mechanism of angiotensin converting enzyme inhibitor-related anemia in renal transplant recipients.,J Gossmann; P Thürmann; T Bachmann; S Weller; H G Kachel; W Schoeppe; E H Scheuermann,"To delineate the pathogenesis of the reduction in hemoglobin occurring in renal transplant patients treated with angiotensin converting enzyme inhibitors (ACEI) and azathioprine (AZA) a controlled, prospective trial of ACEI withdrawal was conducted. The ACEI was replaced by nifedipine or clonidine in 15 kidney transplant patients immunosuppressed with AZA and prednisone (enalapril in 14 and captopril in 1). Before and during 10 to 12 weeks after withdrawal of the ACEI, AZA metabolites, renal function parameters and hematological parameters including erythropoietin and reticulocytes were evaluated. Enalaprilat levels were measured and compared with 15 similar patients matched for transplant function and enalapril dosage immunosuppressed with cyclosporine and prednisone. AZA metabolites did not differ significantly in the presence or absence of the ACEI. Enalaprilat levels also showed no significant difference between the two patient groups treated with AZA or cyclosporine. Hematocrit and hemoglobin increased significantly from 37.5 +/- 6.4 to 39.7 +/- 3.6% (mean +/- SD, P = 0.02) and 12.8 +/- 2.2 to 13.5 +/- 1.2 g/dl, P = 0.04, respectively, 10 to 12 weeks after ACEI treatment had been discontinued. Simultaneously numbers of reticulocytes and erythropoietin concentrations rose significantly after 2, 4 and 10 weeks, with a peak at two weeks (from 14.1 +/- 3.8 to 20.6 +/- 8.0/1000, P < 0.05 and from 14.3 +/- 12.4 to 29.3 +/- 54.5 mU/ml, P < 0.05, respectively). In conclusion, ACEI-related anemia in renal transplant recipients seems to be due to the erythropoietin-lowering effect of this group of drugs. A pharmacokinetic interaction between AZA and enalapril is not likely since plasma enalaprilat levels were independent of the immunosuppressive regimen and AZA metabolite levels were unchanged in the presence and absence of the ACEI. Several mechanisms by which angiotensin converting enzyme blockade may cause a decrease in circulating erythropoietin are discussed.",1996.0,0,0
1984,8873580,Effect of spirapril and hydrochlorothiazide on platelet function and euglobulin clot lysis time in patients with mild hypertension.,G Gleerup; J R Petersen; J Mehlsen; K Winther,"Thirteen patients with mild hypertension (untreated diastolic blood pressure of 95 to 114 mmHg) received, in random order, three successive treatments of four weeks with placebo, spirapril (6 mg daily), or hydrochlorothiazide (HCT2) (24 mg daily). At the end of each treatment, blood samples for assessment of platelet aggregation and platelet release of platelet factor 4 (PF4) and for assessment of fibrinolysis, estimated by tissue plasminogen activator (t-PA), plasminogen activator inhibitor-type 1 (PAI-1), and euglobulin clot lysis time (ECLT), were taken, first at rest, then immediately after five to ten minutes of vigorous exercise, and finally after the subsequent hour of recovery rest. Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2, the threshold rising to 10 microM as compared with 1.0 with placebo (P < 0.05) at rest, and the threshold for adenosine diphosphate (ADP) aggregation also rose, from 2 microM to 4 (NS). The resting plasma PF4 value fell, although not significantly, during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sampled at rest, and the PF4 plasma levels showed no significant reductions at rest. However, during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy. This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo (P < 0.05). ECLT and t-PA did not shift significantly from the placebo level during either therapy. PAI-1 did not change during spirapril therapy, but during HCT2 treatment it fell, although not significantly, to 9.36 IU/mL from 15.91 with placebo (NS). Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis. HCT2 seems to decrease platelet activity at rest, whereas spirapril seems to some extent to decrease platelet activity at exercise.",1996.0,0,0
1985,8877260,Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial.,R O Estacio; S Savage; N J Nagel; R W Schrier,"The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large, prospective, randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and of an angiotensin-converting enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations: a hypertensive one (diastolic blood pressure of > or = 90.0 mm Hg at the time of randomization) and a normotensive one (diastolic blood pressure of 80.0-89.0 mm Hg at the time of randomization). A total of 950 men and women aged 40-74 years were randomized and are being followed for 5 years at a single center. There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population.",1996.0,0,0
1986,8877596,Pharmacokinetic-pharmacodynamic model relating lisinopril plasma concentrations to regional hemodynamic effects in healthy volunteers.,E Bellissant; P C Nguyen; J F Giudicelli,"In a previous placebo-controlled, randomized, double-blind, cross-over study performed in 6 healthy volunteers, we investigated the pharmacokinetics and pharmacodynamics of a single oral administration of two doses (5 and 20 mg) of the angiotensin-converting enzyme inhibitor (ACEI), lisinopril. The purpose of the present study was to investigate the relation between lisinopril plasma concentrations (C, ng/ml), and lisinopril-induced effects on plasma converting enzyme activity (PCEA, nmol/ml/min), brachial artery flow (BAF, ml/min), and brachial vascular resistance (BVR, mm Hg . s/ml). PCEA and BVR were expressed in percent changes from initial values and BAF was expressed in absolute values. Effects (E) were related to C by the Hill model: E = Emax . C gamma/CE50 gamma + C gamma). For PCEA, the model was fitted to the data of both doses simultaneously. Emax was fixed at -100%, and we obtained (mean +/- SD) CE50 = 1.4 +/- 0.6 ng/ml and gamma = 0.6 +/- 0.1. For BAF and BVR, the model was fitted to the data of the 20-mg dose for 5 subjects and to those of the 5-mg dose for 1 subject. We obtained Emax = 45 +/- 20 ml/min, CE50 = 24.0 +/- 12.4 ng/ml, and gamma = 3.2 +/- 1.3 for BAF, and Emax = -45 +/- 15%, CE50 = 22.0 +/- 10.2 ng/ml, and gamma = 3.1 +/- 1.1 for BVR. Therefore, the concentration-effect relations for BVR (or BAF) and PCEA display quite different shapes (CE50, gamma), which emphasizes the necessity of performing pharmacokinetic-pharmacodynamic (PK-PD) modeling on hemodynamic parameters to determine the optimal dosages of ACEIs.",1996.0,0,0
1987,8877673,A comparison of the antihypertensive effectiveness of a combination of moexipril or sustained-release verapamil with low-dose hydrochlorothiazide.,S G Chrysant; M Stimpel,"The antihypertensive effectiveness of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, and sustained-release verapamil (verapamil SR) in combination with low-dose hydrochlorothiazide was investigated in patients with moderate to severe (Stages II and III) essential hypertension. Of 147 patients treated for 4 weeks with hydrochlorothiazide 25 mg/day, 108 patients with sitting diastolic blood pressure (SDBP) of 100 to 114 mmHg were randomly assigned to receive either moexipril 7.5 mg/day (n = 56) or verapamil SR 180 mg/day (n = 52) in addition to hydrochlorothiazide 25 mg/day. After 4 weeks of treatment, doses of moexipril or verapamil SR were increased to 15 and 240 mg/ day respectively for patients with SDBP of > or = 90 mmHg. These patients were evaluated for an additional 8 weeks. Electrocardiograms, blood chemistries, blood counts, urinalysis, plasma renin activity, and plasma aldosterone levels were monitored during the study. Moexipril or verapamil SR, in combination with low dose hydrochlorothiazide, resulted in decreased blood pressure in the sitting and standing positions. No correlation between blood pressure response and baseline plasma renin activity was demonstrated. The results of this study indicate that both moexipril and verapamil SR produced an additive hypertensive effect when added to low-dose hydrochlorothiazide. These combinations were well tolerated by the patients and did not result in serious clinical and metabolic side effects.",1996.0,0,0
1988,8879328,Clinical and economic effects of replacing enalapril with benazepril in hypertensive patients.,T A Briscoe; C J Dearing,,1996.0,0,1
1989,8879340,Long-term renal preservation in essential hypertension. Angiotensin converting enzyme inhibition is superior to beta-blockade.,A Himmelmann; L Hansson; B G Hansson; H Hedstrand; K Skogström; J Ohrvik; A Furängen,"Antihypertensive treatment is known to slow down the decline in glomerular filtration rate (GFR) with time. Angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. In a recent prospective, randomized, double blind trial in 257 patients with essential hypertension, the loss of GFR, determined with 51Cr-EDTA clearance, was significantly less with an ACE inhibitor (cilazapril) than with a beta-adrenoceptor blocker (atenolol) during the first year of treatment. However, after 2 years, the two therapies were equally effective in this regard, thereby creating doubts about the long-term superiority of ACE inhibition in this regard. In order to elucidate whether the superior renal preservation with the ACE inhibitor was a transient effect, GFR was measured after 1 more year of treatment, i.e., after 36 months. At that time, the decline in GFR was significantly smaller in the ACE inhibitor group as compared to the beta-adrenoceptor blocker group (-3.0 [-5.5, -1.0; 95% CI] v -7.0 [-9.0, -4.5; 95% CI] mL/min x 1.73 m2; P = .026). This demonstrates that in the treatment of essential hypertension ACE inhibition preserves GFR significantly better than beta-adrenoceptor blockade during long-term therapy.",1996.0,0,0
1990,8879341,"Antihypertensive therapy and quality of life. Influence of blood pressure reduction, adverse events, and prior antihypertensive therapy.",M R Weir; L M Prisant; V Papademetriou; M A Weber; I A Adegbile; D Alemayehu; M P Lefkowitz,"Quality of life is an important attribute of antihypertensive therapy. Previous studies have not addressed the importance of a patient's prior pharmacotherapy on quality of life, which may serve as the basis of reference for a new therapy. Nor have previous studies compared commonly used quality of life instruments for consistency, or investigated whether improvement or worsening of quality of life correlates with adverse events or blood pressure reduction. Two hundred eighteen hypertensive patients with diastolic blood pressure (95 to 114 mm Hg) after a 4- to 5-week placebo washout period were enrolled in a randomized double-blind, parallel group dose-escalation trial to compare the effects of amlodipine (2.5 to 10 mg), bisoprolol (2.5 to 10 mg)/hydrochlorothiazide (HCTZ) 6.25, and enalapril (5 to 20 mg) on blood pressure, adverse events, and quality of life. Three quality of life instruments (General Well-Being Index, Vital Signs Quality of Life, Zung Self-Rating Depression Scale) were administered during original therapy, after placebo washout, and after 12 weeks of optimally titrated clinical trial pharmacotherapy. Our results demonstrated that removal from prior therapy had no detectable influence on subsequent evaluation of quality of life. The three quality of life instruments were consistent with the changes observed with the three therapies: a trend toward better quality of life with amlodipine and bisoprolol/HCTZ. Adverse events, but not systolic or diastolic blood pressure reduction correlated directly with changes in quality of life.",1996.0,0,0
1991,8879348,Enalapril does not improve left ventricular diastolic dysfunction in young and mild hypertensives without concomitant hypertrophy.,N C Chang; Z Y Lai; T C Wang,"The aim of the study was to determine whether enalapril monotherapy can improve left ventricular diastolic dysfunction (LVDD) in young and mild hypertensive patients without concomitant left ventricular hypertrophy (LVH). Fifty patients with hypertension < or = 160/100 mm Hg, aged < or = 50 years, normal two-dimensional echocardiographic (2-D echo) measurements, and LVDD were enrolled in this study. The LVDD was defined as a transmitral early (E) to atrial (A) peak velocity ratio of < or = 1. The mean documented hypertension was 6.3 years. The mean daily dose of enalapril was 13 mg. Baseline and 24-month follow-up echocardiograms were evaluated. Thirty-eight age- and sex-matched healthy subjects served to establish the normal reference values of 2-D echo measurements. After treatment, peak early diastolic velocity (E) (49 +/- 6 cm/sec v 48 +/- 10 cm/sec; P = not significant), peak atrial velocity (A) (62 +/- 9 cm/sec v 62 +/- 10 cm/sec; P = not significant), and E/A ratio (0.80 +/- 0.10 v 0.78 +/- 0.13; P = not significant) remained unchanged. Moreover, early to atrial velocity-time integral ratio (1.24 +/- 0.08 v 1.23 +/- 0.11; P = not significant) did not change. The left ventricular mass index, relative wall thickness, left ventricular end-systolic diameter, left atrial diameter, fractional shortening, heart rate, and body mass index did not show significant changes in all hypertensive patients. In conclusion, long-term antihypertensive therapy with enalapril did not lead to an improvement of LVDD in young and mild hypertension patients without concomitant LVH.",1996.0,0,0
1992,8879603,The Swedish Trial in old patients with hypertension-2 (STOP-hypertension-2): a progress report.,L H Lindholm; L Hansson; B Dahlöf; T Ekbom; T Hedner; U De Faire; B Scherstén; P O Wester,"The Swedish Trial in Old Patients with Hypertension-2 (STOP-Hypertension-2) was designed by a project group of the Swedish Hypertension Society to test whether the ""newer"" treatment alternatives (ACE inhibitors and calcium antagonists) are as good as, better or less good than, the ""older"" ones (beta-blockers and diuretics) in terms of preventing cardiovascular morbidity and mortality in elderly hypertensives. The aim of the present paper is to report on the progress of the study. Prospective, open trial with blinded end-point committee and centralized randomization (PROBE design). STOP-Hypertension-2 may be regarded as a scientific follow-up of the previously published Swedish Trial in Old Patients with Hypertension (STOP-Hypertensioon-1) (6) using the same study organization. By the end of 1994 when recruitment was stopped, 6628 hypertensive men (34%) and women (66%) aged 70-84 (mean age 76) had been included at 312 Swedish health centres (out of approximately 850). In the whole cohort 11% are diabetics and 9% smokers. The mean total cholesterol value is 6.5 mmol/L. In the whole study cohort, blood pressure was lowered from 194/98 mmHg to 167/85 mmHg after one year. At the end of 1995, 319 fatal events (all-cause mortality) had been reported, corresponding to a mortality rate of 21.3 per 1000 person-years. In STOP-Hypertension-2, 6628 elderly hypertensive have been randomized to three different treatment regimes: beta-blocker+diuretics (the active treatment arm in STOP-Hypertension-1), ACE inhibitors, or calcium antagonists. Their average lowering of blood pressure was 27/13 mmHg and end-points have occurred at the expected rate. Thus, it should be possible to terminate STOP-Hypertension-2 within two to three years.",1996.0,0,0
1993,8879890,"Efficacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in patients with essential hypertension.",S Oparil; E Barr; M Elkins; C Liss; A Vrecenak; J Edelman,"A randomized, double-masked, parallel-group, multicenter clinical trial was conducted to compare the efficacy, tolerability, and effects on quality of life associated with treatment regimens including the angiotensin II receptor antagonist losartan, with hydrochlorothiazide (HCTZ) added as needed, with regimens including the dihydropyridine calcium channel blocker amlodipine with HCTZ added as needed. The trial included patients whose sitting diastolic blood pressure (SiDBP) measurements were between 95 and 114 mm Hg, inclusive, at placebo baseline. Patients were randomized to receive either losartan or amlodipine in a double-masked, double-dummy fashion. A 4-week placebo washout period was followed by a 12-week active treatment period. Patients in the losartan arm (n = 97) were initially given 50 mg of oral (PO) losartan once a day (QD); the medication could be titrated to 50-mg losartan/ 12.5-mg HCTZ PO QD after 4 weeks, followed by 50-mg losartan plus 25-mg HCTZ PO QD after 8 weeks as necessary. Patients in the amlodipine group (n = 93) received 5-mg amlodipine PO QD, which could be titrated to 10 mg PO QD after 4 weeks, followed by 10 mg plus 25-mg HCTZ PO QD after 8 weeks. Medication was titrated upward as necessary to achieve trough SiDBP < 90 mm Hg. Efficacy, tolerability, and quality-of-life scores were assessed after 12 weeks of therapy with each regimen. Trough SiDBP reductions after 4, 8, and 12 weeks of therapy were clinically comparable (losartan group: 7.3, 10.4, and 11.1 mm Hg, respectively; amlodipine group: 7.9, 11.2, and 11.8 mm Hg, respectively). Similar reductions in systolic blood pressure were also seen for both treatment groups. The percentage of patients reaching goal SiDBP (defined as trough SiDBP < 90 mm Hg or SiDBP > or = 90 mm Hg with a > or = 10 mm Hg drop from placebo baseline) was comparable for the two groups, with 68% of patients in the losartan group and 71% of patients in the amlodipine group reaching goal. Significantly more patients in the amlodipine group had drug-related adverse experiences (27% vs 13%). In particular, drug-related edema was more common in patients receiving the amlodipine regimen than in those receiving the losartan regimen (11% vs 1%). Patients in the amlodipine arm reported significantly more bother due to edema, regardless of whether edema was present at baseline, than did patients in the losartan arm (12% vs 2%), although overall quality of life was not different in the two treatment groups. This study demonstrates that a regimen of losartan with HCTZ added as needed, when compared with a regimen of amlodipine with HCTZ added as needed, provides comparable efficacy and superior tolerability and less bother to patients with respect to edema.",1996.0,0,0
1994,8879894,"The CARE Study: a postmarketing evaluation of ramipril in 11,100 patients. The Clinical Altace Real-World Efficacy (CARE) Investigators.",N M Kaplan,"A postmarketing surveillance study was undertaken to confirm the efficacy and safety of the angiotensin-converting enzyme inhibitor ramipril and to extend the findings of controlled clinical trials into real-world conditions. A total of 11,100 patients with mild-to-moderate hypertension treated by primary care physicians were enrolled in this 8-week, open-label study. Ramipril was usually initiated at a dosage of 2.5 mg once daily and titrated to achieve target blood pressure. Efficacy was assessed in 8261 patients for whom blood pressure data were recorded after the start of treatment: safety was assessed in all patients. Of patients with combined systolic and diastolic hypertension, 86.0% achieved a final diastolic blood pressure of < or = 90 mm Hg or a > or = 10 mm Hg decrease from baseline; the highest response was seen in elderly patients (87.2%), and the lowest response was seen in black patients (81.2%). Of patients with isolated systolic hypertension, 70.4% achieved a final systolic blood pressure of < or = 140 mm Hg or a > or = 20 mm Hg decrease from baseline, including 70.6% of women, 70.3% of men, and 69.1% of elderly patients; the highest response was seen in white patients (71.8%), and the lowest response was seen in black patients (64.4%). Adverse events were generally mild; cough (3.0%) was the most frequent. Once-daily ramipril was effective and well tolerated during an 8-week period in a large, diverse population of patients who had mild-to-moderate hypertension and who were treated by primary care physicians.",1996.0,0,0
1995,8880050,"Oral therapy with combined enalapril, prazosin and hydrochlorothiazide in the acute treatment of severe hypertension in Nigerians.",A A Ajayi; M A Afolabi; M O Balogun; A Q Adigun; O E Ajayi; A O Akintomide,"The efficacy, safety, tolerability and speed of onset of the hypotensive action of the combination of oral enalapril (10 mg) prazosin (1 mg) and hydrochlorothiazide (50 mg) has been assessed in 12 Nigerians with severe hypertension (Diastolic BP > or = 115 mmHg). The ages of the patients ranged from 30-60 years, and the serum creatinine from 52-732 mumol.l-1. The initial blood pressure was 200/130 mmHg. The combination significantly reduced systolic and diastolic blood pressure respectively. The hypotensive action appeared within 0.5 h and led to a fall in BP to 175/120 mmHg, and the peak action occurred at 4 h, when the BP was 138/99 mmHg, and it persisted upto 24 h (160/101 mmHg). Despite the significant fall in blood pressure, no reflex tachycardia was observed. Transient dizziness was seen in 2 patients, but otherwise all claimed improvement in clinical status and a clearer sensorium. The combination may be a useful oral treatment for the rapid control of severe hypertension in Blacks.",1996.0,0,0
1996,8880057,Effect of the lipase inhibitor orlistat on the pharmacokinetics of four different antihypertensive drugs in healthy volunteers.,C Weber; Y K Tam; G Schmidtke-Schrezenmeier; J H Jonkmann; P van Brummelen,"To study the influence of the lipase inhibitor orlistat on the pharmacokinetics of the antihypertensive drugs atenolol, furosemide, captopril and nifedipine. Four open-label, crossover studies were performed on six to eight healthy male volunteers. Orlistat was given in doses of 50 mg 3 times daily mid-meal for 7 (nifedipine and captopril) or 8 days (atenolol and furosemide). The four antihypertensive drugs (atenolol 100-mg tablet, furosemide 40-mg tablet, captopril 50-mg tablet and nifedipine 20-mg slow-release tablet) were administered in single doses twice, once before and once together, with orlistat at the end of the orlistat treatment period. The plasma concentration time profiles and the pharmacokinetic parameters estimated for these drugs were in the expected range, except for furosemide, whose bioavailability was lower than reported in the literature. This was probably due to the fact that furosemide was given during a meal. There were minor, but statistically significant, differences in one of the pharmacokinetic parameters of furosemide and nifedipine (no difference for captopril and atenolol) when these drugs were given alone and in combination with orlistat: the half-life of furosemide was slightly longer, the time to peak plasma concentrations of nifedipine was slightly longer. None of these are considered to be clinically significant changes. The lipase inhibitor orlistat given 50 mg 3 times daily does not alter the pharmacokinetics of atenolol, furosemide, nifedipine and captopril to a clinically significant extent.",1996.0,0,0
1997,8881946,"The safety of finasteride used in benign prostatic hypertrophy: a non-interventional observational cohort study in 14,772 patients.",L Wilton; G Pearce; E Edet; S Freemantle; M D Stephens; R D Mann,"To examine the safety of finasteride as used in general medical practice to treat benign prostatic hypertrophy (BPH). Information was collected on 14,772 patients who were included in an observational cohort study conducted using Prescription-Event Monitoring. Finasteride was reported to have been effective in 60% of the patients in whom an opinion on efficacy was recorded. Impotence or ejaculatory failure was reported in 2.1% of the patients, decreased libido in 1% and gynaecomastia and related conditions in 0.4%. Impotence was the most frequent reason for stopping treatment with finasteride and was the most commonly reported adverse reaction to the drug. Of the patients included in the elderly cohort involved in this study, 819 (5.5%) died; none of these deaths was attributed to finasteride. Impotence or ejaculatory failure, decreased libido and gynaecomastia in a small proportion of patients were associated with the use of finasteride. The results of this study strongly suggest that this drug is acceptably safe when used in accordance with the current prescribing information.",1996.0,0,0
1998,8886549,An economic analysis of captopril in the treatment of diabetic nephropathy. The Collaborative Study Group.,R A Rodby; L M Firth; E J Lewis,"The results of a recent clinical trial. The Effect of ACE inhibition on Diabetic Nephropathy, demonstrated that captopril reduced the rate of renal failure, end-stage renal disease (ESRD), and death in patients with IDDM and nephropathy. The purpose of this study was to determine the cost-benefit and cost-effectiveness of captopril as a therapy in patients with IDDM as well as the potential savings for all patients with diabetes and nephropathy. We used the results from a randomized, placebo-controlled trial comparing captopril (207 patients) with placebo (202 patients), whose purpose was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy to develop a model of medical treatment for patients before progression to ESRD. To model the course of illness after progression to ESRD and to extend the model to patients with NIDDM, we used data from the U.S. Renal Data System and published literature. Medical resource cost data were based predominantly upon Medicare reimbursement levels, published wholesale drug prices, and surveying health care providers. The economic model uses a payer perspective to estimate direct cost. The cost to society (indirect cost) associated with lost patient productivity due to ESRD was also estimated. Using this information, we predicted the costs incurred annually and over a lifetime if patients with IDDM and NIDDM and overt nephropathy were treated with either placebo or captopril. We also constructed a model of the overall prevalence of diabetic nephropathy to estimate the aggregate savings in total U.S. health care expenditures. Treatment with captopril resulted in an absolute direct cost savings or benefit of $32,550 per patient with IDDM over the course of a lifetime compared to treatment with placebo. For patients with NIDDM, the direct cost savings totaled $9,900 per patient. Absolute savings were found for indirect costs as well: $84,390 per patient with IDDM and $45,730 per patient with NIDDM. If captopril therapy were initiated in 1995 for patients with either IDDM or NIDDM and nephropathy, the aggregate health care cost savings (i.e. direct cost savings alone) would be $189 million a year for the year 1999 and $475 million a year in 2004, the present value of cumulative health care cost savings for these 10 years would be $2.4 billion. The use of captopril in diabetic nephropathy will provide significant savings in health care costs; in addition, it will result in savings in indirect cost, which reflects the broader societal benefit.",1996.0,0,0
1999,8888079,A new class of antihypertensive therapy: angiotensin II receptor antagonists.,M L Ellis; J H Patterson,"Despite the availability of safe and efficacious antihypertensive agents, hypertension continues to be a major source of morbidity and mortality in the United States. Losartan, the first of a new class of agents, the angiotensin II receptor antagonists, can be administered as monotherapy in the treatment of hypertension or to complement existing therapy. The angiotensin II receptor antagonists block the effects of angiotensin II through preferential binding to angiotensin II receptor subtype AT1 on the cell membrane. Compared with angiotensin-converting enzyme inhibitors, they may provide more complete blockade of the renin-angiotensin system and be associated with a lower frequency of cough as a side effect.",1996.0,0,0
2000,8888661,"Baseline quality of life as a predictor of mortality and hospitalization in 5,025 patients with congestive heart failure. SOLVD Investigations. Studies of Left Ventricular Dysfunction Investigators.",V Konstam; D Salem; H Pouleur; J Kostis; L Gorkin; S Shumaker; I Mottard; P Woods; M A Konstam; S Yusuf,"This study examined the independent relation of health-related quality of life (HRQL) to mortality and congestive heart failure (CHF)-related hospitalizations in patients with an ejection fraction of < 0.35 followed for a mean of 36.5 months. A brief HRQL questionnaire was administered at baseline to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD) trial. Participants had an ejection fraction of < 0.35 and either symptomatic CHF (treatment trial, n = 2,465) or asymptomatic CHF (prevention trial, n = 2,560). Baseline assessment of HRQL predicted mortality and CHF-related hospitalizations in symptomatic and asymptomatic patients randomized to enalapril and placebo treatment. Domains that were the stronger univariate predictors of mortality and CHF-related hospitalizations were activities of daily living (relative risk [RR] for mortality: 1.163, p < 0.000; for hospitalization: 1.215, p < 0.000), general health (RR for mortality: 1.205, p < 0.000; for hospitalization: 1.188, p < 0.000), and social functioning (RR for mortality 1.098, p < 0.000; for hospitalization: RR 1.156, p < 0.000). In the multivariate model, activities of daily living (RR for mortality 1.41, p < 0.000; for hospitalization: RR 1.43, p < 0.002), general health (RR for mortality 1.21, p < 0.000; for hospitalization RR 1.16, p < 0.013) and heart failure symptoms (RR for mortality 1.02, p < 0.025; for hospitalization RR 1.03, p < 0.004) were found to be independent risk factors. HRQL independently predicted mortality and CHF-related hospitalizations after adjustment for ejection fraction, age, treatment, and New York Heart Association classification in patients with an ejection fraction of < 0.35, randomized to enalapril and placebo treatment. HRQL provides additional clinical information regarding disease course and outcome that is not captured by traditional indexes of clinical status.",1996.0,0,1
2001,8888663,Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (the Randomized Aldactone Evaluation Study [RALES]).,,"The present study enrolled 214 patients, aged 26 to 83 years, with symptomatic New York Heart Association class II through IV congestive heart failure. Patients were continued on their previous therapeutic regimens, which included an angiotensin-converting enzyme (ACE) inhibitor and a loop diuretic with or without digitalis. Patients were randomized to 1 of 5 parallel treatment groups: placebo or spironolactone at a single daily dose of 12.5, 25, 50, or 75 mg for 12 weeks. Serum levels of creatinine, urea nitrogen, potassium, plasma renin activity, and N-terminal proatrial natriuretic factor (pro-ANF), as well as urinary aldosterone levels, were measured periodically. Measurements at 12 weeks versus baseline values indicated significant increases in plasma renin activity and aldosterone excretion and significant decreases in systolic and diastolic blood pressure and pro-ANF. Hypokalemia (serum potassium < 3.4 mmol/L) occurred in 10% of placebo-treated patients and in 0.5% of the spironolactone group. The incidence of hyperkalemia (serum potassium > or = 5.5 mmol/L) was 5% for the placebo group, whereas it was 5%, 13%, 20%, and 24% for the 12.5-, 25-, 50- and 75-mg spironolactone treatment groups, respectively. Predictors of hyperkalemia included the use of ACE inhibitors other than captopril, ACE inhibitor dose, and baseline elevation of serum creatinine or potassium levels. Thus, daily doses of 12.5 to 25 mg of spironolactone coadministered with conventional therapy of ACE inhibitors, loop diuretics, and digitalis are relatively safe (provided that serum potassium levels are monitored) and effective in blocking the effects of aldosterone, while reducing the potential for hypokalemia in patients with heart failure.",1996.0,0,0
2002,8888665,Study design and baseline characteristics of the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E: SECURE.,E M Lonn; S Yusuf; C I Doris; M J Sabine; V Dzavik; K Hutchison; W A Riley; J Tucker; J Pogue; W Taylor,"Atherosclerotic cardiovascular disease remains a major cause of mortality and morbidity in most developed countries. Experimental and clinical evidence suggests that angiotensin-converting enzyme inhibitors and vitamin E therapy may retard the atherosclerotic process; however, definitive proof in humans is lacking. The Study to Evaluate Carotid Ultrasound Changes in Patients Treated with Ramipril and Vitamin E (SECURE) is designed to assess the effects of ramipril--an angiotensin-converting enzyme inhibitor, at 2 doses: 2.5 mg daily (which has little effect on lowering blood pressure) and 10 mg daily--and the antioxidant vitamin E, 400 IU daily, on atherosclerosis progression in 732 patients using a factorial 3 x 2 study design. High-risk patients with a documented history of significant cardiovascular disease or with diabetes and additional risk factors were enrolled and will be followed for 4 years. The extent and progression of atherosclerosis are assessed noninvasively by B-mode carotid ultrasonography. The SECURE trial is a substudy of the larger Heart Outcomes Prevention Evaluation (HOPE) study of 9,541 high-risk patients evaluating the effects of ramipril and vitamin E on major cardiovascular events (cardiovascular death, myocardial infarction, and stroke). The 2 studies are complementary. Whereas HOPE is expected to provide information on major clinical outcomes, SECURE will shed light on the mechanisms by which these effects may be mediated.",1996.0,0,0
2003,8891468,Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction.,K L Goa; J A Balfour; G Zuanetti,"Following establishment of its efficacy in hypertension and congestive heart failure, the ACE inhibitor lisinopril has now been shown to reduce mortality and cardiovascular morbidity in patients with myocardial infarction when administered as early treatment. The ability of lisinopril to attenuate the detrimental effects of left ventricular remodelling is a key mechanism; however, additional cardioprotective and vasculoprotective actions are postulated to play a role in mediating the early benefit. The GISSI-3 trial in > 19 000 patients has demonstrated that, when given orally within 24 hours of symptom onset and continued for 6 weeks, lisinopril (with or without nitrates) produces measurable survival benefits within 1 to 2 days of starting treatment. Compared with no lisinopril treatment, reductions of 11% in risk of mortality and 7.7% in a combined end-point (death plus severe left ventricular dysfunction) were evident at 6 weeks. Advantages were apparent in all types of patients. Thus, those at high risk-women, the elderly, patients with diabetes mellitus and those with anterior infarct and/or Killip class > 1 -also benefited. These gains in combined end-point events persisted in the longer term, despite treatment withdrawal after 6 weeks in most patients. At 6 months, the incidence rate for the combined end-point remained lower than with control (a 6.2% reduction). The GISSI-3 results concur with those from recent large investigations (ISIS-4, CCS-1, SMILE) of other ACE inhibitors as early management in myocardial infarction. However, the results of the CONSENSUS II trial (using intravenous enalaprilat then oral enalapril) were unfavourable in some patients. These findings, together with the development of persistent hypotension and, to a lesser extent, renal dysfunction among patients in the GISSI-3 trial, have prompted considerable debate over optimum treatment strategies. Present opinion generally holds that therapy with lisinopril or other ACE inhibitors shown to be beneficial may be started within 24 hours in haemodynamically stable patients with no other contraindications; current labelling in the US and other countries reflects this position. There is virtually unanimous agreement that such therapy is indicated in high-risk patients, particularly those with left ventricular dysfunction. The choice of ACE inhibitor appears less important than the decision to treat; it seems likely that these benefits are a class effect. Lisinopril has a tolerability profile resembling that of other ACE inhibitors, can be given once daily and may be less costly than other members of its class. However, present cost analyses are flawed and this latter points remains to be proven in formal cost-effectiveness analyses. In conclusion, early treatment with lisinopril (within 24 hours of symptom onset) for 6 weeks improves survival and reduces cardiovascular morbidity in patients with myocardial infarction, and confers ongoing benefit after drug withdrawal. While patients with symptoms of left ventricular dysfunction are prime candidates for treatment, all those who are haemodynamically stable with no other contraindications are also eligible to receive therapy. Lisinopril and other ACE inhibitors shown to be beneficial should therefore be considered an integral part of the early management of myocardial infarction in suitable patients.",1996.0,0,0
2004,8891854,A randomized crossover trial of levodopa in congestive heart failure.,P Leszek; T Zieliński; J Janas; M Brodzki; H Klimkiewicz; J Korewicki,"The short- and long-term effects of levodopa (L-dopa), an oral dopaminergic prodrug, were assessed in patients with severe left ventricular dysfunction. Initially, 26 patients were included in the study group. After clinical, radiographic, and radionuclide examination, each patient underwent right heart catheterization (Swan-Ganz thermodilution catheter). Plasma noradrenaline levels were measured. In two patients, a favorable hemodynamic response to L-dopa was not observed, another two required permanent pacemaker implantation. These four patients were excluded from the study. Two patients required permanent pacemaker implantation. The remaining 22 patients with favorable hemodynamic response to L-dopa (increase in cardiac index, stroke volume index, reduction in total systemic resistance) were randomized in a nonblinded fashion to the conventional (11 patients) or conventional plus L-dopa (11 patients) treatment groups. During the study period, two patients, one from each group, died. They were excluded from the analysis. The final analyzed study group consisted of 20 men, aged 33-69, in New York Heart Association functional class IV (9 patients) and III (11 patients). The cause of congestive heart failure was primary dilated cardiomyopathy in 11 patients and ischemic heart disease in 9 patients. After 3 months' treatment, all patients were crossed over. Clinical, radiographic, radionuclide, and hemodynamic evaluation was repeated at the end of the 3-month treatment period. After 3 months of therapy with L-dopa in each group (covariance analysis), there was improvement in clinical, radiographic (relative heart volume, -128 mL/m2), radionuclide (left ventricular ejection fraction, +4.6; right ventricular ejection fraction, +4.8%), hemodynamic (mean pulmonary wedge pressure, -8 mmHg; total systemic resistance, -1.8 Wu; total pulmonary resistance, -3.5 Wu), and neurohumoral (noradrenaline, -218 pg/mL) measures. The addition of L-dopa to conventional therapy has beneficial short- and long-term effects in patients with severe left ventricular dysfunction.",1996.0,0,0
2005,8891856,Clinical and autonomic effects of ibopamine as adjunct to angiotensin-converting enzyme inhibitors in chronic heart failure.,B M Szabó; D J van Veldhuisen; P H van der Burgh; J Kruik; A R Girbes; K I Lie,"The purpose of this study was to determine the additive value of ibopamine in heart failure patients who are treated with angiotensin-converting enzyme inhibitors. Ibopamine exerts hemodynamic and neurohumoral effects, and is beneficial in mild heart failure; however, its additive value in more advanced disease in unclear. The study was a stand-alone, double-blind, randomized parallel group comparison of ibopamine (100 mg 3 times daily) and placebo in 59 patients with New York Heart Association functional class III-IV heart failure. Patients were clinically stable on drug treatment, including an angiotensin-converting enzyme inhibitor, and they were randomized to ibopamine (n = 29) or placebo (n = 30). Assessments were performed at baseline and after 3 months of treatment, and included measurement of peak oxygen consumption, plasma neurohormones, ambulatory arrhythmias, and heart rate variability. At baseline, the two groups were well matched, including age (mean, 63 years), left ventricular ejection fraction (0.23), and peak oxygen consumption (15.4 mL/min/kg). After 3 months, four patients had dropped out of the study because of progressive heart failure (ibopamine, n = 1; placebo, n = 3; not significant) and two because of side effects (n = 1/1). Exercise time and peak oxygen consumption were not significantly affected (exercise time: ibopamine, +54 [95% confidence interval, -12, 120] seconds; placebo, +19 [-42, 81] seconds; peak oxygen consumption: ibopamine, +0.3 [-0.5, 1,2] mL/min/kg; placebo, +0.2 [-0.7, 1.0] mL/min/kg). Plasma neurohormones and ventricular arrhythmias during ambulatory monitoring were also unaffected. In contrast, heart rate variability parameters, in particular those associated with vagal tone (rMMSD, high-frequency power), significantly increased after 3 months on ibopamine (P = .01 vs placebo). In this group of patients with clinically stable moderate to severe chronic heart failure, only a marginal and statistically nonsignificant effect on clinical parameters was observed after 3 months of treatment with ibopamine. Heart rate variability parameters, however, were significantly affected by ibopamine, despite the absence of an effect on plasma neurohormones.",1996.0,0,0
2006,8894262,Analysis of adverse effects among patients with essential hypertension receiving an ACE inhibitor or a beta-blocker.,J Rosenthal; H Bahrmann; K Benkert; P Baumgart; G Bönner; G Klein; A Neiss; K Schnelle; E D Frohlich,"Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients. This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied. Consequently, we designed a double-blind 12-week trial comparing the new angiotensin-converting enzyme (ACE) inhibitor, quinapril (n = 5,053), with a well-established beta-adrenergic receptor blocker, metoprolol (n = 506). Essentially hypertensive patients (diastolic blood pressure 95-114 mm Hg) received either 10 mg quinapril or 50 mg metoprolol once daily, and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg, respectively, in nonresponders. Responder rates were similar under both regimens. Adverse events were assessed by interview as well as by a standard questionnaire. The overall prevalence of adverse events reported by standard questionnaire was higher than that reported spontaneously during interviews. With respect to typical ACE inhibitor adverse reactions (e.g. cough and taste disturbances), there was no difference between quinapril and metoprolol independent of the mode of reporting. In summary, both drugs showed comparable overall tolerance and safety. The discrepancy between spontaneously reported and questionnaire-reported adverse events was noteworthy, and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks. Thus, a questionnaire is of great significance in addition to the patient history/interview in a large-scale, double-blind study designed to learn about details of drug safety.",1996.0,0,0
2007,8901825,Left ventricular hypertrophy and QT dispersion in hypertension.,J Mayet; M Shahi; K McGrath; N R Poulter; P S Sever; R A Foale; S A Thom,"The interlead variation in QT length on a standard electrocardiograph reflects regional repolarization differences in the heart. To investigate the association between this interlead variation (QT dispersion) and left ventricular hypertrophy, we subjected 100 untreated subjects to 12-lead electrocardiography and echocardiography. Additionally, 24 previously untreated subjects underwent a 6-month treatment study with ramipril and felodipine. In the cross-sectional part of the study, QT dispersion corrected for heart rate (QTc dispersion) was significantly correlated with left ventricular mass index (r = .30, P < .01), systolic pressure (r = .30, P < .01), the ratio of peak flow velocity of the early filling wave to peak flow velocity of the atrial wave (E/A ratio) (r = -.22, P = .02), isovolumic relaxation time (r = .31, P < .01), and age (r = .21, P < .04). In the treatment part of the study, lead-adjusted QTc dispersion decreased from 24 to 19 milliseconds after treatment, and after a subsequent 2 weeks of drug washout remained at 19 milliseconds (P < .01). The changes in left ventricular mass index at these stages were 144, 121, and 124 g/m2 (P < .01). Systolic pressure decreased from 175 to 144 mm Hg and increased again to 164 mm Hg after drug washout (P < .01). The E/A ratio (0.97, 1.02, and 1.02; P = 69) and isovolumic relaxation time (111, 112, and 112; P = .97) remained unchanged through the three assessment points. In conclusion, QT dispersion is increased in association with an increased left ventricular mass index in hypertensive individuals. Antihypertensive therapy with ramipril and felodipine reduced both parameters. If an increased QT dispersion is a predictor of sudden death in this group of individuals, then the importance of its reduction is evident.",1996.0,0,0
2008,8902551,Interruption of prolonged ramipril treatment in hypertensive patients: effects on the renin-angiotensin system.,D Stephan; M Grima; M Welsch; M Barthelmebs; D Vasmant; J Imbs,"The increase in renin secretion and the induction of the converting enzyme (ACE) observed during treatment by ACE inhibitors (CEIs) could result in increased angiotensin II (ang II) synthesis when the treatment is stopped. The object of this study was to compare changes in the components of the renin-angiotensin system with changes in arterial pressure in hypertensives, following the cessation of long-term ramipril treatment. Twenty hypertensives, treated for at least three months with ramipril, in monotherapy for the last three weeks, were randomly allocated to two parallel groups and received for fifteen days, on a double-bind basis, either a placebo (withdrawal group W, n = 12) or ramipril at the previous doses (treated group T, n = 8). Blood pressure was measured using four different techniques. The active renin (AR), angiotensinogen, angiotensin I (ang I), angiotensin II (ang II) and aldosterone plasma concentrations were measured, as was plasma angiotensin I converting enzyme (ACE) activity in vitro (colorimetric and fluorimetric method) and in vivo (the ang II/ang I ratio). The biological effects of cessation of long-term ramipril treatment in hypertensives were a decline in AR and angiotensin I concentrations, an increase in ACE activity and no significant changes in angiotensinogen, angiotensin II and aldosterone levels. Fifteen days after withdrawal, the different parameters of the renin-angiotensin system appear to have returned to basal value. A slow rise in blood pressure was also observed but no rebound increase was noted during the 15 days neither in angiotensin II levels nor in blood pressure. Following the cessation of prolonged ramipril treatment, in vivo converting enzyme inhibition disappears slowly, probably on account of the slow tight binding inhibitor properties of ramiprilat, the active metabolite of this CEI. The gradual decline in AF, plasma levels, together with the prolonged ACE inhibition as measured in vivo by the ang II/ang I ratio, explains the absence of a rise in ang II synthesis.",1996.0,0,0
2009,8903533,Functional significance of alterations in cardiac contractile protein isoforms.,R N Kitsis; J Scheuer,"Multiple closely related, yet distinct, isoforms exist for each of the cardiac contractile proteins. The isoform composition of the heart changes in response to developmental and physiologic cues. This paper reviews the molecular basis for cardiac contractile protein isoform diversity and the functional consequences of isoform shifts.",1996.0,0,1
2010,8903665,An equivalence study of the safety and efficacy of a fixed-dose combination of perindopril with indapamide versus fixed-dose combinations of captopril with hydrochlorothiazide and enalapril with hydrochlorothiazide in the treatment of hypertension.,R Luccioni; P S Sever; T Di Perri; J Redon; I Laurandin; Y Brault; C Chastang; D Guez,"The aim of this multicenter, randomly allocated, double-blind, parallel-group study was to evaluate the equivalence of three fixed-dose combination drugs in mild to moderate hypertension: perindopril + indapamide (4 + 1.25 mg), captopril + hydrochlorothiazide (50 + 25 mg) and enalapril + hydrochlorothiazide (20 + 12.5 mg). After a single-blind, 4-week, placebo run-in phase, 527 patients (mean +/- SD age 54.5 +/- 1.2 years) with a supine diastolic blood pressure of 101.2-101.7 mmHg were randomly assigned to one of the three treatments for 8 weeks. The main evaluation criteria were diastolic blood pressure and serum potassium concentration. Equivalence was assessed on an intention-to-treat basis, using Schuirmann's method, which involves performing two one-tailed statistical tests on the data. Thirty-five patients were withdrawn from the study but there were no differences between groups in the reasons for withdrawal. Diastolic blood pressure decreased by between 13.1 and 14.2 mmHg in the three groups. The 90% confidence intervals for the differences between perindopril + indapamide and the other treatments were -1.1, +1.7 mmHg for captopril + hydrochlorothiazide and -0.4, +2.6 mmHg for enalapril + hydrochlorothiazide. Schuirmann's test was highly statistically significant (P<0.001 for perindopril + indapamide versus captopril + hydrochlorothiazide; P<0.002 for perindopril + indapamide versus enalapril + hydrochlorothiazide), so that the two one-sided hypotheses that the treatments were not equivalent were rejected at the nominal level of alpha = 0.05. Similarly, the safety of the treatments was equivalent in terms of serum potassium. The 90% confidence intervals of the differences between perindopril + indapamide and the other treatments were -8.7, -1.6% for captopril + hydrochlorothiazide (P = 0.004) and -1.5, +2.7% for enalapril + hydrochlorothiazide (P<0.001). We conclude that the safety and efficacy of perindopril + indapamide, captopril + hydrochlorothiazide and enalapril + hydrochlorothiazide were equivalent after 8 weeks of treatment in patients with mild to moderate hypertension.",1995.0,0,0
2011,8903669,PROGRESS (perindopril protection against recurrent stroke study):  rationale and design. PROGRESS Management Committee [corrected].,B Neal; S MacMahon,"Patients with a history of cerebrovascular disease have a very high risk of stroke, and usual levels of both systolic and diastolic blood pressure are directly and continuously associated with this risk. Trials of blood pressure lowering in patients with transient ischaemic attacks or stroke have been too small to reliably detect the effects on stroke risk of the modest blood pressure reductions achieved. The primary objective of PROGRESS is to determine precisely the effects of blood pressure reduction with an angiotensin converting enzyme (ACE) inhibitor-based regimen on the stroke risk in patients with a history of transient ischaemic attacks or minor stroke. The study is a randomized, double-blind, placebo-controlled clinical trial. Before randomization, there is a 4-week run-in phase on open-label ACE inhibitor treatment. The scheduled duration of treatment and follow-up is 4-5 years. The study will be conducted in collaborating clinical centres in Australia, Belgium, the People's Republic of China, France, Italy, Japan, New Zealand, Sweden and the United Kingdom. The study will involve 6000 patients with a history of transient ischaemic attacks or stroke (ischaemic or haemorrhagic) in the past 5 years. To be eligible patients should have no definite indication for or contra-indication to treatment with an ACE inhibitor and no disability likely to prevent regular attendance at study clinics. Study treatment will comprise perindopril and indapamide or matching placebos for patients without an indication for or contra-indication to treatment with a diuretic, perindopril alone or matching placebo for all other patients. The primary study outcome is total strokes and secondary outcomes include fatal or disabling strokes, total major cardiovascular events, cardiovascular deaths, cognitive function and dementia, and disability and dependency.",1995.0,0,1
2012,8904273,Angiotensin-converting enzyme inhibitors and anaesthesia.,H Tohmo; M Karanko,,1996.0,0,0
2013,8906524,Shanghai trial of nifedipine in the elderly (STONE).,L Gong; W Zhang; Y Zhu; J Zhu; D Kong; V Pagé; P Ghadirian; J LeLorier; P Hamet,To assess the effectiveness of nifedipine treatment in elderly hypertensives. A single-blind trial was conducted under the direction of the Shanghai Institute of Hypertension in 1632 subjects aged 60-79 years alternatively allocated to either nifedipine or placebo after a 4-week placebo run-in period between 1987 and 1990 with mean follow-up of 30 months. Clinical events and risk modification were analysed in collaboration with the University of Montreal. Seventy-four patients with severe hypertension were reallocated to active nifedipine treatment after placebo run-in. Cox's proportional hazards model accounting for covariates demonstrated a highly significant decrease in the probability of events: 'original treatment assignment' analysis indicated that 77 events occurred in the placebo and 32 in the nifedipine group. Similar significances were achieved with 'actual treatment' or 'changes excluded' (excluding reallocated subjects) analyses. A significant reduction in relative risk was observed for strokes and severe arrhythmia with an overall decrease from 1.0 to 0.41 (95% confidence interval 0.27-0.61). Nifedipine treatment diminished the number of severe clinical outcomes in elderly hypertensives significantly.,1996.0,0,0
2014,8907805,Indapamide is as effective as captopril in the control of microalbuminuria in diabetes.,L M Molyneaux; K A Willey; D K Yue,"Microalbuminuria is a predictor of overt diabetic nephropathy and macrovascular disease. Thirty-one diabetic patients with persistent urinary albumin excretion rate (AER) of 20-200 mu g min-1 were randomised to receive indapamide 2.5 mg or captopril 37.5 mg daily for 12 weeks. After a 4-week washout, patients received the alternate agent for 12 weeks. Resting blood pressure (BP), AER, cholesterol, triglycerides, and HbA1c were measured at baseline, after 6 and 12 weeks of each treatment, and after a 4-week washout period following each treatment arm. Results from patients who completed at least one treatment arm were analysed by repeated-measures analysis of variance (ANOVA). AER (median value and interquartile range) decreased significantly from baseline after treatment with indapamide and captopril [60(27-106) vs. 40(14-112) and 33(17-100); p < 0.005], but there was no difference between the effects of the two agents. Mean systolic BP (SBP) was also significantly reduced with treatment, and no difference was noted between the effects of the two agents. No correlation between changes in AER and SBP was noted with either agent. Diastolic blood pressure (DBP), cholesterol, triglycerides, and HbA1c did not change during the study. These results suggest that indapamide is an effective alternative to angiotensin-converting enzyme (ACE) inhibitors in the treatment of diabetic patients with microalbuminuria.",1996.0,0,0
2015,8908384,"Rationale and design of a large study to evaluate the renal and cardiovascular effects of an ACE inhibitor and vitamin E in high-risk patients with diabetes. The MICRO-HOPE Study. Microalbuminuria, cardiovascular, and renal outcomes. Heart Outcomes Prevention Evaluation.",H C Gerstein; J Bosch; J Pogue; D W Taylor; B Zinman; S Yusuf,"To describe the rationale and design of a large international study (microalbuminuria, cardiovascular, and renal outcomes [MICRO] in the HOPE [Heart Outcomes Prevention Evaluation] study) of an ACE inhibitor and vitamin E for the prevention of diabetic nephropathy (DN) and cardiovascular disease (CVD) in patients with diabetes and microalbuminuria (MA). A total of 3,657 diabetic subjects, including 1,129 with MA, are randomly allocated to receive the ACE inhibitor ramipril (or placebo) and vitamin E (or placebo) for 4 years in a two-by-two factorial design. Diabetic subjects are a subset of the 9,541 subjects enrolled in the HOPE study. The development of DN in microalbuminuric diabetic subjects and the development of MA in normoalbuminuric subjects, as well as cardiovascular death, myocardial infarction, and storke, are the main outcomes. The correlation of changes in albuminuria with changes in carotid atherosclerosis documented in a subset of subjects will also be analyzed. The effect of both an ACE inhibitor and vitamin E on the progression of renal and CVD in patients with diabetes is being assessed in the MICRO-HOPE study.",1996.0,0,1
2016,8909907,"Effects of captopril on ventricular arrhythmias in the early and late phase of suspected acute myocardial infarction. Randomized, placebo-controlled substudy of ISIS-4.",A Budaj; J Cybulski; K Cedro; S Karczmarewicz; J Maciejewicz; M Wiśniewski; L Ceremuzyński,"The antiarrhythmic effect of oral captopril was studied during the early (day 3) and late (day 14) phase of acute myocardial infarction among 304 patients in a randomized placebo-controlled substudy of ISIS-4. Ventricular arrhythmias (ventricular ectopic beats per hour) occurred significantly less frequently among captopril-allocated patients than among those allocated placebo at day 3 (logarithmic scale: 0.48 +/- 0.8 captopril vs 0.84 +/- 1.3 placebo; P < 0.003) and at day 14 (0.51 +/- 1.0 vs 0.77 +/- 1.3; P < 0.05). The number of patients with frequent ventricular arrhythmias (more than 10 ventricular ectopic beats per hour) was also significantly lower among those allocated captopril at day 3 (7.3% vs 14.4%; P < 0.05) and at day 14 (7.3% vs 14.8%; P < 0.05). These results support the hypothesis that the activation of the renin-angiotensin-aldosterone and sympathetic system may underlie heart rhythm disturbances in acute myocardial infarction, and that early use of converting enzyme inhibitor therapy may ameliorate these disturbances.",1996.0,0,1
2017,8910823,Medications as risk factors for periodontal disease.,S G Ciancio,"As the United States population ages, people will be taking more medications which may benefit their general health but not necessarily their periodontal health. The effects of medications have been grouped into six categories as follows: behavioral alteration of oral hygiene methods, alteration of plaque composition, effect on gingival tissues, effect on alveolar bone, effect on gingival crevicular fluid, and effect on salivary flow. Although most medications discussed in this paper increase the risk for periodontal disease, a few may actually decrease the risk. These include the effect of phenytoin on alveolar bone, the antibacterial effect of antibiotics, the anticollagenolytic effects of tetracyclines, and the effect of non-steroidal anti-inflammatory drugs on decreasing alveolar bone resorption.",1996.0,0,0
2018,8911875,Angiooedema and urticaria with angiotensin converting enzyme inhibitors.,P I Pillans; D M Coulter; P Black,"To review reports of angiooedema and urticaria associated with angiotensin converting enzyme inhibitors (ACEI) in the New Zealand Centre for Adverse Reactions Monitoring and Intensive Medicines Monitoring Programme (IMMP) database. Adverse reaction reports describing angiooedema and/or urticaria between April 1981 and December 1994 were examined. Captopril, enalapril and lisinopril were intensively monitored on the IMMP during this period. Of a total of 116 reports there were 68 reports of angiooedema and 37 of urticaria alone and 11 where angiooedema and urticaria occurred in the same patient. The total number of patients is unknown, but cohorts of patients on captopril, enalapril and lisinopril in the IMMP were 16342, 25686 and 11235, totalling 53263 patients. There were 63 reports of angiooedema/urticaria in patients monitored on the IMMP, giving a reported rate of 1.2/1000 (0.9-1.5). Forty seven reactions occurred between 3 weeks and 4 years after commencement of therapy. Severe angiooedema occurred in 9 patients with early-onset angiooedema and 6 with late-onset angiooedema. There were no deaths. Seventeen patients had up to 12 episodes before diagnosis. Angiooedema/ urticaria occurred without gender preference. Although a dose relationship was not apparent, 3 patients developed angiooedema or urticaria after an increase in dose. Although reactions are more common shortly after initiation of ACEI therapy, late onset reactions may be less well recognised. Clinicians should be reminded, and ACEI data sheets should emphasise, that onset may be delayed for weeks or months, that patients may have multiple episodes with long symptom free intervals, and that angiooedema may occur with or without urticaria.",1996.0,0,0
2019,8913404,Use of baclofen to suppress cough induced by angiotensin-converting enzyme inhibitors.,P V Dicpinigaitis,"To determine whether baclofen can suppress the cough induced by angiotensin-converting enzyme (ACE) inhibitors. Prospective, open-label, clinical trial of a 4-week course of low-dose oral baclofen (5 mg tid days 1-7, 10 mg tid days 8-28). Seven patients with severe, persistent ACE inhibitor-induced cough. University-affiliated teaching hospital. Study participants kept daily diaries monitoring the frequency of cough during and after completion of baclofen therapy. All subjects demonstrated diminution of cough after initiation of baclofen. Initial improvement was noted by a mean of 4.0 days (range 3-6), and maximal improvement during treatment was achieved by a mean of 10.7 days (range 5-15). In addition, all subjects demonstrated persistent suppression of cough (range 25-74 d) after discontinuation of the study drug. Low-dose oral baclofen therapy caused a prolonged antitussive effect in all subjects without inducing any adverse reactions. Baclofen may offer an alternative to the discontinuation of ACE inhibitor therapy in patients for whom these drugs are required.",1996.0,0,0
2020,8914031,Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy.,G L Bakris; J B Copley; N Vicknair; R Sadler; S Leurgans,"Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria. Calcium channel blockers (CCBs) have variable effects on proteinuria; their long-term effects on progression of diabetic nephropathy are not known. The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus (NIDDM) by a degree comparable to ACE inhibitors, given similar levels of blood pressure control. To test this hypothesis we randomized 52 patients with NIDDM associated nephropathy and hypertension, mean age of 63 +/- 8 years, to either the ACE inhibitor, lisinopril (N = 18), nondihydropyridine CCBs (NDCCBs), verapamil SR (N = 8) or diltiazem SR (N = 10), or the beta blocker, atenolol (N = 16). Goal blood pressure was < or = 140/90 mm Hg. Patients were followed for a mean period of 63 +/- 7 months. The primary end point was change in creatinine clearance (CCr) slope in each group. There was no significant difference in mean arterial pressure reduction among the groups over the study period (P = 0.14). The mean rate of decline in CCr was greatest in the atenolol group (-3.48 ml/min/year/1.73 m2; P < 0.0001). There was no difference in the CCr slopes between lisinopril and NDCCBs groups (P = 0.36). Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups (P > 0.99). Therefore, in persons with renal insufficiency secondary to NIDDM, similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol. Moreover, this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria, findings not observed in the atenolol group.",1996.0,0,0
2021,8914032,Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.,J A Breyer; R P Bain; J K Evans; N S Nahman; E J Lewis; M Cooper; J McGill; T Berl,"We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.",2001.0,0,0
2022,8915309,Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities.,V Callot; J C Roujeau; M Bagot; J Wechsler; O Chosidow; P Souteyrand; P Morel; L Dubertret; M F Avril; J Revuz,"To test the hypothesis that drug-induced pseudolymphoma and hypersensitivity syndrome are 2 distinct clinical entities. Retrospective study from 1980 to 1993. Departments of dermatology and medicine of 5 referral universitary hospitals. Twenty-four patients who met arbitrary criteria selected as being suggestive of lymphoma, with probable drug cause. Patients with other definite cutaneous drug-induced eruptions were excluded. None. Suspect drugs; clinical, biological, and pathological findings; and evolution of each case and of 110 published case reports. Two groups were separated according to their mode of onset and clinical aspect. Three patients (and 15 cases in the literature) had subacute papulonodular or infiltrated plaques, without visceral involvement. Skin biopsy specimens showed a dense lymphocytic infiltrate mimicking lymphoma. Healing was constant when the drug was stopped. The 21 remaining patients (and 95 published cases) had an acute widespread eruption, with fever, enlarged lymph nodes, and multivisceral involvement. Lymphocytosis, atypical lymphocytes, eosinophilia, hepatitis, and high levels of lactate dehydrogenase were frequent. Skin biopsy findings were usually not specific (lymphocytic infiltrate and keratinocyte necrosis) but sometimes mimicked lymphoma. Severe forms and relapses occurred, even after the drug was stopped. The inducing drugs were the same in the 2 groups. These 2 groups correspond to drug-induced pseudolymphoma and hypersensitivity syndrome. We think that they are 2 distinct entities with different clinical and biological features and outcome, even if the pathological findings are sometimes similar. Prospective studies are needed to confirm these facts, to evaluate the therapy, and to follow up patients.",1996.0,0,0
2023,8916480,Baseline clinical and angiographic data in the Quinapril Ischemic Event (QUIET) Trial.,R S Lees; B Pitt; R C Chan; G Holmvang; R E Dinsmore; L W Campbell; H E Haber; M I Klibaner; L Cashin-Hemphill,"The QUinapril Ischemic Event Trial (QUIET) is the first prospective, double-blind, placebo-controlled trial to investigate the long-term antiatherosclerotic effects of angiotensin-converting enzyme inhibition. Normotensive, nonhyperlipidemic subjects (1,750) with normal left ventricular systolic function were randomly assigned to treatment or placebo at percutaneous transluminal coronary angioplasty (PTCA). The primary end point is time to first cardiac ischemic event. Baseline clinical characteristics are (mean +/- SD): age 58 +/- 9 years; blood pressure 123 +/- 15/74 +/- 10 mm Hg; low density lipoprotein cholesterol 124 +/- 27 mg/dL; high density lipoprotein cholesterol 37 +/- 10 mg/dL; and triglycerides 167 +/- 91 mg/dL. In addition, 81% are men; 22% are current smokers; 49% give a history of myocardial infarction. Baseline angiographic characteristics are (mean +/- SD): left ventricular ejection fraction 59% +/- 11%; per patient diameter stenosis (excluding the PTCA segment) 49% +/- 31%; 8.9 +/- 3.5 analyzable segments per patient (excluding the PTCA segment), 3.8 +/- 2.3 of which have visible stenosis. Including the PTCA segment, 52% have single vessel disease and 48% have multivessel disease. Baseline angiographic data for non-PTCA segments will be correlated with cardiac ischemic events which occur after 6 months. Up to 500 subjects will undergo follow-up angiography with quantitative coronary angiographic analysis (QCA) of baseline and follow-up films. The primary QCA end point will be per-patient categorical designation as progressor or nonprogressor based on the presence or absence of > or = 400 microns narrowing in > or = 1 vessels that did not undergo PTCA.",1996.0,0,0
2024,8918517,Severe hyperkalaemia induced by trimethoprim in combination with an angiotensin-converting enzyme inhibitor in a patient with transplanted lungs.,J F Bugge,"A 40-year-old woman with transplanted lungs developed life threatening hyperkalaemia (6.8 mmol L-1) during high dose treatment with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia. Trimethoprim has an amiloride-like effect on the distal nephron and may thus induce hyperkalaemia, particularly if other contributing factors coexist. The present patient was also treated with the angiotensin-converting enzyme (ACE) inhibitor enalapril, and the combination of ACE-inhibition and potassium-sparing diuretics is known to induce hyperkalaemia. Hyperkalaemia was probably induced by the combination of ACE-inhibitor and trimethoprim, and this combination may be as dangerous as the combination of ACE-inhibitors with other potassium-sparing diuretics.",1996.0,0,0
2025,8922912,The prognostic value of predischarge quantitative two-dimensional echocardiographic measurements and the effects of early lisinopril treatment on left ventricular structure and function after acute myocardial infarction in the GISSI-3 Trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico.,G L Nicolosi; R Latini; P Marino; A P Maggioni; S Barlera; M G Franzosi; E Geraci; L Santoro; L Tavazzi; G Tognoni; C Vecchio; A Volpi,"Left ventricular dilatation and a low ejection fraction after acute myocardial infarction are independent indicators of a poor prognosis. ACE inhibitors have been shown to decrease left ventricular dilatation after myocardial infarction. In the GISSI-3 trial, patients were randomly assigned, within 24 h of onset of myocardial infarction symptoms, to 6 weeks of treatment with lisinopril, nitroglycerin, both or neither, in an open, 2 x 2 factorial design. The study showed that early treatment in relatively unselected patients with lisinopril decreases mortality at 6 weeks and severe left ventricular dysfunction. We assessed (1) the prognostic value of pre-discharge 2-D echocardiographic variables, and (2) the effects of lisinopril on the progression of left ventricular dilatation. 2-D echocardiograms were available pre-discharge in 8619 GISSI-3 trial patients discharged alive. In 6405 of these patients, a 2-D echocardiographic study was also available at 6 weeks, and at 6 months. Pre-discharge end-diastolic and end-systolic volumes, and ejection fraction predicted 6-month mortality and non-fatal clinical congestive heart failure (P < 0.01). The increase in left ventricular volumes over time was significantly reduced by 6 weeks' lisinopril treatment in patients with wall motion asynergy pre-discharge of > or = 27%. Patients with wall motion asynergy < 27% showed no dilatation and lisinopril did not affect volumes at 6 months. Patients randomized to lisinopril also had smaller volumes after withdrawal of treatment at 6 weeks. Lisinopril did not affect left ventricular ejection fraction. 2-D echocardiography independently contributes to pre-discharge risk stratification in terms of 6-month mortality and clinical heart failure after myocardial infarction, and early, short-term treatment with lisinopril in unselected myocardial infarction patients attenuates left ventricular dilatation; an effect evident in patients with larger infarcts. These results probably only partly explain the effect of lisinopril on total mortality concentrated in the first week after infarction.",1996.0,0,0
2026,8931343,"Effects of captopril on renal functions, renal and portal hemodynamics in patients with cirrhosis.",Y T Tsai; H C Lin; F Y Lee; M C Hou; S S Wang; S D Lee,"Renin-angiotensin system plays a prominent role in the sodium and water homeostasis. In addition, activation of renin-angiotensin system frequently occurs in patients with cirrhosis and ascites. Theoretically, administering of angiotensin converting enzyme inhibitors can enhance sodium and water retention in cirrhotic patients with ascites. In this study, we evaluate the role of low-dose captopril on renal function changes, renal plasma flow and hemodynamics in patients with cirrhosis and ascites. Fifty patients are randomly assigned to receive captopril or placebo for 14 days. Renal functions, renal plasma flow, plasma renin activity, plasma aldosterone concentration and systemic and hepatic hemodynamics are measured before and after treatment. Our results indicate that placebo administration did not affect any of the parameter measured in this study. The finding that low-dose captopril significantly increases plasma renin activity suggests that the dose used in this study effectively blocks the enzyme activity. However, low-dose captopril does not affect renal plasma flow, renal functions and systemic and hepatic hemodynamics. Results in this study demonstrate that inhibition of angiotensin converting enzyme alone may not improve sodium and water retention in cirrhotic patients with ascites.",1996.0,0,0
2027,8931831,Albuminuria and transferrinuria in essential hypertension. Effects of antihypertensive therapy.,C Alli; M Lombardo; D Zanni; A M Agrati; M Cassani; S Granata,"The objectives of this study were to evaluate the effects of an ACE inhibitor (fosinopril) and a calcium antagonist (amlodipine) on the urinary albumin and transferrin excretion and their relationship to the blood pressure in essential hypertension. Twenty-four never-treated patients (mean age, 46.4 +/- 8.9 years) with a diastolic blood pressure between 90 and 114 mm Hg and normal renal function, randomly received amlodipine or fosinopril and, if the diastolic blood pressure was not normalized, doxazosin was added to the therapy. Twenty-four-hour ambulatory blood pressure monitoring and 24-h urine collection for albumin and transferrin measurements were performed before and after 3 and 6 months of therapy. Diastolic blood pressure was normalized in 23 patients (96%). Before treatment, microalbuminuria was present in 50% of patients. In the amlodipine and fosinopril group, antihypertensive therapy significantly decreased blood pressure and, only in the fosinopril group, albuminuria. Transferrinuria did not change significantly in both groups. Fosinopril lowered albuminuria in all patients, whereas amlodipine only in half of patients. Albuminuria, but not transferrinuria, was significantly correlated to the ambulatory blood pressure. This correlation was more pronounced for systolic than for diastolic pressure. In essential hypertensive patients with normal renal function, a high prevalence of microalbuminuria can be observed. Albuminuria appears to correlate with ambulatory blood pressure, particularly with systolic pressure. Intrarenal hemodynamic changes seem to play a more important role than systemic blood pressure decrease in the reduction of albuminuria. Transferrinuria does not seem a useful marker to follow-up nondiabetic hypertensive patients with early signs of glomerular dysfunction.",1996.0,0,0
2028,8932538,Losartan: first of a new class of angiotensin antagonists for the management of hypertension.,A A Carr; L M Prisant,"Angiotensin receptor antagonists represent a new class of drugs for the treatment of patients with hypertension. Reduction of blood pressure in patients with essential hypertension requires increased activity of the renin-angiotensin system. Losartan, the first orally active, nonpeptide angiotensin antagonist, specifically competes with angiotensin II (Ang II) for the AT1 receptor and reversibly alters the receptor. Maximum blood pressure reductions occur after doses of approximately 50 mg, although some patients will require 100 mg; the parent compound and a metabolite are responsible for a smooth 24-hour effect on blood pressure. Once-daily dosing with losartan has been documented to be safe. The drug's safety has been evaluated in 4,058 patients; of these patients, more than 1,200 were treated for longer than 6 months and more than 800 were treated for longer than 1 year with doses of 10 mg to 150 mg. Overall, no hypertensive patients were withdrawn from treatment because of elevated serum creatinine or potassium levels, and there were no reports of angioedema. In addition, some reductions in plasma uric acid levels were noted. Cough occurred significantly less often in patients treated with losartan than in those treated with hydrochlorothiazide or lisinopril. In contrast to angiotensin-converting enzyme (ACE) inhibitors, losartan does not activate bradykinin-nitric oxide-prostanoid vasodilation.",1996.0,0,0
2029,8938674,Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors.,M S MacGregor; P A Rowe; M A Watson; R S Rodger; B J Junor; J D Briggs,"Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.",1996.0,0,0
2030,8944344,Are acantholysis and transglutaminase inhibition related phenomena?,C Esposito; V Ruocco; A Cozzolino; A LoSchiavo; M L Lombardi; R Porta,"The loss of intercellular cohesion among keratinocytes (acantholysis) may be considered the histologic marker of pemphigus. Many drugs, especially thiol drugs, proved to be able to provoke in vitro acantholysis by biochemical mechanisms interfering with the disulfide and thiol group balance. As to nonthiol drugs, the pathomechanism of acantholysis is still unexplained. To explain the molecular mechanism of enalapril-induced acantholysis a potential link between transglutaminase (TGase) activity and the effects of this drug was investigated. TGase activity in extracts from human breast skin cultured in the presence of thiopronine, captopril and enalapril were evaluated in vitro. The acantholytic potential of cystamine, a known TGase inhibitor, was also investigated. Enalapril, the most powerful acantholytic drug in vitro, was found to inhibit both the purified enzyme and the TGase activity in the extracts from cultured human breast skin explants. Kinetic studies showed that enalapril inhibition was competitive with respect to the amino acceptor substrate and uncompetitive with respect to the amino donor substrate. Moreover, an acantholytic effect of cystamine on explants of normal human skin was shown. These results suggest that acantholysis and the inhibition of TGase activity could be two related phenomena.",1996.0,0,0
2031,8948517,The benefits of ACE inhibitors and calcium antagonists in slowing progressive renal failure: focus on fixed-dose combination antihypertensive therapy.,M Epstein,"During the past two decades, major investigative interest has been focused on the determinants of chronic renal disease and interventions to retard the inexorable progression to end-stage renal disease. Recent studies have provided a theoretic framework for anticipating that angiotensin-converting enzyme (ACE) inhibitors, and possibly calcium antagonists, may preferentially retard the progression of renal disease. Whereas the majority of available clinical trials have assessed the effects of ACE inhibitors in patients with insulin-dependent diabetes mellitus (IDDM), there are relatively few long-term studies that have evaluated the renal protective effects of ACE inhibitors and calcium antagonists in patients with nondiabetic renal disease. Although clinical trials have been initiated using both of these drug classes as monotherapy, theoretical considerations suggest that fixed-dose combinations of an ACE inhibitor and a calcium antagonist might be appealing as renal protective agents. Several lines of evidence suggest that the renal microcirculatory effects of coadministration of both agents should be complementary. Similarly, recent observations suggest that the two classes may act in a complementary manner to countervail pathogenetic mechanisms at the level of the mesangium. A recent study in type II diabetic patients demonstrated that combination therapy with an ACE inhibitor and a calcium antagonist induced the greatest reduction in proteinuria, and reduced the rate of decline in glomerular filtration rate (GFR) more than did either agent alone at the same level of blood pressure reduction. Based on such considerations, recent randomized prospective studies have been initiated to compare the renal protective effects of combination calcium antagonist-ACE inhibitor therapy versus monotherapy with agents of either of these two antihypertensive classes.",1996.0,0,0
2032,8952600,Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals.,A Benetos; F Cambien; S Gautier; S Ricard; M Safar; S Laurent; P Lacolley; O Poirier; J Topouchian; R Asmar,"Angiotensin-converting enzyme inhibitors improve arterial stiffness independently of blood pressure reduction. Since we have recently shown that in hypertensive individuals the A1166C polymorphism of the angiotensin II type 1 receptor (AT1-R) is an independent determinant of aortic stiffness, we designed the present study to assess the influence of this polymorphism on the changes of aortic stiffness after chronic treatment with the angiotensin-converting enzyme inhibitor perindopril and the calcium channel blocker nitrendipine. Forty perindopril- and 42 nitrendipine-treated hypertensive individuals were studied. We evaluated aortic stiffness by measuring the carotid-femoral pulse wave velocity. Carriers of the AT1-RC allele showed higher baseline values of pulse wave velocity than AA homozygotes (P < .05). In the perindopril group, a threefold greater reduction in pulse wave velocity was observed in carriers of the C allele than in AA homozygotes (-2.85 +/- 0.62 versus -0.94 +/- 0.32 m/s, respectively; P < .001), whereas in the nitrendipine group, pulse wave velocity decreased only in AA homozygotes and not in AT1-R C carriers (-1.38 +/- 0.35 versus +0.04 +/- 0.60 m/s, respectively; P < .01). These results indicate that according to the AT1-R A1166C genotype, an angiotensin-converting enzyme inhibitor and a calcium channel blocker affect pulse wave velocity in opposite ways. Since some evidence shows that increased pulse wave velocity may enhance cardiovascular risk, it might be useful for physicians to consider the AT1-R genotype when prescribing an angiotensin-converting enzyme inhibitor or calcium channel blocker to a hypertensive individual.",1996.0,0,0
2033,8957033,The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy.,A L Kamper; N H Holstein-Rathlou; P P Leyssac; S Strandgaard,"The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P < 0.001) and C(Li) was 88% (P < 0.01) of the baseline values, APR and FPR had not changed significantly, and potassium clearance was significantly decreased. Through the rest of the study period, APR remained nearly unchanged and FPR even increased in the enalapril group. In the group of patients randomized to treatment with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P < 0.05). An unchanged or increased APR in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P < 0.01), whereas the clearances of immunoglobulin G and retinol-binding protein were unchanged in this group. In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional antihypertensive therapy. During ACE inhibition, the reabsorptive capacity of the proximal tubule appeared to be better preserved, which might be of importance for the beneficial effect of this treatment in chronic renal disease.",1996.0,0,0
2034,8957034,Effect of ramipril on blood pressure and protein excretion rate in normotensive nondiabetic patients with proteinuria.,R D Toto; B Adams-Huet; A Z Fenves; H C Mitchell; W Mulcahy; R D Smith,"Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.",1996.0,0,0
2035,8960842,Hypertension in Diabetes Study IV. Therapeutic requirements to maintain tight blood pressure control.,,"We report the efficacy of therapy over 5 years follow-up in 758 non-insulin-dependent diabetic patients in a prospective, randomised controlled study of therapy of mild hypertension. Patients were recruited who on antihypertensive therapy had systolic blood pressure over 150 mmHg or diastolic over 85 mmHg, or if not on therapy had systolic blood pressure over 160 mmHg or diastolic over 90 mmHg. Their mean blood pressure at entry to the study was 160/94 mmHg at a mean age of 57 years. They were allocated to tight control (aiming for systolic < 150/diastolic < 85 mmHg) or to less tight control (aiming for systolic < 180/diastolic < 105 mmHg). The tight control group were allocated to primary therapy either with a beta blocker (atenolol) or with an antiotensin converting enzyme inhibitor (captopril), with addition of other agents as required. Over 5 years, the mean blood pressure in the tight control group was significantly lower (143/82 vs 154/88 mmHg, p < 0.001). No difference was seen between those allocated to atenolol or captopril. The proportion of patients requiring three or more antihypertensive therapies to maintain tight control in those allocated to atenolol or captopril increased from 16 and 15%, respectively at 2 years to 25 and 26%, respectively at 5 years, whereas in the less tight control group at 2 and 5 years only 5 and 7%, respectively required three or more therapies. There was no difference in the incidence of side effects or hypoglycaemic episodes between those allocated to atenolol or captopril, but those allocated to atenolol increased their body weight by a mean of 2.3 kg compared with 0.5 kg in those allocated to captopril (p < 0.01). Allocation to atenolol was also associated with small increases in triglyceride, and decreases in LDL and HDL cholesterol, which are of uncertain clinical relevance. The study is continuing to determine whether the improved blood pressure control, which was obtained, will be beneficial in maintaining the health of patients by decreasing the incidence of major clinical complications, principally myocardial infarction and strokes, and microvascular complications, such as severe retinopathy requiring photocoagulation and deterioration of renal function.",1996.0,0,0
2036,8960851,Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria.,C Schnack; W Hoffmann; P Hopmeier; G Schernthaner,"The clinical importance of selection of different antihypertensive drugs for the treatment of diabetic patients is still unclear. Thus we performed a randomised, controlled study in 105 hypertensive non-insulin-dependent diabetic (NIDDM) patients with microalbuminuria over 1 year. Patients received either the angiotensin converting enzyme (ACE) inhibitor ramipril (2.5-5.0 mg/day; in addition 24% of patients also received felodipine) or the beta blocking agent atenolol (50-100 mg/day; in addition 24% of patients also received hydrochlorothiazide). Blood pressure, metabolic control, lipid levels and albumin excretion rate were studied during the follow-up. After 1 year an almost identical fall (p < 0.001) in blood pressure was observed with ramipril (170/100 vs 150/ 85 mmHg, median) and atenolol (180/100 vs 150/ 80 mmHg, median). With ramipril a reduction of total cholesterol (6.3 vs 5.9 mmol/l), of LDL cholesterol (3.8 vs 3.6 mmol/l) and HDL cholesterol (1.3 vs 1.2 mmol/l) was found, whereas triglycerides slightly increased (1.8 vs 2.0 mmol/l). With atenolol a similar reduction of total cholesterol (6.3 vs 5.9 mmol/l), LDL cholesterol (3.8 vs 3.7 mmol/l) and HDL cholesterol (1.4 vs 1.2 mmol/l) and an increase of triglycerides (1.4 vs 1.7 mmol/l) was noted. Metabolic control of the patients was maintained with both ramipril and atenolol treatment. With ramipril treatment urinary albumin creatinine ratio (14.4 vs 13.8 mg/mmol) and creatinine clearance (82 vs 84 ml/min) were constant, but with atenolol an increase of albumin creatinine ratio (13.9 vs 19 mg/mmol, p < 0.001) and a slight decrease of creatinine clearance (80 vs 66 ml/min, p < 0.05, not significant after Bonferroni correction) was observed. 1-year treatment of NIDDM patients with ramipril or atenolol does not influence metabolic control, the changes in serum lipids were similar. Despite almost identical blood pressure reduction in both groups the albumin creatinine ratio was constant under ramipril, but increased under atenolol treatment.",1996.0,0,0
2037,8960857,Appropriate Blood Pressure Control in NIDDM (ABCD) Trial.,R W Schrier; R O Estacio; B Jeffers,"The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM.",1996.0,0,0
2038,8961069,Circadian variation in blood pressure and heart rate in nonhypertensive congestive heart failure.,T D Giles; L Roffidal; A Quiroz; G Sander; O Tresznewsky,"This study was designed to determine whether decreases in the circadian variability of arterial blood pressure and heart rate measured in ambulatory patients would correlate with neurohumoral indices of the severity of congestive heart failure not the result of systemic arterial hypertension, and whether treatment with angiotensin-converting enzyme (ACE) inhibitors would restore a more normal pattern. The study also examined the ability of ambulatory blood pressure monitoring to discern pharmacodynamic patterns in patients with congestive heart failure, which is associated with decreased variability in circadian variations in blood pressure and heart rate among hospitalized patients. Increased plasma norepinephrine, renin activity, and atrial natriuretic peptide (ANP) have a positive correlation with worsening clinical status. ACE inhibitors have been found to be beneficial in the treatment of congestive heart failure. Ambulatory 24-h blood pressure and neurohumoral measurements were recorded in 30 patients with congestive heart failure (class II-IV, New York Heart Association) before treatment with lisinopril or captopril and repeated after 6 weeks of treatment. Fourier analysis was used as a curve-smoothing technique to compare the pharmacodynamics of the two ACE inhibitors. The absolute amplitude of systolic blood pressure correlated inversely with plasma norepinephrine and ANP (p = 0.004) but not with renin activity. Mean 24-h systemic arterial blood pressure did not decrease significantly after treatment with ACE inhibitors. An increase in absolute amplitude of systolic blood pressure correlated inversely with baseline amplitude (p < 0.00001). Inspection of the Fourier-smoothed curves demonstrated differences in the circadian effect of lisinopril and captopril on systolic blood pressure and rate-pressure product. Ambulatory 24-h blood pressure monitoring may prove useful in the assessment of the severity and treatment of congestive heart failure.",1996.0,0,0
2039,8961074,Moexipril versus captopril in patients with mild to moderate hypertension.,M Stimpel; B Koch; T Jansen; A Fox; I Loh,"Moexipril is a new, long-acting angiotensin-converting enzyme (ACE) inhibitor. In contrast to captopril, it is a prodrug of the pharmacologically active agent moexiprilat and will be administered once daily. The objective of this study was to compare the efficacy, safety, and tolerability of moexipril with that of captopril during a 12-week treatment of patients with mild to moderate hypertension. Patients with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg, inclusive, were randomized in a 2:1 ratio to receive moexipril, 7.5 mg, once daily or captopril, 25 mg, twice daily. After 6 weeks of treatment, the dose of moexipril and captopril was increased to 15 mg once daily and 50 mg twice daily, respectively, if the patient's SDBP remained > or = 90 mm Hg. Blood pressure was measured at biweekly visits. At study endpoint, adjusted mean reductions in SDBP were comparable between the moexipril and captopril groups (-9.8 vs. -8.7 mm Hg), and moexipril was more effective than captopril in reducing sitting systolic blood pressure. Adverse experiences (headache, dizziness, and upper respiratory infection) occurred at similar frequencies in the moexipril and in the captopril groups. The data indicate that moexipril at dosages of 7.5 and 15 mg once daily is as efficacious as twice daily captopril in reducing blood pressure in patients with mild to moderate hypertension.",1996.0,0,0
2040,8961239,CYP 2D6 PM phenotype hypothesis of antidepressant extrapyramidal side-effects.,P Vandel; B Bonin; S Vandel; D Sechter; P Bizouard,"Extrapyramidal symptoms occur as side-effects of neuroleptics. For many years, case reports of such side-effects, linked to antidepressant treatments, have been published, but this phenomenon is not well known. Tricyclic and serotonergic antidepressants are both involved. The authors present an hypothesis which provides one possible neurobiochemical explanation for the aetiology of these side-effects. The proposed explanation is related to the inhibition of the CYP 2D6 isoenzyme by antidepressants (or neuroleptics) that may be involved in the genesis of the observed extrapyramidal side-effects.",1996.0,0,0
2041,8964641,"A comparison of the effect of enalapril and metoprolol on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance and quality of life in hypertensive dialysis patients.",K C Wong; K S Woo; W K Lam; K T Li; K N Lai; M G Nicholls; S F Lui,"26 patients with hypertension while on hemodialysis or continuous ambulatory peritoneal dialysis for end-stage renal diseases were treated first with enalapril and then changed to metoprolol. Both drugs were shown to be similarly effective in controlling blood pressure. There was no difference between the two drugs in their effects on renal function, potassium balance, lipid profile, cardiac function, exercise tolerance, and quality of life. Mild worsening of anemia was observed during treatment with enalapril. No serious side effects were reported. Use of enalapril is safe in the treatment of hypertension in dialysis patients.",1995.0,0,0
2042,8972892,The effects of replacing beta-blockers with an angiotensin converting enzyme inhibitor on the quality of life of hypertensive patients.,E Paran; O Anson; L Neumann,"The aim was to evaluate the effects of a change of treatment from beta-blocker to captopril on the quality of life of hypertensive patients. One hundred forty-nine mild to moderate hypertensive patients who were being treated with beta-blockers were randomly assigned to receive captopril (12.5 to 50 mg twice daily), or to continue on beta-blocker treatment (atenolol: 25 to 100 mg once daily [n = 121], or propranolol, 10 to 80 mg twice daily [n = 12]). When required, 25 mg hydrochlorothiazide was added in each group. The patients were followed over periods ranging from 6 to 12 months. Blood pressure, treatment side effects, and quality of life were monitored. Blood pressure was equally well managed in both groups, though a lower level of treatment was required in the captopril group. The captopril treated patients exhibited favorable changes in several aspects of quality of life: sleep-related, gastrointestinal, and physical activity-related symptoms improved from baseline to end of follow-up. Drowsiness and the ability to concentrate significantly improved in the captopril group only (P <.01). Change in treatment from beta-blocker to captopril resulted in equally well controlled blood pressure on a lower drug dose. Moreover, the change to captopril had a positive impact on the quality of life.",1996.0,0,0
2043,8973771,Effect of protection and repair of injury of mitochondrial membrane-phospholipid on prognosis in patients with dilated cardiomyopathy.,A Ma; W Zhang; Z Liu,"We have already proved that the mitochondrial membrane-phospholipid (MMP) injury changes of peripheral lymphocytes in patients with heart failure can be used as an injury indicator of myocardia, and are related to the long-term prognosis. In the present study, MMP localization of the peripheral lymphocytes was performed by modified Demer's tricomplex flocculation method, and we compared the changes, after classification, between the pre-treatment and the 12-week post-treatment, of coenzyme Q10 (Co.Q10) and captopril in 61 hospitalized patients with dilated cardiomyopathy (DCM). They were followed up for 16.1 +/- 7.8 months (mean). The results showed that compared with the placebo, Co.Q10 and captopril could significantly protect against and repair MMP injury and improve the heart function of patients with DCM after 12 weeks, and the 2-year survival rate rose significantly by 72.7% for Co.Q10, and 64.0% for captopril, vs 24.7% for placebo. As for Longrank test, X2 equals 4.660 and 6.318, respectively, with both p < 0.05. The aforementioned results indicate that MMP injury of peripheral lymphocytes can predict the prognosis of the patients with DCM, thus the protection and repairment of MMP injury can improve the life-quality and prolong the life-span of the patients.",1996.0,0,0
2044,8977366,"Inhibition of the renin-angiotensin system after acute myocardial infarction--treat first, select later?",A S Hall; R Sapsford; S G Megarry; S G Ball,,1996.0,0,0
2045,8979626,Study on the effectiveness of enalapril as a monotherapy in mild to moderate hypertension.,M Poulose; R Jayadevan; J V Peter; A M Cherian,"This study highlights our experience with 53 patients with mild to moderate hypertension who had monotherapy with Enalapril, one of the newer Angiotensin Converting Enzyme inhibitors. Enalapril was found to be effective in controlling blood pressure in 41 patients (77%). In 12 patients (23%) addition of one more drug was necessary for control of hypertension. Side effects were noted in 9 patients (17%). In two patients the adverse reactions were severe enough to warrant withdrawal of the drug.",1996.0,0,0
2046,8983318,Efficacy of ramipril versus enalapril in patients with mild to moderate essential hypertension.,J Yasky; M Verho; T P Erasmus; H G Luus; M Angela; L Grandin; M A Akbary; B Rangoonwala,"This double-blind, randomised, cross-over study investigated the antihypertensive efficacy of ramipril and enalapril was completed by 30 patients with mild-to-moderate essential hypertension. After a four-week placebo run-in phase, the patients received either 2.5mg ramipril or 10mg enalapril once daily for four weeks. The dosages were increased to 5mg ramipril and 20mg enalapril for a further four weeks. After a placebo washout phase of four weeks, the patients were crossed over to the alternative treatment. The decrease in average 24-hour ambulatory diastolic blood pressure from week 0 to week 8 was 1.6mmHg greater with ramipril than enalapril (90% confidence interval 0.6-2.7mmHg). The corresponding reduction in for systolic blood pressure was also greater with ramipril than enalapril by 2.4mmHg (90% confidence interval: 0.5-4.2mmHg). For the difference in the drop of 24-hour ambulatory diastolic blood pressure between ramipril and enalapril the lower level of the 90% confidence interval (CI) is above the clinically relevant difference of -3mmHg. This is an indication that ramipril (2.5 and 5mg dose) is at least as effective as enalapril (10 and 20mg dose) in decreasing blood pressure in patients with mild-to-moderate essential hypertension. The duration of adequate antihypertensive effect was relatively long for both ramipril and enalapril; however, ramipril tended to have a more prolonged antihypertensive effect. Ramipril had a higher diastolic and systolic trough/peak ratio than enalapril, resulting in a more uniform antihypertensive effect over the 24-hour treatment period. Both ramipril and enalapril were well tolerated and the two treatment groups had similar safety profiles.",1996.0,0,1
2047,8984131,ACE inhibitor ramipril is more effective than the beta-blocker atenolol in reducing left ventricular mass in hypertension. Results of the RACE (ramipril cardioprotective evaluation) study on behalf of the RACE study group.,E Agabiti-Rosei; E Ambrosioni; C Dal Palù; M L Muiesan; A Zanchetti,"To compare the effect of the angiotensin converting enzyme (ACE) inhibitor ramipril with that of the beta-blocker atenolol on reversal of left ventricular hypertrophy, on blood pressure and on other echocardiographic parameters. The study was conducted in accord with the PROBE (prospective randomized open blinded endpoint) design. Randomized treatment either with ramipril or with atenolol was continued for 6 months, and echocardiograms were recorded before and after 3 and 6 months of treatment. The echo tracings were blindly evaluated in a single reading centre. M-mode, two-dimensional guided echocardiography was used to measure left ventricular wall thicknesses and dimensions, from which left ventricular mass was calculated, according to the Penn convention. Of 193 patients at 16 centres, 111 had echocardiograms that could be quantitatively evaluated. The primary analysis of the study was performed using data from those patients. In addition, echocardiograms of 88 patients were analysed on an 'according to protocol' basis (patients with preset values of left ventricular mass). Systolic and diastolic blood pressures were significantly reduced both by ramipril and by atenolol without any significant difference between the two drug treatments. The heart rate was significantly reduced by atenolol only. Both the 'primary' and the 'according to protocol' analyses showed that the left ventricular mass was significantly reduced by ramipril only. Comparison between treatments according to a multivariate analysis demonstrated a significantly greater reduction in left ventricular mass during ramipril than during atenolol treatment. The present study is the first of suitably large size in which a direct comparison of the effects of an ACE inhibitor and a beta-blocker on echocardiographic left ventricular mass has been performed. It has demonstrated that ramipril is more effective than atenolol in reversing left ventricular hypertrophy in essential hypertensive patients.",1995.0,0,0
2048,8984133,Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension.,I Tikkanen; P Omvik; H A Jensen,"To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.",1995.0,0,0
2049,8986916,Antihypertensive effects and arterial haemodynamic alterations during angiotensin converting enzyme inhibition.,G M London; B Pannier; E Vicaut; A P Guérin; S J Marchais; M E Safar; J L Cuche,"To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis. Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis. Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels. The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.",1996.0,0,0
2050,8986917,"Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril.",N J Holwerda; R Fogari; P Angeli; C Porcellati; C Hereng; P Oddou-Stock; R Heath; F Bodin,"To compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril. A total of 348 adult outpatients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind, parallel, study. Patients were allocated randomly in a ratio of 2:2:1 to receive 80 mg valsartan once a day, 20 mg enalapril once a day, or placebo for 8 weeks in general practice. Patients were assessed at 4 and 8 weeks of therapy. The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Secondary variables included the change in sitting systolic blood pressure (SSBP) and response rates at 8 weeks. Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo. Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of -9.5 mmHg for valsartan and -9.4 mmHg for enalapril (-4.5 mmHg for placebo). No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater for valsartan (54%) and enalapril (58%) than for placebo (20%), with no significant difference between the two active treatments. Both valsartan and enalapril demonstrated a consistent antihypertensive effect over time, with 90% of patients with a response at 4 weeks responding at 8 weeks. Both of the treatments were tolerated well. Although the incidence of coughing was generally low in the study, more cases were reported with enalapril (three) than with valsartan (one) or placebo (none). The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing.",1996.0,0,0
2051,8989129,Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators.,H C Doval; D R Nul; H O Grancelli; S D Varini; S Soifer; G Corrado; S Dubner; O Scapin; S V Perrone,"The goal of the study was to determine the prognostic value of nonsustained ventricular tachycardia (NSVT) in total mortality in severe congestive heart failure (CHF) and in death modes. NSVT is associated with an increased mortality in CHF. However, the predictive value of NSVT as a marker for sudden death or death due to progressive heart failure has not been determined. Five hundred sixteen patients from the GESICA trial (33.4% with NSVT) were initially studied with the results of 24-hour Holter and 2 years of follow-up. Within 2 years, 87 of 173 patients (50.3%) with NSVT and 106 of 343 patients (30.9%) without NSVT died. Relative risk (RR) was 1.69 (95% confidence interval [CI], 1.27 to 2.24; P < .0002), and Cox proportional hazard analysis was 1.62 (95% CI, 1.22 to 2.16; P < .001). Sudden death increased from 8.7% (30 of 343) to 23.7% (41 of 173) in patients with NSVT (RR, 2.77; 95% CI, 1.78 to 4.44; P < .001). Progressive heart failure death was also increased from 17.5% (60 of 343) to 20.8% (36 of 173) (P = .22). Quantitative analysis of 24-hour Holter (first 295 patients) demonstrated that couplets had a similar RR to that of NSVT for both total mortality (RR, 1.81; 95% CI, 1.22 to 2.66; P < .002) and sudden death (RR, 3.37; 95% CI, 1.57 to 7.25; P < .0005). Couplets and/or NSVT (ventricular repetitive beats) were even more predictive for sudden death (RR, 10.1; 95% CI, 1.91 to 52.7; P < .01). In patients with CHF, NSVT is an independent marker for increased overall mortality rate and sudden death. The absence of NSVT and ventricular repetitive beats in a 24-hour Holter indicates a low probability of sudden death.",1996.0,0,0
2052,8995963,Enalapril-associated acute pancreatitis: recurrence after rechallenge.,A Maringhini; A Termini; R Patti; M Ciambra; P Biffarella; L Pagliaro,"Three patients with acute pancreatitis diagnosed while they were taking enalapril are described. In two of these patients, enalapril was the only drug taken immediately before the symptoms began, and other etiologies were accurately excluded. In the third patient, the relationship between enalapril and acute pancreatitis was shown by a rechallenge with the drug that resulted in severe acute pancreatitis. This report is a definite demonstration of the relationship between enalapril and acute pancreatitis. We suggest stopping treatment with enalapril in patients suspected of having acute pancreatitis. We also recommend not rechallenging patients with the drug because of the risk of inducing severe acute pancreatitis.",1997.0,0,0
2053,8996294,Angiotensin-converting enzyme inhibitor therapy affects left ventricular mass in patients with ejection fraction > 40% after acute myocardial infarction.,D B Johnson; R E Foster; F Barilla; G G Blackwell; M Roney; A W Stanley; K Kirk; R A Orr; R J van der Geest; J H Reiber; L J Dell'Italia,"We tested the hypothesis that angiotensin-converting enzyme (ACE) inhibitor therapy decreases left ventricular (LV) mass in patients with a left ventricular ejection fraction (LVEF) > 40% and no evidence of heart failure after their first acute Q wave myocardial infarction (MI). Recently, ACE inhibitor therapy has been shown to have an early mortality benefit in unselected patients with acute MI, including patients without heart failure and a LVEF > 35%. However, the effects on LV mass and volume in this patient population have not been studied. Thirty-five patients with a LVEF > 40% after their first acute Q wave MI were randomized to titrated oral ramipril (n = 20) or conventional therapy (control, n = 15). Magnetic resonance imaging (MRI) performed an average of 7 days and 3 months after MI provided LV volumes and mass from summated serial short-axis slices. Left ventricular end-diastolic volume index did not change in ramipril-treated patients (62 +/- 16 [SD] to 66 +/- 17 ml/m2) or in control patients (62 +/- 16 to 68 +/- 17 ml/m2), and stroke volume index increased significantly in both groups. However, LV mass index decreased in ramipril-treated patients (82 +/- 18 to 73 +/- 19 g/m2, p = 0.0002) but not in the control patients (77 +/- 15 to 79 +/- 23 g/m2). Systolic arterial pressure did not change in either group at 3-month follow-up. In patients with a LVEF > 40% after acute MI, ramipril decreased LV mass, and blood pressure and LV function were unchanged after 3 months of therapy. Whether the decrease in mass represents a sustained effect that is associated with a decrease in morbid events requires further investigation.",2001.0,0,1
2054,9000551,Renal failure related to angiotensin-converting enzyme inhibitors.,S C Textor,"The introduction of agents that block the renin-angiotensin system has provided major benefit to patients with hypertension, renal diseases, and congestive heart failure. Some of the therapeutic advantages related to the kidney derive from removing angiotensin II at the efferent arteriole. Under some circumstances when afferent blood supply is compromised, particularly beyond a renal arterial stenosis, use of angiotensin-converting enzyme (ACE) inhibitors can lead to decrements of glomerular filtration rate (GFR) and impaired potassium excretion, which clinicians should be prepared to identify and manage. How often this occurs and when such a decrement poses a hazard to renal parenchymal viability depends on the starting conditions of the renal vasculature and sodium balance. Although these observations have been made primarily with ACE inhibitors, the basic principles apply to other agents interacting with components of the renin-angiotensin system, including angiotensin II antagonists and renin-inhibitors. When promptly identified and treated, changes in kidney function under these conditions represent a modest and acceptable risk worth taking in exchange for major therapeutic benefits.",1997.0,0,0
2055,9001832,"An open-label, noncomparative, multicenter study of ramipril in the treatment of patients with mild-to-moderate hypertension.",A Sadick; M Z Yusuf; M Reuter,"Ramipril, a once-a-day angiotensin-converting enzyme inhibitor, was studied in the treatment of mild-to-moderate hypertension in 240 patients. A total of 194 patients (111 women and 83 men; mean +/- SD age, 46.0 +/- 11.5 years) were considered assessable for study. After a 2-week placebo washout phase, all patients received ramipril 2.5 mg once daily for 4 weeks. At 4 weeks, blood pressure was evaluated for response to therapy. Responders to 2.5 mg were continued on the same dose; nonresponders received 5 mg once daily for another 4 weeks. Results showed that 91% of patients responded after 8 weeks of therapy, 60% to 2.5 mg and 31% to 5 mg. Ramipril was well tolerated and, because of its long half-life, can be considered a true once-a-day angiotensin-converting enzyme inhibitor for the treatment of patients with mild-to-moderate hypertension.",1996.0,0,0
2056,9001838,"Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.",E Kuschnir; E Acuña; D Sevilla; J Vasquez; M Bendersky; J Resk; R Glazer,"This multicenter, double-masked, randomized, parallel-group study compared the efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential hypertension. After a placebo run-in period, 308 patients (all white) were randomized to treatment groups and took medication once daily for 8 weeks. Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing. Patients wore a noninvasive blood pressure monitor for 24 hours before randomization and before the final visit. Investigators recorded adverse experiences at randomization and at study weeks 4 and 8, and obtained specimens for laboratory testing at randomization and at study week 8. Three hundred seven patients were evaluated for efficacy, and 308 for tolerability and safety. At end point (the last postrandomization measurement for each patient), the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy. The results of 24-hour monitoring showed that the amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean diastolic blood pressure at < or = 90 mm Hg. A responder rate of 87.0% was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8% with amlodipine, benazepril, and placebo, respectively. This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant. Drug-related adverse events occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%, 6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups, respectively. Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group. Overall, once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinically superior to amlodipine 5 mg alone, benazepril 20 mg alone, and placebo, was well tolerated, and was associated with less edema than the amlodipine treatment.",1996.0,0,0
2057,9004094,Recent data on hypertension and progressive renal disease.,P Zucchelli; A Zuccalà,Arterial hypertension may favour the progression of non-diabetic primary renal disease and participate in the appearance of atheromatous renovascular disease. In AIPRI trial (ACE-inhibition in the progression of renal insufficiency) the ACE-inhibitor benazepril was able to protect patients with mild-to-moderate renal disease against the progression of renal insufficiency. Some clinical observations suggest that in many aged patients with long-standing hypertension the appearance of renal failure may be related to atheromatous reno-vascular disease. This disease may be responsible for progressive renal failure through renal artery stenosis and/or cholesterol microembolization.,1996.0,0,0
2058,9004103,Long-term blood pressure control in older Chinese patients with isolated systolic hypertension: a progress report on the Syst-China trial.,J G Wang; G Liu; X Wang; S Zhang; M Sun; X Pan; M Jian; L Gong; L Thijs; J Staessen; R Fagard; L Liu,"This report on the ongoing double-blind placebo-controlled Syst-China trial investigated whether antihypertensive drug treatment based mainly on a calcium entry blocker and a converting enzyme inhibitor, would be suitable for maintaining long-term blood pressure (BP) control in older Chinese patients (average age: 67 years) with isolated systolic hypertension (systolic pressure 160-219 mm Hg and diastolic pressure < 95 mm Hg). Active treatment consisted of nitrendipine (10- 40 mg/day) with the possible addition of captopril (12.5- 50 mg/day) and hydrochlorothiazide (12.5-50 mg/day), as necessary to reduce systolic pressure to a level of 150 mm Hg or lower and by at least 20 mm Hg. Matching placebos were used in the control group. This progress analysis was restricted to BP control up to 3 years of follow-up. The placebo (n = 1134) and active treatment n = 1245) groups had similar characteristics at enrolment. The sitting BP averaged 170/86 mm Hg. Systolic pressure fell (P < 0.001) on average 8 mm Hg more on active treatment than on placebo and diastolic pressure 3 mm Hg more. Fewer patients remained on monotherapy in the placebo than in the active treatment group (P < 0.001); on placebo the second and third line medications were started more frequently (P < 0.001). This progress report showed that significant BP reduction can be achieved and maintained in older Chinese patients treated with a calcium antagonist, associated with a converting-enzyme inhibitor and a thiazide, as necessary. Whether this BP reduction would result in a clinically meaningful decrease of cardiovascular complications is still under investigation.",1996.0,0,0
2059,9004108,Evaluation of enalapril/diltiazem ER in hypertensive patients with coexisting renal dysfunction. Enalapril/Diltiazem ER in Hypertensive Renal Disease Group.,D E Hricik; B S Levine; H J Adrogue; M S Weinberg; R Goldstein,"Both enalapril and long-acting diltiazem have been shown to effectively lower blood pressure (BP) in hypertensive patients. Furthermore, in clinical studies, these two agents provided beneficial renal effects in these patients when administered on a long-term basis. A combination of enalapril/diltiazem ER was evaluated in 62 patients with Stage 1-3 hypertension and coexisting renal disease. This trial used a multicenter, randomized, double-blind, parallel group design. The study consisted of a 12-week double-blind phase followed by a 6-month open-label extension phase. The combination of enalapril/diltiazem ER was shown to reduce BP following both short-term and long-term treatment phases. Patients in Renal Group I (creatinine clearance CrCl): 30-59 ml/min/1.73 m2) had decreases of -18/-16 and -25/-20 mm Hg after 12 weeks and 9 months of therapy, respectively. Those in Renal Group II (CrCl: 10-29 ml/min/1.73 m2) had similar decreases of -23/-18 and -23/-19 mm Hg at these time points. The adverse events, in both phases, were those associated with the respective monotherapies. A reduction in CrCl with a coincident decrease in proteinuria was noted for both renal groups. The combination of enalapril/diltiazem ER lowered BP and was generally well tolerated by the patients. The combination of these two agents should improve the management of hypertensive patients.",1996.0,0,0
2060,9007680,The practical assessment of compliance with ACE-inhibitor therapy--a novel approach.,R J MacFadyen; A D Struthers,"Poor compliance may be responsible for symptomatic decompensation or neurohormonal ""escape"" in patients with heart failure treated over the long term with angiotensin-converting enzyme-1 (ACEI) drugs. Serum ACE activity is a poor index of neurohormonal suppression or haemodynamic effect after ACE-inhibitor treatment. Serum ACE activity may, however, be a useful index of compliance with treatment, as serum ACE is sensitive to the presence of an ACE inhibitor in the blood. Sixteen normotensive male volunteers of known ACE genotype received 7 days of randomised, double-blind therapy on four occasions 2 weeks apart with lisinopril 20 mg (L) or matched placebo (P) to simulate (A) noncompliance (all P), (B) full compliance (all L), (C) partial compliance (L days, 1, 3, 6; P days, 2, 4, 5, 7), or (D) single dose (L day 7; P, 1-6). Supine (30 min) blood pressure (BP)/heart rate (HR), ACE, and angiotensins were measured on d7 before dose and 4-6 h after dose. Results are mean +/- 1 SD. BP showed the expected small decrease with active treatment on d7 (B or D) but not with placebo (A) or partial compliance (C). Prestudy serum ACE, despite a wide range (16-124 U/L), was reproducible within subjects [coefficient of variation (CV), 1.7%]. Serum ACE activity, before (41.9 +/- 30) and after (41 +/- 30) angiotensin (A) I or II, were unaffected by treatment (placebo A). Active treatment (B) resulted in very low serum ACE activity and d7 and a small further suppression after dosing (before, 3.9 +/- 4; after, 1.8 +/- 4). AI was elevated in this group with further elevation after dosing (before, 234 +/- 116; after, 551 +/- 250). AII was only modestly reduced from baseline and showed little further suppression after dosing (before, 7.8 +/- 4; after, 6.3 +/- 5). Partial compliance (C) showed low ACE but no reduction after treatment (before, 7 +/- 3; after, 7 +/- 4), an elevated AI but no dosing effect (before, 187 +/- 198; after, 200 +/- 151) and reduced AII but with no further dose suppression (before, 6.4 +/- 3.4; after, 7 +/- 4) induced increase in peptide (compared with B). Single-dose treatment (D) showed ACE inhibition as expected (before, 47 +/- 30; after, 2.2 +/- 3). There was a dosing-related increase of AI but to a lesser extent than seen with chronic active dosing (B) (before, 39 +/- 10; after, 240 +/- 200). In contrast to long-term dosing, there was marked ANG II suppression (before, 8.8 +/- 4; after, 2.9 +/- 3). With this long-acting ACEI in a dose relevant to congestive heart failure management, we suggest that 4-6 h after-dosing serum ACE (< 5 EU/L) and elevated ANG I (> 300 pg/ml) can be used to confirm compliance with treatment. These absolute values may be altered in patients treated concomitant with loop diuretics. In principle, however, this may be a useful tool in clinical trials or in clinical practice after further work has been done to assess the limits in patients across the doses and across the range of available drugs used.",1997.0,0,0
2061,9008256,Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension.,J L Pool; W C Cushman; R K Saini; C E Nwachuku; J P Battikha,"The combination of angiotensin converting enzyme (ACE) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension. Previous study designs have often been inadequate to demonstrate the details of interactions between these antihypertensive agents. This study used a modified 4 x 4 factorial randomized, double-blind, placebo-controlled, parallel group design to study the efficacy of 17 different doses of fosinopril (Fos), a phosphinic acid derived ACE inhibitor, and hydrochlorothiazide (HCTZ) in 550 patients with mild to moderate hypertension. Data from these variables were fit to quadratic response surface models (QRSM) using polynomial functions in the doses of the two components. Using QRSM, seated systolic (SeSBP) and diastolic blood pressure (SeDBP) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied. Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP. Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg. Coadministration of Fos and HCTZ produced an additive antihypertensive effect. This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology.",1997.0,0,0
2062,9010369,Medications that may contribute to sexual disorders. A guide to assessment and treatment in family practice.,W W Finger; M Lund; M A Slagle,"Approximately 15% to 25% of family practice patients have concerns about sexual function and are most comfortable discussing these issues with their family physician. While many physicians have avoided this topic in the past, citing lack of knowledge and skill, the family practice setting is ideal for a preliminary evaluation of sexual dysfunction and treatment for certain etiologies. This especially is true for changes in sexual function secondary to medication effects. This article provides basic guidelines designed to assist physicians in evaluating the effects of medications and other substances on sexual function. Also included are lists of medications known or suspected to have adverse effects on sexual function. Physicians are encouraged to address the sexual concerns of their patients and to incorporate these guidelines and the medication lists into their evaluation.",1997.0,0,0
2063,9010643,A risk-benefit assessment of losartan potassium in the treatment of hypertension.,L M Burrell,"Losartan potassium is the first of a new class of orally active antihypertensive drugs which antagonise the action of angiotensin (AT) II at the AT1 receptor subtype. Losartan potassium is converted by the liver to the active metabolite E-3174, which is a more potent antagonist at the AT1 receptor. E-3174 is responsible for most of the pharmacological effects of losartan potassium, and its long half-life contributes to the extended duration of action of the drug. Losartan potassium is effective as a once-daily antihypertensive agent. In mild to moderate hypertension, losartan potassium has similar efficacy to enalapril, atenolol and felodipine extended release. When losartan potassium is combined with hydrochlorothiazide there is a further reduction in blood pressure. Losartan potassium is well tolerated in mild, moderate and severe essential hypertension, with dizziness being reported as the only drug-related adverse effect. The overall rate of patient withdrawal from therapy due to adverse experiences with losartan potassium is lower (2.3%) than that of placebo (3.7%). First-dose hypotension is uncommon, perhaps due to the slower onset of action of the drug, and cough does not appear to be a significant problem. A number of areas concerning the safety and efficacy of losartan potassium remain to be clarified. In particular, long term tolerability studies are needed; cough only became apparent as an adverse effect of ACE inhibitors after 3 to 4 years of use. Postmarketing surveillance has shown that angioedema, a rare but life-threatening adverse effect of ACE inhibitors, also occurs with losartan potassium. Further data are needed on the use of losartan potassium in patients with renal impairment before accepting the recommendation that dosage adjustment is not necessary. The pharmacokinetics and pharmacodynamics of losartan potassium in patients with hepatic disease also require further investigation. Losartan potassium increases uric acid secretion and lowers plasma uric acid levels, which may be of benefit when losartan potassium is combined with a thiazide diuretic, but which may otherwise lead to uric acid stone formation and possibly to nephropathy. Simple control of blood pressure is no longer an adequate goal in the management of hypertension. Any new antihypertensive agent should also reduce cardiovascular events, prevent or cause regression of end-organ damage such as left ventricular hypertrophy, atherosclerosis and renal failure, and should not impair quality of life. Such data on losartan potassium are not currently available. Losartan potassium is likely to be used in patients who are intolerant of ACE inhibitors, but its future in the management of hypertension will depend on long term tolerability studies and data on its effects beyond simple blood pressure control.",1997.0,0,0
2064,9013270,Concurrent alpha 1 adrenergic blockade and angiotensin converting enzyme inhibition in the treatment of congestive heart failure.,A A Ajayi; G G Sofowora; M O Balogun,"We tested the hypothesis that concurrent inhibition of the renin angiotensin system by enalapril (5 mg) and the sympathetic nervous system by alpha 1 adrenergic blockade (prazosin 1 mg) will be superior to enalapril alone in 17 patients with heart failure on standard therapy, in a single blind, placebo-controlled, randomized parallel group study for 4 weeks. Enalapril alone induced a significant increase in exercise time from 499 +/- 412 s to 707 +/- 608 s (P < 0.05, ANOVA), but the increase induced by the enalapril + prazosin combination was significantly greater (P < 0.025, MANOVA) from 214 +/- 271 to 1007 +/- 784 s as was the increase in creatinine clearance (P < 0.05).",1996.0,0,0
2065,9015418,"Plasma endothelin in congestive heart failure: effect of the ACE inhibitor, fosinopril.",S Galatius-Jensen; H Wroblewski; C Emmeluth; P Bie; S Haunsø; J Kastrup,"The study evaluates the influence of treatment with the angiotensin-converting enzyme inhibitor, fosinopril, on the plasma endothelin level in patients with congestive heart failure, and the relationship between plasma endothelin and clinical study parameters (bicycle exercise test, echocardiography, heart failure score and blood pressure). Plasma endothelin was measured in 34 patients with moderately severe congestive heart failure at randomisation in the fosinopril/placebo-controlled study 'Fosinopril Efficacy and Safety Trial' and at the end of the 12-week study period. The patients had elevated pre-treatment plasma endothelin concentrations (3.5 +/- 1.2 pg/ml, mean +/- s.d., n = 34) compared with healthy volunteers (2.0 +/- 0.4 pg/ml, n = 21, P < 0.0001). Treatment with fosinopril for 12 weeks lowered plasma endothelin from 3.5 +/- 1.2 to 2.5 +/- 0.7 pg/ml (m = 18, P < 0.005), in contrast to the non-significant increase in the placebo-treated group 3.5 +/- 1.3 to 4.3 +/- 2.4 pg/ml, n = 16). A multiple regression analysis for baseline study parameters, demonstrated a significant relationship between plasma endothelin and exercise test duration and a composite heart failure score classification (r = 0.53, P < 0.001). Treatment of patients with congestive heart failure with the angiotensin-converting enzyme inhibitor, fosinopril, reduce the elevated plasma endothelin level to normal values. The relation between plasma endothelin and clinical parameters indicates that endothelin may play a pathophysiological role in the progression of congestive heart failure.",1996.0,0,0
2066,9017770,Long-term effectiveness of enalapril plus extended-release diltiazem in essential hypertension.,W Applegate; J D Cohen; P Wolfson; A Davis; S Green,"To evaluate the efficacy and safety of a new combination product, enalapril-diltiazem ER, when administered over the long term. Open-label, titration to response, with treatment lasting 46 weeks after a 6-week, double-blind phase. Medical clinics in the private and academic sectors. Of 265 patients (68% men, 83% Caucasian, mean age 54.9 yrs) with essential hypertension (sitting diastolic blood pressure 95-115 mm Hg) enrolled, 167 completed the trial. Patients received either the dosage of enalapril-diltiazem ER that they were given during the double-blind phase, or were prescribed enalapril 5 mg-diltiazem ER 120 mg once/day. The dosage was increased until blood pressure was controlled or to a maximum of enalapril 10-diltiazem ER 360 mg/day. Combination therapy decreased sitting blood pressures by -11.1/-10.6 mm Hg. Overall, 58% of the patients achieved a sitting diastolic blood pressure of 90 mm Hg or below at the end of the study. There was no evidence of tolerance to the agents' antihypertensive effects. The most common drug-related adverse events were cough, headache, dizziness, and asthenia or fatigue. The combination effectively managed essential hypertension when administered on a long-term basis and was generally well tolerated. It should improve both compliance and management of hypertension.",1997.0,0,0
2067,9028424,"ASHP therapeutic guidelines on angiotensin-converting-enzyme inhibitors in patients with left ventricular dysfunction. This official ASHP practice standard was developed through the ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 16, 1996.",,,1997.0,0,0
2068,9028507,Epidemiological study of angioedema and ACE inhibitors.,G M Gabb; P Ryan; L M Wing; K A Hutchinson,"Angioedema is an uncommon and poorly recognised adverse reaction to angiotensin converting enzyme inhibitors (ACE-Is). The epidemiology of this association has not been described. To examine the epidemiology of angioedema and its relation to ACE inhibitor prescribing. To examine the characteristics of angioedema occurring in patients taking ACE inhibitors. A retrospective case control study and a case note audit were conducted of 40 patients who presented to a teaching hospital Accident and Emergency Department with angioedema on 48 occasions. One hundred and sixty control subjects presenting to the same Accident and Emergency Department but without angioedema were matched to cases by age, sex and presentation date. An ecological study comparing the numbers of angioedema admissions by age cohorts to South Australian (SA) public hospitals with the prescription volumes of ACE-Is in Australia was also undertaken. Case control study: In patients presenting with angioedema compared with controls, the exposure odds ratio for ACE-Is was 5.1 (95% CI 2.03-12.89) and for non-steroidal anti-inflammatory drugs (NSAIDs) was 4.13 (95% CI 1.28-13.39). CASE NOTE AUDIT: 15/40 (38%) patients presenting with angioedema on 19/48 (40%) occasions were taking an ACE-I. These patients were older and less likely to have an atopic history than those not taking an ACE-I. The onset of angioedema after starting an ACE-I was delayed for greater than six months in nine patients. ACE-I therapy was continued after 53% of presentations. ECOLOGICAL STUDY: The number of admissions with angioedema to SA public hospitals increased between 1985-86 and 1994-95, predominantly in older patients, and paralleled the increasing prescription volumes of ACE-Is. A considerable proportion of patients presenting with angioedema will be taking an ACE-I or a NSAID. The association of ACE-Is and angioedema is not well recognised, partly because the onset of angioedema may be delayed for months or years after commencement of an ACE-I. A persisting risk of angioedema is present in patients who have initially commenced an ACE-I uneventfully. The epidemiology of angioedema is now changing in parallel with the increasing use of ACE-Is.",1996.0,0,0
2069,9032106,Differences between nisoldipine and lisinopril on glomerular filtration rates and albuminuria in hypertensive IDDM patients with diabetic nephropathy during the first year of treatment.,P Rossing; L Tarnow; S Boelskifte; B R Jensen; F S Nielsen; H H Parving,"Our objective was to compare the effect of a long-acting calcium antagonist (nisoldipine) versus an ACE inhibitor (lisinopril) on albuminuria, arterial blood pressure, and glomerular filtration rate (GFR) in hypertensive IDDM patients with diabetic nephropathy. We performed a 1-year, double-blind, double-dummy, randomized, controlled study comparing nisoldipine (20-40 mg once daily) with lisinopril (10-20 mg once daily) in 52 hypertensive IDDM subjects with diabetic nephropathy. Three patients dropped out, and results for the remaining 49 (25 nisoldipine, 24 lisinopril) are presented. Diuretics were required in 10 nisoldipine- and 8 lisinopril-treated patients. Every 3 months, 24-h ambulatory blood pressure (TM2420, A&D, Tokyo, Japan) and albuminuria in three 24-h samples (enzyme immunoassay) were measured; GFR (51Cr-EDTA plasma clearance) was recorded every 6 months. Mean arterial blood pressure (24 h) was reduced from (mean +/- SE) 108 +/- 3 mmHg at baseline to 101 +/- 2 in average during treatment in the lisinopril group and from 105 +/- 2 to 103 +/- 2 in the nisoldipine group (P = 0.06 comparing changes in the two groups). Albuminuria was reduced 47% (95% CI 21-65) in the lisinopril group versus an increase of 11% (-3 to 27) in the nisoldipine group (P = 0.001). Fractional albumin clearance was reduced 37% (95% CI 4-59%) in the lisinopril versus an increase of 35% (8-69%) in the nisoldipine group (P < 0.01). GFR decreased from 85 +/- 5 ml x min(-1) x 1.73 m(-2) to 73 +/- 5 in the lisinopril group and from 84 +/- 6 to 80 +/- 7 in the nisoldipine group (P < 0.05). The effect of study medication on albuminuria and GFR was independent of changes in systemic blood pressure and baseline variables in multiple regression analyses. In summary, lisinopril reduced albuminuria, but also GFR, to a greater extent than did nisoldipine in hypertensive IDDM patients with diabetic nephropathy during the 1st year of treatment. Longer follow-up is required to clarify whether these drugs have different renoprotective effects.",1997.0,0,0
2070,9036753,Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease.,C S Barr; A A Naas; M Fenwick; A D Struthers,"This study was designed to investigate the possible mechanisms whereby enalapril improves cardiac function and mortality in chronic heart failure. We explored potential mechanisms by following 41 patients with early heart failure over the course of 1 year. These patients were randomized in a prospective triple-blind manner to receive either enalapril or placebo. Over the 1 year, repeated measurements were obtained of echocardiographic parameters, glomerular filtration rate, renal blood flow, hematocrit, plasma neurohormones, and QTc dispersion. Echocardiographic parameters improved with enalapril but deteriorated with placebo (cardiac output 4.6 +/- 1.6 to 3.7 +/- 1.5 L/min with placebo, and 4.5 +/- 1.3 to 5.8 +/- 2.0 L/min with enalapril; p <0.01). In contrast, there were no significant changes in renal blood flow (518 +/- 185 to 509 +/- 180 ml/min/1.73 m2 with placebo, and 541 +/- 142 to 504 +/- 162 ml/min/1.73 m2 with enalapril). Glomerular filtration rate changed from 79 +/- 20 to 78 +/- 19 ml/min/1.73 m2 with placebo, and from 85 +/- 21 to 73 +/- 27 ml/min/1.73 m2 with enalapril (p = 0.051). Enalapril reduced hematocrit (0.414 +/- 0.041 to 0.377 +/- 0.040%) significantly more than placebo (0.420 +/- 0.029 to 0.411 +/- 0.023 l/l; p <0.01). In addition, enalapril produced a marked reduction in QTc dispersion (93 +/- 36 to 88 +/- 28 ms with placebo and 93 +/- 35 to 60 +/- 22 ms with enalapril; p <0.05). Thus, enalapril significantly reduced hematocrit and reduced QTc dispersion in early heart failure. Both of these effects, but especially the latter, could be an important mechanism for the reduced mortality seen with angiotensin-converting enzyme inhibitors in heart failure. In contrast, renal hemodynamics did not parallel either the placebo-induced deterioration in cardiac function or the enalapril-induced improvements in cardiac function.",1997.0,0,0
2071,9037321,The alterations in insulin sensitivity during angiotensin converting enzyme inhibitor treatment are related to changes in the calcium/magnesium balance.,A Haenni; L Berglund; R Reneland; P E Anderssson; L Lind; H Lithell,"The present analysis was undertaken to investigate the relations between alterations in mineral factors, especially the balance between serum calcium and magnesium concentrations (S-Ca and S-Mg, respectively), and variables reflecting glucose and lipid metabolism during angiotensin converting enzyme (ACE) inhibitor treatment. A total of 96 patients with essential hypertension, participating in four double-blind studies with four different ACE inhibitors and similar protocols, were included. At the end of the initial placebo period and at the end of the period of active drug treatment, a hyperinsulinemic euglycemic clamp test was carried out, lipoprotein status was assessed, and the concentrations of serum electrolytes were measured. The serum ACE activity was determined in the group treated with fosinopril. Changes in insulin sensitivity index (M/I) were directly correlated to alterations in S-Mg (r = 0.24, P < .02), and inversely correlated to changes in S-Ca (r = -0.19, P = .07) and the ratio between serum calcium and magnesium concentrations (Ca/Mg) (r = -0.27, P < .008). The change in total serum triglycerides (S-Tg) was inversely correlated to the change in S-Mg (r = -0.35, P < .0005), and directly correlated to the change in Ca/Mg ratio (r = 0.36, P < .0004). The reduction in serum ACE activity correlated to a more pronounced increase in S-Mg r = -0.62, P < .002), and decrease in the Ca/Mg ratio (r = 0.73, P = .0002). We conclude that the changes in the studied metabolic variables and serum ACE activity during ACE inhibitor treatment are related to alterations in mineral status and the balance between calcium and magnesium concentrations in serum.",1997.0,0,0
2072,9037327,The antihypertensive efficacy of the novel calcium antagonist mibefradil in comparison with nifedipine GITS in moderate to severe hypertensives with ambulatory hypertension.,Y Lacourcière; L Poirier; J Lefebvre; F Archambault; S Dalle Ave; C Ward; E Lindberg,"Mibefradil is a novel calcium antagonist that blocks selectively the T-type calcium channels. In this double-blind forced titration study design we compared the effects of mibefradil 50, 100, and 150 mg and nifedipine GITS 30, 60, and 90 mg monotherapies or combined with lisinopril 20 mg in 71 moderate to severe hypertensives (59 men and 12 women) with confirmed ambulatory hypertension. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters during treatment with mibefradil and nifedipine GITS alone and combined with lisinopril. At maximal dosage, patients treated with mibefradil experienced a greater (P < .05) reduction in clinic and ambulatory diastolic blood pressures as well as a greater response rate (86% v 69%). Trough:peak ratios for systolic and diastolic blood pressures were > 90% at each dose level. Significant decrease in baseline heart rate was observed with mibefradil 150 mg alone or combined with lisinopril, but no patients experienced clinically significant atrioventricular conduction abnormalities. Adverse events related to vasodilation were more prevalent in the nifedipine GITS group. Consequently, the results of the present study demonstrate that the novel calcium channel blocker mibefradil, either alone or in combination with lisinopril, is effective in reducing clinic and 24-h blood pressures while decreasing heart rate and is well tolerated in patients with moderate to severe hypertension.",1997.0,0,0
2073,9038030,Lisinopril use in a large military medical center.,S R Wirebaugh; G A Spencer; T H McIntyre,"The results of a drug use evaluation of lisinopril at a large teaching military medical center are reported. Indicators and thresholds were developed and approved by the Pharmacy and Therapeutics Committee. The medical charts of 227 patients for whom lisinopril was prescribed from June 1991 to June 1992 were reviewed for appropriateness of prescribing, appropriateness of monitoring, occurrence of any adverse drug reactions, and detection of drug interactions. Prescribing was appropriate in 97% and monitoring was appropriate in all reviewed cases. The most common adverse drug reactions detected were cough (7%), hypotension (3%), and rash (2%). Patients were also prescribed several drugs that may interact with lisinopril. Lisinopril appeared to be well tolerated and efficacious. Forty patients (18%) experienced adverse drug reactions related to lisinopril. There did not appear to be any major deficiencies with lisinopril prescribing and no corrective action needed to be taken other than educational activities for the appropriate use of lisinopril. Information from this drug use evaluation is useful in formulary decision making.",1997.0,0,0
2074,9039073,Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS),R H Grimm; G A Grandits; R J Prineas; R H McDonald; C E Lewis; J M Flack; C Yunis; K Svendsen; P R Liebson; P J Elmer,"Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported a problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication.",2001.0,0,0
2075,9039154,Combined sympathetic suppression and angiotensin-converting enzyme inhibition in congestive heart failure.,A J Manolis; C Olympios; M Sifaki; S Handanis; D Cokkinos; M Bresnahan; I Gavras; H Gavras,"Neurohormonal activation is a pathogenic contributor and prognostic marker in congestive heart failure (CHF). While angiotensin-converting enzyme (ACE) inhibition is now first-line therapy, sympathetic inhibition has only lately been proposed to this aim. Recently, we reported improvement of preload parameters by sympathetic suppression with clonidine. In the present paper we studied the effects of a single oral dose of clonidine 0.15 mg+captopril 6.25 mg combination, compared with captopril 6.15+placebo in a single-blind parallel study on 16 patients with Class III or IV CHF (13 males, 3 females, aged 62 +/- 8 years, with an ejection fraction of 33 +/- 8%). Hemodynamic and hormonal measurements were taken at baseline after a diagnostic cardiac catheterization and again 2 hours after treatment. The results indicate that preload parameters such as RAP, PCWP and MPAP decreased significantly with the combination therapy but not with captopril alone. On the contrary, SVR decreased significantly with both treatments and SVI increased significantly with both-but the latter change was significantly greater with the captopril/clonidine combination than with captopril alone. Suppression of plasma norepinephrine occurred with the combination only (evidently attributable to clonidine), whereas plasma renin activity increased with both regimens, due apparently to captopril. Our results indicate that the combination of clonidine with captopril induces significant improvements in both preload and afterload parameters of CHF and correction of activated neurohormones, suggesting additive hemodynamic and hormonal benefits from the two treatment modalities.",1997.0,0,0
2076,9040453,Determining the trough-to-peak ratio in parallel-group trials. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.,J A Staessen; L Thijs; G Bijttebier; D Clement; E T O'Brien; P Palatini; J L Rodicio; J Rosenfeld; R Fagard,"We explored how in parallel-group trials interindividual variability, correction for placebo effects, and smoothing of blood pressure profiles can be handled in measuring the trough-to-peak ratio in 244 individuals with isolated systolic hypertension (> or = 60 years) enrolled in the placebo-controlled Systolic Hypertension in europe Trial. Net treatment effects were computed by subtracting the mean changes from baseline during placebo (n = 133) from those during active treatment (n = 111). At entry, systolic/diastolic pressures averaged 176/86 mm Hg in the clinic and 149/80 mm Hg on 24-hour ambulatory monitoring. With corrections applied for baseline and placebo, nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d), reduced (P < .001) these blood pressure values by 16.6/7.3 and 9.8/4.7 mm Hg, respectively. The net trough-to-peak ratios were first determined from blood pressure profiles (12 hours) with 1-hour precision, synchronized by the morning and evening doses of the double-blind medication. According to the usual approach, disregarding interindividual variability, the systolic/diastolic net trough-to-peak ratios were 0.46/0.40 in the morning and 0.77/0.99 in the evening. In individual subjects, the baseline-adjusted trough-to-peak ratios were nonnormally distributed. We therefore used a nonparametric technique to calculate the net trough-to-peak ratios from the results in individual subjects. In the morning, these ratios averaged 0.25 systolic (95% confidence interval, 0.09 to 0.41) and 0.15 diastolic (95% confidence interval, 0.00 to 0.31) and in the evening, 0.19 and 0.36 (95% confidence intervals, 0.00 to 0.38 and 0.14 to 0.56), respectively. When the blood pressure profiles were smoothed by substituting the 1-hour averages by moving or fixed 2-hour averages or by Fourier modeling, the trough-to-peak ratios remained unchanged after the morning dose (0.20/0.13, 0.20/0.14, and 0.16/0.21, respectively) but tended to increase in the evening (0.32/0.38, 0.28/0.40, and 0.48/0.49). In conclusion, the parallel-group analysis proposed makes it possible for one to correct the trough-to-peak ratio for baseline as well as placebo, to account for interindividual variability, and to calculate a confidence interval for the net trough-to-peak ratio. Accounting for interindividual variability reduces the trough-to-peak ratio. Smoothing affects the individualized net trough-to-peak ratios in an unpredictable way and should therefore be avoided.",1997.0,0,0
2077,9042620,Drugs that may injure the respiratory system.,P Foucher; M Biour; J P Blayac; P Godard; C Sgro; M Kuhn; J M Vergnon; D Vervloet; P Pfitzenmeyer; M Ollagnier; C Mayaud; P Camus,,1997.0,0,0
2078,9048272,Perindopril/hydrochlorothiazide dose combinations for the treatment of hypertension: a multicenter study.,S G Chrysant,"The primary goal of combination therapy is to enhance efficacy without compromising safety. In this multicenter study, the efficacy and tolerability of perindopril added to continuing hydrochlorothiazide therapy were evaluated in patients with mild to moderate (stage I and II), essential hypertension. Two hundred fifty-two patients with supine diastolic blood pressure of 95 mmHg to 114 mmHg were treated for 4 weeks with open-label hydrochlorothiazide at 25 mg/day. The 208 patients whose supine diastolic blood pressure was > or = 90 mmHg at the end of hydrochlorothiazide monotherapy entered a 12-week, double-blind treatment, where placebo or perindopril were added to the 25-mg/ day hydrochlorothiazide therapy as follows: placebo (n = 50) and doses of perindopril at 2 mg/day (n = 52), 4 mg/day (n = 53), and 8 mg/day (n = 53). The perindopril-hydrochlorothiazide combinations decreased both supine systolic blood pressure and supine diastolic blood pressure by 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg, for perindopril doses of 2, 4, and 8 mg/day, respectively; there was no difference among the three drug groups. Placebo decreased blood pressure by 1.6/2.0 mmHg, an effect that was significantly lower compared with perindopril-hydrochlorothiazide combinations. Adverse events were mild and similar among all treatment groups, except cough, which was 4.0%, 3.9%, 7.6%, and 13.2% for placebo and perindopril doses of 2, 4, and 8 mg, respectively. The results of this multicenter study indicate that the combination of perindopril and hydrochlorothiazide is safe and effective in lowering blood pressure. The findings also demonstrate that lower doses of perindopril are as effective as higher doses when combined with hydrochlorothiazide.",1997.0,0,0
2079,9049514,Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators.,J G Cleland; L Erhardt; G Murray; A S Hall; S G Ball,"The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ramipril reduced the risk of sudden death by 30% (95% CI: 8-47%; P = 0.011). However, overall, 45% of those patients who died suddenly had severe or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure. Ramipril did not selectively alter the proportion of in- to out-of-hospital deaths. Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.",1997.0,1,1
2080,9049526,Assessing the clinical need for short-term conversion from oral to parenteral angiotensin converting enzyme inhibitor therapy in hypertensive patients. A quinapril to quinaprilat placebo-controlled model.,A Whelton; L McCormick; D Wombolt; R Goldstein; D Canter,"RATIONALE AND STUDY DESIGN: This study assesses safety and efficacy when hypertensive patients convert from an oral angiotensin converting enzyme inhibitor, quinapril, to its intravenous counterpart, quinaprilat, and evaluates the need for short-term conversion from oral to parenteral therapy. Blood pressure was measured by clinical measurements using a sphygmomanometer and by 24-h ambulatory blood pressure monitoring. During a placebo-baseline phase, patients blood pressure had to increase within 3 days in the absence of an angiotensin converting enzyme inhibitor. Responding patients were stabilized on oral quinapril and then randomized to 3 days of double-blind treatment with one 5 ml or 10 ml injection twice daily of quinaprilat or placebo. Overall response to quinaprilat in ambulatory blood pressure monitoring and clinic blood pressure measurements was not statistically or clinically different from the response to oral quinapril therapy during baseline. Withdrawal from quinapril resulted in clinically significant increases in all blood pressure measurements compared with baseline therapy; the differences between placebo and quinaprilat therapy were statistically and clinically significant. Two patients treated with quinaprilat withdrew due to hypotension; one patient required a dosage reduction. Parenteral quinaprilat safely maintained blood pressure control whereas placebo control did not during the 72-h interruption of quinapril.",1997.0,0,0
2081,9050975,"Comparison of different fixed antihypertensive combination drugs: a double-blind, placebo-controlled parallel group study.",P W de Leeuw; T Notter; P Zilles,"To compare the effects of fixed-dose preparations containing 180 mg sustained-release verapamil and 2 mg trandolapril, 100/25 mg atenolol/chlorthalidone, 20/12.5 mg lisinopril/hydrochlorothiazide and placebo in patients with essential hypertension. A 4-week placebo run-in period followed by a double-blind, placebo-controlled parallel group study lasting 8 weeks. Office practices (21 centres). Patients with essential hypertension (World Health Organization grades I or II); supine diastolic blood pressure 101-114 mmHg in week 4 of the run-in period; 215 patients were enrolled, of whom 205 were assigned randomly to double-blind therapy. Reduction in supine and standing blood pressures. All three active treatments with a single daily dose were significantly more effective than was placebo in reducing the blood pressure of seated subjects (P=0.0001). The reductions in sitting diastolic blood pressure (DBP) from baseline to the last visit with each active treatment were comparable: 13 mmHg [95% confidence interval (CI) 16-9] with sustained-release verapamil/trandolapril, 13 mmHg (16-9) with atenolol/chlorthalidone and 12 mmHg (15-8) with lisinopril/hydrochlorothiazide. Normalization of blood pressure (DBP < 90 mmHg) was observed in 48% of patients with sustained-release verapamil/trandolapril, in 46% with atenolol/chlorthalidone and in 40% with lisinopril/hydrochlorothiazide. Response rates (normalization of DBP or a reduction in DBP by > 10 mmHg) with each active treatment were 72% for sustained-release verapamil/trandolapril, 76% for atenolol/chlorthalidone and 69% for lisinopril/hydrochlorothiazide. All three active treatments were tolerated well. This study demonstrates that the low-dose combination sustained-release verapamil/trandolapril may be a suitable alternative for combinations containing a thiazide diuretic or a beta-blocker for longer term management of hypertensive patients for whom combination therapy is indicated.",1997.0,0,0
2082,9050976,Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension.,H E Küppers; B A Jäger; J H Luszick; M A Gräve; P R Hughes; E C Kaan,"To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine, a centrally acting antihypertensive, with the angiotensin converting enzyme inhibitor enalapril. An 8-week, double-blind, randomized, placebo-controlled study involving 140 outpatients with mild-to-moderate essential hypertension. Outpatients with WHO stage I or II hypertension were enrolled in the study. After a 4-week placebo-controlled stabilization phase patients were allocated randomly to placebo, 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks. Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks. Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring. The mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril (19.5 +/- 16.0/12.3 +/- 8.7 versus 18.9 +/- 13.7/11.8 +/- 8.0 mmHg) and significantly superior to that with placebo (-4.6 +/- 12.3/-4.7 +/- 6.8 mmHg, P< 0.001). In addition to reducing blood pressure during conventional measurements, moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements. The trough:peak ratio for moxonidine was 0.7. Both moxonidine and enalapril were tolerated well. Moxonidine is an effective and well-tolerated antihypertensive, at least as good as other established forms of antihypertensive medication. The trough:peak ratio of 0.7 indicates that the drug will be effective administered once a day.",1997.0,0,0
2083,9051387,Effect of chronic quinapril administration on heart rate variability in patients with diabetic autonomic neuropathy.,A G Kontopoulos; V G Athyros; T P Didangelos; A A Papageorgiou; M J Avramidis; M C Mayroudi; D T Karamitsos,"Heart rate variability (HRV) time and frequency domain indexes are strong predictors of malignant arrhythmias and sudden cardiac death. Patients with diabetic autonomic neuropathy (DAN) have an increased cardiovascular mortality rate compared with diabetic patients without DAN. The present double-blind, randomized, and placebo-controlled study analyzed the effect of quinapril, an ACE inhibitor, on HRV time and frequency domain variables in patients with DAN. Forty patients (17 men and 23 women) of a mean age of 51 (range 19-68) years, free of coronary artery disease and arterial hypertension, were randomized into a quinapril or placebo group. HRV was recorded at months 0, 3, and 6. The parameters measured were 1) time domain indexes: SD of all 24-h R-R intervals (intervals between consecutive electrocardiogram R waves), or SDNN/24-h; mean of SD of R-R intervals of all 5-min segements (SDNN/5-min); root-mean-square of the differences of successive R-R intervals (RMSSD); and percentage of the R-R intervals differing more than 50 ms (pNN50); and 2) frequency domain indexes: total power (TP), high-frequency power (HFP), low-frequency power (LFP), and very-low-frequency power (VLFP). HRV level of the 40 patients were compared with one of 20 matched diabetic patients, of analogous glycemic control without DAN, and 20 healthy control subjects. Quinapril, compared with placebo, increased total HRV: SDNN/24-h (P < 0.05), TP (P < 0.05), and HRV parameters related to parasympathetic activity: pNN50 (P < 0.01). RMSSD (P < 0.05), and HFP in absolute and normalized units (P < 0.01). LFP/HFP ratio was decreased (P < 0.01). Despite the beneficial effect of quinapril on parasympathetic variables of HRV these remained less than those of diabetic patients without DAN and healthy control subjects. Our findings suggest that quinapril significantly increases parasympathetic activity in patients with DAN 3 months after treatment initiation and sustains this effect until the 6th month. This might contribute to the reduction of the risk for malignant ventricular arrhythmias in these patients.",1997.0,0,0
2084,9052345,Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group.,A H Gradman; N R Cutler; P J Davis; J A Robbins; R J Weiss; B C Wood,"This multicenter, placebo-controlled, double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor, enalapril, and the vascular selective calcium antagonist felodipine extended release (ER) in patients with essential hypertension. After a 4-week, single-blind placebo baseline period, 707 patients with sitting diastolic blood pressures (BPs) in the range of 95 to 115 mm Hg received placebo, enalapril (5 or 20 mg), felodipine ER (2.5, 5, or 10 mg), or their combinations for an 8-week double-blind treatment period. All doses of enalapril and felodipine ER had a statistically significant (p < 0.05) additive effect in reducing both systolic and diastolic BP. The trough to peak ratios for the combinations ranged from 0.63 (enalapril 5 mg-felodipine ER 2.5 mg) to 0.79 (enalapril 20 mg-felodipine ER 10 mg) and were consistent with effective BP control with 1 dose/day. Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP. Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema (4.1%) compared to felodipine ER monotherapy (10.8%). There were no serious drug-related adverse effects observed during the study. In this trial, the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension.",1997.0,0,0
2085,9053816,Quinapril versus lisinopril in the treatment of essential hypertension in elderly patients with low blood renin.,F Rengo; V Canonico,"The aim of the study was to evaluate efficacy and tolerability of quinapril 20 mg once-a-day versus lisinopril 20 mg, in the treatment of old patients suffering from essential mild or moderate hypertension and presenting low levels of plasmarenin. It was a cross-over study with open treatments randomly assigned. Ten patients were treated, 6 females and 4 males, with average age of 67.1 years +/- 7.1. Two wash-out periods with placebo were scheduled, each lasting one week before the onset of active therapy; each treatment period lasted 21 days. Blood pressure controls (including the 24 hours monitoring) were done at basal time, after seven days and at the end of each treatment. Results show the efficacy and the safety of both the drugs and a more effective and constant control of hypertension by Quinapril was confirmed.",1996.0,0,0
2086,9055135,"Valsartan, a new angiotensin II receptor antagonist: a double-blind study comparing the incidence of cough with lisinopril and hydrochlorothiazide.",J Benz; C Oshrain; D Henry; C Avery; Y T Chiang; M Gatlin,"The present study compares the occurrence of a dry, persistent cough with doses of 80 mg of valsartan, 10 mg of lisinopril, or 25 mg of hydrochlorothiazide in patients with a history of angiotensin-converting enzyme inhibitor-induced cough. This was a randomized, double-blind, active-controlled, parallel group, multicenter trial involving 129 adult outpatients with essential hypertension. After confirmation of angiotensin-converting enzyme inhibitor-induced cough during a 2 to 4 week challenge with lisinopril (followed by a washout period of 2 weeks), patients were randomized to receive 6 weeks of double-blind treatment once daily with 80 mg valsartan, 10 mg lisinopril, or 25 mg hydrochlorothiazide. Assessments were made at baseline and after 3 and 6 weeks of treatment. Comparability of response to treatment was assessed by mean sitting diastolic and systolic blood pressure at the end of treatment. The occurrence of a dry, persistent cough was significantly less (P < 0.001) at 3 and 6 weeks with valsartan (19.5%) than with lisinopril (68.9%), with no significant difference between valsartan and hydrochlorothiazide (19.0%). There were no statistically significant differences in reduction of blood pressure among the three treatment groups. The overall incidence of adverse experiences, whether or not treatment-related, was highest for lisinopril (86.7%) compared with valsartan (57.1%), and hydrochlorothiazide (61.9%). A dry cough in the lisinopril group accounted for this difference. There were no clinically significant changes in physical signs or in results of clinical laboratory evaluations during double-blind treatment, except for from metabolic changes in 3 patients receiving hydrochlorothiazide. In hypertensive patients with a history of angiotensin-converting enzyme inhibitor-induced cough, a single daily dose of 80 mg of valsartan produced therapeutic efficacy comparable to lisinopril but with significantly less cough.",1997.0,0,0
2087,9056614,Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke.,A G Dyker; D G Grosset; K Lees,"The relationship between high blood pressure and the incidence of stroke is well established. Currently the effects of lowering blood pressure in patients with established cerebrovascular disease is undetermined, and there is continuing concern regarding the treatment of patients soon after a stroke event. Angiotensin-converting enzyme inhibitors maintain cerebral blood flow despite lowering blood pressure in patients with heart failure and otherwise uncomplicated hypertension. We tested the hypothesis that perindopril, an angiotensin-converting enzyme inhibitor with a gradual onset of action and a minimal first-dose hypotensive effect, lowers blood pressure without adversely affecting cerebral blood flow in patients 2 to 7 days after symptoms of cerebral infarction. Patients were randomized to receive 15 days of oral perindopril (4 mg) or placebo in a double-blind study. Blood pressure was monitored semiautomatically. Cerebral blood flow was calculated from internal carotid artery and vertebral Doppler ultrasound, supplemented by middle cerebral artery blood velocities. Twenty-four patients completed the protocol; four additional patients were withdrawn for reasons unrelated to treatment. Patients on perindopril had a placebo-corrected reduction in blood pressure of 19/11 mm Hg. Blood pressure remained reduced after 2 weeks of treatment. In contrast, total cerebral blood flow was unaffected by perindopril. Neurological symptoms improved similarly in both groups. Perindopril was well tolerated and effectively reduced blood pressure without reducing carotid territory blood flow in patients with symptoms of recent cerebral ischemia.",1997.0,0,0
2088,9056686,Effects of erythropoietin on endothelin-1 synthesis and the cellular calcium messenger system in vascular endothelial cells.,V Vogel; H J Kramer; A Bäcker; H Meyer-Lehnert; W Jelkmann; J Fandrey,"A rise in blood pressure is the main side effect of erythropoietin (EPO) treatment in patients with renal anemia. The mechanisms, however, by which EPO may cause hypertension are still unclear. We therefore investigated the effects of EPO on endothelin (ET) synthesis and cytosolic free calcium concentration ([Ca2+]i) in vascular endothelial cells. Porcine endothelial cells were isolated from thoracic aorta, pulmonary artery, and vena cava. Studies were performed with cells of the first subculture. ET concentrations were measured radioimmunologically. Changes in [Ca2+]i were determined with the fluorescent probe fura-2. Cytotoxicity was assessed by sodium 3'-[1-(phenyl-amino-carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro)ben zene sulfonic acid hydrate (XTT) assay. ET synthesis was similar in cells of different vascular origins and was time-dependent, reaching approximately 2 pmol ET/mg protein within 12 h of incubation. EPO (12 to 200 U/mL) stimulated ET release time- and dose-dependently by up to 83.2% (P < .01) within 12 h in the absence of fetal calf serum and heparin. EPO induced an immediate significant rise in [Ca2+]i from 58 +/- 12 nmol/L to 495 +/- 85 nmol/L (P < .01) with a subsequent slow return to 257 +/- 3 nmol/L. During 2 h of incubation, the Ca-ionophore A 23187 (10(-8) mol/L) moderately but significantly stimulated endothelial ET synthesis. However, the Ca-channel blocker verapamil, the intracellular Ca-release blocker TMB-8, and nickel, an unspecific calcium channel blocker, had no consistent effects on [Ca2+]i or ET synthesis. The protein kinase C inhibitor H-7 stimulated basal [Ca2+]i and cellular ET synthesis. The tyrosine kinase inhibitor genistein suppressed the EPO-induced rise in [Ca2+]i and cellular ET synthesis. From these data we conclude that EPO may stimulate ET synthesis in vascular endothelial cells by activation of an EPO-receptor and via intracellular signalling mechanisms that comprise tyrosine kinase activation and a rise in [Ca2+]i. Therefore, the systemic hypertensive effects of EPO may be due at least in part to local stimulation of vascular endothelial ET synthesis via calcium mobilization.",1997.0,0,0
2089,9057069,Early captopril treatment reduces plasma endothelin concentrations in the acute and subacute phases of myocardial infarction: a pilot study.,P Di Pasquale; L Valdes; V Albano; V Bucca; S Scalzo; D Pieri; G Maringhini; S Paterna,"It has been reported that endothelin-1 (ET-1) increases in acute myocardial infarction (AMI). Experimental studies showed that captopril administration reduces ET-1 secretion. In addition, it was reported that the increased ET-1 levels are a negative prognostic index. The study sought to verify whether captopril can reduce plasma ET levels in the acute and subacute phases of reperfused anterior AMI. Forty-five patients, hospitalized for suspected anterior AMI within 4 h from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-2, were randomized (double blind) into two groups: group A (23; seven women/16 men) received captopril (as first dose) 2-4 h after starting thrombolysis (the dose was then increased up to 25 mg every 8 h). Group B (22; five women/17 men) received placebo after thrombolysis. All the patients met the reperfusion criteria. The two groups were similar with regard to age, sex, CK peak, ejection fraction, end-systolic volume and risk factors. Plasma ET levels were measured at entry, and 2, 12, 24, 48, and 72 h after starting thrombolysis. Mean concentrations of ET +/- SD: Group A basal, 1.50 +/- 0.67; at 2h, 2.31 +/- 1.24; 12 h, 1.84 +/- 1.45; 24 h, 1.30 +/- 0.72; 48 h, o.95 +/- 0.50; 72 h, 0.60 +/- 0.15 fmol/ml; p < 0.001. Group B basal, 1.58 +/- 0.83; at 2 h, 2.38 +/- 1.35; 12 h, 2.33 +/- 1.71; 24 h, 1.80 +/- 1.41; 48h, 1.46 +/- 0.88; 72 h, 0.93 +/- 0.44 fmol/ml; p < 0.001. Difference between the two groups was significant at the beginning of the test (between 2 and 12 h, p[=]0.002). After that, the values of the plasma endothelin decreased in parallel, p < 0.001. Our data suggest that captopril affects plasma ET levels in the acute and subacute phases of AMI. Moreover, these results provide additional evidence for a beneficial effect of early captopril treatment.",1997.0,0,0
2090,9057740,Failure of losartan to control blood pressure in scleroderma renal crisis.,F J Caskey; E J Thacker; P A Johnston; J N Barnes,,1997.0,0,0
2091,9060793,Effects of nisoldipine and/or enalapril on left ventricular function and exercise capacity in patients with recent anterior myocardial infarction and mild cardiac dysfunction.,M Romano; S Cardei; E de Arcangelis; I Monteforte; M Capaldo; P Muto; R Marchegiano; M O Kilama; M Condorelli,"Treatment of abnormal remodeling and dysfunction of left ventricle after myocardial infarction is one of the major goals of recent therapeutic interventions. The current study, the Nisoldipine Enalapril Anterior Myocardial infarction Study pilot investigation, was designed to investigate the effects of 12 weeks of treatment with enalapril or nisoldipine or their combination on left ventricular (LV) function and exercise capacity in patients with recent (< 1 month) anterior myocardial infarction and mild LV dysfunction (LV ejection fraction [EF] 38% to 48%). Forty-six patients were studied and received, by random assignment, enalapril (5 mg once per day) plus placebo (n = 14) or nisoldipine (10 mg two times per day) plus placebo (n = 18) or enalapril (5 mg once per day) plus nisoldipine (10 mg two times per day) (n = 14). All patients received aspirin (325 mg) throughout the study. Data on LV EF and peak filling rate at rest and LV EF during exercise were collected during radionuclide ventriculography. In addition, the product of heart rate and systolic blood pressure (rate-pressure product) and exercise time were determined during exercise stress testing. The analyzed parameters were not significantly modified after treatment with enalapril or with nisoldipine. In contrast, the combination of enalapril and nisoldipine significantly raised LV EF at rest (from 43% +/- 3% to 48% +/- 6%, p < 0.01) and during exercise (from 45% +/- 8% to 50% +/- 9%, p < 0.01) and raised peak filling rate at rest (fraction of end-diastolic volume per second) from 1.57 +/- 0.3 to 1.67 +/- 0.3 (p < 0.05). In addition, the combined administration of the two drugs increased the rate-pressure product (values x 10(3)) (from 20.7 +/- 5 to 22.7 +/- 4, p < 0.05) and increased exercise time (from 573 +/- 173 seconds to 668 +/- 178 seconds, p < 0.05). These results show that in patients with recent anterior myocardial infarction and mild LV dysfunction, the combination of the angiotensin-converting enzyme inhibitor enalapril and the dihydropyridine nisoldipine improves resting LV systolic and diastolic function and exercise LV systolic function and exercise capacity.",1997.0,0,0
2092,9061270,Lisinopril. A review of its pharmacology and clinical efficacy in elderly patients.,H D Langtry; A Markham,"Lisinopril, the lysine analogue of enalaprilat, is a long-acting angiotensin converting enzyme (ACE) inhibitor which is administered once daily by mouth. The efficacy of lisinopril in reducing blood pressure is well established in younger populations, and many trials now show it to be effective in lowering blood pressure in elderly patients with hypertension. In comparative and non-comparative clinical trials, 68.2 to 89.1% of elderly patients responded (diastolic pressure < or = 90 mm Hg) to > or = 8 weeks' lisinopril treatment. Age-related differences in antihypertensive efficacy do not appear to be clinically significant, and dosages effective in elderly patients tend to range from 2.5 to 40 mg/day. Dosages usually need to be lower in patients with significant renal impairment. In congestive heart failure, lisinopril 2.5 to 20 mg/day increases exercise duration, improves left ventricular ejection fraction and has no significant effect on ventricular ectopic beats. It is similar in efficacy to enalapril and digoxin and similar or superior to captopril on most end-points. Data from the GISSI-3 post-myocardial infarction trial show that lisinopril reduced mortality and left ventricular dysfunction when given for 42 days starting within 24 hours of the onset of infarction symptoms. Results at 6 weeks and 6 months were similar in elderly and younger patients. Elderly patients, however, among other subgroups, exhibited a strong reduction in risk of low ejection fraction after treatment (-25.5%). Economic studies suggest that lisinopril is cost saving compared with other ACE inhibitors in some markets. When given according to the GISSI-3 protocol, lisinopril appears to be one of the less expensive of the successful ACE inhibitor regimens for acute myocardial infarction. In other trials, patients with diabetic nephropathy and hypertension improved or did not deteriorate during lisinopril treatment. Blood pressure was controlled and reductions or trends towards reductions in albuminuria were observed. These reductions were similar to those in diltiazem, nifedipine and verapamil recipients, and greater than those in patients receiving atenolol. Lisinopril appears to reduce mortality in diabetic patients after myocardial infarction and may also improve neuropathy associated with diabetes. Lisinopril is well tolerated and the profile of adverse events seen is typical of ACE inhibitors as a class. There is a tendency for more elderly than younger patients to discontinue treatment, but this trend is not clearly related to the incidence of adverse events in these age groups. Drug interactions occur with few other agents and are usually clinically significant only between lisinopril and either diuretics or lithium. Lisinopril is, thus, an effective treatment for elderly patients with hypertension, congestive heart failure and acute myocardial infarction and has shown promising benefits in patients with diabetic nephropathy.",1997.0,0,0
2093,9067125,Pharmacoepidemiology of ACE inhibitor--induced cough.,B Tomlinson; R P Young; J C Chan; T Y Chan; J A Critchley,,1997.0,0,0
2094,9067912,A short-term antihypertensive treatment-induced fall in glomerular filtration rate predicts long-term stability of renal function.,A J Apperloo; D de Zeeuw; P E de Jong,"In long-term intervention studies on renal function outcome an initial decline in the glomerular filtration rate (GFR) may occur after starting therapy. If this initial GFR decline is the result of a treatment-induced hemodynamic change reflecting a fall in intraglomerular pressure, it should be reversible after treatment withdrawal, even after long-term treatment. In fact, it could be beneficial for renal function in the long term. We therefore studied systemic and renal hemodynamics in 40 non-diabetic patients with impaired renal function before treatment, during four years treatment with either atenolol or enalapril, and after withdrawal of that treatment. The acute change in GFR 12 weeks after start of treatment varied widely from -11 to + 11 ml/min (mean +/- SD -1.0 +/- 4.1 ml/min, NS). After four years of treatment, withdrawal for 12 weeks resulted in a rise in GFR of +2.2 +/- 5.4 ml/min, P = 0.011, again with a wide range of +14 to -6 ml/min). The initial fall in GFR was related to the rise after withdrawal (r = 0.32, P < 0.05). Interestingly, the acute treatment induced change in GFR correlated with the long-term slope, such that a patient with a greater initial decline in GFR showed a more stable course during the follow up (r = -0.36, P < 0.05). The patients were arbitrarily divided in group A (N = 20), with the largest initial treatment-induced fall in GFR, and group B (N = 20), with the smallest initial fall in GFR. Group A had a significantly less steep slope than group B (-0.41 +/- 1.52 vs. -2.09 +/- 2.79 ml/min/year, P = 0.023) during the four year follow-up. In group A GFR increased again after withdrawal of treatment (+3.8 +/- 5.6 ml/min, P = 0.011) whereas it did not change in group B (+0.5 +/- 4.0 ml/min, NS). As a consequence, GFR post-treatment was not different compared to pre-treatment in group A (-2.5 +/- 7.2 ml/min, NS), whereas it was 5.9 +/- 12.1 ml/min lower in group B (P = 0.023). Patients treated with enalapril had a similar response as patients treated with atenolol. In conclusion, an initial fall in GFR after starting antihypertensive treatment in patients with a mild to moderate renal function impairment (GFR 30 to 90 ml/min) is reversible even after years of treatment, suggesting that this therapy-induced fall is of hemodynamic and not of structural origin. This initial GFR fall was associated with a subsequent stable renal function. These data lead to the hypothesis that the initial fall in GFR in response to antihypertensive therapy reflects renal protection.",1997.0,0,0
2095,9068723,Angiotensin-converting enzyme (ACE) inhibitors and angio-oedema.,R A Sabroe; A K Black,"Angiotensin-converting enzyme inhibitors (ACEIs) are used increasingly for the treatment of hypertension and chronic heart failure, and they reduce mortality when given after myocardial infarction. Of the patients prescribed these drugs 0.1-0.7% develop angio-oedema, but the association is not widely recognized. In 60% of cases the onset occurs during the first week of treatment; however, it may be considerably delayed. Angio-oedema nearly always occurs on the head and neck, frequently involving the mouth, tongue, pharynx and larynx. The course is unpredictable, and attacks vary in severity from mild to fatal from laryngeal obstruction. Severe ACEI-induced angio-oedema may require emergency treatment with adrenalin and early intubation. The drug should be withdrawn in any patient who presents with ACEI-induced angio-oedema, and treatment continued with an appropriate drug of a different class. Therapy with ACEIs is contraindicated in patients with a prior history of idiopathic angio-oedema, or in patients with hereditary or acquired C1 esterase inhibitor deficiency.",1997.0,0,0
2096,9070551,Cardiac event rates after acute myocardial infarction in patients treated with verapamil and trandolapril versus trandolapril alone. Danish Verapamil Infarction Trial (DAVIT) Study Group.,J F Hansen; L Hagerup; B Sigurd; F Pedersen; K Mellemgaard; O Pedersen-Bjergaard; L S Mortensen,"Angiotensin-converting enzyme (ACE) inhibitors improve survival in patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), but mortality may be as high as 10% to 15% after 1 year. Verapamil prevents cardiac events after an AMI in patients without CHF. We hypothesized that in postinfarct patients with CHF already prescribed diuretics and an ACE inhibitor, additional treatment with verapamil may reduce cardiac event rate. In this multicenter, double-blind study, patients with CHF receiving diuretic treatment were consecutively randomized to treatment with trandolapril 1 mg/day for 1 month and 2 mg/day the following 2 months (n = 49), or to trandolapril as mentioned plus verapamil 240 mg/day for 1 month and 360 mg/day for 2 months (n = 51). Trial medication started 3 to 10 days after AMI. All patients were followed for 3 months. End points in the trandolapril/trandolapril-verapamil groups were death 1/1, reinfarction 7/1, unstable angina 9/3, and readmission for CHF 6/2. The 3-month first cardiac event rate was 35% in trandolapril-treated patients and 14% in trandolapril-verapamil-treated patients (hazard ratio 0.35, 95% confidence interval 0.15 to 0.85, p = 0.015). These data suggest that verapamil reduces cardiac event rates in post-AMI patients with CHF when added to an ACE inhibitor and a diuretic.",1997.0,0,0
2097,9074572,"Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)",B Pitt; R Segal; F A Martinez; G Meurers; A J Cowley; I Thomas; P C Deedwania; D E Ney; D B Snavely; P I Chang,"To determine whether specific angiotensin II receptor blockade with losartan offers safety and efficacy advantages in the treatment of heart failure over angiotensin-converting-enzyme (ACE) inhibition with captopril, the ELITE study compared losartan with captopril in older heart-failure patients. We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 26.5 mumol/L or more (> or = 0.3 mg/dL) on therapy; the secondary endpoint was the composite of death and/or hospital admission for heart failure; and other efficacy measures were total mortality, admission for heart failure, NYHA class, and admission for myocardial infarction or unstable angina. The frequency of persisting increases in serum creatinine was the same in both groups (10.5%). Fewer losartan patients discontinued therapy for adverse experiences (12.2% vs 20.8% for captopril, p = 0.002). No losartan-treated patients discontinued due to cough compared with 14 in the captopril group. Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan and 13.2% of the captopril patients (risk reduction 32% [95% CI -4% to + 55%], p = 0.075). This risk reduction was primarily due to a decrease in all-cause mortality (4.8% vs 8.7%; risk reduction 46% [95% CI 5-69%], p = 0.035). Admissions with heart failure were the same in both groups (5.7%), as was improvement in NYHA functional class from baseline. Admission to hospital for any reason was less frequent with losartan than with captopril treatment (22.2% vs 29.7%). In this study of elderly heart-failure patients, treatment with losartan was associated with an unexpected lower mortality than that found with captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. A further trial, evaluating the effects of losartan and captopril on mortality and morbidity in a larger number of patients with heart failure, is in progress.",1997.0,0,1
2098,9078981,Alcoholism in the elderly: physicians can make a difference.,D C Lewis,"The prevalence of alcoholism among the elderly is significant. Drinking problems in the aged may be masked by a physical or psychological conditioning. Diagnosis can thus be difficult but once it is made, treatment is fairly standard.",1997.0,0,0
2099,9079233,Effects of lisinopril or lisinopril/hydrochlorothiazide compared with adjusting of previous medication and intensifying non-pharmacological treatment in patients with mild to moderate hypertension.,S Keinänen-Kiukaanniemi; M Rasmusen; T Pekkarinen; T Pitkäjärvi; M Romo; J Takala,"The objective of this study was to compare the effectiveness of three treatment methods available for treatment of previously medicated patients with mild to moderate hypertension. The comparison was made between adjusting or increasing previous medication and switching the previous drug treatment to lisinopril (CAS 76547-98-3) or lisinopril hydrochlorothiazide (CAS 58-93-5) therapy and in both of these treatment groups the effect of additional intensified health education was tested. An open, randomised, controlled multi-centre study lasting 36 weeks involving 189 doctors and 69 nurses was carried out in 155 centres of primary health care and occupational health care system in Finland. The study population consisted of 1156 patients, age 30-70 years, (mean DBP 95-115 mmHg in the last three to five measurements during follow-up). The number of patients achieving target pressure (DBP < 90 mmHg) at the end of the study, defined daily doses (DDD) of antihypertensive drugs and side-effects in different treatment groups were regarded as the main outcome measures of the study. After exclusions and drop-outs the final analysis was carried out with 900 patients, 419 women (46.6%) and 481 men (53.4%). Patients receiving lisinopril treatment achieved target pressure significantly more often (p < 0.001) than those continuing their previous or adjusted medication at 36 weeks (59.2 and 55.5% vs 40.3 and 42.7%). Only a small additional but statistically non-significant blood pressure lowering effect was achieved with intensified non-pharmacological treatment at weeks 12 and 24, but this difference had disappeared at week 36. The mean DDDs of different antihypertensive drugs did not differ between groups except for female patients on previous or adjusted medication not receiving health education, the mean DDD being significantly (p < 0.05) higher at weeks 24 and 36 in this group. The profile of adverse effects at the end of the study clearly favoured patients on lisinopril treatment except for cough which was reported in 18% of patients vs 10% in the control groups. 81 patients on lisinopril treatment were withdrawn from the study because of cough. The results showed that hypertensive patients with poor treatment control benefit from all three approaches. A greater proportion of patients on lisinopril treatment achieved target pressure and also experienced fewer side effects than those continuing on adjusted previous medication. Intensified personal health education given once a month during six months had only a small additional beneficial effect on reaching the target pressure and this effect was lost in three months after the health education period.",1997.0,0,0
2100,9080918,Relationships of quality-of-life measures to long-term lifestyle and drug treatment in the Treatment of Mild Hypertension Study.,R H Grimm; G A Grandits; J A Cutler; A L Stewart; R H McDonald; K Svendsen; R J Prineas; P R Liebson,"To compare 5 antihypertensive drugs and placebo for changes in quality of life (QL). To assess the relationship of lifestyle factors and change in lifestyle factors to QL in participants with stage I diastolic hypertension. The Treatment of Mild Hypertension Study (TOMHS) was a randomized, double-blind, placebo-controlled clinical trial with minimum participant follow-up of 4 years. It was conducted at 4 hypertension screening and treatment academic centers in the United States. The cohort consisted of 902 men and women with hypertension, aged 45 to 69 years, with diastolic blood pressures less than 100 mm Hg. Informed consent was obtained from each participant after the nature of the procedures had been fully explained. Sustained nutritional-hygienic intervention was administered to all participants to reduce weight, to reduce dietary sodium and alcohol intake, and to increase physical activity. Participants were randomized to take (1) acebutolol (n = 132); (2) amlodipine maleate (n = 131); (3) chlorthalidone (n = 126); (4) doxazosin mesylate (n = 134); (5) enalapril maleate (n = 135); or placebo (n = 234). Changes in 7 QL indexes were assessed based on a 35-item questionnaire: (1) general health; (2) energy or fatigue; (3) mental health; (4) general functioning; (5) satisfaction with physical abilities; (6) social functioning; and (7) social contacts. At baseline, higher QL was associated with older age, more physical activity, lower obesity level, male gender, non-African American race, and higher educational level. Improvements in QL were observed in all randomized groups, including the placebo group during follow-up; greater improvements were observed in the acebutolol and chlorthalidone groups and were evident throughout follow-up. The amount of weight loss, increase in physical activity, and level of attained blood pressure control during follow-up were related to greater improvements in QL. In patients with stage I hypertension, antihypertensive treatment with any of 5 agents used in TOMHS does not impair QL. The diuretic chlorthali-done and the cardioselective beta-blocker acebutolol appear to improve QL the most. Success with lifestyle changes affecting weight loss and increase in physical activity relate to greater improvements in QL and show that these interventions, in addition to contributing to blood pressure control, have positive effects on the general well-being of the individual.",2001.0,0,0
2101,9081852,The DIAB-HYCAR Study.,P Passa; G Chatellier,"Microalbuminuria and proteinuria are strong independent predictors for increased cardiovascular mortality in non-insulin-dependent diabetic (NIDDM) patients. In such patients, angiotensin converting enzyme (ACE) inhibition improves the evolution of diabetic nephropathy; however, no data are currently available on the effects of such intervention on cardiovascular morbidity and mortality. The aim of the Diab-Hycar study is to test the hypothesis that ACE inhibition with a low daily dose of 1.25 mg ramipril, which has no significant effect on blood pressure, may reduce cardiovascular morbidity and/or mortality in normotensive or hypertensive NIDDM patients with persistent albuminuria. Selected and followed by general practitioners, 4000 patients will receive their usual oral antidiabetic treatment and if necessary antihypertensive treatment (ACE inhibitors excluded). In addition in a randomized, double-blind trial they will be given either a placebo or 1.25 mg ramipril daily. The follow-up is currently scheduled to last 3 years. The efficacy of ACE-inhibition will be assessed by the following major end-points: cardiovascular death, sudden death, myocardial infarction, stroke, renal replacement therapy. The Diab-Hycar study started on 3 February 1995. By 1 September 1995, 11,000 urine samples were tested. The prevalence of persistent albuminuria was 23%, 964 patients were initially included in the study, with 619 eligible patients included soon after. Different strategies have been developed to record cardiovascular events correctly and to minimize the number of patients lost to follow-up.",1996.0,0,0
2102,9088591,"The effect of the neutral endopeptidase inhibitor drug, candoxatril, on circulating levels of two of the most potent vasoactive peptides.",G McDowell; W Coutie; C Shaw; K D Buchanan; A D Struthers; D P Nicholls,"Candoxatril is a specific neutral endopeptidase (NEP) 24.11 inhibitor, and previous work has documented the effect of NEP inhibition on atrial and brain natriuretic peptides (ANP, BNP). The aim of the present study was to ascertain the effect of NEP inhibition on circulating levels of vasoactive peptides. We studied seven patients with chronic heart failure who were randomized to receive candoxatril, candoxatril/captopril, captopril and placebo in a four way cross over, double-blind pattern. The mean circulating level of endothelin (ET) was increased 2 h after placebo (10 to 20 pg ml-1) and also calcitonin gene-related peptide (CGRP) (27 to 51 pg ml-1), but ANP levels changed little during this time (73 to 75 pg ml-1). Following candoxatril, however, ET (10 to 39 pg ml-1, P < 0.05), CGRP (34 to 99 pg ml-1, P < 0.05) and ANP (72 to 108 pg ml-1, P < 0.05) increased further. A similar result was observed following combined treatment with candoxatril and captopril. We conclude that neutral endopeptidase inhibition increases circulating plasma levels of ET and CGRP in addition to the natriuretic peptides.",1997.0,0,0
2103,9089428,"Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough.",P Chan; B Tomlinson; T Y Huang; J T Ko; T S Lin; Y S Lee,"This study compared the incidence of cough with the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the diuretic metolazone with angiotensin II receptor antagonist losartan in elderly hypertensive patients with previous histories of ACE inhibitor-induced cough. A randomized, double-blind, stratified, parallel-group comparison of lisinopril at 10 mg, losartan at 50 mg, and metolazone at 1 mg, each given once daily for a maximum of 10 weeks, was performed in four hypertension clinics in four centers in two countries. Cough was detected by a questionnaire (the primary end point) given to elderly patients with hypertension, and the cough frequency was quantified by a visual analog scale (a secondary end point). A total of 84 elderly patients with hypertension, all who were nonsmokers with ACe inhibitor-induced cough and were confirmed by lisinopril rechallenge then placebo dechallenge, were randomized to the three treatment groups. The incidence of cough with losartan (18%) was significantly lower than with lisinopril (97%) and similar to that for metolazone (21%). Cough frequency evaluated by the visual analog scale was significantly lower for losartan than for lisinopril and similar to that for metolazone. The specific, selective angiotensin II receptor antagonist losartan is associated with a decrease in the incidence of cough in patients with previous ACE inhibitor-induced cough.",1997.0,0,0
2104,9096809,LDL apheresis with dextran sulfate and angiotension receptor antagonist (Losartan).,N Elicio; S Bertolini; R Garbarini; G Nardiello; A Elicio; V Aimale,Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis with dextran sulphate adsorption have been reported in patients taking angiotensin converting enzyme (ACE) inhibitors.,1997.0,0,0
2105,9101305,Effects of nifedipine and enalapril on cardiac autonomic nervous function during the tilt test in elderly patients with hypertension.,J Okabayashi; K Matsubayashi; Y Doi; T Sato; T Ozawa,"To clarify the effects of nifedipine and enalapril on cardiac autonomic nervous function during postural changes, power spectral analysis of heart rate variability and humoral factors was performed during tilt tests before and after 3 months of drug administration. The study group consisted of 29 elderly patients with hypertension (mean age, 69 yr), who were divided into two groups: 15 patients received nifedipine (group N) and 14 received enalapril (group E). In group N, systolic blood pressure was significantly decreased and the percent changes in low-frequency coefficient of component variance, normalized low-frequency: high-frequency ratio, and plasma norepinephrine concentration were significantly altered by nifedipine administration. Group E, in contrast, showed no significant decrease in SBP, and only the percent change in high-frequency coefficient of component variance increased significantly after enalapril administration. These results suggest that cardiac autonomic nervous function is markedly impaired during the tilt test after long-term treatment with nifedipine, whereas it is well-maintained after long-term treatment with enalapril.",1997.0,0,0
2106,9101306,Effects of ACE inhibitors versus calcium antagonists on left ventricular morphology and function in patients with essential hypertension.,K Matsuzaki; M Mukai; T Sumimoto; E Murakami,"We compared the effects of two long-term antihypertensive treatments (ACE inhibitors vs. Ca antagonists) on left ventricular hypertrophy (LVH) and LV function in patients with essential hypertension and LVH. After a washout period of at least 4 wk, ceronapril or delapril was administered to 18 patients and nifedipine or nicardipine to 15 patients for 6 months. Mean blood pressure (MBP), LV mass (LVM), LV fractional shortening (FS), systolic time intervals (ejection time/pre-ejection period ratio = ET/PEP), and isovolumic relaxation time (IRT) were examined in the pretreatment phase and after 6 months of treatment. MBP and LVM significantly and similarly decreased after treatment in both groups (ACE inhibitors vs. Ca antagonists, delta MBP: -17.1 +/- 1.3 vs. -16.9 +/- 1.6%; delta LVM: -11.7 +/- 2.7 vs. -10.0 +/- 3.8%, both p = not significant). ACE inhibitors produced significant beneficial changes in FS, ET/PEP, and IRT after treatment as compared with Ca antagonists (ACE inhibitors vs. Ca antagonists, delta FS: 11.8 +/- 3.3 vs. 5.1 +/- 4.1%, p < 0.05; delta ET/PEP: 11.9 +/- 2.3 vs. 4.7 +/- 6.4%, p < 0.05; delta IRT: -12.0 +/- 3.4 vs. -3.8 +/- 6.1%, p < 0.05). The results indicate that both ACE inhibitors and Ca antagonists induce significant and similar reductions in blood pressure and LVM in hypertensive patients. ACE inhibitors produce significant improvements in LV function in both systolic and diastolic phases as compared with Ca antagonists.",1997.0,0,0
2107,9104896,"Use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization in the United States, Europe, and Canada. Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) and Canadian Coronary Atherectomy Trial (CCAT) investigators.",M J Eisenberg; R M Califf; E A Cohen; A G Adelman; D B Mark; E J Topol,"The objective of this study was to examine whether there are international variations in the use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization. We analyzed the medical therapy of patients in the United States (US) (n = 878), Europe (n = 134), and Canada (n = 274) who underwent percutaneous coronary revascularization in either the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT-I) (enrollment from August 1991 to April 1992) or the Canadian Coronary Atherectomy Trial (CCAT) (enrollment from July 1991 to August 1992). We found that at the time of hospital admission, Canadian patients had the highest rates of treatment with aspirin (95% vs 57% US and 78% Europe; p = 0.002), calcium antagonists (75% vs 48% US and 43% Europe; p 0.0001), beta blockers (60% vs 32% US and 46% Europe; p = 0.02), and combination anti-ischemic therapy (67% vs 43% US and 56% Europe; p = 0.0001). By discharge, however, Canadian patients had the lowest rates of treatment with nitrates (12% vs 40% US and 44% Europe; p = 0.0001) and combination anti-ischemic therapy (29% vs 53% US and 47% Europe; p < 0.01). At both admission and discharge, rates of treatment with angiotensin-converting enzyme inhibitors and lipid-lowering agents were < 15% in all 3 regions. We conclude that significant international variations exist in the use of evidence-based medical therapy in patients undergoing percutaneous coronary revascularization.",1997.0,0,0
2108,9104905,Effect of antithrombotic therapy on risk of sudden coronary death in patients with congestive heart failure.,D L Dries; M J Domanski; M A Waclawiw; B J Gersh,"Data from epidemiologic, autopsy, Holter monitoring, and electrophysiologic studies support the hypothesis that acute myocardial ischemia, even in the absence of myocardial infarction, is a critical component of the pathophysiology of sudden coronary death. Acute myocardial ischemia superimposed upon ventricles damaged from previous infarctions has been demonstrated to enhance the generation of lethal ventricular arrhythmias. This is a retrospective analysis of 6,797 participants in the Studies of Left Ventricular Dysfunction prevention and treatment trials. Both univariate and multivariate Cox proportional-hazards modeling were used to study the association of anticoagulant and antiplatelet therapy with the risk for sudden cardiac death. The following covariates were adjusted for in the analysis: age, ejection fraction, gender, atrial fibrillation, diabetes, a history of angina, prior infarction, prior revascularization, and the regular use of beta blockers, diuretics, digoxin, antiarrhythmic agents, or enalapril. The overall incidence of sudden cardiac death per 100 patient-years of follow-up was 2.24%. In multivariate analysis, antiplatelet and anticoagulant monotherapy each remained independently associated with a reduction in the risk of sudden cardiac death: antiplatelet therapy with a 24% reduction (relative risk [RR] 0.76; 95% confidence interval [CI] 0.61-0.95) and antiplatelet monotherapy with a 32% reduction (RR 0.68; 95% CI 0.48-0.96). Thus, in patients with moderate to severe left ventricular systolic dysfunction resulting from coronary artery disease, antiplatelet and anticoagulant therapy are each associated with a reduction in the risk of sudden cardiac death.",1997.0,0,0
2109,9105649,Inhibitor index: a novel method for measuring pharmacological inhibition of angiotensin-converting enzyme.,R Reneland; H Lithell,"Research into the exact mechanism and site of action of ACE inhibiting compounds has been hampered by methodological difficulties concerning the quantitation of ACE inhibition in tissues. This paper describes an attempt to address this difficulty. ACE activity in serum and uncentrifuged skeletal muscle homogenates was measured with a fluorometric assay before and during treatment in 24 fosinopril-treated and 26 atenolol-treated hypertensives. The absolute difference in activity between the higher and the lower of two different sample dilutions divided by the mean activity was taken to represent competitive inhibition in the sample, ""inhibitor index"". The reduction in muscle ACE activity coinciding with fosinopril treatment was not statistically significant (-2.6%, p = 0.68). The inhibitor index, however, increased by 46% (p = 0.045) and no change was seen in the atenolol-treated group (-12%, p = 0.51). The change in muscle inhibitor index (but not the reduction in serum ACE activity) correlated inversely with the change in blood pressure (r = -0.50, p = 0.034) and serum aldosterone (r = -0.54, p = 0.031) in the fosinopril group, but not in the atenolol group. In a second study, serum inhibitor index increased by 0.28 (95% CI 0.24-0.32) in 12 trandolapril-treated, but was unchanged in 11 atenolol-treated patients (+0.0097, 95% CI -0.029-0.048). In conclusion, the present study indicates that the inhibitor index described recognizes physiologically relevant ACE inhibition. The value of the method needs to be investigated further.",1997.0,0,0
2110,9107160,Nonselective beta-adrenergic blockade with carvedilol does not hinder the benefits of exercise training in patients with congestive heart failure.,L Demopoulos; M Yeh; M Gentilucci; M Testa; R Bijou; S D Katz; D Mancini; M Jones; T H LeJemtel,"Long-term beta-adrenergic blockade does not appear to be associated with drug-induced training in patients with congestive heart failure (CHF); whether exercise training can increase peak aerobic capacity in patients with CHF who are treated with beta-adrenergic blockers is currently unknown. We studied 23 patients with CHF who were treated with carvedilol or propranolol in addition to ACE inhibitors, furosemide, and digoxin. Of the patients treated with carvedilol, 8 underwent exercise training and 8 remained sedentary. All 7 patients treated with propranolol underwent exercise training. Peak oxygen consumption (mL.kg-1.min-1) was serially measured in trained and sedentary patients. Peak reactive hyperemia (mL.min-1.100 mL-1) was determined in the calf and forearm immediately before and after 12 weeks of training. The peak oxygen consumption of trained patients treated with either carvedilol or propranolol increased from 12.9 +/- 1.4 to 16.0 +/- 1.6 (P < .001) and 12.4 +/- 1.0 to 15.7 +/- 0.9 (P < .001) mL.kg-1.min-1, respectively, whereas it did not change in the sedentary patients. Peak reactive hyperemia increased significantly in the calves but not the forearms of trained patients. Long-term, nonselective beta-adrenergic blockade with carvedilol or propranolol does not prevent patients with CHF from deriving systemic and regional benefits from physical training.",1997.0,0,0
2111,9107182,Improvement of alveolar-capillary membrane diffusing capacity with enalapril in chronic heart failure and counteracting effect of aspirin.,M Guazzi; G Marenzi; M Alimento; M Contini; P Agostoni,"KII ACE, the enzyme that converts angiotensin I and inactivates bradykinin, is highly concentrated in the lungs; its blockade reduces exposure to angiotensin II and enhances exposure to prostaglandins generated by local kinin hyperconcentration. Our hypothesis is that ACE inhibitors improve pulmonary function in chronic heart failure (CHF) by readjusting lung vessel tone and permeability or alveolar-capillary membrane diffusion. In 16 CHF patients and 16 normal volunteers or mild untreated hypertensives, pulmonary function and exercise tests with respiratory gas analysis were assessed on placebo, enalapril (10 mg BID), enalapril plus aspirin (325 mg/d), or aspirin, in random order and double blind, for 15 days each. In CHF, enalapril increased pulmonary carbon monoxide diffusion (DLCO), oxygen consumption (VO2), and exercise tolerance and reduced the ratio of dead space to tidal volume (VD/VT) and the ventilatory equivalent for carbon dioxide production (VE/VCO2). On enalapril, VO2 (r = .80, P < .0001) and VD/VT (r = -.69, P = .003) changes from placebo correlated with those in DLCO. These effects were inhibited by aspirin and were absent in control subjects. In 8 additional patients, hydralazine-isosorbide dinitrate, as an alternative treatment for reducing pulmonary capillary wedge pressure (PCWP) and increasing exercise capacity, were more effective than enalapril for the PCWP but did not affect DLCO and VE/VCO2; amelioration in VO2 and VD/VT was unrelated to DLCO and was not modified by aspirin. ACE inhibition improved pulmonary diffusion in CHF. Hydralazine-isosorbide dinitrate failed to provide this result. Counteraction by aspirin, a prostaglandin inhibitor, bespeaks prostaglandin participation while on enalapril that might readjust capillary permeability or alveolar-capillary membrane diffusion.",1997.0,0,0
2112,9108812,Clozapine and associated diabetes mellitus.,A P Popli; P E Konicki; G J Jurjus; M A Fuller; G E Jaskiw,"Clozapine is an effective therapy for the treatment of refractory psychosis. Clozapine-associated adverse effects include sedation, weight gain, sialorrhea, palpitations, seizures, and hematologic changes such as agranulocytosis. We present a four-case series in which clozapine use was associated with either a de novo onset or severe exacerbation of preexisting diabetes mellitus. The change in glycemic control was not significantly related to weight gain. Three of the patients have been able to continue on clozapine therapy and have experienced a reduction in psychotic symptoms. Patients with a family history of diabetes mellitus or with preexisting diabetes mellitus may need to have blood sugar monitored closely during initiation of clozapine treatment.",1997.0,0,0
2113,9108836,,,,,0,0
2114,9114765,Effects of atenolol versus enalapril on cardiovascular fitness and serum lipids in physically active hypertensive men.,N F Gordon; C B Scott; J J Duncan,"An ideal drug regimen for physically active hypertensive patients should not offset exercise-induced improvements in cardiovascular health or fitness. In this randomized, double-blind, placebo-controlled, crossover study of 39 physically active men with uncomplicated essential hypertension, we compared the effects of atenolol and enalapril on cardiovascular fitness and serum lipids. Drugs (atenolol, 50 or 100 mg once daily; enalapril, 10 or 20 mg once daily) were each administered for 4 weeks and each active drug period was preceded by 4 weeks of placebo therapy. Both drugs effectively (p < 0.001) lowered resting blood pressure when measured at the time of theoretical peak (i.e., 3 to 4 hours postdrug) and trough (i.e., 24 hours postdrug) drug blood levels. Atenolol reduced maximal oxygen uptake (by 7.3%, p < 0.001) 3 to 4, but not 24, hours after drug ingestion; no changes occurred with enalapril. Similarly, whereas serum lipids were essentially unchanged with enalapril, serum triglycerides (18.9% increase), high-density lipoprotein cholesterol (10.6% decrease), and ratio of low-density to high-density lipoprotein cholesterol (15.4% increase) were adversely impacted (p < or = 0.05) with atenolol. It is concluded that in contrast to enalapril, atenolol adversely impacts cardiovascular fitness and serum lipids and lipoproteins in physically active hypertensive men.",1997.0,0,0
2115,9114905,The effects of age on the pharmacokinetics and pharmacodynamics of single oral doses of benazepril and enalapril.,N J Macdonald; A Sioufi; C A Howie; J R Wade; H L Elliott,"1. Eighteen healthy, normotensive subjects (nine young and nine elderly) participated in a double-blind, 3-way, crossover study to compare aspects of the pharmacokinetics and pharmacodynamics of single oral doses of 10 mg benazepril, 10 mg enalapril and placebo. 2. The hypotensive effect was similar after both drugs but the absolute reductions were greater in the elderly who had higher initial levels of blood pressure. 3. The AUCs for both benazeprilat and enalaprilat were higher in the elderly but by a significantly greater amount for enalaprilat (+ 113% vs 40%; P < 0.01). 4. The AUCs for both drugs tended to be highest in subjects with the lowest creatinine clearance. 5. The changes in kinetics and dynamics observed in the elderly after benazepril are qualitatively similar to those with other ACE inhibitors. The clinical significance of the quantitative differences requires further investigation.",1993.0,0,0
2116,9115065,Early treatment with low-dose enalapril after acute myocardial infarction: an equilibrium radionuclide angiographic study. Enalapril despues del Infarto (EDI) Trial Investigators.,O Bazzino; J L Navarro Estrada; A Sosa Liprandi; C Presti; O Masoli; J Santopinto; A Ahuad; M Amuchástegui; R Méndez,"To further elucidate the mechanisms involved in the treatment of acute myocardial infarction (AMI) with angiotensin-converting enzyme inhibitors, we compared the effects on left ventricular volumes of early (< 48 hours) versus late (45 days) administration of a fixed low dose of enalapril (10 mg) in patients with AMI. We also analyzed the changes of left ventricular volumes after withdrawal of the study drug. Reduced dilation of the left ventricle is one of the beneficial effects of angiotensin-converting enzyme inhibition after AMI. However, the nature of this effect is not completely understood. We included 89 patients within 48 hours after onset of a first AMI and radionuclide left ventricular ejection fraction less than 45%. The study was double-blind and compared enalapril and placebo with a crossover design. All patients were randomly assigned to a sequence A (enalapril, 45 days; placebo, 45 days) or B (placebo, 45 days; enalapril, 45 days). The end point was the change of left ventricular volume at 45 and 90 days. Thrombolysis was administered to 26 patients (70%) in group A and 25 (75%) in group B. All pretreatment clinical variables were similar in both groups. Median and 95% confidence intervals (CIs) of left ventricular diastolic volumes were 46.8 ml/m2 (39 to 61 ml/m2) and 46.6 ml/m2 (39 to 60 ml/m2) for groups A and B, respectively. Baseline end systolic volumes were 28.5 ml/m2 (20 to 36 ml/m2) and 28.9 ml/m2 (23 to 28 ml/m2) in the same groups. Placebo treatment during the initial 45 days was associated with an increase of left ventricular diastolic volume of 8.75 ml/m2 (95% CI, 3.25 to 17.1 ml/m2; p < 0.01) and end-systolic volume of 4.20 ml/m2 (95% CI, 0.00 to 10.1 ml/m2; p < 0.05). No significant changes during other phases of the study were observed. At 45 days left ventricular diastolic volume was 11.1 ml/m2 (95% CI, 0.5 to 2.2 ml/m2), greater in placebo-treated patients compared with patients receiving enalapril. In patients with a first Q wave AMI and left ventricular ejection fraction less than 45%, treatment with enalapril can prevent left ventricular dilation. This protective effect involves at least partially a structural modification of the left ventricle. Hence, maximal benefit can be obtained only with early initiation of treatment.",1997.0,0,1
2117,9115928,Ramipril-associated lichen planus pemphigoides.,G S Ogg; B S Bhogal; T Hashimoto; R Coleman; J N Barker,"We report the first case of lichen planus pemphigoides (LPP) secondary to ingestion of ramipril, an angiotensin-converting enzyme inhibitor. Clinical, histological and immunofluorescent findings were all consistent with a diagnosis of LPP. Linear basement membrane zone (BMZ) staining with IgG and C3 was only seen at the roof of split-skin preparations and circulating autoantibody to the BMZ was present at a titre of 1/100. Controlled immunoblotting of epidermal extracts detected the bullous pemphigoid antigens of 230 and 180 kDa.",1997.0,0,0
2118,9116923,Captopril does not blunt the sympathoadrenal response to cigarette smoking in normotensive humans.,M M Ottesen; R Worck; H Ibsen,"The aim of this study was to assess whether an interaction exists between the renin-angiotensin system and the sympathetic nervous system at the level of the adrenal medulla during smoking in normal humans. Thirteen habitual smoking volunteers were studied in a randomized, single-dose, double-blind, cross-over fashion using 50 mg captopril vs placebo followed by smoking of two high nicotine content cigarettes within 15 min. Blood samples were obtained at frequent intervals before, during and after smoking. We found that the increase in plasma adrenaline concentration during cigarette smoking was modest. There was no difference between captopril treatment as compared to placebo. Thus, the adrenaline response to cigarette smoking was not blunted by acute blockade of angiotensin II generation. A significant increase in heart rate, and blood pressure was found as well. No increase in plasma noradrenaline concentration was found. Plasma renin concentration increased significantly during captopril treatment, whereas it decreased throughout the study period in the placebo phase. Plasma angiotensin II concentration decreased in both the captopril treatment and the placebo phase throughout the study period, but this was more pronounced during captopril treatment. In conclusion, cigarette smoking-induced activation of the sympathetic nervous system was not blunted by acute ACE-inhibition by captopril. This indicates that angiotensin II does not facilitate smoking-induced activation of sympathoadrenal activity in humans.",1997.0,0,0
2119,9118514,Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE Study Group. Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation.,G Mancia; A Zanchetti; E Agabiti-Rosei; G Benemio; R De Cesaris; R Fogari; A Pessina; C Porcellati; A Rappelli; A Salvetti; B Trimarco; E Agebiti-Rosei; A Pessino,"In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression of organ damage over time better than clinic BP, however, is unknown. In 206 essential hypertensive subjects with left ventricular hypertrophy (LVH), we measured clinic supine BP, 24-hour ABP, and left ventricular mass index (LVMI, echocardiography) before and after 12 months of treatment with lisinopril (20 mg UID) without or with hydrochlorothiazide (12.5 or 25 mg UID). Measurements included random-zero, clinic orthostatic, and home BP. In all, 184 subjects completed the 12-month treatment period. Before treatment, clinic supine BP was 165 +/- 15/105 +/- 5 mm Hg (systolic/diastolic), 24-hour average BP was 149 +/- 16/95 +/- 11 mm Hg, and LVMI was 158 +/- 32 g/m2. At the end of treatment, they were 139 +/- 12/87 +/- 7 mm Hg, 131 +/- 12/83 +/- 10 mm Hg, and 133 +/- 26 g/m2, respectively (P < .01 for all). Before treatment, LVMI did not correlate with clinic BP, but it showed a correlation with systolic and diastolic 24-hour average BP (r = .34/.27, P < .01). The LVMI reduction was not related to the reduction in clinic BP, but it was related to the reduction in 24-hour average BP (r = .42/.38, P < .01). Treatment-induced changes in average daytime and nighttime BPs correlated with LVMI changes as strongly as 24-hour BP changes. No substantial advantage over clinic supine BP was shown by clinic orthostatic, random-zero, and home BP. In hypertensive subjects with LVH, regression of LVH was predicted much more closely by treatment-induced changes in ABP than in the clinic BP. This provides the first longitudinally controlled evidence that ABP may be clinically superior to traditional BP measurements.",1997.0,0,0
2120,9122965,Benefit of angiotensin II receptor blockade in the treatment of posttransplant polycythemia in renal transplant recipients.,W Kupin; K K Venkat; M Goggins; M Abouljoud; F Escobar; M Mozes,,1997.0,0,0
2121,9126880,Thromboxane A2 synthetase inhibition suppresses cough induced by angiotensin converting enzyme inhibitors.,K Umemura; M Nakashima; T Saruta,"Based on our earlier animal study, we became interested to investigate if thromboxane A2 (TXA2) is involved in angiotensin converting enzyme (ACE) induced cough in man. To 11 patients with hypertension, who had developed cough induced by ACE inhibitors, a TXA2 synthetase inhibitor, ozagrel was given for 1 to 2 months together with the ACE inhibitors. One patient developed headache induced by ozagrel and was eliminated from the study after 3 weeks. In other 10 patients, no obvious drug attributable abnormality was observed in subjective and objective symptoms or laboratory tests. In ten patients, cough scores were taken just before and after the administration of a combination of an ACE inhibitor with ozagrel. Median values of cough scores after the combination was significantly (p=0.012) lower than before the combination. Ozagrel reduced cough scores in 5 patients, completely suppressed cough in 3 patients and in 2 of 10 patients, ozagrel did not affect cough scores. Our observations suggest that TXA2 may somehow, mediate coughing induced by the ACE inhibitors. Further, patients on ACE inhibitors who develop cough may benefit from TXA2 synthetase inhibitors.",1997.0,0,0
2122,9129851,Potential proischemic effect of early enalapril in hypotension-prone patients with acute myocardial infarction. The CONSENSUS II Holter Substudy Group.,P Søgaard; K Thygesen,"The objective of this study was to evaluate the relationship between early hemodynamic instability and myocardial ischemia and the effect of early intravenous enalapril therapy on this relationship. In patients with myocardial infarction (MI), early treatment with angiotensin-converting enzyme inhibitors is controversial. In hypotensive patients, initiation of treatment may exacerbate myocardial ischemia and thereby affect the clinical outcome. Therefore, in the CONSENSUS II study, a total of 60 patients randomly allocated to either intravenous enalapril or placebo treatment commenced within 24 h after the onset of MI were evaluated by repeated blood pressure measurements, ambulatory ST-segment monitoring before discharge and exercise testing. Significant ST-depression was present in 34 patients. Patients with ST-depression before discharge (residual ischemia) during either exercise testing or ambulatory monitoring or both had a decrease in initial mean arterial blood pressure (MAP) of 20 vs. 9 mm Hg in those without ST-depression (n = 24), (p < 0.00001). However, patients (n = 13) with long-lasting ST-depression during Holter monitoring, (> 60 min of ST-depression) presented with the most severe fall in MAP of 29 mm Hg (p < 0.00001) and a lower systolic blood pressure at inclusion (p < 0.01) compared to the remainder of patients. Furthermore, the number of recurrent acute ischemic events during follow-up was higher in these patients (7 vs. 1; p < 0.01). Ten of the patients treated with enalapril showed a long-lasting ST-depression versus only 3 in the placebo group (p = 0.08), and the average duration of all significant ST-depressions during Holter monitoring was significantly longer in the enalapril group compared to the placebo group (p < 0.05). Finally, 7 enalapril patients (20%) suffered an acute ischemic event in contrast to 1 patient (4%) in the placebo group (p = 0.07). In conclusion, early administration of enalapril had a potential proischemic effect in hypotension-prone patients mediated through exacerbation of the hemodynamic response, inasmuch as initial blood pressure fall after MI is related to residual myocardial ischemia and recurrent acute ischemic syndromes.",1997.0,0,0
2123,9133508,Effect of single-drug therapy on reduction of left ventricular mass in mild to moderate hypertension: comparison of six antihypertensive agents. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,J S Gottdiener; D J Reda; B M Massie; B J Materson; D W Williams; R J Anderson,"Antihypertensive drugs may differ in their ability to reduce LV mass. Covariates other than drug selection, such as pretreatment LV mass, body weight, the magnitude of blood pressure reduction, race, and age may modify the response of LV mass to therapy. Patients with mild to moderate hypertension (diastolic blood pressure, 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Patients achieving the goal diastolic blood pressure of <90 mm Hg during drug titration entered a 1-year maintenance period. Longitudinal analysis examined changes from baseline echocardiogram in LV mass at 8 weeks and at 1 year, statistically adjusted for pretreatment LV mass, systolic blood pressure, body weight, sodium excretion, physical activity, race, and age. Significant reductions at 1 year in adjusted LV mass were seen for patients in the highest tertile of pretreatment LV mass treated with hydrochlorothiazide (mean, -42.9; 95% confidence limits, -65.5, -20.2 g), captopril (mean, -38.7; 95% confidence limits, -61.0, -16.4 g), and atenolol (mean, -28.1; 95% confidence limits, -50.9, -5.3 g). These treatment effects differed from those of prazosin, diltiazem, or clonidine. Antihypertensive drugs have disparate effects on LV mass independent of the magnitude of blood pressure reduction. Patients with adequate blood pressure control on captopril, hydrochlorothiazide, and atenolol show a reduction of LV mass after 1 year of treatment, whereas patients on diltiazem, clonidine, or prazosin do not.",1997.0,0,0
2124,9134274,Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction.,H Soejima; H Ogawa; H Yasue; H Suefuji; K Kaikita; K Nishiyama,"Treatment with an angiotensin-converting enzyme (ACE) inhibitor in patients with myocardial infarction has been shown to modify endogenous fibrinolysis. We investigated the effects of the ACE inhibitor imidapril on endogenous fibrinolysis in association with the serum ACE activity. In a randomized, double-blind, placebo-controlled study beginning 4 weeks after uncomplicated myocardial infarction, 15 patients received imidapril (5 mg daily) (imidapril group) and another 15 received placebo therapy (placebo group) for 4 weeks. Blood sampling was performed before the start of administration and on Days 3, 7, and 28 after the start of administration. Serum ACE activity and plasma fibrinolytic variables [plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor type 1 (PAI-1) antigen level, and tissue type plasminogen activator (TPA) antigen level] were measured. There was no difference between the imidapril and placebo groups in serum ACE activity or plasma fibrinolytic variables before administration. Serum ACE activity decreased significantly on Days 3, 7, and 28 in the imidapril group. The decrease of PAI activity and PAI-1 antigen levels was significantly less on Days 7 and 28, but not on Day 3. The TPA antigen level in the imidapril group was unchanged. None of the parameters in the placebo group was changed. The ACE inhibitor imidapril modified fibrinolysis, but the effects occurred after the inhibition of serum ACE activity.",1997.0,0,0
2125,9137136,Exacerbation of respiratory symptoms in patients with panic disorder.,C D Bouwer; D J Stein; S M Hawkridge,,1997.0,0,0
2126,9140533,Angioedema of ACE inhibitors.,D G Ebo; W J Stevens,,1997.0,0,0
2127,9140792,"A multicenter, parallel comparative study of the antihypertensive efficacy of once-daily lisinopril vs enalapril with 24-h ambulatory blood pressure monitoring in essential hypertension.",A Coca; J Sobrino; J Módol; J Soler; A Mínguez; J Plana; A De la Sierra,"The aim of the study was to compare the antihypertensive efficacy of once-daily lisinopril vs enalapril both during normal daily activity and sleep, in mild-to-moderate essential hypertension. After a 4-week wash-out period, 34 patients (17 M, 17 F) aged 22 to 67 years were randomized in a multicenter, open, parallel fashion: 17 received lisinopril (10-20 mg) and 17 enalapril (10-20 mg) for a 12-week period. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed using an oscillometric non-invasive automated device at both the end of the 4-week drug-free baseline period and during the last week of treatment. With no differences in initial blood pressure (BP) between groups, both drugs significantly reduced office and ABPM values. Lisinopril tended to reduce BP in a greater extension than enalapril, but only the reduction of office systolic BP (SBP) (p = 0.0062), 24-h SBP load (P = 0.0182) and night time SBP load (P = 0.0316) reached statistical significance. We conclude that, in spite of a more prominent reduction of SBP by lisinopril, both drugs have a similar efficacy in reducing BP, assessed by both office and ABPM measurements.",1996.0,0,0
2128,9140801,Antihypertensive treatment with moexipril plus HCTZ vs metoprolol plus HCTZ in patients with mild-to-moderate hypertension.,M Stimpel; B Koch,"Combination therapy with the new ACE inhibitor moexipril plus hydrochlorothiazide (HCTZ) results in significant blood pressure (BP) reductions. This study compares the efficacy and safety of moexipril plus HCTZ to that of a standard combination treatment in patients with mild-to-moderate hypertension. After a 1 month placebo run-in period, 140 hypertensive patients whose sitting diastolic BP (DBP) averaged 95-114 mm Hg were randomized to receive either once daily moexipril 7.5 mg/HCTZ 12.5 mg or metoprolol 100 mg/HCTZ 12.5 mg for the following 12-week double-blind treatment period. At biweekly visits BP was controlled sphygmomanometrically and the occurrence of adverse events (AE) was documented. At study endpoint adjusted mean reductions in sitting systolic/diastolic BP seen with both combinations were -17.6 mm Hg/-12.8 mm Hg and -17.2 mm Hg/-13.9 mm Hg in the moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The response rate to both kinds of combinations were very similar, 69% and 74% in the moexipril/HCTZ and metoprolol/HCTZ groups, respectively. The percentage of patients which experienced one or more AEs were 46% in the moexipril/HCTZ and 61% in the metoprolol/HCTZ group. Headache and cough which are the most frequently reported AEs after treatment with ACE inhibitors were seen in 9% and 10% of the patients in the moexipril/HCTZ group compared to 10% and 4% in the metoprolol/HCTZ group. The study indicates that the combination of moexipril 7.5 mg plus HCTZ 12.5 mg is as efficacious and safe as metoprolol 100 mg plus HCTZ 12.5 mg in the treatment of mild-to-moderate hypertension.",1997.0,0,0
2129,9141231,Effects of atenolol as add-on therapy to fosinopril in heart failure.,R Pacher; M Hülsmann; R Berger; J Koller-Strametz; T Kos; B Frey; A Dukat; B Stanek,"Several trials have demonstrated functional benefit with beta-blockers in patients with chronic heart failure. The aim of this observational study was to investigate if additional beneficial effects can be obtained from beta-blockade in a heart failure population that is already receiving high-dose ACE-inhibitor therapy. Atenolol is a long-acting cardioselective beta-blocking agent and is devoid of additional vasodilatory properties. Twenty-five male patients with class II or III heart failure and background therapy of digitalis, furosemide and 20 mg fosinopril per day were treated with 40 mg fosinopril per day and additional 75 mg atenolol per day (beta-blocker group) or with 40 mg fosinopril per day alone (control group). At the end of one year, changes in left ventricular function, exercise parameters and plasma neurohumoral variables reflecting vasoconstriction (noradrenaline, big endothelin) were measured and compared in the two treatment groups. Nineteen patients completed the study. Drop-outs were due to death (4 patients) and non-compliance (2 patients) with no significant difference between the groups. There was a beta-blocker related improvement in left ventricular ejection fraction (p < 0.05 between groups) and an increase in peak oxygen consumption in the control group only (p < 0.05 between groups). Thus, in a heart failure population receiving high-dose ACE inhibitor background therapy beta-blockade with atenolol produced additional benefit by reversing left ventricular dysfunction.",1997.0,0,0
2130,9141377,Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction.,J B Kostis; C R Lacy; N M Cosgrove; A C Wilson,"The Studies of Left Ventricular Dysfunction (SOLVD) assessed the effect of enalapril in patients with systolic left ventricular dysfunction (LVD). We performed retrospective analyses of the association between calcium channel blocker (CCB) use and fatal and nonfatal myocardial infarction (MI) in these patients. MI occurred in 11.5% of 845 patients receiving CCBs versus 7.5% of 2551 patients not receiving CCBs in the enalapril group and in 14.4% of 874 patients receiving CCBs versus 9.3% of 2527 patients not receiving CCBs in the placebo group. By multivariate Cox regression analysis, adjusting for comorbidity, cause and severity of LVD, heart failure, and concomitant drug use, CCB use was an independent predictor of MI (relative risk [RR] 1.37, confidence interval [CI] 1.14 to 1.63). The increase in MI risk was greater among patients with a higher heart rate (RR 1.46, CI 1.14 to 1.86) and lower blood pressure (RR 1.45, CI 1.14 to 1.86). The adjusted risk ratio for all-cause mortality associated with CCB use was 1.14 (CI 1.00 to 1.28; p = 0.0454). In this analysis of patients with LVD, CCB use was associated with significantly increased risk of fatal or nonfatal MI.",1997.0,0,0
2131,9141913,Hemodynamic effects of anesthesia in patients with ischemic heart failure chronically treated with angiotensin-converting enzyme inhibitors.,F Ryckwaert; P Colson,"Anesthesia may induce hemodynamic instability in patients treated with angiotensin-converting enzyme inhibitors (ACEIs). To assess the hemodynamic effects of anesthesia in patients treated (n = 9) or not treated (n = 9) with ACEIs for ischemic left ventricle dysfunction after myocardial infarction, we studied 18 patients scheduled for elective coronary artery bypass graft surgery. Induction of anesthesia with fentanyl (5 micrograms/kg), flunitrazepam (30 micrograms/kg), and pancuronium (100 micrograms/kg) was followed by a significant decrease in mean arterial blood pressure in both groups (-18.6% +/- 8.1% in controls and -25.7% +/- 7.8% in ACEI-treated patients, P = 0.01). In controls, cardiac index and systemic vascular resistance were not significantly altered (-11.2% +/- 9.4% and -16.2% +/- 4.6%, respectively, not significant [NS]). In ACEI-treated patients, cardiac index decreased significantly (-27.3% +/- 11.6%, P = 0.01 from baseline and P = 0.03 when compared with controls), and systemic vascular resistance was unchanged (1.0% +/- 18.7%, NS from baseline and P = 0.04 when compared with controls). Two patients from each group experienced a transient severe hypotensive episode. ACEI treatment in patients with infarction-induced myocardial dysfunction does not increase the incidence of severe hypotension after induction of anesthesia.",1997.0,0,0
2132,9142703,The pediatric cardiology pharmacopoeia.,R Abdulla; S Young; S D Barnes,"Keeping up with a rapidly growing list of medications has always been a breathtaking and, at times, impossible task to master. Contrary to common belief, the enormity of keeping abreast with the more recently developed medications is not a modern phenomenon resulting from the great technological advances of the past few years, but an ongoing struggle spanning the latter half of this century. It appears that there are more drugs to use than to know how, when, or what to do with them. This sentiment was expressed in 1973 by the editors of Martindale's The Extra Pharmacopoeia, twenty-sixth edition [3]: ""The unprecedented rate at which our knowledge of medicine and pharmacy is advancing makes it a formidable challenge to provide within a single volume an up-to-date source of basic information on the properties and uses of the many drugs in current use."" In this article, a review of the medications currently used in the management of children with heart diseases is presented. The medications have been collected in groups based upon their pharmacological actions: Antiarrhythmic, antihypertensive, diuretics, sedatives and miscellaneous agents. Within each group the agents are listed alphabetically using chemical names. We attempted to include as many drugs as thought to be of relevance to the team of health practitioners involved in the care of children with cardiac problems. Various routes of administration are presented, some of which have been infrequently described in the pediatric literature, such as continuous infusion of diuretic agents [22]. The dosing ranges were adopted from many sources [1, 5, 8, 9, 17-19, 22, 23, 26], and we sought to include the widest ranges of dosages published. All dosages listed in Table 1 are quantitated per dose and not per day. This approach was adopted as it reduces calculations and the potential for medication errors.",1997.0,0,0
2133,9152644,The treatment of heart failure. Task Force of the Working Group on Heart Failure of the European Society of Cardiology.,,,1997.0,0,0
2134,9152782,Captopril reduced plasminogen activator inhibitor activity in patients with acute myocardial infarction.,Y Moriyama; H Ogawa; S Oshima; K Takazoe; Y Honda; O Hirashima; H Arai; T Sakamoto; H Sumida; H Suefuji; K Kaikita; H Yasue,"Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction. It has also been reported that an elevated level of plasminogen activator inhibitor (PAI) appears to constitute a marker of the risk of recurrent coronary thrombosis. To determine whether the ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA) antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial infarction receiving captopril therapy (37.5 mg daily) and compared them with the values in 15 placebo-treated patients chosen at random. Blood sampling was performed at 07.00 h. In the captopril-treated group, serum ACE activity decreased significantly, from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after captopril therapy (p < 0.01), and those of PAI activity and t-PA antigen also decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml (p < 0.02) and from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml (p < 0.05), respectively 48 h after captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA antigen remained unchanged during the study period in the placebo group. Thus, our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity.",1997.0,0,0
2135,9153985,Quinapril for coronary artery disease.,S Seth; A Mohan,,1997.0,0,0
2136,9156120,The management of congestive heart failure.,F A McAlister; K K Teo,"Despite the remarkable advances in cardiovascular therapeutics over the past four decades, little impact has been made on either the incidence or mortality rate of congestive heart failure and it remains a major clinical and public health problem. Recent practice audits have suggested that proven efficacious therapies are not maximally applied in patients with this condition. An approach to the patient with congestive heart failure is presented, emphasizing the two distinct syndromes of systolic dysfunction and diastolic dysfunction. Treatment recommendations are derived from consideration of the underlying pathophysiology and the evidence from randomised clinical trials.",1997.0,0,0
2137,9158534,Cystitis associated with allopurinol.,F J Bramble; R Morley,,1997.0,0,0
2138,9159306,Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: the African-American Study of Kidney Disease and Hypertension Pilot Study.,W D Hall; J W Kusek; K A Kirk; L J Appel; G Schulman; L Y Agodoa; R Glassock; C Grim; O S Randall; S G Massry,"The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.",1997.0,0,0
2139,9160080,Angioedema associated with angiotensin II receptor antagonist losartan.,P K Sharma; J J Yium,"Angioedema has not been associated with losartan therapy in hemodialysis patients, as it has been with angiotensin converting enzyme (ACE) inhibitors. We report the case of a hemodialysis patient who previously had angioedema after therapy with ACE inhibitors and again had angioedema while taking losartan. We suggest caution in using losartan in patients with known sensitivity to ACE inhibitors manifested by angioedema.",1997.0,0,0
2140,9160758,"Effects of verapamil SR, trandolapril, and their fixed combination on 24-h blood pressure: the Veratran Study.",Veratran Study Group,"The Veratran study investigated the antihypertensive efficacy of verapamil sustained release (SR) (180 mg), trandolapril (1 mg), and their fixed combination during a 24-h period. After a 4-week placebo run-in period, 272 patients (age 49 +/- 9 years, mean +/- SD) with essential hypertension and a clinic diastolic blood pressure > or =100 mm Hg were randomized to verapamil, trandolapril, their fixed combination, or placebo for 8 weeks, according to a multicenter double-blind parallel group study design. Clinic and semiautomatic blood pressure at trough and 24-h ambulatory blood pressure were measured at the end of run-in period and after 8 weeks of treatment. In the 234 patients included in the efficacy analysis, run-in clinic and semiautomatic blood pressures were reduced by verapamil, trandolapril, and combined verapamil and trandolapril significantly more than by placebo. The reductions obtained with the combination were significantly greater than those obtained by verapamil alone. Twenty-four-hour average blood pressures were not modified by placebo and were reduced by 8/6 mm Hg (systolic/diastolic) by verapamil, 11/7 mm Hg by trandolapril, and 14/11 mm Hg by the combination of the two drugs. The differences between the effect of the combination and the combination components were, in most instances, statistically significant. The verapamil-trandolapril combination was more effective also on day average blood pressure and superior to the monotherapies for the trough-to-peak ratio of the antihypertensive effect as well. Twenty-four-hour heart rate was slightly but significantly reduced by verapamil and the reduction was manifest in the group taking verapamil plus trandolapril. Thus, the antihypertensive treatment with the fixed verapamil SR-trandolapril combination is more effective and balanced over the 24 hours than the effect of the combination components administered alone.",1997.0,0,0
2141,9161644,Reliability of drug utilization evaluation as an assessment of medication appropriateness.,P S Shelton; J T Hanlon; P B Landsman; M A Scott; I K Lewis; K E Schmader; G P Samsa; M Weinberger,"To test the reliability of drug utilization evaluation (DUE) applied to medications commonly used by the ambulatory elderly. A DUE model was developed for four domains: (1) justification for use, (2) critical process indicators, (3) complications, and (4) clinical outcomes. DUE criteria specific to use in the elderly were developed for angiotensin-converting enzyme (ACE) inhibitors and histamine2 (H2)-antagonists, and consensus was reached by an external expert panel. After pilot testing, two clinical pharmacists independently evaluated these medications, applying the DUE criteria and rating each item as appropriate or inappropriate. Interrater and intrarater reliability was assessed by using kappa statistics. In a sample of 208 ambulatory elderly veterans, 42 (20.2%) were taking an ACE inhibitor and 56 (26.9%) an H2-antagonist. The interrater agreement for individual domains, represented by kappa statistics, were 0.10-0.58 and 0-0.83 for ACE inhibitors and H2-antagonists, respectively. The kappa statistic for overall agreement, which considered ratings from all criteria across all domains, was 0.24 for ACE inhibitors and 0.18 for H2-antagonists. Intrarater reliability was assessed 3 months later, and kappa statistics were 0.61-0.65 (0.49 overall) and 0-0.96 (0.81 overall) for ACE inhibitors and H2-antagonists, respectively. Intrarater reliability for DUE was good to excellent. However, interrater reliability exhibited only marginal reproducibility, particularly where evaluators were required to use subjective judgement (i.e., complications, clinical outcomes). DUE may not be a suitable standard for assessing medication appropriateness in ambulatory elderly patients.",1997.0,0,0
2142,9165552,Disturbances of taste and smell induced by drugs.,B H Ackerman; N Kasbekar,"We reviewed the current literature (1980-1990, 1991-1996) concerning drugs associated with anosmia, hyposmia, dysgeusia, parageusia, and ageusia, and the impact of these adverse effects. Case reports of patients with sudden and delayed onset of one of these disorders with evidence for implication of a drug were included. Disturbances of taste and smell among the elderly and chronically ill, including those with thermal injury, decreases interest in eating and secondarily impairs healing of wounds. Mechanisms involved with these sensory disturbances include deposition of silver sulfate in nerves after use of topical agents containing silver, altered influx of calcium and other ions, chelation or depletion of tissue-bound zinc, disturbed bradykinin catabolism and second messenger synthesis, catabolism, and altered prostaglandin systems. Other mechanisms, particularly prolonged chemosensory disorders after early drug discontinuation, remain unknown.",1997.0,0,0
2143,9167457,Follow-up study of patients randomly allocated ramipril or placebo for heart failure after acute myocardial infarction: AIRE Extension (AIREX) Study. Acute Infarction Ramipril Efficacy.,A S Hall; G D Murray; S G Ball,"In the Acute Infarction Ramipril Efficacy (AIRE) Study, the effect of angiotensin-converting-enzyme (ACE) inhibition on the survival of patients with clinical heart failure after acute myocardial infarction (AMI), was assessed. At an average follow-up time of 15 months after randomisation, all-cause mortality was reduced from 22.6% (placebo group) to 16.9% (ramipril group) representing an absolute mortality reduction of 5.7% and a relative risk reduction of 27% (95% CI 11-40%; p = 0.002). Our aim in this study was to assess the long-term (3 years after the AIRE Study closed) magnitude, duration, and reliability of the survival benefits observed after treatment with ramipril (target dose 5 mg twice a day) when compared with placebo. We investigated the mortality status of all 603 patients recruited from the 30 UK centres involved in the AIRE Study. Through government records we were able to confirm the death or survival of all 603 patients exactly 3 years after the close of the AIRE Study. Follow-up was for a minimum of 42 months and a mean of 59 months. The average duration of treatment with masked trial medication was 13.4 months for placebo and 12.4 months for ramipril. By 0000 h March 1, 1996, death from all causes had occurred in 117 (38.9%) of 301 patients randomly assigned placebo and 83 (27.5%) of 302 patients randomly assigned ramipril, representing a relative risk reduction of 36% (95% CI 15-52%; p = 0.002) and an absolute reduction in mortality of 11.4% (114 additional 5-year survivors per 1000 patients treated for an average of 12.4 months). Our data provide robust evidence that administration of ramipril to patients with clinically defined heart failure after AMI results in a survival benefit that is not only large in magnitude, but also sustained over many years.",1997.0,0,1
2144,9167653,Drug-induced nephrotoxicity.,D Choudhury; Z Ahmed,"Drug-induced renal dysfunction is not an uncommon event, which can cause significant morbidity and can be easily overlooked. Many medications can lead to renal dysfunction through various mechanisms. The most common medications or classes of medications along with their clinical presentations are discussed in this article. As can be noted, many drugs can cause nephropathy in more than one way. Because it is difficult to discuss nephrotoxicities of every reported medication, Tables 1, 2, and 3 are provided; although these tables are by no means comprehensive, they may serve as further reference. This article is intended to provide a broad overview of the spectrum of presentation associated with drug-induced nephrotoxicity to guide the clinician to familiarity with this entity.",1997.0,0,0
2145,9176849,Contrasting effects of calcium channel blockade versus converting enzyme inhibition on proteinuria in African Americans with non-insulin-dependent diabetes mellitus and nephropathy.,A Guasch; M Parham; C F Zayas; O Campbell; C Nzerue; E Macon,"Hypertension is a common finding in non-insulin-dependent diabetes mellitus (NIDDM) nephropathy. African Americans have a high prevalence of NIDDM and hypertension, and are relatively resistant to the antihypertensive effects of converting enzyme inhibitors (CEI) but respond well to calcium channel blockers (CCB). In the long-term study presented here, the effects of isradipine, a dihydropyridine calcium antagonist, on the course of the nephropathy were investigated and compared with the effects of captopril in 31 African Americans with NIDDM and proteinuria (> or = 500 mg/day). The patients were stratified by levels of GFR and proteinuria, and they were randomized to receive isradipine (N = 16) or captopril (N = 15); doses were adjusted to maintain similar BP levels (< 140/90). At 6 months, mean arterial pressure was similar (102 +/- 3 and 104 +/- 3 mm Hg in the isradipine and captopril groups, respectively) and GFR was unchanged (delta = -4 +/- 3 and +1 +/- 3 ml/min/1.73 in the isradipine and captopril groups, respectively; P = NS). However, proteinuria in the isradipine group increased by approximately 50% (2.01 +/- 0.40 versus 3.04 +/- 0.70 mg/mg creatinine at baseline versus 6 months, respectively, P < 0.05), whereas captopril reduced proteinuria by 30% after 6 months (2.85 +/- 0.70 at baseline versus 2.30 +/- 0.70 mg/mg creatinine, P < 0.05). Dietary protein, sodium intake, and HbA1C levels were similar in both groups and did not differ from baseline. It was concluded that over 6 months, captopril reduces and isradipine increases proteinuria in African Americans with NIDDM and nephropathy. Whether this contrasting effect on proteinuria will result in different rates of progression is not known, but dihydropyridine CCB should be used cautiously in African Americans with diabetic nephropathy.",1997.0,0,0
2146,9179087,Effect of angiotensin-converting enzyme inhibitor therapy in mitral regurgitation with normal left ventricular function.,F Marcotte; G N Honos; A D Walling; D Beauvais; M J Blais; C Daoust; A Lisbona; J L McCans,"Mitral regurgitation (MR) is a common, frequently asymptomatic valvulopathy that can ultimately lead to left ventricular failure. With the objective of forestalling MR progression, a prospective, placebo controlled, double-blind study was conducted. It measured the effectiveness of lisinopril, an angiotensin-converting enzyme inhibitor, in reducing the echocardiographic signs of MR severity over a one-year period. Severe coronary disease was excluded by stress echocardiography. Treatment effectiveness was estimated to be proportional to the reduction in MR fraction and cardiac chamber dimensions, compared with baseline, according to intention-to-treat analysis. A final patient population of 23 asymptomatic adults aged 53.3 +/- 2.4 years (mean +/- SEM), with moderate, organic MR and normal left ventricular function was selected from the echocardiographic database. All baseline patient characteristics were comparable in the two treatment groups, including the MR fraction (55 +/- 3%). Twelve patients received lisinopril (18 +/- 1 mg) and 11 received placebo. After one year of treatment, a statistically significant difference in the MR fraction was observed between the two groups. For the lisinopril group the MR fraction dropped by 6.4 +/- 3.5% and for the placebo group it increased by 3.7 +/- 3.2% versus baseline (P < 0.05). No differences in left atrial or ventricular dimensions were observed. The study drug was stopped in four patients after one patient presented with rapid atrial fibrillation and angina while three patients were intolerant to lisinopril. Only one patient receiving placebo was taken off therapy. In conclusion, treatment with lisinopril indicates some reduction in the severity of chronic moderate MR in asymptomatic patients with normal left ventricular function. This approach appears to be safe, but side effects are not uncommon, warranting regular follow-up.",1997.0,0,0
2147,9179532,Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus.,K L Goa; M Haria; M I Wilde,"Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data supporting an additional place in managing normotensive patients with microalbuminuria and IDDM. These findings, together with some evidence for an effect of lisinopril in delaying progression of retinopathy and in reducing mortality, suggest a broader role for the drug in managing diabetic vascular complications.",1997.0,0,0
2148,9181250,Is hypertension a risk factor for cancer?,T Hedner; L Hansson; S Jern,,1997.0,0,0
2149,9183041,Effects of enalapril on left ventricular function and exercise performance after a first acute myocardial infarction. The EDEN Study Investigators.,,"To study the effects of early use of enalapril on left ventricular function and exercise capacity after a first acute myocardial infarction, 356 patients without overt signs of congestive heart failure were randomly allocated to receive placebo or enalapril between days 7 and 14 after a first myocardial infarction. The study was conducted double-blind in 40 hospitals throughout Spain. At baseline and after 26 weeks of follow-up exercise stress tests, Doppler-echocardiograms and isotopic ventriculography were performed in study participants. At the end of follow-up, patients in the enalapril group had lower end-systolic volume compared to those in the placebo group (55 vs. 62 ml; P=0.05). No difference in exercise capacity was evident between both groups. The present study shows that enalapril therapy administered between 7 and 14 days after a first acute myocardial infarction decreases end-systolic volume and may inhibit the remodeling process of the left ventricle.",1997.0,0,1
2150,9186076,Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibition: a prospective double-blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency.,H C Mitchell; R D Smith; R E Cutler; D Sica; J Videen; S Thompsen-Bell; K Jones; C Bradley-Guidry; R D Toto,"This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was -13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P < 0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -12 to -21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26 to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35 +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.",1997.0,0,0
2151,9186393,Adverse event with first-dose perindopril in congestive heart failure.,J P Bagger,,1997.0,0,1
2152,9188926,"Angiotensin-converting enzyme inhibitor-induced angioedema: late onset, irregular course, and potential role of triggers.",P I Schiller; S L Messmer; W E Haefeli; R G Schlienger; A J Bircher,"Angioedema is a rare but potentially life-threatening adverse effect of angiotensin-converting enzyme inhibitors (ACEI) which usually occurs within the first weeks of therapy. We report three patients in whom ACEI-induced angioedema began with a late onset of 12-33 months, and who had an irregular, unpredictable course under ACEI therapy. In two patients, other drugs or trauma appeared to trigger some of the episodes. After withdrawal of the ACEI, the trigger drugs were well tolerated in provocation tests and upon re-exposure. To avoid putting some patients unnecessarily at risk for long periods, one should consider this irregular pattern of ACEI-induced angioedema and regularly monitor patients for this adverse effect.",1997.0,0,0
2153,9191456,Autoimmune bullous diseases.,B Rye; J M Webb,"Patients with autoimmune bullous diseases are occasionally encountered in primary care practice, usually in middle-aged and older patients. The differential diagnosis includes nonimmune causes, such as contact dermatitis, infections and bullous reactions to drugs or insect bites. An autoimmune blistering disease may be distinguished by the age of the patient when the disease first appears, the morphology and distribution of the lesions and the presence or absence of mucosal lesions and scarring. Because the clinical presentations of blistering disorders are often similar, special immunofluorescence tests are used to confirm the specific diagnosis. Since diagnosis and management of an autoimmune bullous disease may involve systems other than the skin, coordination by the primary care physician is crucial.",1997.0,0,0
2154,9191512,A dose-response study of perindopril in hypertension: effects on blood pressure 6 and 24 h after dosing. Perindopril Multicentre Dose-Response Study Group.,M G Myers,"To examine the dose-response characteristics of perindopril at the time of its peak and trough antihypertensive effects, with the primary outcome measure being changes in diastolic blood pressure. After a four-week, single-blind placebo run-in, patients were randomly allocated to four doses of perindopril or placebo using a parallel group design. Sixteen specialist centres in the United States. Of 483 patients entered into the run-in phase, 293 were eligible for randomization to perindopril or placebo therapy, with 260 patients included in the final efficacy analysis. Eligible patients were randomized to 12 weeks of therapy with perindopril 2, 4, 8 or 16 mg or placebo. At the final visit, all doses of perindopril significantly (P < 0.05) lowered diastolic blood pressure compared with placebo. The ratio of changes in placebo-corrected diastolic blood pressure at 24 versus 6 h for perindopril 2, 4 and 8 mg was 1.0, 1.0 and 0.97, respectively. The maximum antihypertensive effect was seen with perindopril 8 mg, with the 16 mg dose providing no additional response. Changes in systolic and diastolic blood pressure were similar. Perindopril is most effective at doses of 4 and 8 mg once daily, with similar reductions in diastolic blood pressure present at 6 and 24 h after dosing.",1996.0,0,0
2155,9193008,Interaction between enalapril and aspirin on mortality after acute myocardial infarction: subgroup analysis of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II),K N Nguyen; I Aursnes; J Kjekshus,"The use of angiotensin-converting enzyme (ACE) inhibitors early after an acute myocardial infarction to reduce mortality has been studied in several trials with inconsistent results. Aspirin (ASA) has become a well-documented therapeutic adjunct in patients with coronary heart disease. Attention has recently been focused on a possible interaction between ASA and ACE inhibitors. We therefore reanalyzed data from the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II) to find any evidence of differential effects of the ACE inhibitor enalapril in subgroups defined by use of ASA at baseline. Logistic regression tested the multiplicative interaction. We used Rothman synergy index S, which would be equal to unity under additivity, and less than unity when suggesting antagonism, to examine the postulated interaction with departure from an additive model. Logistic regression showed that the enalapril-ASA interaction term was a significant predictor of mortality at the end of the study (p = 0.047), and was a borderline significant predictor of mortality 30 days after randomization (p = 0.085). The Rothman synergy index S was 0.66 (95% confidence interval 0.46 to 0.94) for mortality at the end of the study, and 0.68 ( 0.44 to 1.04) for 30-day mortality, indicating antagonism between enalapril and ASA with departure from an additive model. Thus, we found evidence of enalapril-ASA interaction. The effect of enalapril was less favorable among patients taking ASA than among patients not taking ASA at baseline.",1997.0,0,0
2156,9193433,Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. The healing and early afterload reducing therapy trial.,M A Pfeffer; S C Greaves; J M Arnold; R J Glynn; F S LaMotte; R T Lee; F J Menapace; E Rapaport; P M Ridker; J L Rouleau; S D Solomon; C H Hennekens,"Although ACE inhibitor therapy has been shown to reduce mortality in patients with acute myocardial infarction (MI), the optimal dose and the timing of its initiation have not been determined. In a double-blind trial of 352 patients with anterior MI, we compared the safety and effectiveness of early (day 1) versus delayed (day 14) initiation of the ACE inhibitor ramipril (10 mg) on echocardiographic measures of left ventricular (LV) area and ejection fraction (EF). An early, low-dose ramipril (0.625 mg) arm was also evaluated. Clinical events did not differ. During the first 14 days, the risk of manifesting a systolic arterial pressure of < or = 90 mm Hg was increased in both ramipril groups. LVEF increased in all groups during this period, but the early, full-dose ramipril group had the greatest improvement in EF (increase: full, 4.9 +/- 10.0; low, 3.9 +/- 8.2%; delayed, 2.4 +/- 8.8%; P for trend < .05) and was the only group that did not demonstrate a significant increase in LV diastolic area. The results of the present study demonstrated that in patients with anterior MI, the early use of ramipril (titrated to 10 mg) attenuated LV remodeling and was associated with a prompter recovery of LVEF. The use of low-dose regimen did not prevent hypotension and had only intermediate benefits on LV size and function. The more favorable effects on LV topography of the early use of full-dose ramipril support the results of the major clinical trials, which have demonstrated an early survival benefit of ACE inhibition.",2001.0,0,0
2157,9195116,Fosinopril. Clinical pharmacokinetics and clinical potential.,H Shionoiri; M Naruse; K Minamisawa; S Ueda; H Himeno; S Hiroto; I Takasaki,"Fosinopril is a phosphorus-containing ester prodrug of an angiotensin-converting enzyme (ACE) inhibitor. It is hydrolysed mainly in the gastrointestinal mucosa and liver to the active diacid, fosinoprilat, which has unique pharmacological properties. The majority of the active moieties of other ACE inhibitors are excreted in the urine. This means that an adjustment in either the dosage and/or the administration interval is needed in patients with moderate to severe renal dysfunction, in order to reduce drug accumulation and the possibility of an excessive decrease in blood pressure or other adverse effects. On the other hand, fosinoprilat is excreted both in urine and bile (as with temocaprilat, zofenoprilat and spiraprilat), and thus an adjustment of dosage and/or administration interval may be unnecessary in patients with moderate to severe renal dysfunction, as impaired renal function influences little of the pharmacokinetics of fosinoprilat. Furthermore, the available evidence suggests that the pharmacokinetic variables of fosinoprilat in patients receiving haemodialysis were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dose administration following dialysis may be unnecessary. The hypotensive effect of the combination of fosinopril and a diuretic is synergistic. Pharmacokinetic interactions with fosinopril are unlikely in patients receiving thiazide or loop diuretics. Fosinopril has beneficial effects for patients with hypertension and left ventricular hypertrophy because it produces an adequate reduction in blood pressure and reversal of left ventricular hypertrophy. There are a large number of studies of the pharmacokinetics of fosinopril. However studies of its pharmacokinetic drug interactions with other drugs are far fewer. Further investigations are needed in several clinical settings.",1997.0,0,0
2158,9195548,Scleroderma and eosinophilic fasciitis in patients taking fosinopril.,D Biasi; P Caramaschi; A Carletto; L M Bambara,,1997.0,0,0
2159,9200654,Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.,F S Nielsen; P Rossing; M A Gall; P Skøtt; U M Smidt; H H Parving,"The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10-20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50-100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 +/- 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (51Cr-EDTA plasma clearance) was 75 +/- 6 and 74 +/- 8 ml x min(-1) x 1.73 m(-2), mean 24-h ambulatory blood pressure (A&D TM2420) was 110 +/- 3 and 114 +/- 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331-5,727) and 1,578 (476-5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 +/- 2 and 10 +/- 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 +/- 0.49 and 0.81 +/- 0.29 ml x min(-1) x month(-1) followed by a slower sustained decline (6 to 42 months) of 0.59 +/- 0.10 and 0.54 +/- 0.13 ml x min(-1) x month(-1) in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29-72) and 15% (-13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the beta-blocker atenolol and the ACE inhibitor lisinopril.",1997.0,0,0
2160,9204055,Recognition of pemphigus antigens in drug-induced pemphigus vulgaris and pemphigus foliaceus.,S Brenner; A Bialy-Golan; G J Anhalt,"The clinical appearance and biologic behavior of drug-induced pemphigus depend on the type of inducing drug. Our purpose was to investigate patients with drug-induced pemphigus vulgaris and pemphigus foliaceus antigens and compare results of studies to detect antibody reactivity in sera of these patients with the serology of patients with idiopathic pemphigus. Ten patients with drug-induced pemphigus were studied. Antibody reactivity was determined against the pemphigus vulgaris antigen, desmoglein 3, and against desmoglein 1. The patient with pemphigus foliaceus and low levels of autoantibodies precipitated neither antigen. One patient with pemphigus vulgaris and high levels of antibody also failed to precipitate any specific antigen. Sera from eight patients with drug-induced pemphigus vulgaris had circulating autoantibodies directed to either the pemphigus vulgaris or pemphigus foliaceus antigen. Low levels of antibody in two of these eight patients precipitated only the pemphigus foliaceus antigen. High levels of antibody in five of the eight patients precipitated the pemphigus vulgaris antigen; two of these also reacted with the pemphigus foliaceus antigen. The autoantibody response was similar in both spontaneous and drug-related disease. A similar molecular mechanism in the two types of pemphigus is suggested.",1997.0,0,0
2161,9205849,Optimal treatment of heart failure in the elderly.,R Doughty; V Andersen; N Sharpe,"Heart failure is a common condition in the elderly and one that is likely to become more prevalent as the population ages. Many drugs have been developed for the treatment of heart failure, but because clinical trials of these agents have often not included elderly patients their results need to be extrapolated from younger to older patients. Age-related physiological changes that affect how the available treatments are used occur in many organ systems. Effective management strategies can be implemented in elderly patients as well as in younger age groups, and these can improve both functional status and quality of life as well as reducing hospital admission and improving survival. This article reviews the physiological changes that occur in the elderly and the treatment approach that can be taken in elderly patients with heart failure.",1997.0,0,0
2162,9205931,Therapy in old patients with isolated systolic hypertension: fourth progress report on the Syst-Eur trial.,R Antikainen; J Tuomilehto; L Thijs; H Vanhanen; C Sarti; W Birkenhäger; G Arabidze; R Fagard; M Grigorow; K Jankulova; M Jääskivi; P Kohonen-Jalonen; T Laks; L Lazebnic; S Mantova; C Nachev; P Kermova; O Vänskä; Y Yodfat; C J Bulpitt; J A Staessen,"The Syst-Eur trial is a multicentre, randomized, double-blind, placebo controlled therapeutical trial in patients at least 60 years old and with isolated systolic hypertension. Its scope is to investigate the effects of modern antihypertensive drug treatment on morbidity and mortality and to assess possible adverse effects of the drugs used. Patients were recruited in 22 countries in western and eastern Europe and Israel. At three run-in visits 1 month apart their sitting systolic blood pressure (SBP) on single-blind placebo treatment averaged 180-219 mm Hg with diastolic blood pressure (DBP) lower than 95 mm Hg. After stratification for sex and the presence of cardiovascular complications, the patients were randomized either to active treatment or placebo. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day) and/or hydrochlorothiazide (12.5-25 mg/day), titrated or combined to reduce the sitting SBP by at least 20 mm Hg to below 150 mm Hg. Matching placebos were employed similarly. The present progress report is based on the data received at the Coordinating Office before 1 March 1996. At that time 3433 subjects had been randomized. A total of 2015 patients had been followed for at least 1 year on double-blind treatment and 1298 patients for at least 2 years. At baseline BP was similar in both treatment groups and averaged 174/86 mm Hg. According to a per-protocol analysis at 1 year, BP fell (P < 0.001) on average by 22.6 +/- 15.7/6.0 +/- 8.0 mm Hg in the active treatment group and by 12.2 +/- 15.9/1.7 +/- 7.3 mm Hg in the placebo group. At 2 years BP was 10.2/5.7 mm Hg lower (P < 0.001) on active treatment than on placebo. At 1 year the percentage of patients who had reached goal BP was 19.9% in the placebo group and 41.4% in the active treatment group. At 2 years these percentages were 20.9 and 43.2 respectively.",1997.0,0,0
2163,9206057,Beneficial effects of captopril on prognosis in patients with acute myocardial infarction. Shanghai Secondary Prevention of Acute Myocardial Infarction Study Group.,W Shen; M Li; L Gong,"To assess the effects of early and long-term angiotensin-converting enzyme inhibitor treatment with captopril on clinical outcome in patients with acute myocardial infarction (AMI). Eight hundred and twenty-two patients with AMI who were hospitalised within 72 hours of symptoms and had no cardiogenic shock were randomly allocated to captopril (n = 478, Group I) and conventional treatment (n = 344, Group II). Cardiac events including congestive heart failure, reinfarction, severe arrhythmias and cardiac death during hospitalization and follow-up period (average 20 months) were determined. The overall mortality rate during hospitalization was lower in group I than in group II (P = 0.0001), this was true for patients with anterior (P = 0.0003), inferior (P = 0.0411) and anterior inferior AMI (P = 0.0232). During follow-up, despite similar occurrence rate of reinfarction and severe arrhythmias in the two groups, the mortality rate (P = 0.0324) and total cardiac event rate (P = 0.055) were lower in group I than in group II. After AMI, early and long-term treatment with captopril exerts a beneficial effect on the prognosis of patients.",1996.0,1,1
2164,9208358,Comparison of enalapril to captopril by 24-hour ambulatory blood pressure monitoring.,T Bental; M Lishner; A Lalkin; A Elis; M Ravid,"The efficacy of a once-daily dose of enalapril was compared with a thrice-daily dose of captopril in an open-label, randomized parallel group study of 27 hypertensive patients. The patients were monitored using conventional measurements of blood pressure and with 24-hour ambulatory blood pressure monitoring at baseline and after 12 weeks of therapy. The end points were 24-hour, daytime, and nighttime mean blood pressure values and the percentage of elevated systolic and diastolic measurements, reflecting the ""hypertensive load."" Enalapril reduced mean 24-hour systolic blood pressure by 18 mmHg and diastolic blood pressure by 11 mmHg. The comparative values for captopril were 9 mmHg and 2 mmHg, respectively. The mean daytime systolic blood pressure was reduced by 20 mmHg with enalapril versus 7 mmHg with captopril; the diastolic values were lowered by 11 mmHg with enalapril versus 4 mmHg with captopril. The mean nighttime systolic blood pressure was lowered by 16 mmHg with enalapril versus 12 mmHg with captopril; the diastolic values were reduced by 10 mmHg with enalapril and 5 mmHg with captopril. No major side effects were recorded in either group. A single daily 20-mg dose of enalapril, therefore, proved to be equipotent or superior to 75 mg of captopril administered in three divided doses.",1997.0,0,0
2165,9210809,Late-onset life-threatening angioedema and upper airway obstruction caused by angiotensin-converting enzyme inhibitor: report of a case.,P K Weng; H W Wang; J K Lin; W Y Su,"Angioedema is a rare but potentially lethal adverse effect when associated with upper airway obstruction. Sporadic cases of angioedema secondary to angiotensin converting enzyme inhibitors (ACEI) have been reported in the literature. The overall incidence is around 0.1% to 0.2%, and the time of onset is usually during the first week of ACEI therapy. Late-onset angioedema secondary to treatment with ACEIs is much more frequent than appreciated, and is largely unrecognized because of the absence of temporal correlation between ACEI therapy and the development of angioedema. Since angioedema may progress to upper airway obstruction, otolaryngologists must be aware of this association. Most importantly, late-onset angioedema should alert the clinician to discontinue the ACEI immediately to prevent further morbidity. This report presents an example of late-onset angioedema which was precipitated by taking a double dose of captopril incidentally. The case is discussed, and the literature, pathophysiology and treatment of angioedema are reviewed.",1997.0,0,0
2166,9211084,Fosinopril. A review of its pharmacology and clinical efficacy in the management of heart failure.,R Davis; A Coukell; D McTavish,"Fosinopril is the prodrug of the active diacid ACE inhibitor fosinoprilat. In patients with heart failure, fosinopril reduces pulmonary capillary wedge pressure, mean arterial blood pressure, mean right atrial pressure and heart rate, and increases stroke volume index and cardiac index. The drug has compensatory dual elimination routes via renal and hepatic systems and accumulates to a lesser extent than enalapril and lisinopril in patients with chronic renal insufficiency with or without heart failure. Comparative studies of 3 or 6 months' duration with fosinopril 10 to 40 mg/day have demonstrated clinical efficacy significantly superior to that of placebo in patients with heart failure [mostly New York Heart Association (NYHA) functional class II or III]. Fosinopril treatment consistently increased exercise duration and improved heart failure symptoms in these patients. Significantly fewer fosinopril than placebo recipients withdrew or were hospitalised because of worsening heart failure. Additionally, significantly more fosinopril than placebo recipients showed improvement, and fewer patients had deteriorated, in terms of NYHA functional class. Fosinopril and enalapril showed similar clinical efficacy over 6 and 12 months' treatment in patients with NYHA functional class II to IV heart failure. As yet, there are no data showing a mortality benefit with fosinopril. Fosinopril was well tolerated in clinical trials in patients with heart failure. Dizziness (11.9 vs 5.4% for placebo), cough (9.7 vs 5.1%) and hypotension (4.4 vs 0.8%) were the most commonly reported adverse events. In 6- or 12-month comparative studies, fosinopril therapy was associated with a lower incidence of dizziness and hypotension, but a higher incidence of vertigo, than enalapril therapy. 0.8% of patients discontinued the drug because of cough, which occurred to a similar extent with fosinopril and enalapril. Thus, based on available clinical evidence, fosinopril is an effective and well tolerated option for the management of patients with heart failure. Although clinical data are limited, fosinopril may be especially useful in patients with renal or hepatic impairment.",1997.0,0,0
2167,9213203,Assessment of antihypertensive effect by blood pressure monitoring: applications to bisoprolol and lisinopril in a double-blind study.,B Vaïsse; D Herpin; R Asmar; P Battistella; F Zannad; S Boutelant; A Lyon; D Conte; J Denis; P Honore; S Contard; P L Prost; J M Mallion; L Poggi,"The aim of this study was to evaluate the antihypertensive effect of drugs according to the initial ambulatory blood pressure (BP) level. After a 15-day placebo run-in period, 105 patients with moderate essential hypertension (mean age, 52 years) underwent 24-h BP monitoring (spacelabs: 1 measure/15 min). Patients were subdivided into two groups: the ""High"" group, with 24-h mean values of systolic BP (SBP) > 137 or diastolic BP (DBP) > 87 mm Hg, and the ""Low"" group, with SBP < or = 137 and DBP < or = 87 mm Hg. All patients received, in a random and double-blind design, either bisoprolol (10 mg q.d.) or lisinopril (20 mg q.d.) for 8 weeks. At the end of this active treatment period, office and ambulatory BP measurements were performed. Casual measurements revealed similar BP decreases in all subgroups receiving bisoprolol and lisinopril; BP monitoring showed that the antihypertensive effect depended on the baseline mean 24-h value; -15/-12 mm Hg for bisoprolol and -18/-13 mm Hg for lisinopril in the High group; -7/-6 mm Hg for bisoprolol and -6/-6 mm Hg for lisinopril in the Low group. This study shows that the antihypertensive effect depended on initial ambulatory BP values, with a lower BP decrease in the Low group. Assessment of the antihypertensive effect on ambulatory BP is useful in clinical trials.",1997.0,0,0
2168,9215232,Rationale and design features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). SCAT Investigators.,K K Teo; J R Burton; C Buller; S Plante; S Yokoyama; T J Montague,"In the treatment of coronary atherosclerotic artery disease (CAD), the mechanisms by which lipid lowering, a proven therapy, produces beneficial clinical effects remain unclear. Moreover, although potential mechanisms of benefit are well known and increasingly applied clinically, there are no conclusive data from clinical trials studying primarily the antiischemic effects of angiotensin-converting enzyme (ACE) inhibition in patients with normal heart function. The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) is designed to clarify some of these issues in CAD patients with normal or mildly elevated cholesterol. DESIGN AND OBJECTIVES: SCAT is a three- to five-year, multicentre, randomized, double-blind, placebo controlled, 2 x 2 factorial trial evaluating the effects of cholesterol lowering therapy by simvastatin and/or ACE inhibition by enalapril on anatomic coronary atherosclerosis progression assessed by quantitative coronary angiography in CAD patients with preserved left ventricular function and total cholesterol levels between 4.1 and 6.2 mmol/L. Of 460 patients (age 61 +/- 9 years; 409 males, 51 females) enrolled between June 1991 and July 1995, 230 were randomized to simvastatin and 230 to placebo, and 229 to enalapril and 231 to placebo. Average baseline total cholesterol level was 5.20 +/- 0.61 mmol/L, high density lipoprotein cholesterol was 0.99 +/- 0.25 mmol/L, low density lipoprotein cholesterol was 3.36 +/- 0.57 mmol/L and triglycerides were 1.82 +/- 0.75 mmol/L. The trial will be completed in June 1998. Insights gained from this long term angiographic trial will lead to a better understanding of the mechanisms of benefits of these two treatments, both alone and in combination. Of particular interest is that this trial will be able to examine a suspected beneficial interaction, if present, between these two treatments.",1997.0,0,0
2169,9217714,Thromboxane antagonism and cough induced by angiotensin-converting-enzyme inhibitor.,P L Malini; E Strocchi; M Zanardi; M Milani; E Ambrosioni,"The increased prostaglandin synthesis that might follow stimulation of the arachidonic acid cascade by angiotensin-converting-enzyme inhibition (ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough.",1997.0,0,0
2170,9217756,"Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia)",,"In diabetic nephropathy, angiotensin-converting-enzyme (ACE) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate (GFR). Whether this difference applies to progression of nondiabetic proteinuric nephropathies is not clear. The Ramipril Efficacy in Nephropathy study of chronic nondiabetic nephropathies aimed to address whether glomerular protein traffic influences renal-disease progression, and whether an ACE inhibitor was superior to conventional treatment, with the same blood-pressure control, in reducing proteinuria, limiting GFR decline, and preventing endstage renal disease. In this prospective double-blind trial, 352 patients were classified according to baseline proteinuria (stratum 1: 1-3 g/24 h; stratum 2: > or = 3 g/24 h), and randomly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg. The primary endpoint was the rate of GFR decline. Analysis was by intention to treat. At the second planned interim analysis, the difference in decline in GFR between the ramipril and placebo groups in stratum 2 was highly significant (p = 0.001). The Independent Adjudicating Panel therefore decided to open the randomisation code and do the final analysis in this stratum (stratum 1 continued in the trial). Data (at least three GFR measurements including baseline) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients. The decline in GFR per month was significantly lower in the ramipril group than the placebo group (0.53 [0.08] vs 0.88 [0.13] mL/min, p = 0.03). Among the ramipril-assigned patients, percentage reduction in proteinuria was inversely correlated with decline in GFR (p = 0.035) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure (18 ramipril vs 40 placebo, p = 0.04). The risk of progression was still significantly reduced after adjustment for changes in systolic (p = 0.04) and diastolic (p = 0.04) blood pressure, but not after adjustment for changes in proteinuria. Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups. In chronic nephropathies with proteinuria of 3 g or more per 24 h, ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering.",1997.0,0,1
2171,9219164,Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy.,G C Burns; S K Paul; I R Toth; S L Sivak,"Angiotensin-converting enzyme inhibition (ACEI) delays progression of diabetic and nondiabetic renal disease. This study examined the effect of fosinopril, 10 mg by mouth daily, in HIV-associated nephropathy (HIV-AN). Twenty patients with HIV-AN were studied. Of 11 patients with non-nephrotic-range proteinuria, 7 received treatment and 4 did not. Average baseline creatinine (mg/dl) for treated and nontreated patients was 1.3 +/- 0.24 and 1.0 +/- 0.25, respectively (P = 0.07). At 24 wk, creatinine of treated and nontreated patients was 1.5 +/- 0.34 and 4.9 +/- 2.4 (P = 0.006). Average baseline 24-h urine protein excretion (g/d) for treated and nontreated patients was 1.6 +/- 0.68 and 0.78 +/- 0.39, respectively (P = 0.02). At 24 wk, 24-h protein excretion of treated and non-treated patients was 1.25 +/- 0.86 and 8.5 +/- 1.4 (P = 0.006). Of nine patients with nephrotic-range proteinuria, five were treated and four were not. Average baseline creatinine for treated and nontreated patients was 1.7 +/- 0.46 and 1.9 +/- 0.42, respectively (P = 0.4). At 12 wk, creatinine for treated and nontreated patients was 2.0 +/- 1.0 and 9.2 +/- 2.0 (P = 0.02). The baseline 24-h protein excretion for treated and nontreated patients was 5.4 +/- 1.6 and 5.2 +/- 0.97 (P = 0.9). At 12 wk, 24-h protein excretion for treated and nontreated was 2.8 +/- 1.0 and 10.5 +/- 3.5 (P = 0.008). These preliminary data suggest that treatment with ACEI may stabilize serum creatinine and 24-h protein excretion for up to 24 wk in patients with non-nephrotic-range proteinuria and for up to 12 wk in patients with nephrotic-range proteinuria when initial serum creatinine is < or = 2.0 mg/dl. Furthermore, the renin-angiotensin system may play a role in HIV-AN, and early treatment with ACEI may be beneficial in HIV-AN.",1997.0,0,0
2172,9220210,Efficacy and tolerability of doxazosin versus enalapril in the treatment of patients with mild-to-moderate hypertension.,K W Tan; S A Frise,"The effects of 4 weeks of treatment with doxazosin or enalapril on diastolic blood pressure (DBP) and plasma lipid levels were studied in 160 patients 18 to 50 years old with mild-to-moderate hypertension. Comparing baseline measurements with measurements taken after 4 weeks, DBP was significantly reduced by 6.8 +/- 7.4 (mean +/- SD) mm Hg and 12.0 +/- 7.1 mm Hg in the doxazosin and enalapril groups, respectively. Systolic blood pressure was significantly decreased from baseline to end of treatment in both groups. There were no significant changes in heart rate from baseline to end of treatment in the doxazosin group, but there was a statistically significant decrease in heart rate in the enalapril group. High-density lipoprotein cholesterol increased statistically significantly in the doxazosin group but not in the enalapril group. A decrease in triglycerides was statistically significant with respect to the doxazosin group and was close to significance for the enalapril group. Forty-nine (62%) patients in the doxazosin group and 43 (54%) patients in the enalapril group reported at least one adverse event. Significant reductions in DBP after 4 weeks of treatment were achieved by both drugs, each taken once daily. This reduction was more pronounced in the enalapril group 24 hours postdose, with a mean final daily dose of 2.8 mg of doxazosin and 12.6 mg of enalapril. However, even relatively short-term treatment with low-dose doxazosin showed a more favorable effect on lipids than did enalapril.",1997.0,0,0
2173,9220212,Effects of cilazapril on ventricular arrhythmia in patients with congestive heart failure.,Y Hattori; S Atsushi; F Hiroaki; J Toyama,"Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and morbidity in patients with congestive heart failure. These effects may be mediated, at least in part, by suppression of lethal ventricular tachycardia (VT). The aims of this study were to examine whether the ACE inhibitor cilazapril reduces ventricular arrhythmia in patients with congestive heart failure and, if cilazapril does reduce ventricular arrhythmia, to determine whether this reduction is associated with suppression of sympathetic nerve activity in these patients. Thirty-two congestive heart failure patients (left ventricular ejection fraction, 35 +/- 6%; New York Heart Association class II or III) with VTs (Lown grade IVa or IVb) were randomly assigned to receive either conventional therapy, consisting of diuretics and digitalis (control group), or conventional therapy plus cilazapril (cilazapril group). Twenty-four-hour ambulatory electrocardiographic monitoring was performed at baseline and after 2 months of therapy. Plasma norepinephrine levels and heart rate variability (standard deviation about the mean RR interval) were compared at baseline and after 2 months of treatment. The control group demonstrated no significant change in arrhythmia frequency after 2 months of treatment. In the cilazapril group, however, the number of ventricular couplets and VT runs was significantly decreased. In association with this reduction, plasma norepinephrine levels were decreased, and heart rate variability was increased. These results suggest that cilazapril has antiarrhythmic effects, which may be produced by suppressing high sympathetic activity, in patients with congestive heart failure. It should be noted that the study group was small and that, although ventricular dysrhythmia was reduced with therapy, it remained substantial. Further study is needed to verify these results and to determine the exact causes of the reduction.",1997.0,0,0
2174,9220308,"Vasodilation by urapidil in the treatment of chronic congestive heart failure in addition to angiotensin-converting enzyme inhibitors is not beneficial: results of a placebo-controlled, double-blind study.",A Dorszewski; E Göhmann; B Dorsźewski; G S Werner; H Kreuzer; H R Figulla,"The therapeutic benefit of an angiotensin-converting enzyme (ACE) inhibitor in combination with a different type of vasodilator is unknown. To evaluate the effects of a combined therapy on quality of life, exercise tolerance, and hemodynamic parameters, patients with severe heart failure (New York Heart Association classes III and IV, ejection fraction below 35%) who were on ACE inhibitor therapy were randomly assigned to additional double-blind treatment with urapidil (60-120 mg/d) or placebo for 12 weeks. After enrollment of 36 patients, the study was terminated early because no beneficial effects on exercise tolerance and hemodynamic parameters could be shown for the urapidil treatment, and a trend toward increased mortality of the urapidil group was observed (odds ratio, 4.92 [0.49-49.6]; P = .167). The combination of urapidil with an ACE inhibitor in the treatment of severe chronic congestive heart failure does not seem to offer any advantages over therapy with an ACE inhibitor alone and may have potentially harmful effects.",1997.0,0,0
2175,9222948,"Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension. TRACE Study Group, Trandolapril Cardiac Event.",F Gustafsson; C Torp-Pedersen; L Køber; P Hildebrandt,"To evaluate the influence of a history of arterial hypertension on the efficacy of the angiotensin converting enzyme (ACE) inhibitor trandolapril in patients with acute myocardial infarction (AMI) and left ventricular dysfunction. A retrospective analysis of data from the Trandolapril Cardiac Event (TRACE) study. The TRACE study was a randomized, double-blind, placebo-controlled study in which patients with an enzyme-verified AMI and ejection fraction < or = 35% were assigned randomly to be administered oral trandolapril or placebo 3-7 days after the infarction. Of 1749 patients who entered the study, 400 (23%) had a history of arterial hypertension. The mean follow-up time was 26 months. Mortality from any cause. Secondary endpoints were sudden death, cardiovascular mortality, reinfarction and development of severe heart failure. Of the patients in the hypertensive group, 173 (43%) died during follow-up, versus 500 (37%) in the normotensive group. Treatment with trandolapril resulted in a relative risk of death from any cause for the hypertensive group of 0.59 (96% confidence interval 0.44-0.80), versus 0.85 (0.72-1.02) for normotensive patients. In a multivariate analysis, treatment with trandolapril was associated with a reduction in mortality among patients with a history of hypertension (P = 0.03). In this retrospective analysis, ACE inhibition after AMI complicated with left ventricular dysfunction was of greater benefit to patients with a history of arterial hypertension. ACE inhibition might be of particular importance in this group of patients but further studies to establish the clinical impact are necessary.",1997.0,0,0
2176,9230162,"Effect of propranolol versus no propranolol on total mortality plus nonfatal myocardial infarction in older patients with prior myocardial infarction, congestive heart failure, and left ventricular ejection fraction > or = 40% treated with diuretics plus angiotensin-converting enzyme inhibitors.",W S Aronow; C Ahn; I Kronzon,"At 32-month follow-up of older patients with prior myocardial infarction, congestive heart failure, and a left ventricular ejection fraction > or = 40% treated with diuretics plus angiotensin-converting enzyme inhibitors, and also with digoxin if atrial fibrillation was present, propranolol caused a 35% significant reduction in total mortality and a 37% significant decrease in total mortality plus nonfatal myocardial infarction compared with no propranolol. At 1-year follow-up, propranolol caused a significantly greater increase in left ventricular ejection fraction (6%) and a significantly greater reduction in left ventricular mass (34 g) than did no propranolol (2% and 20 g, respectively).",1997.0,0,0
2177,9230164,Response of symptomatic myocardial ischemia in ischemic cardiomyopathy to intensive vasodilator therapy.,T B Levine; A B Levine; A Vincenzi; S J Keteyian; J Billings; M Lesch,"To determine the cardiovascular protective effects of angiotensin-converting enzyme inhibitors, we examined the response to intensive vasodilator therapy in patients with ischemic cardiomyopathy and ongoing angina pectoris. We found that for patients with ischemic cardiomyopathy and ongoing active angina, intensive vasodilator therapy with angiotensin-converting enzyme inhibition and nitrates improved not only heart failure-related symptoms, but also resulted in a significant improvement in symptomatic ischemia and ischemia-related morbid events.",1997.0,0,0
2178,9231557,Enalapril-induced renal artery thrombosis in unilateral renal artery stenosis.,S S Kothari; S Sharma; M Sharma; A Saxena,,1997.0,0,0
2179,9231815,Endothelin-1-induced vasopressor responses in essential hypertension.,K A Kaasjager; H A Koomans; T J Rabelink,"The potential role of endothelin-1 (ET-1) in essential hypertension in humans is still subject to debate. We recently reported strong sodium retention and renal vasoconstriction during pathophysiological increments in plasma ET-1. Apart from this vasoconstrictor action, ET-1 also has mitogenic properties that play a role in the pathophysiology of hypertension. On the other hand, some data refute an important role of ET-1 in hypertension. We therefore investigated in nine subjects with essential hypertension the constrictor actions of ET-1 by challenging these subjects with a systemic infusion of ET-1 (0.5 ng/kg per minute for 60 minutes, then 1.0 ng/kg per minute for 60 minutes, and finally 2.0 ng/kg per minute for 60 minutes). Furthermore, we studied whether these effects of ET-1 could be modulated by oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD). ET-1 infusion increased plasma ET-1 levels from 2.5+/-0.4 to 11.6+/-1.0 pmol/L (P<.05). Blood pressure rose by approximately 10 mm Hg (P<.05). Cardiac index decreased by 21+/-22%, whereas calculated systemic vascular resistance increased by 27+/-6% (P<.05). Renal blood flow decreased from 1051+/-94 to 707+/-60 mL/min at the end of the ET-1 infusion (P<.05), and calculated renal vascular resistance increased from 118+/-19 to 189+/-19 mm Hg x min/L (P<.05). Sodium excretion decreased from 227+/-39 to 111+/-15 micromol/min (P<.05). Both enalapril and nifedipine treatment prevented the systemic effects of ET-1 infusion in these subjects. However, during enalapril treatment, despite renal predilatation, ET-1 reduced renal blood flow (from 1119+/-132 to 701+/-75 mL/min, P<.05) and increased renal vascular resistance (from 111+/-16 to 187+/-28 mm Hg x min/L, P<.05) to the same levels as during ET-1 infusion alone. Nifedipine pretreatment attenuated the ET-1-induced fall in renal blood flow (from 1088+/-93 to 907+/-68 mL/min) and increase in renal vascular resistance (from 105+/-9 to 133+/-10 mm Hg x min/L). Although neither drug modulated the antinatriuretic effect of ET-1, nifedipine increased basal sodium excretion (P<.05), which compensated for the decrease during ET-1 infusion. In conclusion, essential hypertensive subjects are sensitive to the vasoconstrictor effects of ET-1. Both enalapril and nifedipine can prevent the systemic effects of ET-1, but nifedipine seems more effective in attenuating the renal constrictor effects of ET-1.",1997.0,0,0
2180,9231834,,,,,0,0
2181,9234823,"The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.",B Dahlöf; R Devereux; U de Faire; F Fyhrquist; T Hedner; H Ibsen; S Julius; S Kjeldsen; K Kristianson; O Lederballe-Pedersen; L H Lindholm; M S Nieminen; P Omvik; S Oparil; H Wedel,"The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.",1997.0,0,0
2182,9234828,Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension.,P Chan; C N Lin; B Tomlinson; T H Lin; Y S Lee,"A multicenter, double-blind, placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem, in a sustained release preparation, and the angiotensin converting enzyme inhibitor, lisinopril, in the treatment of elderly Chinese patients with mild-to-moderate hypertension. In addition to the hypotensive effects of combinations of both drugs compared with monotherapy, all given once daily, the effect on quality of life was also evaluated. This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg, after a 4-week placebo washout phase, were randomized to one of six treatment groups for 12 weeks of active treatment. Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure. Compared with placebo, lisinopril 10 mg had an effect intermediate between the diltiazem doses. The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy, but the effect of the combinations was less than predicted by an additive model. Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo, lisinopril-induced cough was common with an incidence of 31% after rechallenge. Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril, due to intractable cough. The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life. Thus, combination therapy with these agents was well tolerated and resulted in increased efficacy in these elderly patients.",1997.0,0,0
2183,9236429,Intracoronary angiotensin II potentiates coronary sympathetic vasoconstriction in humans.,A Saino; G Pomidossi; R Perondi; R Valentini; A Rimini; L Di Francesco; G Mancia,"In humans with coronary artery disease, ACE inhibition attenuates coronary sympathetic vasoconstriction. Whether this is due to removal of angiotensin (Ang) II production or to a reduced bradykinin breakdown, however, is unknown. In eight normotensive patients with angiographic evidence of mild left coronary artery lesions (< or = 50%), mean arterial pressure (MAP, intra-arterial catheter), heart rate (HR, ECG lead), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between MAP and CBF) were measured before and during a 15-minute left intracoronary infusion of Ang II at a dose that had no direct coronary or systemic vasomotor effects. The same measurements were made before and during a 15-minute infusion of saline. A 2-minute cold pressor test (CPT) and a 45-second diving were performed at the end of either infusion period. These maneuvers were used because their coronary vasomotor effects are abolished by phentolamine and thus depend on sympathetic activation. During saline infusion, both CPT and diving caused a marked increase in MAP. HR increased with CPT and fell with diving. CBF increased in parallel to the MAP increase, with little change in CVR. The MAP and HR responses were similar during Ang II infusion, which, however, caused either no change or a reduction in CBF with a consequent marked increase in CVR with both CPT and diving. In four additional patients, the diameter of the stenotic vessels remained unchanged during the CPT performed under saline and Ang II infusion. Ang II markedly enhances sympathetic influences on coronary circulation in humans, presumably by acting at the arteriolar level. This may explain the blunting effect of ACE inhibition on sympathetic coronary vasoconstriction in patients with coronary artery disease.",1997.0,0,0
2184,9236432,Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease.,J L Zhuo; P Froomes; D Casley; J J Liu; C Murone; S Y Chai; B Buxton; F A Mendelsohn,"ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease. Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.",1997.0,0,0
2185,9241099,Further evidence that chronic perindopril treatment maintains neurohormonal suppression but does not lower blood pressure in chronic cardiac failure.,R J MacFadyen; C S Barr; N D Sturrock; M Fenwick; A D Struthers,"Previous studies in heart failure (CHF) after temporary diuretic withdrawal have suggested that perindopril is associated with no first dose hypotension in comparison with other ACE inhibitors (ACEI) or placebo. The aim of this study was to explore further the profile of perindopril during chronic dosing. We report the effects of acute and chronic (8 weeks) treatment with the ACE inhibitor perindopril (Per, 2-->4 mg daily) or placebo (P) in a double-blind parallel group study of 24 diuretic treated patients (17M; 67 +/- 8 years, 80 +/- 17 kg) with ischaemic cardiomyopathy (fractional shortening, 19 +/- 5%; radionuclide ejection fraction, 31 +/- 3%). Baseline biochemical, hormonal (ACE, Ang I, Ang II), isotopic renal function (GFR, ERPF, ECFV), pretreatment diuretic dose and heart failure scores were similar between groups. Concomitant cardiac treatments remained unchanged and diuretic withdrawal was not used to introduce treatment. There were no significant effects on electrolytes, liver function tests, serum or erythrocyte magnesium. There was no significant first dose fall in SBP over 6 h) (P, baseline 137 +/- 18; min 115 +/- 16 mmHg; Per, baseline 137 +/- 15; min 118 +/- 17 mmHg). Neither supine nor erect BP was significantly affected by chronic treatment (P, erect baseline 134 +/- 23/76 +/- 10 to 124 +/- 41/74 +/- 10 mmHg; Per, baseline 135 +/- 21/76 +/- 14 to 128 +/- 22/70 +/- 12 mmHg, P=NS). Active treatment was associated with significant ACE inhibition (P, baseline 47 +/- 17 to 43 +/- 17; Per baseline 49 +/- 15 to 14 +/- 7); aldosterone (P, baseline 337 +/- 179 to 375 +/- 306; Per, baseline 335 +/- 357 to 293 +/- 155 pg ml(-1)) and Ang II suppression (P, baseline 9 +/- 9 to 20 +/- 39; Per baseline 10 +/- 9 to 3 +/- 3 pM). Isotopic renal function was unaffected by either treatment. At this dose (2-4 mg orally) chronic perindopril therapy has no significant effect on blood pressure or renal function. Sustained neurohormonal suppression of ACE and AII occurred without evidence of AII reactivation. A lack of effect on BP at these doses may make perindopril suitable for study in unstable patients with acute HF or useful in those patients where there are concerns over ACEI induced hypotension.",1997.0,0,0
2186,9241623,Effects of simvastatin and enalapril on serum lipoprotein concentrations and left ventricular mass in patients on dialysis. The Perfect Study Collaborative Group.,R Robson; J Collins; R Johnson; R Kitching; M Searle; R Walker; J Douglas; J Leary; G Whalley; N Sharpe; S MacMahon,"A randomised trial of simvastatin and enalapril in patients with chronic renal failure on dialysis: effects on serum lipoprotein concentrations and left ventricular mass. Left ventricular hypertrophy and abnormalities of lipoprotein metabolism are both possible contributors to the high risk of cardiovascular death in patients with chronic renal failure on dialysis. We investigated the effects of simvastatin on lipid and lipoprotein concentrations and the effects of enalapril on left ventricular mass in 107 patients receiving haemodialysis or continuous ambulatory peritoneal dialysis. Patients were randomised in a factorial design to receive simvastatin (10 mg daily) or placebo and enalapril (2.5-5 mg daily) or placebo. During follow-up, there was a significant excess of patients withdrawn from enalapril because of hypotension (2p = 0.002), and after 6 months only 55% of those assigned enalapril were still on treatment. From baseline to 6 months, there were no statistically significant differences in left ventricular mass or left ventricular dimensions between patients assigned enalapril and those assigned placebo. Among the patients assigned simvastatin, total cholesterol was reduced by 13% (2p = 0.001), LDL cholesterol was reduced by 17% (2p = 0.003) and apolipoprotein B was reduced by 12% (2p = 0.005) compared to patients assigned placebo. There were borderline significant (2p = 0.05 to 0.08) reductions in VLDL cholesterol, total triglyceride and VLDL triglycerides of 26%, 12% and 17% respectively. Large-scale trials are now required to determine whether reductions in lipid and lipoprotein concentrations confer a reduction in coronary heart disease morbidity and mortality in patients on dialysis.",2000.0,0,0
2187,9241712,"Anemia, hypertension, and myocardial dysfunction in end-stage renal disease.",J Venkatesan; W L Henrich,"Cardiovascular disease remains the major cause of mortality in patients with end stage renal disease (ESRD). The pathophysiology of cardiac dysfunction in ESRD is complex and not fully understood. However, it appears that the two major determinants of left ventricular (LV) hypertrophy and dysfunction are anemia and hypertension, both of which are very common in ESRD patients. Early and aggressive correction of anemia and hypertension may have a significant impact on cardiac disease in ESRD patients. This article presents a discussion on the management of anemia and hypertension, and the current information available on the pathogenesis and management of LV dysfunction in ESRD.",1997.0,0,0
2188,9243145,More favourable haemodynamic effects from metoprolol than from captopril in patients with dilated cardiomyopathy.,K Jansson; K E Karlberg; E Nylander; E Karlsson; O Nyquist; U Dahlström,"The object of this study was to investigate and compare the haemodynamic effects of treatment with a beta receptor blocker (metoprolol) or an angiotensin-converting-enzyme inhibitor (captopril) in 54 patients with idiopathic dilated cardiomyopathy. All patients had cardiac catheterization performed at rest and during exercise, before and after 3 months of treatment. The mean dose of metoprolol was 135 mg.day-1 and of captopril 98 mg.day-1. After treatment there was a significant reduction in left ventricular filling pressure both at rest (from 16 to 12 mmHg) and during exercise (from 27 to 20 mmHg) in the metoprolol group. In the captopril group a significant reduction was seen only during exercise (25 to 20 mmHg), compared to baseline. The stroke volume increased significantly after 3 months of therapy in the metoprolol group, both at rest (53 to 70 ml) and during exercise (56 to 79 ml). In the captopril group the increase reached significance only during exercise (72 to 79 ml). Cardiac output was maintained in both groups. There were positive effects on left ventricular function in the metoprolol group as well as in the captopril group. Metoprolol reduced left ventricular filling pressure at rest and increased stroke volume both at rest and during exercise significantly more than captopril.",1997.0,0,0
2189,9244210,Effects of ramipril on plasma fibrinolytic balance in patients with acute anterior myocardial infarction. HEART Study Investigators.,D E Vaughan; J L Rouleau; P M Ridker; J M Arnold; F J Menapace; M A Pfeffer,"The long-term administration of ACE inhibitors to selected patients with left ventricular dysfunction appears to reduce the incidence of recurrent myocardial infarction (MI) and unstable angina pectoris. The mechanisms responsible for the reduction in ischemic events are unknown, but likely candidates include effects on the atherosclerotic process, thrombosis, and/or vascular tone. The effects of ACE inhibitor therapy with ramipril on plasma fibrinolytic variables were assessed in 120 subjects participating in the Healing and Early Afterload Reduction Therapy (HEART) study, a double-blind, placebo-controlled trial of acute anterior MI patients who were randomly assigned within 24 hours of the onset of symptoms to receive low-dose ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured before randomization and on day 14. Clinical characteristics of the three study groups were similar, as were the prerandomization plasma levels of PAI-1 antigen, PAI-1 activity, and TPA antigen. Compared with the placebo group, PAI-1 antigen levels were 44% lower (P=.004) at day 14 in the ramipril-treated patients, and PAI-1 activity levels were 22% lower (P=.02). In contrast, plasma TPA levels were not significantly different between the placebo-treated and ramipril-treated groups. Treatment with ramipril has a significant impact on plasma fibrinolytic variables during the recovery phase after acute MI. The renin-angiotensin system appears to play an important role in the regulation of vascular fibrinolysis, and interruption of this regulatory pathway may contribute to the clinical benefits of ACE inhibitors.",1997.0,0,0
2190,9247017,The treatment of hypertension in older people and its effect on cognitive function.,M J Prince,"The benefits of antihypertensive drug therapy for older people have been clearly established. Meta-analysis suggests a 12% reduction in all-cause mortality, a 20% reduction in coronary heart disease and a 36% reduction in stroke. The absolute benefits of treatment are great due to the high incidence of vascular disease among older people. Clinicians may nevertheless have been deterred from initiating treatment because of concerns regarding adverse effects on cognition, mood, functional ability and quality of life. Recent evidence from randomised controlled trials suggests that these concerns are groundless. In the light of this evidence it is therefore disturbing that up to 50% of all older people with hypertension may remain untreated; and in over 50% of those who are treated, blood pressure may be inadequately controlled.",1997.0,0,0
2191,9247511,,,,,1,1
2192,9250456,Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients.,R Scognamiglio; R Nosadini; M Marin; S Nisti; G Fasoli; M Palisi; F Frigato; F Virgili; A Carraro; G Crepaldi,"To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH). A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks. Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to 147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86 +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/- 1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period. Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs.",1997.0,0,0
2193,9251545,"Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study. HANE Trial Research Group.",T Philipp; M Anlauf; A Distler; H Holzgreve; J Michaelis; S Wellek,"To compare the effectiveness and tolerability of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in patients with mild to moderate hypertension. Randomised multicentre trial over 48 weeks with double blind comparison of treatments. 48 centres in four countries. 868 patients with essential hypertension (diastolic blood pressure 95-120 mm Hg) Initial treatment (step 1) consisted of 12.5 mg hydrochlorothiazide (n = 215), 25 mg atenolol (n = 215), 10 mg nitrendipine (n = 218), or 5 mg enalapril (n = 220) once daily. If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks, doses were increased to 25 mg, 50 mg, 20 mg, 10 mg, respectively, once daily (step 2) and after two more weeks to twice daily (step 3). The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure. Blood pressure by means of an automatic device with repeated measurements. After eight weeks the response rate for atenolol (63.7%) was significantly higher than for enalapril (50.0%), hydrochlorothiazide (44.7%), or nitrendipine (44.5%). After one year atenolol was still more effective (48.0%) than hydrochlorothiazide (35.4%) and nitrendipine (32.9%), but not significantly better than enalapril (42.7%). The treatment related dropout rate was higher (P < 0.001) in the nitrendipine group (n = 28). There is no evidence of superiority for antihypertensive effectiveness or tolerability of the ""new"" classes of antihypertensives (calcium channel blockers and angiotensin converting enzyme inhibitors). As these drugs are now widely used as treatment of first choice, our results further emphasise the need for studies confirming that they also reduce morbidity and mortality, as has been shown for diuretics and beta blockers.",1997.0,0,0
2194,9257084,Valsartan. A review of its pharmacology and therapeutic use in essential hypertension.,A Markham; K L Goa,"Valsartan competitively and selectively inhibits the actions of angiotensin II at the AT1 receptor subtype which is responsible for most of the known effects of angiotensin II. In clinical trials in patients with mild to moderate essential hypertension valsartan was as effective as losartan, lisinopril, enalapril, amlodipine and hydrochlorothiazide. Addition of the latter reduced blood pressure in patients who did not respond sufficiently to valsartan monotherapy. Preliminary data also suggest valsartan may be effective in patients with severe essential hypertension. The drug was as effective as lisinopril as treatment for mild to moderate essential hypertension in patients with renal insufficiency and did not worsen renal function. Headache, dizziness and fatigue were the most common adverse events in placebo-controlled studies; the incidence of these adverse events was not significantly different between placebo and valsartan recipients. Compared with ACE inhibitors, valsartan was associated with a significantly lower incidence of dry cough. Thus, valsartan is an effective treatment for mild to moderate essential hypertension and may be particularly useful in patients who experience persistent cough during ACE inhibitor therapy.",1997.0,0,0
2195,9260574,,,,,0,0
2196,9262922,Management of congestive heart failure in primary care settings.,O Ahmed,,1997.0,0,0
2197,9264489,Clinical significance of mitral regurgitation after acute myocardial infarction. Survival and Ventricular Enlargement Investigators.,G A Lamas; G F Mitchell; G C Flaker; S C Smith; B J Gersh; L Basta; L Moyé; E Braunwald; M A Pfeffer,"Mitral regurgitation (MR) may complicate acute myocardial infarction (MI). However, it is not known whether mild MR is an independent predictor of post-MI outcome. The study cohort consisted of 727 Survival and Ventricular Enlargement Study patients who underwent cardiac catheterization, including left ventriculography, up to 16 days after MI. Left ventriculograms were analyzed for diastolic and systolic volumes, global left ventricular sphericity, extent of wall motion abnormality, and endocardial curvature. The presence of MR was related to the risk of developing a cardiovascular event during 3.5 years of follow-up. MR was present in 141 patients (19.4%). Severe (3+) MR was present in only 2 patients. Patients with MR were more likely to have a persistently occluded infarct artery (MR versus no MR, 27.3% versus 15.2%; P=.001). Although the ejection fractions were similar, MR patients had larger end-systolic and end-diastolic volumes and more spherical ventricles than patients without MR. Sphericity change from diastole to systole was also significantly reduced in MR patients. Patients with MR were more likely to experience cardiovascular mortality (29% versus 12%; P<.001), severe heart failure (24% versus 16%; P=.0153), and the combined end point of cardiovascular mortality, severe heart failure, or recurrent myocardial infarction (47% versus 29%; P<.001). The presence of MR was an independent predictor of cardiovascular mortality (relative risk, 2.00; 95% CI, 1.28 to 3.04). Mild MR is an independent predictor of post-MI mortality. As such, it adds important information for risk stratification of post-MI patients.",2001.0,0,0
2198,9264493,Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.,J N Cohn; S Ziesche; R Smith; I Anand; W B Dunkman; H Loeb; G Cintron; W Boden; L Baruch; P Rochin; L Loss,"Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.",1997.0,0,0
2199,9264494,Comparative effects of enalapril and verapamil on myocardial blood flow in systemic hypertension.,O Parodi; D Neglia; C Palombo; G Sambuceti; A Giorgetti; C Marabotti; M Gallopin; I Simonetti; A L'Abbate,"The comparative effects of calcium channel blockers and ACE inhibitors on myocardial blood flow (MBF) in hypertensive patients after long-term treatment are still unknown. Twenty hypertensive subjects with normal coronary arteries were randomly assigned to verapamil 240 to 480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing tachycardia, and after dipyridamole by positron emission tomography and 13N-ammonia before and 6 months after treatment after 1 week of pharmacological washout. In both groups, blood pressure and heart rate during flow measurements were not different before and after therapy. Before treatment, mean MBF at rest, during pacing tachycardia, and after dipyridamole infusion was similar in the two groups; however, pacing and dipyridamole flows were significantly lower than those obtained in a control group of normotensive subjects. After treatment, in the enalapril-treated patients, MBF did not change in the three study conditions. In the verapamil-treated patients, MBF did not change at rest and significantly increased during pacing and after dipyridamole. The inhomogeneity of regional MBF distribution, evaluated from the coefficient of variation, decreased at rest after both treatments and, in the enalapril group, also during pacing. No relation was found between changes in MBF and changes in left ventricular mass. In arterial hypertension, MBF during pacing tachycardia and after dipyridamole is impaired. Successful therapy with verapamil increases MBF response to these stimuli, independent of changes in perfusion pressure and left ventricular mass. These results suggest that verapamil directly improves coronary microcirculatory function in hypertension. Enalapril does not significantly change MBF but reduces the inhomogeneity of regional flow distribution.",1997.0,0,0
2200,9266781,"Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction.",R D Patten; M W Kronenberg; C R Benedict; J E Udelson; D Kinan; D Stewart; S Yusuf; J J Smith; L Kilcoyne; N Dolan; T R Edens; J Metherall; M A Konstam,"Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.",1997.0,0,0
2201,9266782,A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: The Flolan International Randomized Survival Trial (FIRST).,R M Califf; K F Adams; W J McKenna; M Gheorghiade; B F Uretsky; S E McNulty; H Darius; K Schulman; F Zannad; E Handberg-Thurmond; F E Harrell; W Wheeler; J Soler-Soler; K Swedberg,"This trial evaluated the effects of epoprostenol on patients with severe left ventricular failure. Patients with class IIIB/IV congestive heart failure and decreased left ventricular ejection fraction were eligible for enrollment if angiography documented severely compromised hemodynamics while the patient was receiving a regimen of digoxin, diuretics, and an angiotensin-converting enzyme inhibitor. We randomly assigned 471 patients to epoprostenol infusion or standard care. The primary end point was survival; secondary end points were clinical events, congestive heart failure symptoms, distance walked in 6 minutes, and quality-of-life measures. The median dose of epoprostenol was 4.0 ng/kg/min, resulting in a significant increase in cardiac index (1.81 to 2.61 L/min/m2), a decrease in pulmonary capillary wedge pressure (24.5 to 20.0 mm Hg), and a decrease in systemic vascular resistance (20.76 to 12.33 units). The trial was terminated early because of a strong trend toward decreased survival in the patients treated with epoprostenol. Chronic intravenous epoprostenol therapy is not associated with improvement in distance walked, quality of life, or morbid events and is associated with an increased risk of death.",2001.0,0,0
2202,9268215,Low-dose but not high-dose captopril increases parasympathetic activity in patients with heart failure.,P W Kamen; H Krum; A M Tonkin,"Parasympathetic nervous activity (PSNA) is an important determinant of the risk of sudden death and outcome in patients with cardiovascular disease, so the effects of drug therapy on PSNA may be of prognostic importance in patients with chronic heart failure (CHF). The angiotensin-converting enzyme (ACE) inhibitors are the only drugs that are reasonably accepted to improve prognosis in such patients. Accordingly we determined PSNA by heart-rate variability (HRV) analysis in nine patients (four women and five men, aged 73.6 +/- 6 yrs) with heart failure (NYHA Classes II-III) and in sinus rhythm. HRV was determined during 20-40 min supine rest at baseline and then at 2-weekly intervals during incremental dosing of oral captopril, 12.5 mg b.i.d., 25 mg b.i.d., and 50 mg b.i.d. Poincaré plot and conventional time- and frequency-domain measures were used to analyze the data. Low-dose captopril (12.5 mg b.i.d.) resulted in an increase in SD delta RR (16.0 +/- 6.6 to 22.0 +/- 9.1 ms; p < 0.05). We previously validated this as a measure of PSNA. Higher dose captopril (25 mg b.i.d.) also produced an increase in PSNA activity (16.0 +/- 6.6 to 18.7 +/- 7.8 ms), although this failed to reach statistical significance. However, the highest dose of captopril (50 mg b.i.d.) reduced PSNA activity to near-baseline values, as shown by measures of HRV in both the time and frequency domains. These data suggest that only a low dose of captopril augments PSNA in patients with heart failure. Dosing of ACE inhibitors may be important in optimizing their benefit in CHF.",1997.0,0,0
2203,9269212,Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. The EUCLID Study Group.,,"Renal disease in people with insulin-dependent diabetes (IDDM) continues to pose a major health threat. Inhibitors of angiotensin-converting enzyme (ACE) slow the decline of renal function in advanced renal disease, but their effects at earlier stages are unclear, and the degree of albuminuria at which treatment should start is not known. We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20-59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm Hg diastolic, and no more than 155 mm Hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months. There were no difference in baseline characteristics by treatment group; mean AER was 8.0 micrograms/min in both groups; and prevalence of microalbuminuria was 13% and 17% in the placebo and lisinopril groups, respectively. On intention-to-treat analysis at 2 years, AER was 2.2 micrograms/min lower in the lisinopril than in the placebo group, a percentage difference of 18.8% (95% CI 2.0-32.7, p = 0.03), adjusted for baseline AER and centre, absolute difference 2.2 micrograms/min. In people with normoalbuminuria, the treatment difference was 1.0 microgram/min (12.7% [-2.9 to 26.0], p = 0.1). In those with microalbuminuria, however, the treatment difference was 34.2 micrograms/min (49.7% [-14.5 to 77.9], p = 0.1; for interaction, p = 0.04). For patients who completed 24 months on the trial, the final treatment difference in AER was 38.5 micrograms/min in those with microalbuminuria at baseline (p = 0.001), and 0.23 microgram/min in those with normoalbuminuria at baseline (p = 0.6). There was no treatment difference in hypoglycaemic events or in metabolic control as assessed by glycated haemoglobin. Lisinopril slows the progression of renal disease in normotensive IDDM patients with little or no albuminuria, though greatest effect was in those with microalbuminuria (AER > or = 20 micrograms/min). Our results show that lisinopril does not increase the risk of hypoglycaemic events in IDDM.",1997.0,0,0
2204,9269944,Fixed combination of benazepril and low-dose amlodipine in the treatment of mild to moderate essential hypertension: evaluation by 24-hour noninvasive ambulatory blood pressure monitoring.,R Fogari; A Zoppi; P Lusardi; A Mugellini; P Preti; M Motolese,"The antihypertensive efficacy and tolerability of a fixed combination of benazepril (10 mg) and low-dose amlodipine (2.5 mg) were assessed in 24 patients (mean age, 43.9 years) with uncomplicated mild to moderate essential hypertension [supine diastolic blood pressure (DBP) > or = 95 and < or = 120 mm Hg)]. After 2 weeks of washout taking placebo, patients were randomized to receive the fixed combination or placebo, both administered once daily for 3 weeks, according to a double-blind, crossover design. Patients were checked at the end of the washout period and every 3 weeks thereafter. At each visit, 24-h ambulatory BP monitoring (ABPM) was performed by a noninvasive device (Spacelabs 90207); casual BP (by mercury sphygmomanometer), heart rate (HR), and body weight also were measured. The fixed combination significantly reduced systolic (SBP) and DBP values throughout the 24 h as compared with placebo, without affecting the normal BP circadian variability. The antihypertensive effect of the fixed combination could be observed to a similar extent during the day and night and was still significant 24 h after dosing. HR and body weight were not affected by the treatment. The fixed combination of benazepril 10 mg/amlodipine 2.5 mg was well tolerated, and no patient withdrew from the study because of side effects.",1997.0,0,0
2205,9270085,Comparison of the combination of enalapril and a very low dose of hydrochlorothiazide with atenolol in patients with mild-to-moderate hypertension. Scandinavian Study Group.,I Os; T Hotnes; J Dollerup; C E Mogensen,"The blood pressure lowering effect and tolerability of the angiotensin-converting enzyme inhibitor enalapril combined with a very low dose of hydrochlorothiazide (HCTZ) were compared with the selective betareceptor blocker atenolol in patients with mild-to-moderate hypertension. Three hundred seventy-four patients were randomized into a triple-blind, parallel, active-controlled 12-week study period comparing enalapril/HCTZ (20/6 mg) with atenolol (50 mg) after a 4-week placebo baseline period. Blood pressure (BP), clinical and laboratory safety, and metabolic laboratory variables were assessed. Enalapril/HCTZ as well as atenolol reduced both sitting and standing diastolic and systolic BP (P < .001), but enalapril/HCTZ had a more pronounced effect than atenolol on sitting systolic BP (P = .019); there was a trend toward more patients achieving target diastolic BP (<90 mm Hg, P = .053). No clinically important differences in safety and tolerability were observed.",1997.0,0,0
2206,9278199,Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients?,G Pritchard; D Lyons; J Webster; J C Petrie; T M MacDonald,"To assess the effect of trandolapril (2 mg once daily) and indomethacin (25 mg three times daily), alone and in combination, on renal function and renal functional reserve in hypertensive patients (DBP 95-115 mmHg) requiring regular non-steroidal anti-inflammatory drugs (NSAIDs). Randomized, double-blind, placebo-controlled, four way crossover design. After 3 weeks treatment renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured using the p-aminohippurate (PAH) and inulin methods. Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1) and 10% amino acid solution. There was no significant difference in RPF between treatments: -22.79 ml min(-1) (95% CI -54.82, 9.24) for placebo and trandolapril, -10.37 ml min(-1) (95% CI -30.7, 9.96) for placebo and indomethacin, -14.78 ml min(-1) (95% CI -50.33, 20.77) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve RPF between treatments: -34.96 ml min(-1) (95% CI -119.8, 49.88) for placebo and trandolapril, 29.78 ml min(-1), -15.18, 74.74) for placebo and indomethacin, and -25.84 ml min(-1) (95% CI -87.62, 35.94) for placebo and trandolapril with indomethacin. There was no significant difference in GFR between treatments: -1.01 ml min(-1) (95% CI -7.45, 5.42) for placebo and trandolapril, -7.88 ml min(-1) (95% CI -15.08, -0.68) for placebo and indomethacin, and -0.36 ml min(-1) (95% CI -7.58, 6.86) for placebo and trandolapril with indomethacin. There was no significant difference in functional reserve GFR between treatments: 5.13 ml min(-1) (95% CI -4.97, 15.23) for placebo and trandolapril, 6.31 ml min(-1) (95% CI -1.88, 14.5) for placebo and indomethacin, 7.21 ml min(-1) (95% CI 1.26, 13.16) for placebo and trandolapril with indomethacin. In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR.",1997.0,0,0
2207,9282581,Effect of enalapril on renal profile and right ventricular dimensions in chronic cor pulmonale.,S K Mahajan; V K Sharma; S Thakral,"The effect of enalapril in combination with bronchodilators, diuretics, antibiotics and/or steroids, was compared with that of conventional treatment with diuretics, steroids and antibiotics alone in 30 patients of chronic cor-pulmonale. The effect was studied on right ventricular dimensions and renal profile after a period of 6 weeks treatment. The control patients showed a significant decrease of RVIDED and increase in GFR, but the decrease of RVAWT and increase of 'a' wave amplitude was insignificant. However when the ACE-inhibitor enalapril was added to the treatment, there was a significant decrease of RVIDED, RVAWT and an increase of 'a' wave amplitude with a significant improvement in the GFR. A comparison between both the groups showed that the increase of GFR and decrease of RVIDED was higher in enalapril group than controls. The increase of 'a' wave amplitude was also greater in enalapril group. Thus enalapril appears to be of value in chronic cor-pulmonale, where it decreases pulmonary hypertension and thus right ventricular after load. It also decreases renal vascular resistance increasing the renal blood flow, thus improving the GFR.",1996.0,0,0
2208,9282610,"Nifedipine, captopril, metoprolol and nifedipine with metoprolol in hypertensive crisis in non-intensive care setting.",N D Karnik; A D Bhatt; T H Trivedi; V N Dadkar; N M Kapadia; A B Vaidya; R C Khokhani,"In 102 cases of severe hypertension (DBP > or = 115 mm Hg), with or without acute complications, efficacy and safety of SL Nifedipine 10 mg (NIF), SL Captopril 25 mg (CAP), IV Metoprolol 15 mg (MET) and SL NIF + IV MET were studied in an inpatient trial. Maximum mean percent reduction in SBP was 13.3, 9.7, 15.7 and 19.9 and in DBP was 21.2, 13.9, 12.5 and 20.4 with NIF, CAP, MET and NIF + MET respectively. A safe DBP of < or = 110 mm Hg (Kaplan) was achieved in 90, 61, 72.2 and 95.2 percent of patients. A statistically significant fall in DBP was observed at 5 minutes with all regimens except CAP which was at 15 minutes. Mild side effects observed were palpitations and flushing (NIF n = 4), taste disturbances (CAP n = 3), heaviness of head (CAP n = 1) and giddiness (MET n = 2, NIF + MET n = 2). The trial data suggest that hypertensive crisis can be managed, without intensive care facility, with all four regimens; this implies significant cost containment.",1996.0,0,0
2209,9284593,Angioedema due to angiotensin-converting enzyme inhibition: an association frequently unrecognized.,M Cicardi; L Conciato; A Agostoni,"Angioedema as a side effect of treatment with angiotensin-converting enzyme inhibitors is often under-recognized. We analyzed the subjects seen in our out-patient clinic for angioedema. Over the past 3 years, we have found a cause-effect relationship between angiotensin-converting enzyme inhibitor treatment and angioedema in 14 of the 334 subjects presenting with this condition.",1997.0,0,0
2210,9284842,Calcium channel blockers: an evidence-based review.,D Waters,"Calcium channel blockers are widely used in the treatment of cardiovascular disease, but their proper therapeutic role is controversial. Nevertheless, drugs from this class have been evaluated in many controlled clinical trials of adequate size and duration in different patient populations. Although many important questions remain unanswered, these trials have clarified when and how these drugs should be used. In general, the benefits of calcium channel blockers in controlling angina and hypertension are much more clearly documented than are their long term effects on harder end-points such as mortality. Such long term data are sorely needed, particularly for hypertension. An increased risk with dihydropyridine calcium channel blockers has been clearly seen across several studies of patients with coronary disease. In coronary patients with heart failure, the deleterious effects of nifedipine, diltiazem and verapamil outweigh any possible benefit. Long acting formulations and newer calcium channel blockers may not share all of the adverse effects of the older drugs of this class; however, their long term safety has not yet been documented. An understanding of the limitations of calcium channel blockers, based upon clinical trial evidence, often leads the practitioner to choose a drug from another class, where efficacy has been clearly proven.",1997.0,0,0
2211,9285181,Does long-term angiotensin converting enzyme inhibition affect the concentration of tissue-type plasminogen activator-plasminogen activator inhibitor-1 in the blood of patients with a previous myocardial infarction.,O D Pedersen; J Gram; X Jeunemaitre; E Billaud; J Jespersen,"Large-scale studies have indicated that treatment with angiotensin converting enzyme (ACE) inhibitors reduces the incidence of myocardial infarction and unstable angina pectoris among patients with recent myocardial infarction and moderate left ventricular dysfunction. An improved endogenous fibrinolysis might be responsible for this effect. To investigate the effect of trandolapril on the endogenous tissue-type plasminogen activator (t-PA) in patients with a recent myocardial infarction and moderate left ventricular dysfunction. Fifty-six patients with acute myocardial infarction and a wall motion index < or = 1.2 were allocated randomly either to administration of trandolapril or to placebo. When possible, the study drug dose was increased gradually to 4 mg trandolapril or a corresponding amount of placebo during the first month after randomization. Blood samples for determination of the variables of the fibrinolytic system, ACE activity and ACE genotype were collected prior to randomization and during out-patient visits in months 1, 3, 6, 9 and 12. After the subject had fasted overnight, blood samples were collected in the morning (0800-1000 h) after the subject had rested supine for at least 15 min, from a venous cannula inserted into the forearm. The effect of trandolapril on the fibrinolytic variables was evaluated by calculating the area under the curve (AUC1-12) from month 1 to month 12. The trandolapril group and the placebo group were similar with respect to baseline clinical characteristics, baseline fibrinolytic variables and baseline plasma ACE activity. The trandolapril group did not differ significantly from the placebo group with respect to AUC1-12 t-PA antigen [11.67 (3.95-26.45) versus 10.34 ng/ml (3.71-19.62), P = 0.19] and AUC1-12 plasminogen activator inhibitor type-1 (PAI-1) antigen [27.57 (8.38-89.49) versus 24.40 ng/ml (7.94-90.62), P = 0.92]. A significant and clear trend in variation with time of t-PA antigen was observed for the trandolapril group, but not for the placebo group. The fibrinolytic variables were similar at baseline for the different ACE genotype insertion (I) and deletion (D) groups (II, ID and DD). Trandolapril treatment was associated with a significant (P < 0.04) increase in the AUC1-12 of t-PA antigen in the ID group compared with that of the placebo-treated ID group, whereas PAI-1 antigen concentration did not differ between the groups. Trandolapril treatment was not associated with any significant change in the fibrinolytic variables for the other genotype groups. Chronic ACE-inhibitor treatment with trandolapril was not associated with any significant difference in the blood concentrations of t-PA and PAI-1 compared with placebo. The suggested specific interaction between ACE inhibition and the increase in t-PA in patients with ACE genotype ID will require further confirmation.",1997.0,0,0
2212,9285655,Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction.,S C Greaves; G Zhi; R T Lee; S D Solomon; J MacFadyen; E Rapaport; F J Menapace; J L Rouleau; M A Pfeffer,"Previous studies have reported left ventricular (LV) thrombus in 20% to 56% of patients after anterior wall acute myocardial infarction (AMI). The Healing and Early Afterload Reducing Therapy (HEART) study was a prospective study comparing effects of early (24 hours) or delayed (14 days) initiation of ramipril, an angiotensin-converting enzyme inhibitor, on LV function after anterior wall AMI. This ancillary study assessed prevalence of LV thrombus. Two-dimensional echocardiography was performed on days 1, 14, and 90 after myocardial infarction. The cohort consisted of 309 patients. Q-wave anterior wall AMI occurred in 78%; 87% received reperfusion therapy. The prevalence of LV thrombus was 2 of 309 (0.6%) at day 1, 11 of 295 (3.7%) at day 14, and 7 of 283 (2.5%) at day 90. One patient had thrombus at 2 examinations. The day 1 echocardiogram was not correlated with thrombus development. LV size increased more in patients with thrombus than in those without thrombus. Patients with thrombus had more wall motion abnormality after day 1 than patients without thrombus (p = 0.03). Thus, the current prevalence of LV thrombus in anterior wall AMI is lower than previously reported, possibly due to changes in AMI management. Preservation of LV function is likely to be an important mechanism. Most thrombi are seen by 2 weeks after AMI. Resolution documented by echocardiography is frequent.",1997.0,0,0
2213,9293727,Emergency department management of acute myocardial infarction.,E Mintz,"Myocardial infarction-remains one of the leading causes of death among adults in the United States despite the significant advances in therapy made during the past three decades. However, a significant reduction in mortality following acute myocardial infarction has been accomplished through an aggressive strategy directed toward early recognition and intervention. This approach requires that the emergency physician act promptly and choose appropriately from the ever-expanding therapeutic options. This paper summarizes the recent progress and treatment options in the management of acute myocardial infarction with regard to prehospital care, diagnostic challenges in the emergency department, conventional therapy and pharmacologic advances, newer interventional measures, and future trends.",1997.0,0,0
2214,9295005,Effect of ramipril on mitral regurgitation secondary to mitral valve prolapse.,U Høst; H Kelbaek; P Hildebrandt; K Skagen; J Aldershvile,Ramipril 10 mg/day reduced regurgitation in chronic mitral regurgitation secondary to mitral valve prolapse in patients with sinus rhythm.,1997.0,0,0
2215,9296310,Comparison of temocapril and atenolol in the long-term treatment of mild to moderate essential hypertension.,B Sierakowski; K Püchler; P U Witte; K Renneisen; W Delius,"This 1-year, dose-titration, General Practitioner (GP) study compared efficacy, tolerability and safety of oral temocapril (10-40 mg once daily) with atenolol (25-100 mg once daily) in mild to moderate adult hypertensives (diastolic blood pressure (DBP) 95-114 mmHg). A 12-week dose-titration period, randomized 3:1 temocapril: atenolol, preceded 40 weeks long-term treatment. An intent-to-treat population of 472 patients was analysed for efficacy after 12 weeks dose-titration. Sitting DBP fell significantly (p < 0.001) in both groups, by mean +/- standard deviation (SD) 15.9 +/- 5.7 mmHg on temocapril and by 16.6 +/- 5.9 mmHg on atenolol. Therapeutic equivalence was demonstrated using the two one-sided t-tests procedure according to Schuirmann (equivalence interval [theta 1 - theta 2] < or = 5 mmHg). Responders (DBP < or = 90 mmHg) represented 89.9% of temocapril and 94.0% of atenolol patients. The lower doses were effective in 70.9% of temocapril patients (10 or 20 mg) and in 63.7% of atenolol patients (25 or 50 mg), these doses being continued after the dose titration period. No clinically relevant changes in haematological, biochemical and urinalysis variables occurred. Adverse events were few, largely unrelated to treatment and comparable between groups. In conclusion, temocapril and atenolol proved to be therapeutically equivalent antihypertensives.",1997.0,0,0
2216,9296311,Effect of angiotensin converting enzyme inhibition [Cilazapril] on blood pressure recording in hypertensive obstructive sleep apneic patients.,L Grote; J Heitmann; U Köhler; T Ploch; T Penzel; J H Peter,"We investigated the efficacy of an Angiotensin Converting Enzyme [ACE] inhibitor on daytime and night-time blood pressure in 55 male hypertensive patients with moderately severe to severe obstructive sleep apnea. We resolved to determine if treatment oriented towards the reduction of hypertension would be successful, despite persistent repetitive hypoxemia and sleep-disordered breathing. The study was a randomized, double-blind, single daily dose, placebo-controlled protocol, with 8 days drug intake (placebo or 2.5 mg Cilazapril) and monitoring on the final day of drug administration. Subjects underwent continuous 24-h arterial blood pressure monitoring during baseline and treatment conditions. Polysomnography was performed at night during the 24-h arterial monitoring period. Cilazapril (2.5 mg) lowered systolic, diastolic and mean blood pressure, despite persistence of repetitive obstructive apneas during sleep and the associated repetitive hypoxemia. The lowering of blood pressure occurred without a significant change in heart rate, and was noted during nocturnal sleep, performance testing and graded exercise.",1997.0,0,0
2217,9297663,Angioedema after long-term use of an angiotensin-converting enzyme inhibitor.,A J Pavletic,,1997.0,0,0
2218,9297994,Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.,J A Staessen; R Fagard; L Thijs; H Celis; G G Arabidze; W H Birkenhäger; C J Bulpitt; P W de Leeuw; C T Dollery; A E Fletcher; F Forette; G Leonetti; C Nachev; E T O'Brien; J Rosenfeld; J L Rodicio; J Tuomilehto; A Zanchetti,"Isolated systolic hypertension occurs in about 15% of people aged 60 years or older. In 1989, the European Working Party on High Blood Pressure in the Elderly investigated whether active treatment could reduce cardiovascular complications of isolated systolic hypertension. Fatal and non-fatal stroke combined was the primary endpoint. All patients (> 60 years) were initially started on masked placebo. At three run-in visits 1 month apart, their average sitting systolic blood pressure was 160-219 mm Hg with a diastolic blood pressure lower than 95 mm Hg. After stratification for centre, sex, and previous cardiovascular complications, 4695 patients were randomly assigned to nitrendipine 10-40 mg daily, with the possible addition of enalapril 5-20 mg daily and hydrochlorothiazide 12.5-25.0 mg daily, or matching placebos. Patients withdrawing from double-blind treatment were still followed up. We compared occurrence of major endpoints by intention to treat. At a median of 2 years' follow-up, sitting systolic and diastolic blood pressures had fallen by 13 mm Hg and 2 mm Hg in the placebo group (n = 2297) and by 23 mm Hg and 7 mm Hg in the active treatment group (n = 2398). The between-group differences were systolic 10.1 mm Hg (95% CI 8.8-11.4) and diastolic, 4.5 mm Hg (3.9-5.1). Active treatment reduced the total rate of stroke from 13.7 to 7.9 endpoints per 1000 patient-years (42% reduction; p = 0.003). Non-fatal stroke decreased by 44% (p = 0.007). In the active treatment group, all fatal and non-fatal cardiac endpoints, including sudden death, declined by 26% (p = 0.03). Non-fatal cardiac endpoints decreased by 33% (p = 0.03) and all fatal and non-fatal cardiovascular endpoints by 31% (p < 0.001). Cardiovascular mortality was slightly lower on active treatment (-27%, p = 0.07), but all-cause mortality was not influenced (-14%; p = 0.22). Among elderly patients with isolated systolic hypertension, antihypertensive drug treatment starting with nitrendipine reduces the rate of cardiovascular complications. Treatment of 1000 patients for 5 years with this type of regimen may prevent 29 strokes or 53 major cardiovascular endpoints.",1997.0,0,0
2219,9300234,Life-threatening hyperkalaemia caused by ACE inhibitor and diuretics.,P R Jarman; A M Keheley; H M Mather,,1997.0,0,0
2220,9302344,"Aldosterone blockade reduces vascular collagen turnover, improves heart rate variability and reduces early morning rise in heart rate in heart failure patients.",R J MacFadyen; C S Barr; A D Struthers,"Experimental data suggest that aldosterone has harmful effects promoting myocardial fibrosis and disturbing autonomic balance. There has been no evidence of these potential effects in intact man. We report the findings in 31 patients with stable chronic heart failure (CHF) who were treated with spironolactone (50-100 mg/day) or placebo in addition to diuretics and angiotensin converting enzyme (ACE) inhibition. In a controlled randomised double-blind study, we found that spironolactone treatment reduced circulating levels of procollagen type III N-terminal amino peptide, a marker of vascular collagen turnover, and in addition increased time-domain parameters of heart rate variability (n = 24). These latter parameters suggest a parasympathomimetic effect for additional spironolactone. Spironolactone significantly reduced heart rate (prolonged RR interval) particularly during the dawn hours (06.00-09.00 h). In this unbalanced study it was not possible to provide a detailed diurnal assessment of the impact of spironolactone on heart rate variability, but the preliminary data suggest that there may be an interaction with the autonomic nervous system which varies in time. These are the first human data to show that use of the aldosterone antagonist, spironolactone, can positively improve time-domain heart rate variability and reduce myocardial collagen turnover, as reflected by further reductions in serum procollagen peptide, despite concurrent ACE inhibitor treatment. Residual aldosterone after ACE inhibitor treatment may therefore have a role promoting arrhythmia and cardiac death by two mechanisms. Effects of additional spironolactone on slowing heart rate (and potentially the detrimental effect of aldosterone) were most prominent between 6 a.m. and 10 a.m. when cardiac death is also known to be most prominent.",1997.0,0,0
2221,9314638,Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria.,J Ahmad; M A Siddiqui; H Ahmad,"This study determines the long-term efficacy of the ACE inhibitor, enalapril, in reducing the progression of microalbuminuria to clinical albuminuria in normotensive patients with type 2 diabetes. There were 103 normotensive type 2 diabetic patients with persistent albumin excretion rate (AER) 20-200 micrograms/min and normal renal function followed for 5 years in a prospective randomized single-blind placebo-controlled trial. AER, blood pressure, fasting plasma glucose, and HbA1 were measured very 3-4 months and glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary urea every 12 months. In the patients treated with enalapril, AER decreased from 55 +/- 33 to 20 +/- 59 micrograms/min (geometric mean +/- SD), whereas in the placebo group, AER increased from 53 +/- 31 to 85 +/- 90 micrograms/min after 5 years. Within 5 years, 7.7% (4/52) of enalapril-treated subjects and 23.5% (12/51) of placebo-treated subjects progressed to clinical albuminuria defined as AER > 200 micrograms/min and at least 34% above baseline (risk reduction = 66.7%, P < 0.001). AER increased at an annual rate of 12.3% (95% CI 9.8-14.9) in the placebo group, while it declined by 16.7% (95% CI -18.3 to -15.2) in the enalapril group (P < 0.001). In addition, 8 of the 12 placebo-treated patients had evidence of coronary artery disease. The rest of the parameters remained practically unchanged in the two groups. After 5 years of therapy with enalapril, compared with placebo, normotensive subjects with type 2 diabetes experienced significantly less progression of microalbuminuria to clinical albuminuria, reduced AER, and preserved GFR.",1997.0,0,1
2222,9315539,Enalapril does not enhance exercise capacity in patients after Fontan procedure.,A A Kouatli; J A Garcia; T M Zellers; E M Weinstein; L Mahony,"Angiotensin-converting enzyme inhibitors improve exercise capacity in adults with congestive heart failure by decreasing systemic vascular resistance and improving ventricular diastolic function. Patients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people. To test the hypothesis that afterload reduction therapy alters hemodynamic variables and augments exercise capacity in patients after a Fontan procedure, we compared the results of graded exercise with maximal effort from 18 subjects (14.5+/-6.2 years of age, 4 to 19 years after Fontan procedure) in a randomized, double-blind, placebo-controlled crossover trial using enalapril (0.2 to 0.3 mg x kg[-1] x d[-1], maximum 15 mg). Each treatment was administered for 10 weeks. Diastolic filling patterns at rest were assessed by Doppler determination of the systemic atrioventricular valve flow velocity at the conclusion of each therapy. No difference was detected in resting heart rate, blood pressure, or cardiac index. Diastolic filling patterns were also similar. Exercise duration was not different (6.4+/-2.6 [enalapril] versus 6.7+/-2.6 minutes [placebo]). The mean percent increase in cardiac index from rest to maximum exercise was slightly but significantly decreased in subjects after 10 weeks of enalapril therapy (102+/-34% [enalapril] versus 125+/-34% [placebo]; P<.02). At maximal exercise, cardiac index (3.5+/-0.9 [enalapril] versus 3.8+/-0.9 L x min[-1] x m2 [placebo]), oxygen consumption (18.3+/-9 [enalapril] versus 20.5+/-7 mL x min[-1] x kg[-1] [placebo]), minute ventilation (57.5+/-17 [enalapril] versus 55.4+/-19 L/min [placebo]), and total work (247+/-181 [enalapril] versus 261+/-197 W [placebo]) were not different. We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.",1997.0,0,0
2223,9315764,Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. A randomized controlled trial. Ambulatory Blood Pressure Monitoring and Treatment of Hypertension Investigators.,J A Staessen; G Byttebier; F Buntinx; H Celis; E T O'Brien; R Fagard,"Ambulatory blood pressure (ABP) monitoring is used increasingly in clinical practice, but how it affects treatment of blood pressure has not been determined. To compare conventional blood pressure (CBP) measurement and ABP measurement in the management of hypertensive patients. Multicenter, randomized, parallel-group trial. Family practices and outpatient clinics at regional and university hospitals. A total of 419 patients (> or =18 years), whose untreated diastolic blood pressure (DBP) on CBP measurement averaged 95 mm Hg or higher, randomized to CBP or ABP arms. Antihypertensive drug treatment was adjusted in a stepwise fashion based on either the average daytime (from 10 AM to 8 PM) ambulatory DBP (n=213) or the average of 3 sitting DBP readings (n=206). If the DBP guiding treatment was above (>89 mm Hg), at (80-89 mm Hg), or below (<80 mm Hg) target, 1 physician blinded to the patients' randomization intensified antihypertensive treatment, left it unchanged, or reduced it, respectively. The CBP and ABP levels, intensity of drug treatment, electrocardiographic and echocardiographic left ventricular mass, symptoms reported by questionnaire, and cost. At the end of the study (median follow-up, 182 days; 5th to 95th percentile interval, 85-258 days), more ABP than CBP patients had stopped antihypertensive drug treatment (26.3% vs 7.3%; P<.001), and fewer ABP patients had progressed to sustained multiple-drug treatment (27.2% vs 42.7%; P<.001). The final CBP and 24-hour ABP averaged 144.1/89.9 mm Hg and 129.4/79.5 mm Hg in the ABP group and 140.3/89.6 mm Hg and 128.0/79.1 mm Hg in the CBP group. Left ventricular mass and reported symptoms were similar in the 2 groups. The potential savings in the ABP group in terms of less intensive drug treatment and fewer physician visits were offset by the costs of ABP monitoring. Adjustment of antihypertensive treatment based on ABP monitoring instead of CBP measurement led to less intensive drug treatment with preservation of blood pressure control, general well-being, and inhibition of left ventricular enlargement but did not reduce the overall costs of antihypertensive treatment.",1997.0,0,0
2224,9316528,Comparative effects of losartan and enalapril on exercise capacity and clinical status in patients with heart failure. The Losartan Pilot Exercise Study Investigators.,R M Lang; U Elkayam; L G Yellen; D Krauss; R S McKelvie; D E Vaughan; D E Ney; L Makris; P I Chang,"This study was designed to determine 1) whether 12-week oral administration of losartan, an angiotensin II receptor antagonist, in patients with heart failure is well tolerated; and 2) whether functional capacity and clinical status of patients with heart failure in whom treatment with an angiotensin-converting enzyme (ACE) inhibitor is replaced with losartan for 12 weeks will remain similar to that noted in patients in whom treatment with an ACE inhibitor is continued. Losartan is a specific, nonpeptide angiotensin II receptor antagonist. Although specific receptor blockade with losartan has certain theoretic advantages over nonspecific ACE inhibition, definitive demonstration of comparable effects in patients with congestive heart failure is lacking. A double-blind, multicenter, randomized, parallel, enalapril-controlled study was conducted in 116 patients with congestive heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction < or = 45% previously treated with stable doses of ACE inhibitors and diuretic agents, with or without concurrent digitalis and other vasodilators. After a baseline exercise period, open-label ACE inhibitors were discontinued, and patients were randomly assigned to 12 weeks of therapy with losartan, 25 mg/day (n = 38); losartan, 50 mg/day (n = 40); or enalapril, 20 mg/day (n = 38). Drug efficacy was evaluated by changes in maximal treadmill exercise time (using a modified Naughton protocol), 6-min walk test, left ventricular ejection fraction and dyspnea-fatigue index. Safety was measured by the incidence of clinical and laboratory adverse experiences. The treadmill exercise time and the 6-min walk test did not change significantly after replacement of ACE inhibitor therapy with losartan. Similarly, a significant change was not observed in either the dyspnea-fatigue index or left ventricular ejection fraction at the end of double-blind period relative to baseline. Losartan was generally well tolerated and comparable to enalapril in terms of exercise tolerance in this short-term (12-week) study of patients with heart failure. The clinical effects of long-term angiotensin II receptor blockade compared with ACE inhibition remain to be studied.",1997.0,0,1
2225,9322825,Angiotensin-converting enzyme inhibitors or calcium antagonists for treating hypertension?,R E Ferner,,1997.0,0,0
2226,9322826,Efficacy of captopril and nifedipine in black and white patients with hypertensive crisis.,A Damasceno; B Ferreira; S Patel; E Sevene; J Polónia,"We examined the antihypertensive efficacy of: (1) sublingual-oral single doses of captopril (25 mg) and nifedipine-capsules (10 mg) in 9 + 9 white patients and in 9 + 8 black patients with hypertensive crisis; and (2) a single oral dose of the slow-acting preparation of nifedipine-retard (20 mg) in another 10 black patients. Blood pressure (BP) was assessed at 10 min intervals for 6 h after administration. After 6 h, the BP falls induced by these drugs were still significantly lower than the baseline placebo values. Hypotensive effect of nifedipine-capsules was established more rapidly than that of captopril in both white and black patients, and of nifedipine-retard in black patients. Considering the area under the curve of BP values during the 6-h treatment, the overall hypotensive effect of nifedipine-capsules was similar to captopril in white patients, but significantly more pronounced than captopril and nifedipine-retard in black patients. In white patients similar maximal drops of BP (mean+/-s.e.m.) were obtained with nifedipine-capsules (71+/-4/52+/-4 mm Hg) and with captopril (69+/-4/50+/-3 mm Hg). In black patients the maximal drop of BP of nifedipine-capsules (70+/-4/52+/-4 mm Hg) was greater (P < 0.02) than that of captopril (48+/-4/32+/-3 mm Hg) but similar to that of nifedipine-retard (71+/-4/49+/-4 mm Hg). However, in contrast to nifedipine-capsules and captopril, nifedipine-retard produced a slower drop in BP. The time of peak drop in BP of both nifedipine-capsules and captopril occurred within the first 2 h whereas with nifedipine-retard it occurred only between 4 and 6 h after administration. Fewer patients reported side effects with nifedipine-retard as compared with the other two preparations. We conclude that single doses of captopril and nifedipine reduces BP for at least 6 h in both white and black patients with hypertensive crisis, but nifedipine is more potent than captopril in black patients. The slow release form of nifedipine-retard effectively and safely lowers BP while achieving a rapid enough effect without the critical rapid falls in BP that occur with nifedipine-capsules.",1997.0,0,0
2227,9322827,"The treatment of severe hypertension with trandolapril, verapamil, and hydrochlorothiazide. Trandolapril/Verapamil Multicenter Study Group.",H A Punzi; B A Novrit,"A multiple drug regimen consisting of trandolapril, verapamil and hydrochlorothiazide (HCTZ) were sequentially added in an open-label evaluation of patients with severe hypertension. Ninety patients (58 white and 32 black patients) were titrated on one or more drugs and followed for a 19-week maintenance period. Statistically significant (P = 0.001) mean (+/-s.d.) decreases in supine diastolic blood pressure (DBP) were 9.0 (+/-9.3) mm Hg for trandolapril, 13.9 (+/-11.0) mm Hg for the trandolapril + verapamil (TV) combination, and 19.0 (+/-12.3) mm Hg when hydrochlorothiazide was added to the combination. The decrease in BP observed on TV combination therapy plus HCTZ was significantly (P = 0.001) greater than the decrease observed for the TV combination, which was significantly (P = 0.001) greater than the decrease observed for trandolapril monotherapy. Clinical responder rates were 44.8%, 56% and 77.7% for trandolapril monotherapy, trandolapril + verapamil combination therapy and triple therapy, respectively. Black and white patients had similar response rates, but black patients appeared to benefit more from the addition of HCTZ; 20% of black patients achieved a post-treatment supine DBP <90 mm Hg compared to 12.8% of white patients. This study demonstrates that the addition of verapamil to trandolapril has an additive effect on BP that is maintained throughout the day.",1997.0,0,0
2228,9322828,"Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril.",H R Black; A Graff; D Shute; R Stoltz; D Ruff; J Levine; Y Shi; S Mallows,"To compare the efficacy, safety and tolerability of valsartan to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and placebo in patients with mild-to-moderate essential hypertension. A total of 734 men and women were randomised in this multicentre, double-blind, optional titration, parallel group trial. Volunteers received valsartan 80 mg (n = 364), lisinopril 10 mg (n = 187) or placebo (n = 183) daily for 4 weeks, with subsequent titration of dose depending on response to treatment (valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily, lisinopril 10 mg titrated to lisonopril 20 mg once daily). Patients were assessed at 4, 8 and 12 weeks. The primary variable was change from baseline in mean sitting diastolic blood pressure (SDBP). Other efficacy variables included sitting systolic blood pressure (SSBP) and percentage of 'successful' responders (SDBP <90 mm Hg or > or =10 mm Hg reduction from baseline). All active treatment groups were shown to demonstrate significant reductions in SDBP compared to placebo at endpoint of therapy (least mean square reduction from baseline: valsartan 80/160 mg: -5.25 mm Hg (Cl -7.17, -3.34, P< 0.001); valsartan 80/80 mg twice daily: -5.63 mm Hg (Cl -7.51, -3.75, P< 0.001); lisinopril 10/20 mg: -6.93 mm Hg, (Cl -8.81, -5.05, P< 0.001). There were no statistically significant differences between the active treatment groups at endpoint of therapy. In patients requiring titration to a higher dose (placebo n = 142, valsartan 80/80 twice daily n = 124, valsartan 80/160 n = 114, lisinopril 10/20 n = 120), there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily (P = 0.658). Both valsartan and lisinopril produced similarly high percentages of 'successful' responders at endpoint of therapy. A somewhat higher frequency of drug related cough was observed in lisinopril treated patients (8%) compared to valsartan (1.1%) or placebo (0.5%). Valsartan 80 mg daily, with titration to 160 mg daily as required, provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily. Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough.",1997.0,0,0
2229,9324190,Evaluation of the total cost of treating elderly hypertensive patients with ACE inhibitors: a comparison of older and newer agents.,R E Small; S B Freeman-Arnold; J V Goode; M A Pyles,"We compared total costs and adherence to the regimen of older versus newer angiotensin-converting enzyme (ACE) inhibitors for the treatment of elderly patients with hypertension. A computer search using the data base of a health care insurer identified 6176 subjects age 65 years or older who had ICD-9 coding for hypertension only and had a new prescription for an ACE inhibitor dispensed between April 1, 1992, and January 31, 1993. Subjects receiving concurrent antihypertensive drugs were included. Total cost of therapy included acquisition costs for the ACE inhibitors and concurrent antihypertensive agents, and nondrug costs. Other costs were laboratory tests, hospitalization, and clinic visits associated with monitoring outcomes of antihypertensive therapy. Total median cost per month was greater for older than for newer agents, $59.82 versus $53.09 (p<0.0009). The mean percentage of patients complying with therapy as determined by refill data was greater with newer than with older agents, 66% versus 58% (p<0.0001). Based on our results, newer ACE inhibitors should be first-line antihypertensive therapy in elderly patients. They also should be considered for elderly patients who are unresponsive to older ACE inhibitors.",1997.0,0,0
2230,9327179,Therapy of congestive heart failure in elderly persons.,W S Aronow,"LVEF should be measured in all elderly persons with CHF Underlying causes and precipitating causes of CHF should be treated. Persons with CHF associated with abnormal LVEF should be treated with a low sodium diet, diuretics, and ACE inhibitors. If CHF persists, digoxin should be added. If CHF still persists, isosorbide dinitrate plus hydralazine should be added. If CHF still persists, a beta blocker should also be added. However, calcium channel blockers should not be used. Persons with CHF associated with normal LVEF should be treated with a low sodium diet, diuretics, and ACE inhibitors. If CHF persists, a beta blocker, isosorbide dinitrate plus hydralazine, or a calcium channel blocker should be added to the therapeutic regimen. If sinus rhythm is present, digoxin should not be used. Persons with CHF and abnormal or normal LVEF unable to tolerate ACE inhibitors should be treated with losartan.",1997.0,0,0
2231,9327716,Long-term effects of angiotensin-converting enzyme inhibitors and calcium antagonists on the right and left ventricles in essential hypertension.,M Lombardo; C Alli; M Broccolino; S Ferrari; L Montemurro; G Zaini; D Zanni,"To compare the effects of chronic antihypertensive treatment on left and right ventricular structure and function, 24 patients with mild to moderate, never-treated hypertension were randomized to receive fosinopril (20 mg daily) or amlodipine (10 mg daily) for 12 months. At baseline and subsequently at the end of third, sixth, and twelfth months, each patient underwent an integrated echocardiographic study and noninvasive ambulatory blood pressure monitoring. Both drugs significantly reduced blood pressure, casual or monitored (p < 0.01), and left ventricular mass index (from 125 +/- 32 to 100 +/- 12 gm/m2 [p < 0.02] with amlodipine and from 106 +/- 18 to 89 +/- 10 gm/m2 [p < 0.02] with fosinopril). The decrease in left ventricular mass was essentially caused by a reduction of ventricular thickness. Free right ventricular wall thickness was also lowered in both groups, more consistently with amlodipine (from 8.0 +/- 2.1 to 6.4 +/- 0.8 mm; p < 0.01), without an increase in plasma natriuretic peptide and insulin concentrations or heart rate. With both treatments, the decrease in ventricular mass was not associated with impairment of systolic function, whereas a trend toward an improvement of Doppler echocardiographic indexes of biventricular diastolic function was observed. In conclusion, both amlodipine and fosinopril induced similar qualitative effects on anatomy and function of both ventricles. The clinical meaning of these observations must be defined further by means of adequately sized prospective trials.",1997.0,0,0
2232,9328608,"Effect of ACE inhibition by benazepril, enalapril and captopril on chronic and post exercise proteinuria.",B Székács; Z Vajo; W Dachman,"Although post exercise proteinuria has long been known, its exact pathophysiology is unclear. Our objective was to determine whether long-term angiotensin converting enzyme (ACE) inhibition by different ACE inhibitors had an influence on post exercise proteinuria. We studied 14 patients who also had mild, chronic proteinuria caused by diabetes mellitus or chronic glomerulonephritis. We compared changes both in chronic (baseline) and post exercise proteinuria, during and after treatment with three different ACE inhibitors, with appropriate washout periods for the three drugs to all 14 patients. Proteinuria (mg/24 hours +/- SD), prior to the treatment was 682 +/- 92. Proteinuria after treatment for 30 days with benazepril was 464.4 +/- 82.6 (p < 0.001), with enalapril: 477.1 +/- 105.5 (p < 0.001), and captopril: 504.7 +/- 100.1 (p < 0.001). Proteinuria three days after discontinuing the treatment with benazepril was 532.4 +/- 113.5, (p < 0.01), with enalapril: 561.3 +/- 128.5, (p < 0.01), and with captopril: 620.8 +/- 101.8, p = n.s. Post exercise proteinuria prior to treatment (mg/min. +/- SD) was: 1.38 +/- 0.32, vs. after a 30-day treatment period with benazepril: 0.81 +/- 0.19 (p < 0.001), enalapril: 0.95 +/- 0.24, (p < 0.001), captopril: 1.09 +/- 0.27 (p < 0.02). Post exercise proteinuria three days after discontinuing the treatment was (blood pressure already back to baseline): in case of benazepril: 1.26 +/- 0.36 (p = n.s.), of enalapril: 1.17 +/- 0.46 (p = n.s.), and of captopril: 1.34 +/- 0.41 (p = n.s.). We conclude that the renin-angiotensin system plays a significant role in the pathogenesis of post exercise proteinuria; the antiproteinuric effect of ACE inhibition in exercise-induced proteinuria seems to be associated chiefly with the hemodynamic changes due to these drugs, whereas in chronic proteinuria the antiproteinuric and antihypertensive effects are, at least partially, dissociated.",1997.0,0,1
2233,9330124,Clinical and neurohumoral differences between spirapril and captopril in mild to moderate chronic congestive heart failure.,S A van den Broek; P A de Graeff; D J van Veldhuisen; W H van Gilst; H Hillege; H Wesseling; K I Lie,"This study was done to determine whether the difference in duration of action of the long-acting angiotensin-converting enzyme (ACE) inhibitor spirapril compared with the short-acting ACE inhibitor captopril affects clinical efficacy in patients with congestive heart failure. The effects on exercise capacity, neurohumoral status, and quality of life were studied in 20 patients with mild to moderate congestive heart failure in a double-blind, randomized, comparative study in parallel groups with a duration of 12 weeks. All assessments during the study were performed in the morning, before intake of the study medication, to avoid the expected peak effect of the ACE inhibitors used. Mean peak oxygen consumption (peak Vo2) was 17.4 mL/min/kg (range, 14.2-19.9 mL/min/kg) and mean left ventricular ejection fraction was 28% (range, 13-40%). Exercise duration in the captopril group showed a significant increase after 12 weeks (P < .05) of treatment compared with the spirapril group. Peak oxygen consumption tended only to increase in the captopril-treated patients compared with the spirapril-treated patients. Serum ACE activity was significantly different between the two treatment groups during treatment (P < .0001) and showed only a significant decrease in the spirapril group. There was no difference in improvement of quality of life between the two treatment groups. This study showed that the effects of the ACE inhibitors spirapril and captopril on exercise capacity are not related to the degree of inhibition of serum ACE activity.",1997.0,0,1
2234,9335405,ACE inhibitor effects on platelet function in stages I-II hypertension.,L Moser; K S Callahan; A K Cheung; G J Stoddard; M A Munger,"Angiotensin II enhances platelet aggregation through activation of the G protein-linked pathway present in platelets. Studies of several angiotensin-converting enzyme (ACE) inhibitors have demonstrated marked differences on platelets. Therefore this prospective, randomized, double-blind, crossover study compared the ex vivo effects of equivalent antihypertensive doses of captopril, enalapril, and fosinopril on platelet aggregation and thromboxane B2 (TxB2) formation in subjects with stage I-II essential hypertension. Nineteen male subjects with a baseline mean seated blood pressure of 141 +/- 3/100 +/- 1 mm Hg were enrolled. The decline in mean arterial pressure after 4 weeks of stable dosing was 10 +/- 1, 12 +/- 1, and 11 +/- 1 mm Hg for captopril, enalapril, and fosinopril, respectively (p = NS). There was no significant change in adenosine diphosphate (ADP)-, epinephrine-, or thrombin-stimulated platelet aggregation from baseline or between ACE inhibitors. Compared with baseline, fosinopril decreased TxB2 concentrations 27.5-67.6% with all stimuli after 1 and 5 min. Captopril also decreased TxB2 formation, but this effect was stimulus and time dependent. Enalapril consistently increased TxB2 concentrations, independent of stimuli or time. We conclude that different ACE inhibitors have distinct effects on platelet TxB2 formation without significant effects on platelet aggregation. Fosinopril may be a direct antagonist ofTxA2 synthase, suggesting benefit in syndromes of platelet activation or vascular occlusion.",1997.0,0,0
2235,9335410,Combined therapy with benazepril and amlodipine in the treatment of hypertension inadequately controlled by an ACE inhibitor alone.,R Fogari; L Corea; O Cardoni; F Cosmi; C Porcellati; P Innocenti; M Provvidenza; M Timio; M Bentivoglio; F Bertocchi; A Zoppi,"In a multicenter, randomized, double-blind, placebo-controlled study, we evaluated the efficacy and tolerability of the combination of benazepril, 10 mg, and amlodipine, 2.5 or 5 mg once daily, compared with benazepril, 10 mg, monotherapy in patients with hypertension inadequately controlled with angiotensin-converting enzyme (ACE)-inhibitor monotherapy. After a 2-week placebo and 4-week single-blind benazepril, 10 mg once daily, run-in period, 448 patients, 213 men and 235 women, aged 24-73 years (mean, 55 years), with mean diastolic blood pressure (DBP) > or =95 and < or =120 mm Hg at the end of the benazepril run-in period, were randomized to receive one of the following treatments once daily for 8 weeks: (a) benazepril, 10 mg, plus placebo (BZ10); (b) benazepril, 10 mg, plus amlodipine, 2.5 mg (BZ10/AML2.5); or (c) benazepril, 10 mg, plus amlodipine, 5 mg (BZ10/AML5). Before the patients were admitted to the trial, at the end of the placebo run-in and the benazepril run-in period and at the end of weeks 4 and 8 of the treatment period, sitting and standing blood pressure (BP), heart rate (HR), and body weight were measured 22-26 h after the intake of the trial medication. Both BZ10/AML2.5 and BZ10/AML5 combinations showed better antihypertensive activity than did BZ10 monotherapy at the terminal visit as demonstrated by (a) the 24-h postdosing sitting and standing systolic BP (SBP) and DBP values, which were statistically lower with combination therapy than with BZ10; (b) the success rate, which was statistically higher with both the combinations (69.2% in the BZ10/AML2.5 and 65.8% in the BZ10/AML5 group) compared with the BZ10 group (40.5%). The tolerability was good in the three treatment groups. No significant abnormal laboratory data were detected. There was no difference in efficacy and safety/tolerability between the BZ10/AML2.5 and BZ10/AML5 groups.",1997.0,0,0
2236,9335414,"Relations between fasting serum insulin, glucose, and dihydroepiandrosterone-sulfate concentrations in obese patients with hypertension: short-term effects of antihypertensive drugs.",N T Fuenmayor; E Moreira; V de los Rios; J L Cevallos; L X Cubeddu,"A randomized, single-blind, placebo-controlled study was conducted in 82 obese patients with mild to moderate essential hypertension, to determine the incidence of hyperinsulinemia, the relations between fasting insulin and dihydroepiandrosterone-sulfate (DHEA-S) levels, and the short-term effects of antihypertensives on DHEA-S and insulin serum concentrations. Increased insulin/glucose ratios (IGR) suggestive of insulin resistance were found in half of our patients. Hyperinsulinemic and normoinsulinemic obese patients with hypertension had comparable fasting glucose and DHEA-S concentrations and comparable blood pressure (BP) levels. Thus no relations were found between fasting insulin and DHEA-S levels. Fasting hyperinsulinemia was found in only half of the obese subjects with hypertension, suggesting that not all obese patients with hypertension are at the same high cardiovascular risk. Short-term treatment with captopril, prazosin, verapamil, atenolol, or hydrochlorothiazide (HCTZ) reduced BP; greater BP reduction was observed with drugs with vasodilatory effects. Captopril, prazosin, and verapamil reduced fasting insulin levels, whereas atenolol and hydrochlorothiazide did not. The former drugs reduced fasting insulin levels that were either within normal limits or in the hyperinsulinemic range. None of the drug treatments produced significant increases in serum DHEA-S concentrations, although some of them considerably reduced fasting insulin levels. No relations between insulin and DHEA-S levels were observed either at baseline or at the end of the antihypertensive treatment. The BP reduction resulting from the peripheral vasodilation may explain the insulin-reducing action of captopril, verapamil, and prazosin. These results further emphasize the large heterogeneity present in the pathophysiologic mechanisms operating in obesity and hypertension.",1997.0,0,0
2237,9335416,Angiotensin II-receptor blockade further reduces afterload safely in patients maximally treated with angiotensin-converting enzyme inhibitors for heart failure.,G Hamroff; I Blaufarb; D Mancini; S D Katz; R Bijou; G Jondeau; M T Olivari; S Thomas; T H LeJemtel,"Combined therapy with an angiotensin-II type I receptor (AT1) antagonist and an angiotensin-converting enzyme (ACE) inhibitor results in more complete suppression of the renin-angiotensin system. Accordingly, the blood-pressure response and safety of combining AT1-receptor blockade with losartan for ACE inhibition were evaluated in patients with congestive heart failure who were already treated with maximally recommended or tolerated doses of an ACE inhibitor. Forty-three patients with symptomatic congestive heart failure were evaluated biweekly for 1 month before addition of losartan and weekly during administration of losartan at a daily dose of 25 mg for the first week and 50 mg for the second week. Systolic blood pressure, which remained unchanged before addition of losartan, decreased from 122 +/- 18 mm Hg to 112 +/- 17 and 107 +/- 17 mm Hg (p < 0.001) after 1 week of 25 mg and 1 week of 50 mg losartan, respectively. Diastolic blood pressure also significantly decreased. The decreases in blood pressure were well tolerated by all patients, even by those in whom symptomatic hypotension developed during uptitration of ACE inhibition. Serum potassium and sodium and parameters of renal function remained unchanged. Combining AT1-receptor blockade with losartan to maximally recommended or tolerated ACE inhibition appears safe and leads to further vasodilatation in symptomatic patients with congestive heart failure.",1997.0,0,0
2238,9336607,"Congestive heart failure in elderly patients. The treatment goal is improved quality, not quantity, of life.",A Buchanan; R S Tan,"Primary care physicians who see elderly patients are likely to see cases of congestive heart failure, since this condition is typically the result of long-standing hypertension or coronary artery disease. Recognizing the condition in elderly patients may not be easy, though, because clinical signs can be distorted by accompanying symptoms. In this article, the authors discuss pathophysiologic, diagnostic, and pharmacokinetic issues. They also describe therapy with diuretics, angiotensin-converting enzyme inhibitors, and digoxin and outline special considerations in the elderly.",1997.0,0,0
2239,9346382,Angiotensin-converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Risks of Cardiac Disease in Dialysis Patients Study Group.,M Matsumura; H Nomura; I Koni; H Mabuchi,"The influence of angiotensin-converting enzyme inhibitors (ACEIs) on recombinant human erythropoietin (rhEPO) maintenance doses in hemodialysis patients was studied. One hundred and eight chronic hemodialysis patients (55 males and 53 females, mean age 61.2+/-12.6 years) were investigated. The rhEPO maintenance doses in the ACEI-treated group (n = 49) were 101.7+/-51.7 U/kg/week and in the nontreated group (n = 59) 79.2+/-37.8 U/kg/week (p < 0.05). No difference was observed in hematocrit between the ACEI-treated and nontreated groups. In stepwise regression analysis, the parameters associated with increased rhEPO maintenance doses were female gender, ACEI administration, low total iron binding capacity, and low serum free carnitine levels. In conclusion, ACEI administration might reduce the response to rhEPO. In hemodialysis patients who need high-dose rhEPO to maintain the target hematocrit in the absence of iron deficiency, hyperparathyroidism, infection, malignancy, malnutrition, and aluminum toxicity, ACEI administration should be considered.",1997.0,0,0
2240,9346384,"Reversal of anemia by erythropoietin therapy retards the progression of chronic renal failure, especially in nondiabetic patients.",S Kuriyama; H Tomonari; H Yoshida; T Hashimoto; Y Kawaguchi; O Sakai,"Therapy with human recombinant erythropoietin (EPO) has been accepted as effective for renal anemia in dialysis patients. However, studies in rats have shown that correcting anemia with EPO may affect the progression of renal dysfunction. In humans, however, the effect of EPO on residual renal function is a matter of controversy. We, therefore, investigated whether the long-term administration of EPO to predialysis patients influences residual renal function. Anemic patients at the predialysis stage with a serum creatinine (Cr) concentration ranging from 2 to 4 (average 2.9) mg/dl and a hematocrit (Ht) of less than 30% were randomly assigned to two groups which consisted of anemic patients not treated with EPO (group I, untreated anemic controls, n = 31) and anemic patients treated with EPO (group II, treated anemics, n = 42). Patients with nonsevere or moderate anemia (Ht > 30%) with a Cr ranging from 2 to 4 (average 2.6) mg/dl were also recruited as nonanemic controls (group III, untreated nonanemic controls, n = 35). Blood pressure was controlled to the same degree among the three groups by combined treatment with calcium antagonists and angiotensin-converting enzyme inhibitors. All patients were kept strictly on a low-protein (0.6 g/kg/day) and a low-salt (7 g/day) diet. The degree of control of dietary protein and blood pressure and the frequency of angiotensin-converting enzyme inhibitor administration were comparable among the three groups. The primary end point for each patient was a doubling of the baseline Cr which yielded cumulative renal survival rates which were plotted against time. Ht rose significantly from 27.0+/-2.3 to 32.1+/-3.2% in group II (n = 42, p < 0.001) with a rate of increase of 0.4+/-0.06%/week. However, it declined from 27.9+/-1.8 to 25.3+/-1.9% in group I (n = 31, p < 0.001) and from 35.9+/-3.5 to 32.2+/-3.9% in group III (n = 35, p < 0.001). Cr doubled in 26 patients (84%) in group I as compared with 22 (52%) in group II and 21 (60%) in group III. The cumulative renal survival rates in groups II and III were significantly better than that in group I: p = 0.0003 (group I vs. group II) and p = 0.0024 (group I vs. group III). However, there was no difference in the renal survival rate between groups II and III (p = 0.3111). The better survival rate obtained in group II was attributable to the better survival rate for the nondiabetic patients in this group. The present study suggests that anemia, per se, is a factor in the progression of end-stage renal failure and that reversal of anemia by EPO can retard the progression of renal failure, especially in nondiabetic patients, provided that blood pressure control, rate of increase in Ht, and dietary protein restriction are appropriate.",1997.0,0,0
2241,9356601,"Antihypertensive therapy. Angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and calcium antagonists.",R W Gifford,"ACEIs, angiotensin II receptor antagonists, and calcium antagonists are effective and well-tolerated antihypertensive agents but, except in special situations, should be considered alternative drugs for first line therapy until randomized trials show that they are at least as effective as diuretics and beta-blockers in preventing cardiovascular morbidity and mortality for a broad spectrum of hypertensive patients. ACEIs are particularly indicated for managing patients with congestive heart failure due to systolic dysfunction and patients with diabetic nephropathy, especially in Type I diabetes. Theoretically, the AII receptor antagonists will be equally effective for these indications, and randomized trials are now underway to demonstrate this. Special indications for calcium antagonists in the management of hypertension include angina pectoris, and for the non-dihydropyridine calcium antagonists, paroxysmal supraventricular tachycardia, and atrial fibrillation with rapid ventricular rate. Isolated systolic hypertension in the elderly is a special indication for long-acting dihydropyridine calcium antagonists, although diuretics are preferred. Calcium antagonists have been particularly effective in managing hypertension induced by cyclosporine. They are contraindicated in CHF due to systolic dysfunction and in the management of acute myocardial infarction. The long-term cardioprotective effect of calcium antagonists after a myocardial infarction has been demonstrated only for verapamil and diltiazem in patients with no evidence of LV dysfunction during their infarction. Calcium antagonists should be prescribed for this purpose only when beta-blockers are poorly-tolerated or contraindicated.",2001.0,0,0
2242,9356603,Cyclosporine-induced hypertension in cardiac transplantation.,H O Ventura; M R Mehra; D D Stapleton; F W Smart,"Cyclosporine-induced hypertension occurs in more than 90% of patients following cardiac transplantation. This article underlines the clinical characteristics as well as the mechanisms that can be associated with the development of cyclosporine-induced hypertension. In addition, the clinical trials up to date for the treatment of hypertension following cardiac transplantation are discussed. However, in view of the possible long-term sequelae associated with cyclosporine-induced hypertension, further studies to evaluate the long-term efficacy and safety of antihypertensive agents and finally the long-term effects of hypertension on the cardiac allograft are needed.",1997.0,0,0
2243,9360001,Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor.,R Griebenow; D B Pittrow; G Weidinger; E Mueller; E Mutschler; D Welzel,"The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated. A total of 127 adult outpatients with diastolic blood pressure between 100 and 114 mmHg were randomized into this double-blind, parallel group study. After a 2-week wash-out period and a subsequent 2-week placebo run-in period, they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide (R/C), or 5 mg enalapril. If diastolic blood pressure was not normalized after 3 weeks of therapy (i.e. DBP < 90 mmHg), the dosage was doubled from week 4 to 6. The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure (DBP/SBP) after 3 weeks of therapy. Secondary variables included the change in DBP and SBP after 6 weeks of therapy, the BP normalization rates at 3 and 6 weeks and, concerning tolerability, the rates of adverse events after 6 weeks of therapy. An intent-to-treat analysis was performed. The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics (mean age 57 or 58 years, respectively; 63% or 56% males, respectively; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups). After 3 weeks of treatment with one capsule daily, mean SBP/DBP reduction from baseline (24 h after last medication intake) in the R/C combination group was -19.6/ -17.0 mmHg, in the enalapril group -6.1/ -9.5 mmHg (between-group comparison: 2p < 0.01 for both parameters). The normalization rates for DBP (< 90 mmHg) were 64.1% (R/C) and 28.6% (enalapril) (2p < 0.01). Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients (17.2%) in the R/C group and in 9 patients (14.3%) in the enalapril group (NS). Two patients in the enalapril group discontinued the study prematurely due to adverse events (cough; skin eruption). In the treatment of mild-to-moderate hypertension, a low-dose combination of reserpine and clopamide once a day is considerably more effective than, and as tolerable as, 5-10 mg of enalapril once a day. These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension. Besides, the ""old"" reserpine-diuretic regimen also in these days appears to be a rational alternative to ""modern"" monotherapies.",1997.0,0,0
2244,9360002,Lack of effect of short-term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction.,C Cuspidi; L Lonati; L Sampieri; G Leonetti; M L Muiesan; E Agabiti-Rosei; A Zanchetti,"Arterial hypertension may be associated with altered left ventricular filling dynamics. The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics, assessed by the echocardio-Doppler technique, independently of effects on left ventricular mass. In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity (E/A) < 1 were randomized, after a run-in period of 2 weeks without any antihypertensive treatment, to receive lisinopril (20 mg once a day) and placebo for 4 weeks, respectively. At the end of both the run-in and the treatment periods, blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out. The echocardio-Doppler evaluation was performed both at rest and at the peak of a hand-grip test (3 min at 30% of maximal strength). Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography. Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique. Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest (-13/-9 mmHg vs baseline values, p < 0.05; -6/-4 mmHg vs placebo values, p < 0.05) and during isometric exercise (-17/-9 mmHg vs baseline period, p < 0.05; -6/-5 mmHg vs placebo, p < 0.05). Lisinopril did not induce any significant change in left ventricular structure and systolic function. All the left ventricular filling parameters considered (E velocity, A velocity, E/A ratio) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration. This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients. Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently cannot be significantly improved by short-term blood pressure reduction by antihypertensive therapy.",1997.0,0,0
2245,9360571,Rapid life-threatening hyperkalemia after addition of amiloride HCl/hydrochlorothiazide to angiotensin-converting enzyme inhibitor therapy.,T F Chiu; M J Bullard; J C Chen; S J Liaw; C J Ng,"To highlight the dangers of a precipitous rise in serum potassium levels in patients at risk for renal insufficiency, already receiving an angiotensin-converting enzyme (ACE) inhibitor, who are given a potassium-sparing diuretic. We conducted a retrospective chart review of five patients who were taking the above combination of medications who were seen in our ED with hyperkalemia. All five patients had diabetes and were older than 50 years of age. Except for one patient, they had some degree of renal impairment and all were receiving an ACE inhibitor. Each had amiloride HCl/hydrochlorothiazide added to their therapeutic regimen 8 to 18 days before presenting to our ED with hyperkalemia. Potassium levels were between 9.4 and 11 mEq/L in 4 of the patients; 2 did not respond to resuscitation measures. The concomitant use of ACE inhibitor and potassium-sparing diuretic therapy should be avoided. If impossible, weekly monitoring of both renal function and serum potassium should be performed. In the ED patients who are receiving such a combination should receive immediate ECG monitoring.",1997.0,0,0
2246,9361124,Clinical drug photosensitivity. A retrospective analysis of reports to the Norwegian Adverse Drug Reactions Committee from the years 1970-1994.,E Selvaag,"Adverse drug reactions reported to the Norwegian Medicine Control Authority from 1970 to 1994 were analyzed, especially with regard to cutaneous reactions and photosensitization. In the time period, almost 13,000 unwanted side effects were reported. Of these, 799 reports involved the skin and appendages, of which 64 reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs that most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the basis of experimental data and the prescription rates of these substance.",1997.0,0,0
2247,9363666,Enalapril-induced anemia in a renal transplant patient.,N Ozbek; S Ozen; U Saatçi,"Side-effects of angiotensin converting enzyme (ACE) inhibitors, such as a slight decrease in hematocrit, are increasingly being reported. A 14-year-old renal transplant patient on enalapril therapy developed anemia with reticulocytosis. She was investigated for other causes of anemia and enalapril therapy was ceased. Her hemoglobin level increased and reticulocyte count decreased after cessation of therapy. No other cause of anemia was found. Although anemia in patients receiving ACE inhibitors such as enalapril has previously been reported, this is the first reported patient who developed anemia associated with mild reticulocytosis and macrocytosis.",1997.0,0,0
2248,9365870,Use of losartan in FH patients during treatment with DSC-LDL apheresis.,S Pintus; P Pintus; P Maxia; S Anedda,,2000.0,0,0
2249,9368913,No sex-related pharmacokinetic and pharmacodynamic differences of captopril.,E Massana; M J Barbanoj; C Moros; A Morte; I Gich; F Jané,"Captopril is an angiotensin-converting enzyme inhibitor (ACEI) used in the treatment of hypertension and congestive heart failure and has demonstrated its cardiovascular effects in experimental animal models, healthy volunteers and patients. The aim of this study was to find out whether or not differences in the pharmacokinetic profile and the haemodynamic response of a 100-mg single oral dose of captopril appeared between subjects of both sexes. Twenty-four young healthy volunteers (12 males and 12 females) took part in the trial. Blood samples to assess captopril plasma concentrations, determined by reverse phase high performance liquid chromatography (HPLC), as well as haemodynamic variables, were obtained before and at different times following drug intake. Pharmacokinetic parameters did not show significant sex differences. Systolic and diastolic blood pressure exhibited a statistically significant decrease between 0.5 and 8 h in both sexes. No significant sex-related differences were found. The drug exhibited a good tolerability.",1997.0,0,0
2250,9370181,Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects.,G Cannella; E Paoletti; R Delfino; G Peloso; D Rolla; S Molinari,"Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.",1997.0,0,0
2251,9370501,Losartan-induced hepatotoxicity.,X Bosch,,1997.0,0,0
2252,9371172,Angiotensin-converting-enzyme inhibitors in early pregnancy.,G Y Lip; D Churchill; M Beevers; A Auckett; D G Beevers,,1997.0,0,0
2253,9371190,Drug advertisements in medical journals.,A Vitry; P Mansfield,,1997.0,0,0
2254,9377617,Coadministration of tamsulosin and three antihypertensive agents in patients with benign prostatic hyperplasia: pharmacodynamic effect.,F C Lowe,"Tamsulosin, an alpha 1A-adrenoceptor antagonist, has recently been approved to treat patients with symptomatic benign prostatic hyperplasia (BPH). Tamsulosin is highly selective for prostatic receptors with minimal affinity for vascular receptors. Therefore, it should have little effect on blood pressure and should not potentiate other agents' antihypertensive activity. To test this hypothesis, we conducted three randomized, double-masked, placebo-controlled studies to evaluate how coadministration of tamsulosin would affect the pharmacodynamic profiles of nifedipine, enalapril, and atenolol. Each study enrolled 12 hypertensive men aged 45 years or older whose blood pressure was being controlled with maintenance doses of nifedipine (study 1), enalapril (study 2), or atenolol (study 3). All 36 subjects were treated with placebo for 5 days and then randomly assigned to either placebo (control group) or tamsulosin therapy (0.4 mg/d for 7 days followed by 0.8 mg/d for 7 days) in addition to continuing their maintenance antihypertensive therapy. Blood pressure and pulse rate were monitored over a 24-hour period on study days 4, 11, and 19. Coadministration of tamsulosin in these small studies had no clinically significant effects on the pharmacodynamic action of nifedipine, enalapril, or atenolol; it produced no clinically significant differences in pulse rate and blood pressure, did not alter electrocardiographic or Holter monitoring results, and did not cause increased side effects. Coadministration of tamsulosin with the three antihypertensive agents studied had a favorable safety profile. Our results in these small studies indicate that the dose of nifedipine, enalapril, or atenolol did not require adjustment in patients given tamsulosin, which may give tamsulosin an advantage over other alpha-blocking agents used to treat patients with BPH. Now that tamsulosin has been approved in the United States, further clinical use may confirm these findings.",1997.0,0,0
2255,9383184,Clinical results of the Verapamil inHypertension and Atherosclerosis Study. VHAS Investigators.,E A Rosei; C Dal Palù; G Leonetti; B Magnani; A Pessina; A Zanchetti,"The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. After a 3-week placebo run-in period, 1414 hypertensive patients [692 men and 722 women, aged 53.2 +/- 7 years, blood pressure 168.9 +/- 10.5/ 102.2 +/- 5.0 mmHg (means +/- SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P < 0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to < or = 90 mmHg or to < or = 95 mmHg with a > or = 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P < 0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P < 0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K < 3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P < 0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.",1997.0,0,0
2256,9384458,Drug treatment in acute porphyria.,A Gorchein,"The acute hepatic porphyrias are rare pharmacogenetic diseases inherited as autosomal dominant conditions of low penetrance. The genetic defect is a 50% deficiency of an enzyme of the haem biosynthetic pathway. Patients may develop 'neurovisceral attacks' which include severe abdominal pain, neuropsychiatric manifestations and potentially fatal respiratory paralysis. Attacks occur generally after puberty, are much commoner in females and may be precipitated by endogenous hormonal changes, dieting, alcohol, severe infections, and many drugs. Treatment includes analgesia, early administration of haem, and general supportive measures. Patients are at greater risk of a severe attack on first presentation since an abdominal emergency may be simulated and inappropriate medication, including that for general anaesthesia may exacerbate the crisis. The urine should be tested for raised porphobilinogen, which is pathognomonic of the acute attack, if there is the slightest doubt about diagnosis. The genotype of blood relatives of index cases must be determined so that carriers may avoid drug and other precipitants. Some drugs have been established as safe or unsafe by clinical use, but information about many drugs is not available or is based only on their properties in rodents or in tissue culture systems. The relevance of these to the human condition remains controversial, but drugs shown to be porphyrinogenic in animal systems should be avoided if there is a known safe alternative. Where it is essential to use a drug not known to be safe, close biochemical and clinical observation may warn of an impending attack.",1998.0,0,0
2257,9384470,Reports of hypoglycaemia associated with the use of ACE inhibitors and other drugs: a case/non-case study in the French pharmacovigilance system database.,N Moore; C Kreft-Jais; F Haramburu; C Noblet; M Andrejak; M Ollagnier; B Bégaud,"To test the existence of an association between reports of hypoglycaemia and angiotensin converting enzyme inhibitors, in a spontaneous reports database. The French Pharmacovigilance database was examined for an association between adverse drug reaction reports mentioning hypoglycaemia, and angiotensin converting enzyme inhibitors (ACEI) using the case/non-case methodology, with reports of hypoglycaemia as cases and all other reports as comparators. The association between ACEI or other chosen drugs and hypoglycaemia was also tested in the subgroups of patients taking or not antidiabetic agents (ADA). 428 of 93,338 reports mentioned hypoglycaemia (202/2227 with ADA (OR 40, 95% CI 33-48)). 46/5717 reports mentioned ACEI (OR 1.8 (1.25-2.54)). Other study drugs associated with hypoglycaemia were cibenzoline (OR 80 (57-112)), disopyramide (OR 32 (22-46)), nifedipine (OR 2.16 (1.32-3.51)), diltiazem (OR 1.76 (1.01-3.06)) nitrates (nitroglycerin, molsidomine) (OR 1.91 (1.16-3.16)) and frusemide (OR 1.89 (1.31-1.76)), but not nicardipine, amlodipine, felodipine or nitrendipine, diazepam, atenolol or combination thiazide diuretics. However, ACEI and other drugs were associated with ADA, so that in the subgroups of patients taking or not ADA, the association of ACEI with hypoglycaemia disappeared (OR 0.9 (0.5-1.4) and 1.2 (0.7-2.2), respectively). The same was found for other drugs except cibenzoline. The association between reporting of hypoglycaemia and ACE inhibitors was related to concomitant use of antidiabetic agents. This was true also for other drugs used in arterial disease or renal failure, such as calcium channel blockers, nitrates, and frusemide.",1998.0,0,0
2258,9388035,Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial.,G Mancia; G Grassi,"This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 +/- 5.8 years, mean +/- SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 +/- 14.0/103.7 +/- 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 +/- 9.4/83.6 +/- 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 +/- 13.9/88.7 +/- 8.4 mm Hg (n = 114) and 150.7 +/- 15.5/80.8 +/- 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 +/- 0.9%/9.9 +/- 0.9% in systodiastolic and by 11.8 +/- 1.3%/8.5 +/- 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.",1997.0,0,0
2259,9388037,Comparison of isradipine and enalapril effects on regional carotid circulation in patients with hypertension with unilateral internal carotid artery stenosis.,S E Akopov; N A Simonian,"This randomized, double-blind, placebo-controlled study was aimed at detecting cerebrovascular effects of isradipine and enalapril in patients with moderate hypertension depending on the presence and grade on unilateral stenosis of internal carotid artery (ICA). We evaluated carotid vascular resistance by using Doppler analysis and regional cerebral blood flow (rCBF) by using 133Xe-clearance technique before and after a single 5-mg oral dose of isradipine, enalapril, or placebo. Their effects were randomly and consecutively tested in 73 patients with essential hypertension subdivided into three groups: without carotid occlusive lesions, with moderate (50-75%), and with severe (76-99%) unilateral asymptomatic ICA stenosis. There were no differences in age, gender, and antihypertensive effects of the drugs between these three subgroups. Three major variants of cerebrovascular drug effects were observed: absence of changes (variant I), decrease in carotid vascular resistance with increase in rCBF and elimination of side-to-side asymmetry (variant II), and increase in carotid vascular resistance with further reduction of rCBF ipsilaterally ICA stenosis, and increased side-to-side asymmetry (variant III). Frequency of variant III was significantly higher in patients with severe ICA stenosis. Enalapril produced variant I of cerebrovascular effects in most patients examined; variant III was observed only in 13% of patients with severe ICA stenosis. Isradipine produced variant I of cerebrovascular effects much less frequently than did enalapril. For this drug, variant II was most typical in patients without ICA stenosis and with moderate ICA stenosis. In 43.5% of patients with severe ICA stenosis, however, isradipine produced reduction of cerebral perfusion. Presumably the presence of ICA stenosis, especially >75%, increases the risk of cerebrovascular disorders in antihypertensive therapy. In patients with severe ICA stenosis, treatment with enalapril appears to be safer than that with isradipine.",1997.0,0,0
2260,9388047,The effects of long-term treatment on left ventricular hypertrophy in patients with essential hypertension: relation to changes in neurohumoral factors.,H Ueno; M Takata; S Tomita; S Oh-hashi; K Yasumoto; H Inoue,"This study compared the effects of 1 year of monotherapy with a calcium-channel antagonist (nilvadipine; NIL), an angiotensin-converting enzyme (ACE) inhibitor (temocapril; TEM), or a new vasodilator (cadralazine; CAD) on left ventricular (LV) hypertrophy in essential hypertension. Furthermore, to elucidate the mechanism responsible for regression of LV hypertrophy after treatment, LV mass index (LVMI) by echocardiography, plasma renin activity (PRA), aldosterone (PAC), norepinephrine, and atrial natriuretic peptide (ANP) concentration were measured before and after treatment. Thirty-six patients were randomly assigned to the NIL, TEM, or CAD groups. Blood pressure (BP) before treatment was 174 +/- 10/104 +/- 7, 173 +/- 18/103 +/- 8, and 171 +/- 16/103 +/- 7 mm Hg (mean +/- SD) in NIL, TEM, and CAD groups, respectively. BP was lower after treatment with each of the three test drugs than after the placebo period, and there were no differences in BP reduction among three groups. LVMI, in NIL and TEM, was reduced from 129 +/- 48 to 115 +/- 39 g/m2 and from 117 +/- 39 to 88 +/- 20 g/m2 (p < 0.05 and p < 0.01, respectively), whereas, in the CAD group, it was increased (110 +/- 30 to 138 +/- 27 g/m2; p < 0.01). In the CAD group, PAC decreased and ANP increased significantly. The change in LVMI correlated with that in BP for TEM and with that in ANP in all patients. These data indicated that LV volume overload as well as LV pressure overload may contribute to LV hypertrophy and that monotherapy with CAD is not desirable from the point of view of LV mass reduction in essential hypertension.",1997.0,0,0
2261,9391292,Comparison of captopril and ibopamine in mild to moderate heart failure.,H J Dohmen; P H Dunselman; P A Poole-Wilson,"To determine the effects of ibopamine 100 mg three times daily compared with captopril 25 mg three times daily on exercise capacity in patients with chronic heart failure. A randomised, double blind, parallel group comparison of the addition of ibopamine versus captopril during a period of 24 weeks. 26 outpatient cardiology clinics in seven European countries. 266 patients, with mild to moderate chronic heart failure (New York Heart Association (NYHA) functional class II, 81% and III, 19%) and evidence of an enlarged left ventricle. Patients received concomitant treatment with diuretics and/or digitalis. Exercise duration after 24 weeks of treatment, compared with baseline. Mean (SD) ejection fraction was 29 (8)% and the baseline exercise duration in the captopril and ibopamine groups 665 (160) and 675 (174) seconds, respectively. At the end of the study, exercise duration had improved in both groups, by 29 seconds in the ibopamine group (P < 0.01), and by 24 seconds in the captopril group (P < 0.05). There was no difference between groups (P = 0.69, 95% confidence interval -22 to 33). NYHA class, signs and symptoms score, and dyspnoea and fatigue index improved equally in both groups. The total number of adverse events was the same in both treatment groups, but gastrointestinal complaints occurred more often in the ibopamine group. The number of patients with premature withdrawals was no different. No difference was detected between the effect of captopril and ibopamine on exercise time in patients with mild to moderate heart failure during a treatment period of 24 weeks.",1997.0,0,1
2262,9391695,,,,,0,0
2263,9391702,Absence of cross-reaction between lisinopril and enalapril in drug-induced lupus.,D Leak,,1997.0,0,0
2264,9396419,Cardiovascular death and left ventricular remodeling two years after myocardial infarction: baseline predictors and impact of long-term use of captopril: information from the Survival and Ventricular Enlargement (SAVE) trial.,M St John Sutton; M A Pfeffer; L Moye; T Plappert; J L Rouleau; G Lamas; J Rouleau; J O Parker; M O Arnold; B Sussex; E Braunwald,"We quantified cardiovascular death and/or left ventricular (LV) dilatation in patients from the SAVE trial to determine whether dilatation continued beyond 1 year, whether ACE inhibitor therapy attenuated late LV dilatation, and whether any baseline descriptors predicted late dilatation. Two-dimensional echocardiograms were obtained in 512 patients at 11+/-3 days and 1 and 2 years postinfarction to assess LV size, percentage of the LV that was akinetic/dyskinetic (%AD), and LV shape index. LV function was assessed by radionuclide ejection fraction. Two hundred sixty-three patients (51.4%) sustained cardiovascular death and/or LV diastolic dilatation; 279 (54.5%) had cardiovascular death and/or systolic dilatation. In 373 patients with serial echocardiograms, LV end-diastolic and end-systolic sizes increased progressively from baseline to 2 years (both P<.01). More patients with LV dilatation had a decrease in ejection fraction: 24.8% versus 6.8% (P<.001) (diastole) and 25.7% versus 5.3% (P<.001) (systole). Captopril attenuated diastolic LV dilatation at 2 years (P=.048), but this effect was carried over from the first year of therapy because changes in LV size with captopril beyond 1 year were similar to those with placebo. Predictors of cardiovascular death and/or dilatation were age (P=.023), prior infarction (P<.001), lower ejection fraction (P<.001), angina (P=.007), heart failure (P=.002), LV size (P<.001), and infarct size (%AD) (P<.001). Cardiovascular death and/or LV dilatation occurred in >50% of patients by 2 years. LV dilatation is progressive, associated with chamber distortion and deteriorating function that is unaffected by captopril beyond 1 year.",1997.0,1,1
2265,9397236,A prospective comparison of four study designs used in assessing safety and effectiveness of drug therapy in hypertension management.,M A Levine; P Hamet; S Novosel; B Jolain,"The objective of the study was to compare prospectively the impact of study design on drug therapy safety and effectiveness data obtained in hypertension management. The main study was a randomized controlled clinical trial of four different prospective study designs used in postmarketing assessment involving 1008 primary care practices in nine Canadian provinces. Two thousand nine hundred sixty-four patients with mild to moderate hypertension received an angiotensin converting enzyme (ACE) inhibitor daily for 14 weeks in one of four postmarketing studies--a randomized double-blind clinical trial (RCT) (10 to 40 mg fosinopril daily v 5 to 20 mg enalapril daily), two structured open label trials of 10 to 40 mg fosinopril daily (one with free drugs), or an unstructured open label trial of 10 to 40 mg fosinopril daily. Patient demographic and baseline characteristics, systolic and diastolic blood pressures, adverse events reported, and data quality were recorded as the outcome measures. The results showed that the RCT patients were titrated to higher doses of ACE inhibitor than patients in the open studies, P < .008; patients in the open studies were more likely to receive adjuvant diuretic therapy, P < .008. The decrease in blood pressure was similar for patients in all four studies, mean decrease in systolic BP was between 18 and 20 mm Hg, mean decrease in diastolic BP was between 11 and 13 mm Hg. Fewer patients in the unstructured open trial reported adverse events than patients in the RCT; a 55% relative reduction in reported adverse events (P < .008) was associated with the unstructured trial. There were also fewer drug-related adverse events per patient reported in the unstructured study (17 per 100 patients) than in the other studies (27 to 41 per 100 patients), P < .008. Physician preference for rounding off blood pressure measurements to 0 or 5 occurred most often in the unstructured open trial (P < .008). In conclusion, despite differences in dose titration and in the use of adjuvant therapy, antihypertensive drug therapy effectiveness observed in an RCT may be similar to uncontrolled postmarketing studies. Open trials with scheduled follow-up visits are as effective in detecting severe adverse events as RCT, but postmarketing studies with unstructured schedules of follow-up are insufficient in identifying drug-related adverse events and have poorer quality data.",1997.0,0,0
2266,9397292,Equivalent reduction of proteinuria in hypertensives by either nifedipine GITS or enalapril: disparate effects on neurohormones and ambulatory blood pressure and the influence of salt.,V DeQuattro; D P Lee,"We compared the efficacy of two classes of antihypertensive therapy on ambulatory blood pressure control and proteinuria in patients with hypertension. Furthermore, we determined the effects of the interaction of these therapies on neurohormonal activation and of the patients' ambient sodium intake on the outcomes. Sustained-release nifedipine (nifedipine gastrointestinal therapeutic system, GITS) 30-120 mg/day was compared in a double-blind sequential randomized placebo-controlled trial with enalapril 5-30 mg/day regarding office and 24-hour blood pressure control, plasma renin activity, noradrenaline and adrenaline levels and 24-hour urinary protein and sodium in 46 elderly nondiabetic hypertensive patients in a 16- to 18-week trial. Both nifedipine GITS and enalapril controlled ambulatory blood pressure during the day and at peak effect. Nifedipine GITS controlled ambulatory blood pressure during the early morning surge and at night time as well. Nifedipine GITS increased plasma renin activity and noradrenaline by 50 and 20%, respectively, compared to the 150 and 0% change produced by enalapril. Both nifedipine GITS and enalapril reduced proteinuria by 37%. Patients had increasing levels or proteinuria proportional to higher ambient sodium intake (r = 0.48; p < 0.01). This effect was accentuated during nifedipine GITS therapy as compared to enalapril. Nifedipine GITS was superior to enalapril in controlling ambulatory blood pressure, but they were equivalent in reducing proteinuria (37%). They had disparate effects on neural activation and the duration of action. Raised protein excretion appears to be associated with raised sodium intake. This was apparent especially during nifedipine XL therapy.",1997.0,0,0
2267,9398110,The effects of the angiotensin-converting enzyme inhibitor imidapril on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction.,S Oshima; H Ogawa; Y Mizuno; S Yamashita; K Noda; T Saito; H Sumida; H Suefuji; K Kaikita; H Soejima; H Yasue,"This study sought to determine whether early treatment with angiotensin-converting enzyme (ACE) inhibitors in patients with acute myocardial infarction (AMI) is useful for the improvement of fibrinolytic function, as well as left ventricular function. This study was designed to examine the levels of plasma plasminogen activator inhibitor (PAI) activity and serum ACE activity during the course of 2 weeks in 40 patients with AMI within 12 hours after the onset of the symptom and who randomly received early treatment with either the ACE inhibitor imidapril or a placebo (20 patients in the imidapril group and 20 in the placebo group). The levels of serum ACE activity in the imidapril group decreased significantly (p < 0.01) 8 hours after the administration of imidapril, and the levels 24 hours after administration were significantly lower than those in the placebo group (3.6 +/- 0.6 IU/L vs 7.4 +/- 0.8 IU/L; p < 0.001). The plasma PAI activity increased gradually to peak levels 16 hours after the administration of imidapril and placebo. The levels in the placebo group decreased gradually but remained high during the study period. On the other hand, the levels of PAI activity in the imidapril group decreased rapidly and those 48 hours after administration were significantly lower than those in the placebo group (7.9 +/- 1.9 IU/ml vs 18.4 +/- 3.5 IU/ml; p < 0.01). The levels of left ventricular ejection fraction about 2 weeks after admission were significantly higher in the imidapril group than in the placebo group (65.9% +/- 2.5% vs 49.1% +/- 4.4%; p < 0.01). This study showed that imidapril, an ACE inhibitor, might be useful for the improvement of fibrinolytic function and left ventricular function in the acute phase of myocardial infarction.",1997.0,0,0
2268,9398137,Sickle cell nephropathy during the postpartum period in a patient with SLE.,P T Pham; S Q Lew; J E Balow,,1997.0,0,0
2269,9400588,"Evaluation of hematuria, proteinuria, and hypertension in adolescents.",J D Mahan; M A Turman; M I Mentser,"Signs or symptoms of renal disease in adolescents deserve prompt attention and appropriate evaluation. Adolescents are susceptible to a variety of urinary tract disorders. The key issue in the evaluation of hematuria or proteinuria in adolescents is the existence of concomitant signs of renal disease. For isolated hematuria or proteinuria, demonstration of persistence and a reasoned evaluation are in order. Hypertension in adolescents must be carefully documented and, when present, considered seriously. The fact that most teens with persistent elevated blood pressures have essential hypertension is still a great concern because for most of these adolescents the hypertension will be lifelong and, if left untreated, can be associated with significant morbidity and mortality in the adult years.",1997.0,0,0
2270,9400905,Effects of antihypertensive agents on circadian blood pressure in hypertensive patients with previous brain infarction.,T Azuma; T Matsubara; Y Nagai; M Funauchi; T Fujimoto; T Saito; K Tone; S Sakoda,"To evaluate the effects of antihypertensive agents on the circadian blood pressure (BP) of patients with previous brain infarction, the ambulatory BP was measured non-invasively for 24 h before and after administration of antihypertensive agents. One hundred milligrams of acebutolol twice daily (n = 15) is effective in lowering the BP during the daytime, but has little effect during the night and the morning. Twenty milligrams of slow-release nifedipine twice daily (n = 14) produced a consistent reduction in the BP over the entire 24-h period and effectively blunted the rise in BP in the morning. Captopril (12.5 mg) twice daily (n = 15) produced a mild reduction in BP with little change in the circadian pattern. The slow-release nifedipine group had the greatest decrease in mean systolic and diastolic BP. The heart rate significantly increased after administration of slow-release nifedipine and decreased after administration of acebutolol. To reduce stroke recurrence, we should consider the effects of antihypertensive agents on circadian BP in hypertensive patients with previous brain infarction.",1997.0,0,0
2271,9403220,Acute renal failure with severe tubulointerstitial changes in a patient with minimal change nephrotic syndrome treated with enalapril.,L Grcevska; M Polenaković; S Dzikova; R Grozdanovski,"A 35-year-old nephrotic man developed acute renal failure with serum creatinine to 1543 micromol/l after a month of therapy with enalapril. Renal biopsy demonstrated minimal glomerular changes with fusion of podocytes, tubular necrosis with regeneration of tubular epithelial cells, interstitial edema with focal interstitial fibrosis, and interstitial infiltration with neutrophils, eosinophils, plasma cells and mononuclear cells. Three hemodialyses were performed in the patient during the oliguric phase of the disease. Renal function was restored after withdrawal of enalapril and initiation of steroid therapy. Steroids also contributed to the improvement of the nephrotic syndrome and proteinuria decreased from maximal ranges of 27 g/l to 2.2 g/l after six months of the follow-up. Similar cases were previously described associated with captopril treatment, but not with enalapril.",1997.0,0,0
2272,9403280,Drug-induced chest pain and myocardial infarction. Reports to a national centre and review of the literature.,J P Ottervanger; J H Wilson; B H Stricker,"To analyse reports of drug-induced myocardial infarction and chest pain sent to a national reporting centre. To review which drugs were suspected of exhibiting these adverse events and what mechanisms were involved. During the 20-year period 1975 through 1994, a total of 19,141 reports on adverse reactions to drugs were received by the Netherlands Centre for Monitoring of Adverse Reactions to Drugs. Of these 19,141 reports, 220 (1.1%) were concerned with drug-induced chest pain or myocardial infarction. After excluding reports in which the causal relationship was unlikely, poorly documented reports and reports on cases of overdosage, 183 reports (84%) were analysed. There were 130 reports (71%) of drug-induced chest pain and 53 reports (29%) of drug-induced myocardial infarction. A total of 104 reports concerned females (57%). The most frequently reported suspected drugs were the antimigraine drug sumatriptan (33 reports, 4 concerning myocardial infarction), the calcium antagonist nifedipin (9 reports, 2 of myocardial infarction) and nicotine [9 reports (8 patches, 1 chewing gum), 5 concerning myocardial infarction]. There were 18 reports of a fatal outcome. Several drugs can produce chest pain or myocardial ischaemia. It is important to recognise drugs as a potential cause, especially in patients with normal coronary arteries.",1997.0,0,0
2273,9408513,Oral angiotensin-converting-enzyme inhibitors.,C Verme-Gibboney,"The pharmacology, pharmacokinetics, clinical uses, adverse effects, drug interactions, dosage, cost, and therapeutic interchange of oral angiotension-converting-enzyme (ACE) inhibitors are reviewed. ACE inhibitors attenuate the formation of angiotension II and may lead to the accumulation of kinins. Although the hypotensive effects of many ACE inhibitors may persist for 24 hours, some patients require more than one dose per day to achieve adequate control. These agents accumulate in patients with renal or hepatic dysfunction, but it is unclear whether dosage adjustments are necessary. ACE inhibitors are effective against mild to moderate hypertension; for severe hypertension, additional anti-hypertensive agents may be necessary. Other conditions in which ACE inhibitors have shown efficacy include congestive heart failure, myocardial infarction, left ventricular dysfunction, left ventricular hypertrophy, chronic renal insufficiency, insulin sensitivity, and coronary artery disease. The most common adverse effect is a persistent nonproductive cough. Angioedema, fetal and neonatal morbidity and mortality, acute renal failure, and hyperkalemia may also occur. ACE inhibitors may interact with diuretics, lithium, nonsteroidal anti-inflammatory drugs, oral hypoglycemic agents, and some other drugs. ACE inhibitor therapy should be initiated with low doses that may then be slowly adjusted upward. Many of the agents have similar costs for lower and higher dosages. The only significant differences among the ACE inhibitors are the time of onset of hypotensive effects, time to peak effect, and duration of effect. Each formulary should include, at least, captopril and one intermediate-acting and one long-acting ACE inhibitor.",1997.0,0,0
2274,9416888,Effect of the ACE inhibitor lisinopril on mortality in diabetic patients with acute myocardial infarction: data from the GISSI-3 study.,G Zuanetti; R Latini; A P Maggioni; M Franzosi; L Santoro; G Tognoni,"Mortality of diabetic patients with acute myocardial infarction (MI) remains high despite recent improvement in their management. There is a need to evaluate efficacy and safety of novel treatments of MI in this high-risk population. We evaluated whether treatment with an ACE inhibitor begun within 24 hours from the onset of symptoms is able to decrease mortality and morbidity of diabetic patients with acute MI. A retrospective analysis of the data of the GISSI-3 study in patients with and without a history of diabetes was performed. Patients with suspected acute MI were randomized to treatment with lisinopril (2.5 to 5 up to 10 mg/d) with or without nitroglycerin (5 to 20 microg I.V. then 10 mg/d) begun within 24 hours and continued for 6 weeks. The main end point was mortality at 6 weeks, and the secondary end point was a combined evaluation of mortality and severe left ventricular dysfunction. Information on diabetic status was available for 18,131 patients (approximately 94% of the total population enrolled), of whom 2790 patients had a history of diabetes. Treatment with lisinopril was associated with a decreased 6-week mortality in diabetic patients (8.7% versus 12.4%; OR, 0.68; 95% CI, 0.53 to 0.86; 37+/-12 lives saved per 1000 treated patients), an effect that was significantly (P<.025) higher than that observed in nondiabetic patients. The survival benefit in diabetics was mostly maintained at 6 months despite withdrawal from treatment at 6 weeks (12.9% versus 16.1%; OR, 0.77; 95% CI, 0.62 to 0.95). Early treatment with the ACE inhibitor lisinopril in diabetic patients with acute MI is associated with a decreased 6-week mortality. This beneficial effect supports a widespread and early use of ACE inhibitors in diabetic patients with acute MI. The burden of mortality plus morbidity for ventricular dysfunction in diabetics remains clinically important and warrants further testing of novel therapeutic approaches.",1998.0,1,1
2275,9416890,Sphygmomanometrically determined pulse pressure is a powerful independent predictor of recurrent events after myocardial infarction in patients with impaired left ventricular function. SAVE investigators. Survival and Ventricular Enlargement.,G F Mitchell; L A Moyé; E Braunwald; J L Rouleau; V Bernstein; E M Geltman; G C Flaker; M A Pfeffer,"There is increasing evidence of a link between conduit vessel stiffness and cardiovascular events, although the association has never been tested in a large post-myocardial infarction patient population. We evaluated the relationship between baseline pulse pressure, measured by sphygmomanometry 3 to 16 days after myocardial infarction, and subsequent adverse clinical events in the 2231 patients enrolled in the SAVE Trial. Increased pulse pressure was associated with increased age, left ventricular ejection fraction, female sex, history of prior infarction, diabetes, and hypertension and use of digoxin and calcium channel blockers. Over a 42-month period, there were 503 deaths, 422 cardiovascular deaths, and 303 myocardial infarctions. Pulse pressure was significantly related to each of these end points as a univariate predictor. In a multivariate analysis, pulse pressure remained a significant predictor of total mortality (relative risk, 1.08 per 10 mm Hg increment in pulse pressure; 95% CI, 1.00 to 1.17; P<.05) and recurrent myocardial infarction (relative risk, 1.12; 95% CI, 1.01 to 1.23; P<.05) after control for age; left ventricular ejection fraction; mean arterial pressure; sex; treatment arm (captopril or placebo); smoking history; history of prior myocardial infarction, diabetes, or hypertension; and treatment with beta-blockers, calcium channel blockers, digoxin, aspirin, or thrombolytic therapy. These data provide strong evidence for a link between pulse pressure, which is related to conduit vessel stiffness, and subsequent cardiovascular events after myocardial infarction in patients with left ventricular dysfunction.",1998.0,0,0
2276,9416938,Comparison of changes in respiratory function and exercise oxygen uptake with losartan versus enalapril in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.,M Guazzi; G Melzi; P Agostoni,"In congestive heart failure (CHF), some of the effects of angiotensin-converting enzyme (ACE) inhibitors, such as an increase in exercise oxygen uptake (VO2), are mediated through prostaglandins. Angiotensin (AT1) receptor blockers apparently do not share potentiation of this biosystem. We tested whether losartan improves exercise VO2 in CHF and if the effect is the same as for enalapril. Sixteen men with CHF and 8 volunteers, all nonsmokers and not taking ACE, AT1 receptor, or cyclooxygenase inhibitors, were randomized to receive placebo, enalapril (10 mg 2 times daily), losartan (50 mg/day), each of these 2 drugs plus aspirin (325 mg/day), aspirin, or the same preparations in a reverse order, each for 3 weeks, with a 3-week washout period between treatments. Pulmonary function and VO2 were assessed at the end of each treatment. In CHF, losartan and enalapril caused a similar improvement of VO2 and exercise tolerance, which was absent in controls and was counteracted by aspirin (prostaglandin inhibition) when obtained with enalapril and not with losartan. While on enalapril, we also detected an increase in the diffusing lung capacity for carbon monoxide, which correlated with changes in VO2 and was antagonized by aspirin, suggesting the possibility that a prostaglandin-mediated functional improvement of the alveolar capillary membrane contributes to the rise in VO2. Thus, losartan is as effective as enalapril for exercise VO2 and exercise tolerance, but the mechanism seems to be dissociated from a prostaglandin biosystem activation. Losartan may represent an advancement in CHF because its efficacy on VO2 is similar to that of enalapril, but is not antagonized by aspirin.",1998.0,0,0
2277,9416950,Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators.,P Larochelle; J M Flack; T C Marbury; P Sareli; E M Krieger; R A Reeves,"In this double-blind, randomized study, an antihypertensive regimen based on irbesartan, an angiotensin II receptor antagonist, reduced systolic and diastolic blood pressure by 40/30 mm Hg at week 12 in patients with severe hypertension; this reduction was at least equivalent to that of a regimen using enalapril up to 40 mg. The irbesartan-based regimen had a better tolerability profile with fewer adverse events (55% vs 64%) and significantly less cough (2.5% vs 13.1%, p = 0.007).",1998.0,0,0
2278,9421695,Irbesartan. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension.,J C Gillis; A Markham,"Irbesartan inhibits the activity of angiotensin II (AII) via specific, selective noncompetitive antagonism of the AII receptor subtype 1 (AT1) which mediates most of the known physiological activities of AII. In patients with mild to moderate hypertension, once daily administration of irbesartan 150 or 300 mg, with or without adjunctive antihypertensive agents, provides effective 24-hour BP control. Irbesartan reduced BP to a similar extent to enalapril and atenolol and to a significantly greater extent than losartan. The combination of irbesartan and hydrochlorothiazide resulted in additive antihypertensive effects. The drug is effective in the elderly and dosage adjustment is not required in these patients or in those with renal or hepatic failure. Preliminary studies evaluating the efficacy of irbesartan in patients with heart failure have produced encouraging results. Irbesartan is very well tolerated and neither the frequency nor the pattern of adverse events differed from those seen in placebo recipients, although headache was significantly more frequent with the latter. Similarly, the incidence of adverse events did not differ significantly between irbesartan and enalapril in patients who received either drug as monotherapy. Headache, upper-respiratory tract infection and musculoskeletal pain were the most common complaints. Thus, irbesartan is an effective therapy for patients with mild to moderate hypertension and had an adverse event profile similar to that of placebo in clinical trials. On this basis it would appear to be an effective therapeutic option in this indication.",1998.0,0,0
2279,9424981,Update in nephrology.,S Goldfarb; W L Henrich,,1998.0,0,0
2280,9426022,Long-term nitroglycerin treatment is associated with supersensitivity to vasoconstrictors in men with stable coronary artery disease: prevention by concomitant treatment with captopril.,T Heitzer; H Just; C Brockhoff; T Meinertz; M Olschewski; T Münzel,"We examined whether long-term nitroglycerin (NTG) treatment leads to an increase in sensitivity to vasoconstrictors. To assess a potential role of the renin-angiotensin system in mediating this phenomenon, we treated patients concomitantly with the angiotensin-converting enzyme (ACE) inhibitor captopril. The anti-ischemic efficacy of organic nitrates is rapidly blunted by the development of nitrate tolerance. The underlying mechanisms are most likely multifactorial and may involve increased vasoconstrictor responsiveness. Forearm blood flow and vascular resistance were determined by using strain gauge plethysmography. The short-term responses to intraarterial angiotensin II (1, 3, 9 and 27 ng/min) and phenylephrine (an alpha-adrenergic agonist drug, 0.03, 0.1, 0.3 and 1 microg/min) were studied in 40 male patients with stable coronary artery disease. These patients were randomized into four groups receiving 48 h of treatment with NTG (0.5 microg/kg body weight per min) or placebo with or without the ACE inhibitor captopril (25 mg three times daily). In patients treated with NTG alone, the maximal reductions in forearm blood flow in response to angiotensin II and phenylephrine were markedly greater (-64 +/- 3% and -53 +/- 4%, respectively) than those in patients receiving placebo (-41 +/- 2% and -42 +/- 2%, respectively). Captopril treatment completely prevented the NTG-induced hypersensitivity to angiotensin II and phenylephrine (-33 +/- 3% and -35 +/- 3%, respectively) but had no significant effect on blood flow responses in patients without NTG treatment (-34 +/- 2% and -37 +/- 3%, respectively). We conclude that continuous administration of NTG is associated with an increased sensitivity to phenylephrine and angiotensin II that is prevented by concomitant treatment with captopril. The prevention of NTG-induced hypersensitivity to vasoconstrictors by ACE inhibition indicates an involvement of the renin-angiotensin system in mediating this phenomenon.",1998.0,0,0
2281,9426847,Effect of angiotensin converting enzyme inhibition by perindopril on proteinuria of primary renal diseases.,S M Nosrati; S Khwaja; M el-Shahawy; S G Massry,"Many primary renal diseases are associated with marked proteinuria resistant to immunosuppressive therapy. Short-term treatment with angiotensin converting enzyme (ACE) inhibitors may decrease proteinuria in these patients, but the long-term effect of these agents on urinary protein excretion is not known. We conducted a double-blind, parallel-design, placebo-controlled study of 1 year duration to evaluate the efficacy of the new ACE inhibitor, perindopril, in reducing proteinuria in patients with nephrotic syndrome due to histologically proven membranous and membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Half of the patients treated with perindopril displayed a decrease in urinary protein excretion from 6.1 +/- 1.0 to 1.2 +/- 0.5 g/24 h, and a rise in serum albumin levels. In the placebo group, protein excretion increased modestly and serum albumin level did not change. There was no difference between the responders and nonresponders to perindopril in age, blood pressure, level of creatinine clearance or urinary sodium excretion. However, the degree of proteinuria before treatment with perindopril was significantly (p < 0.01) higher in the nonresponders. In 3 patients in whom the treatment with perindopril was extended for 18-24 months, urinary protein excretion remained below 1 g/24 h. The data show that perindopril: (1) is an effective agent in the treatment of proteinuria of primary renal diseases; (2) the effect is sustained for up to 2 years if the administration of the drugs is maintained, and (3) this action of perindopril does not depend on the level of sodium intake.",1998.0,0,0
2282,9431480,Effect of angiotensin-converting enzyme inhibitors on the power spectrum of heart rate variability in post-myocardial infarction patients.,A G Kontopoulos; V G Athyros; A A Papageorgiou; V M Skeberis; E C Basayiannis; H Boudoulas,"Heart rate variability (HRV) time and frequency domain indices are strong predictors of malignant arrhythmias and sudden cardiac death. The effect of various angiotensin-converting enzyme (ACE) inhibitors on HRV in patients with acute myocardial infarction (AMI) has not been studied. Ninety patients with uncomplicated AMI (age range 39-75 years, median 61 years) were assigned randomly to six groups of 15 patients each. They were treated with placebo or one of the following ACE inhibitors for 30 days: captopril, cilazapril, enalapril, lisinopril or quinapril. HRV was assessed 3 days after the onset of AMI (baseline), and 30 days after treatment. Fifteen patients with stable coronary artery disease and 15 healthy volunteers, age- and sex-matched with AMI patients, served as controls. At baseline, time and frequency domain HRV indices in the AMI groups were equally less than those in patients with stable coronary artery disease and normal volunteers. Compared with placebo, quinapril, lisinopril and captopril changed frequency domain HRV indices 30 days after initiation of treatment, indicating an increase in vagal tone, whereas enalapril and cilazapril had no significant effect on these indices. Most of the time domain HRV indices 30 days after initiation of treatment increased significantly in all patients treated with ACE inhibitors, but remained unchanged in the placebo group. Frequency domain and time domain HRV indices 30 days after treatment in the quinapril group did not differ statistically from those in patients with stable coronary artery disease, but were less than those in normal volunteers. Quinapril, lisinopril and captopril improved frequency domain HRV indices related to vagal tone, whereas cilazapril and enalapril had no effect on these indices. This influence of some ACE inhibitors on HRV may be beneficial in reducing the risk for sudden death in post-myocardial infarction patients.",1998.0,0,0
2283,9431857,Relationships between changes in left ventricular mass and in clinic and ambulatory blood pressure in response to antihypertensive therapy.,R H Fagard; J A Staessen; L Thijs,"To analyse the relationships between changes in left ventricular mass in response to 6-month antihypertensive therapy and changes in conventional and automated measurements of clinic blood pressure, average 24 h ambulatory blood pressure and daytime and night-time blood pressures. After a placebo run-in period, patients with essential hypertension (World Health Organization stages I-II) were treated for 6 months with one or a combination of two first-line antihypertensive drugs. Investigations included echocardiography, conventional and automated clinic blood pressure measurements and ambulatory blood pressure monitoring. Daytime and night-time blood pressures were assessed according to two clock-time-dependent and two clock-time-independent methods, with a wide and a narrow approach for each technique. Fifty-four patients completed the 6-month treatment period. Left ventricular mass, adjusted for sex and body size, was correlated significantly to systolic and diastolic clinic blood pressures, both before (r = 0.57 and r = 0.48, P < 0.001) and during antihypertensive therapy (r = 0.43, P < 0.001 and r = 0.27, P < 0.05). Changes in left ventricular mass were significantly related to changes in blood pressure. The correlation coefficients amounted to 0.39 (P < 0.01) and 0.40 (P < 0.01) for the conventional and automated measurements of clinic systolic blood pressures, respectively, and to 0.45 (P < 0.001) for the average 24 h systolic blood pressure; these r values were 0.27 (NS), 0.20 (NS) and 0.43 (P < 0.01), respectively, for the diastolic blood pressure. The average 24 h blood pressure added 7.4% (P < 0.05) and 6.2% (P = 0.06) to the variance of the changes in mass explained in terms of the conventional and the automated measurements of clinic systolic blood pressures, respectively, and 11.2% (P < 0.05) and 14.5% (P < 0.01) for the diastolic blood pressures. The changes in daytime and night-time blood pressures predicted the changes in left ventricular mass significantly (P < 0.01) and to a similar extent, irrespective of the analytical method. The treatment-induced changes in left ventricular mass were significantly related to the changes in clinic, 24 h, daytime and night-time blood pressures; the changes in 24 h ambulatory blood pressure add to the variance of the changes in left ventricular mass explained in terms of clinic blood pressure data.",1998.0,0,0
2284,9433426,Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. The EUCLID Study Group. EURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus.,N Chaturvedi; A K Sjolie; J M Stephenson; H Abrahamian; M Keipes; A Castellarin; Z Rogulja-Pepeonik; J H Fuller,"Retinopathy commonly occurs in people with type 1 diabetes. Strict glycaemic control can decrease development and progression of retinopathy only partially. Blood pressure is also a risk factor for microvascular complications. Antihypertensive therapy, especially with inhibitors of angiotensin-converting enzyme (ACE), can slow progression of nephropathy, but the effects on retinopathy have not been established. We investigated the effect of lisinopril on retinopathy in type 1 diabetes. As part of a 2-year randomised double-blind placebo-controlled trial, we took retinal photographs at baseline and follow-up (24 months) in patients aged 20-59 in 15 European centres. Patients were not hypertensive, and were normoalbuminuric (85%) or microalbuminuric. Retinopathy was classified from photographs on a five-level scale (none to proliferative). The proportion of patients with retinopathy at baseline was 65% (117) in the placebo group and 59% (103) in the lisinopril group (p = 0.2). Patients on lisinopril had significantly lower HbA1c at baseline than those on placebo (6.9% vs 7.3 p = 0.05). Retinopathy progressed by at least one level in 21 (13.2%) of 159 patients on lisinopril and 39 (23.4%) of 166 patients on placebo (odds ratio 0.50 [95% CI 0.28-0.89], p = 0.02). This 50% reduction was the same when adjusted for centre and glycaemic control (0.55 [0.30-1.03], p = 0.06). Lisinopril also decreased progression by two or more grades (0.27 [0.07-1.00], p = 0.05), and progression to proliferative retinopathy (0.18 [0.04-0.82], p = 0.03). Progression was not associated with albuminuric status at baseline. Treatment reduced retinopathy incidence (0.69 [0.30-1.59], p = 0.4). Lisinopril may decrease retinopathy progression in non-hypertensive patients who have type 1 diabetes with little or no nephropathy. These findings need to be confirmed before changes to clinical practice can be advocated.",1998.0,0,1
2285,9438650,Angiotensin converting enzyme inhibitors and reflux nephropathy: 2-year follow-up.,G Lama; M E Salsano; M Pedulla'; C Grassia; G Ruocco,"We evaluated the effect of 2 years' therapy with an angiotensin converting enzyme inhibitor (captopril) in 16 patients who had severe reflux nephropathy and microalbuminuria. During the period of therapy, microalbuminuria decreased, glomerular filtration rate measured by diethylenetriamine pentaacetate scan, serum creatinine, and blood pressure remained stable. We suggest the captopril was useful in reducing microalbuminuria and may have slowed the progression of renal damage in our patients.",1998.0,0,0
2286,9442441,Are me-too drugs justified?,S Garattini,"The successful progress of pharmacology in the treatment of several diseases has led to the development of a powerful pharmaceutical industry with an estimated market of over $250 billion. It is therefore understandable that as drug development and marketing has become a major business it has adopted the rules common to other commercial fields. This is a potentially dangerous trend because it undermines what should be the main goal of drug development, i.e. to make active medicinal agents available to the patient with precise and reliable information, at the lowest possible cost, particularly when a national health system has to supply the drugs to patients who have too low an income to pay for them. The huge drug market has also set in motion a competition among pharmaceutical firms. This has meant that as soon as a prototype drug becomes available several other similarly active compounds immediately follow. These followers are usually called ""me-too drugs"". Me-too drugs can be broadly defined as chemically related to the prototype, or other chemical compounds which have an identical mechanism of action. This increasing marketing of me-too drugs has been questioned, so pharmaceutical firms are justifying the development of not-so-innovative drugs. The most common arguments can be summarized as follows: me-too drugs offer an improvement on the efficacy of the prototype; they show a different profile of adverse effects; they are effective in patients resistant to the prototype; they improve compliance in long-term treatment; they are less expensive than the prototype. It is the purpose of this paper to review the evidence substantiating these statements, giving some figures regarding me-too drugs and presenting a few examples.",2000.0,0,0
2287,9443770,Bisoprolol and captopril effects on insulin receptor tyrosine kinase activity in essential hypertension.,L J Dominguez; M Barbagallo; S J Jacober; D B Jacobs; J R Sowers,"Angiotension converting enzyme (ACE) inhibitors and beta-blockers have been reported to possess disparate effects on insulin sensitivity. The aim of this study was to study the effects of the selective beta-1 blocker bisoprolol and of the ACE inhibitor captopril on cellular insulin action in hypertensive individuals. After washout, 12 mild to moderate essential hypertensives were randomized in a double-blind manner to 5 mg bisoprolol daily or 25 mg captopril twice daily for 8 weeks. Erythrocyte insulin binding and insulin-stimulated tyrosine kinase (TK) activity were measured before and after therapy. Both agents decreased diastolic blood pressure significantly (bisoprolol 96.5+/-0.9 to 87.8+/-3.1 mm Hg; captopril 96.5+/-0.9 to 91.5+/-1.8 mm Hg; P < .05). Fasting plasma glucose, insulin, and insulin/glucose indices remained unchanged after both therapies, as did lipid profiles. Maximal insulin-stimulated TK activity, assessed by phosphorylation of the exogenous substrate poly-Glu80Tyr20, was significantly higher (P < .05) after bisoprolol treatment, but not after captopril treatment, when compared to placebo (bisoprolol 8.5+/-1.8; captopril 7.3+/-1.5; placebo: 6.4+/-1.3 pmol 32P-ATP/fmol bound insulin). However, captopril, but not bisoprolol, increased the sensitivity of the receptor TK activity, as measured by the half-maximal activity concentration (ED50). Specific insulin binding was not affected by these two agents. Thus, both captopril and bisoprolol may have favorable but different effects on TK activity and insulin action at the cellular level.",1998.0,0,0
2288,9444298,"Combination neurohormonal blockade with ACE inhibitors, angiotensin II antagonists and beta-blockers in patients with congestive heart failure: design of the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study.",R T Tsuyuki; S Yusuf; J L Rouleau; A P Maggioni; R S McKelvie; E M Wiecek; Y Wang; J Pogue; K K Teo; M White; A Avezum; R Latini; P Held; E Lindgren; J Probstfield,"The Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study is a trial of combination neurohormonal blockade using an angiotensin II antagonist (candesartan), an angiotensin-converting enzyme inhibitor (enalapril) and a beta-blocker (metoprolol) in patients with congestive heart failure (CHF). Primary objectives of stage I are to determine the efficacy (via the 6 min walk test) and safety of candesartan alone, and in combination with enalapril, versus enalapril alone. Secondary objectives are to determine the effect of the above combinations on neurohormones, ventricular function, quality of life and symptoms. Stage II objectives are similar, evaluating the effect of the addition of metoprolol or placebo to the above medication(s). Randomized, two-stage trial consisting of a three-way comparison (stage I), followed by a 3 x 2 partial factorial design (stage II). Sixty out-patient clinics in five countries. Patients with symptoms of CHF (New York Heart Association functional classes II to IV), ejection fraction less than 40% and 6 min walk distance of 500 m or less. In stage I, 770 patients are randomized to receive candesartan alone, enalapril alone, or candesartan plus enalapril. After five months (end of stage I), patients are assessed for eligibility to be randomized in stage II. Those who are not candidates for randomization to beta-blocker or placebo are followed on their stage I medications until the end of the study. In stage II, patients are randomized to receive metoprolol or placebo for a further six months in addition to their stage I medications. Endpoints are measured at baseline, end of stage I (week 20) and end of stage II (week 46). STUDY STATUS: The study has recently completed follow-up in both stages. The findings from this study will be used to design a large scale mortality study that will help further define the role of neurohormonal blockade in patients with CHF.",2001.0,0,0
2289,9455569,Rhabdomyolysis in human immunodeficiency virus--positive patients taking trimethoprim-sulfamethoxazole.,S J Singer; J A Racoosin; R Viraraghavan,,1998.0,0,0
2290,9458406,Evaluation of Losartan in the Elderly (ELITE) Trial: clinical implications.,B Pitt,,1998.0,0,0
2291,9458425,Beneficial effect of enalapril on left ventricular remodelling in patients with a severe residual stenosis after acute anterior wall infarction.,L H Baur; J J Schipperheyn; E E van der Wall; E A van der Velde; M J Schalij; B L van Eck-Smit; A van der Laarse; P J Voogd; M I Sedney; J H Reiber; A V Bruschke,"The present study was designed to evaluate the effects of early angiotensin converting enzyme (ACE) inhibition on left ventricular enlargement in patients with anterior wall infarction following reperfusion therapy. Seventy-one consecutive patients with an anterior wall myocardial infarction were randomly allocated to enalapril (n = 36) or placebo (n = 35). All patients received either thrombolytic therapy (n = 46) or underwent primary coronary angioplasty (n = 25). Medication was started within 48 h admission to hospital and continued for 48 weeks. The process of left ventricular remodelling was assessed with two-dimensional echocardiography at 3 weeks and 1 year after the acute onset, and was related to the severity of the residual stenosis of the infarct-related artery. Baseline left ventricular ejection fraction was 39.2% +/- 8.7%. During the study period left ventricular end-diastolic volume index increased from 48.2 +/- 9.9 ml.m-2 to 54.6 +/- 12.2 ml.m-2 at 3 weeks, and to 59.4 +/- 17.0 ml.m-2 after 1 year I control patients (P < 0.001). In the enalapril-treated patients, left ventricular end-diastolic volume index increased from 50.0 +/- 16.1 to 57.7 +/- 19.3 ml.m-2 at 3 weeks, and to 61.9 +/- 22.7 ml.m-2 after 1 year (P < 0.001). Both at 3 weeks and after 1 year, no overall differences in left ventricular volumes were observed between the enalapril and the placebo group (both ns). However, patients with a residual stenosis severity of > or = 70% in the infarct-related artery (n = 43) showed significant attenuation of remodelling by enalapril (n = 22) when compared to placebo (n = 21). In patients on enalapril, left ventricular end-diastolic volume index increased from 47.0 +/- 13.0 to 53.7 +/- 17.7 ml.m-2 compared to 48.0 +/- 9.6 to 60.3 +/- 16.3 ml.m-2 in control patients (P < 0.03). Also diastolic filling parameters were significantly improved in patients with > or = 70% residual stenosis. In patients with an anterior wall infarction and a severe residual infarct-related coronary artery stenosis following reperfusion, treatment with enalapril prevents the process of left ventricular remodelling. As left ventricular dilatation is an early process we suggest that treatment with ACE inhibition should be started as soon as possible in this group of patients.",1998.0,0,0
2292,9462588,Antiplatelet agents and survival: a cohort analysis from the Studies of Left Ventricular Dysfunction (SOLVD) trial.,A S Al-Khadra; D N Salem; W M Rand; J E Udelson; J J Smith; M A Konstam,"This study sought to evaluate the relation between antiplatelet agent (APA) use and survival and morbidity from cardiac disease in patients with left ventricular (LV) systolic dysfunction. APAs play an important role in the prevention and treatment of coronary disease. Their effects in patients with LV systolic dysfunction are unknown. We reviewed data on APA use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between their use and all-cause mortality as well as the combined end point of death or hospital admission for heart failure (HF). We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between APA use and selected patient variables in relation to outcome. APA use (46.3% of patients) was associated with significantly reduced mortality from all causes (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.73 to 0.92, p = 0.0005) and reduced risk of death or hospital admission for HF (adjusted HR 0.81, 95% CI 0.74 to 0.89, p < 0.0001) but was not influenced by trial assignment, gender, LV ejection fraction, New York Heart Association class or etiology. A strong interaction was observed among APA use, randomization group and all-cause mortality. The association between APA use and survival was not observed in the enalapril group, nor was an enalapril benefit on survival detectable in patients receiving APAs at baseline. However, randomization to enalapril therapy significantly reduced the combined end point of death or hospital admission for HF in APA users. In patients with LV systolic dysfunction, use of APAs is associated with improved survival and reduced morbidity. This association is retained after adjustment for baseline characteristics. APA use is associated with retained but reduced benefit from enalapril.",1998.0,0,0
2293,9468009,Nebivolol vs enalapril in the treatment of essential hypertension: a double-blind randomised trial.,L Van Nueten; A Schelling; C Vertommen; A G Dupont; J I Robertson,"The efficacy and acceptability of nebivolol 5 mg and enalapril 10 mg, each given once daily, were compared in essential hypertension in a multicentre, randomised, double-blind trial over 3 months. For the index pre-declared variable, sitting diastolic pressure at trough drug level, nebivolol achieved greater falls in pressure (-12.3 vs -9.9 mmHg; P = 0.009) and a higher response rate (70% vs 55%; P = 0.002). The trough-to-peak sitting diastolic ratios also favoured nebivolol (84% vs 60%, P = 0.002). Nebivolol, but not enalapril, slightly but significantly lowered heart rate. Both drugs were well-tolerated, although enalapril was accompanied by a significantly higher incidence of coughing.",1998.0,0,0
2294,9468078,Effect of early captopril treatment on blood adrenaline levels in acute myocardial infarction (the substudy of ISIS-4). International Study of Infarct Survival-4.,A Budaj; K Herbaczyńska-Cedro; F Kokot; L Ceremuzyński,"Of patients with acute myocardial infarction eligible for the International Study of Infarct Survival-4, randomized to captopril (n = 30) or placebo (n = 33), the captopril group had a significant decrease in blood adrenaline on day 3 compared with baseline values. Results suggest that suppression of sympathetic activity contributes to the beneficial effects of treatment with angiotensin-converting enzyme inhibitors in the early phase of acute myocardial infarction.",1998.0,0,0
2295,9468459,Reduction of left ventricular mass by antihypertensive treatment does not improve exercise performance in essential hypertension.,R H Fagard; P J Lijnen,"To test the hypothesis that a reduction in left ventricular mass by long-term antihypertensive treatment, possibly associated with an improvement of diastolic function, would increase exercise performance in patients with essential hypertension. DESIGNS After a placebo run-in period, 27 patients with essential hypertension World Health Organization stages I and II were assigned randomly to 6-month double-blind treatment with either a diuretic (hydrochlorothiazide plus triamterene) or a converting enzyme inhibitor (trandolapril), to which the calcium antagonist amlodipine could be added after 3 months if required for better blood pressure control. Investigations included clinic and ambulatory blood pressure measurements, left ventricular imaging and transmitral Doppler echocardiography and graded maximal exercise testing on the bicycle ergometer with respiratory gas analysis. Six-month antihypertensive therapy, which caused significant (P < 0.001) reductions in blood pressure (by 16% for clinic pressure) and in left ventricular mass (by 13%), but without convincing evidence of improved diastolic function, did not affect exercise performance or peak oxygen uptake. The influence on clinic, exercise and ambulatory blood pressures and on the peak oxygen uptake was similar in the two treatment arms but left ventricular wall thickness decreased to a greater extent in the trandolapril group (P< 0.05 at 3 months and P= 0.06 at 6 months). Regression of left ventricular mass caused by 6-month antihypertensive therapy does not improve exercise performance of patients with essential hypertension.",1998.0,0,0
2296,9470059,Captopril plus losartan in early post-infarction. Neurohormonal effects: a pilot study.,P Di Pasquale; S Cannizzaro; A M Longo; G Maringhini; R Iachininoto; S Paterna,"Suppression of the formation of angiotensin II (A II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-inhibitor) therapy. However, during ACE-inhibitor treatment, A II plasma levels may also recover through tissue chymase. This study has attempted to verify the feasibility, safety and tolerability of a combined treatment using captopril (75 mg/day) and losartan (25 mg/day), and to ascertain its ability to reduce the formation and action of A II in the early post-infarction phase of reperfused anterior myocardial infarction (AMI). Forty-four patients hospitalized for suspected AMI within 4 hours of the onset of symptoms, who were suitable for thrombolysis (first episode), in Killip class I-II, reperfused, treated with 75 mg/day of captopril within 3 days of admission and with a blood pressure level of more than 120 mmHg, were randomized (single-blind) into two groups that were similar with regard to age, sex, blood pressure, CK peak, ejection fraction, end-systolic volume and risk factors. Group A (22 subjects: 6 women/16 men) received captopril (75 mg/day) and placebo, while group B (22 subjects: 5 women/17 men) was given captopril (75 mg/day) plus losartan, initially at 12.5 mg and then at 25 mg/day thereafter (BP > 110 mmHg). Norepinephrine (NE) and A II plasma levels were measured on the third and tenth day after admission. Ten days after admission, group B (captopril plus losartan) showed a significant decrease in blood pressure (BP) on an intragroup level (p < 0.001) as well as in comparison with group A (p < 0.001), with values of 108 + 6.4 and 118 + 11 mmHg respectively. At the same time interval, NE and A II values did not show significant differences within or between groups. CONCLUSIONS. For the first time, our data suggest that a combined captopril-losartan treatment is feasible and that it has no particular side effects. In addition, it shows no significant increase of A II that would be produced by losartan alone.",1998.0,0,0
2297,9473956,An open trial of lisinopril ('ZESTRIL') in mild to moderate hypertension in Nigeria.,C U Abengowe; E N Ezedinachi; M O Balogun,"Fifty-one native Nigerian patients with mild to moderate essential hypertension received Lisinopril ('Zestril') in doses of 10 mg to 40 mg once daily. All patients received an initial dose of 10 mg, which was titrated up to a maximum of 40 mg if normotensive diastolic blood pressure had not been achieved. Reduction in mean diastolic blood pressure, when compared with baseline data, was significant (p < 0.001) following 16 weeks of treatment. Of the 46 evaluable patients, 32 (70%) had their blood pressure controlled (i.e. diastolic blood pressure < or = 90 Hg). Lisinopril ('Zestril') was well tolerated, with 27% of patients reporting adverse reactions of which cough was the most common. In conclusion, this study shows that Lisinopril ('Zestril""), when administered to Nigerian patients, is a clinically effective and well-tolerated for mild to Customer to supply Mss.",1998.0,0,0
2298,9475259,Effect of quinapril and triamterene/hydrochlorothiazide on cardiac and vascular end-organ damage in isolated systolic hypertension.,W F Heesen; F W Beltman; A J Smit; J F May; P A de Graeff; T K Havinga; F H Schuurman; E van der Veur; B Meyboom-de Jong; K I Lie,"We compared, in a prospective double-blind randomized study, the effect of the angiotensin-converting enzyme inhibitor quinapril (QUI) with that of triamterene/hydrochlorothiazide (THCT) treatment on cardiovascular end-organ damage in subjects with untreated isolated systolic hypertension (ISH). End-organ damage measurements, performed initially and after 6 and 26 weeks of treatment, included echocardiographic determination of left ventricular mass index (LVMI) and of diastolic function and measurement of aortic distensibility and peripheral vascular resistance. Blood pressure was significantly reduced in the 44 subjects (21 QUI, 23 THCT) completing the study. Both LVMI and aortic distensibility had changed at 6 weeks, with comparable improvements in both groups. LV diastolic function showed overall no significant changes, although patterns of early filling did differ between the two drug groups. Peripheral vascular resistance appeared to increase between 6 and 26 weeks in THCT subjects only, along with a decreased aortic distensibility. Blood pressure and LV mass were rapidly and markedly reduced in both treatment groups of ISH subjects, paralleled by an improvement of aortic distensibility. In interpreting these results, the pathophysiologic alterations in ISH need to be taken into account, because these differ strongly from those in diastolic hypertension. Results of LV diastolic function and peripheral vascular resistance were less clear but appear to show less favorable changes in the THCT subjects treatment group.",1998.0,0,0
2299,9475903,Trials of CCBs.,S R Sukkari; L D Sasich,,1998.0,0,0
2300,9477394,Effects of captopril and enalapril on zinc metabolism in hypertensive patients.,A Golik; R Zaidenstein; V Dishi; A Blatt; N Cohen; G Cotter; S Berman; J Weissgarten,"To investigate the effect of chronic captopril and enalapril treatment on zinc metabolism in hypertensive patients by assessing zinc levels in serum, urine and monocytes. Patients with newly diagnosed essential hypertension were randomly divided into two treatment groups: those treated with captopril only (n = 16) and those treated with enalapril only (n = 18). Ten healthy subjects served as controls. Prior to the start of treatment and again 6 months later, zinc was assessed in the serum, in urine collected over 24 hours, and in peripheral blood monocytes. Significant enhancement of 24-hour urinary zinc excretion (micrograms/24 hour) after 6 months of treatment was observed only in the captopril-treated group (p < 0.01). However, intramonocytic zinc levels decreased significantly in both of the treated groups over the same period (p < 0.01 and P < 0.04 in the captopril- and enalapril-treated groups, respectively). Treatment of hypertensive patients with captopril or enalapril may result in zinc deficiency.",1998.0,0,0
2301,9482137,Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.,N Martell; B Gill; R Marin; C Suarez; J L Tovar; P Cia; C Fernandez; L Gonzalez; A Maldonado; F Fernández; C del Arco; I Garcia; I Yuste; M Luque,"The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.",1998.0,0,0
2302,9486936,Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension.,T Ishimitsu; S Yagi; A Ebihara; Y Doi; A Domae; A Shibata; M Kimura; Y Sugishita; E Sagara; T Sakamaki; K Murata,"For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.",1998.0,0,0
2303,9486993,The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension.,R O Estacio; B W Jeffers; W R Hiatt; S L Biggerstaff; N Gifford; R W Schrier,"It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications. Because this issue remains controversial, we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were randomly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study. The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial is a prospective, randomized, blinded trial comparing the effects of moderate control of blood pressure (target diastolic pressure, 80 to 89 mm Hg) with those of intensive control of blood pressure (diastolic pressure, 75 mm Hg) on the incidence and progression of complications of diabetes. The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes. In the current study, we analyzed data on a secondary end point (the incidence of myocardial infarction) in the subgroup of patients in the ABCD Trial who had hypertension. Analysis of the 470 patients in the trial who had hypertension (base-line diastolic blood pressure, > or = 90 mm Hg) showed similar control of blood pressure, blood glucose and lipid concentrations, and smoking behavior in the nisoldipine group (237 patients) and the enalapril group (233 patients) throughout five years of follow-up. Using a multiple logistic-regression model with adjustment for cardiac risk factors, we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infarctions (a total of 24) than enalapril (total, 4) (risk ratio, 9.5; 95 percent confidence interval, 2.7 to 33.8). In this population of patients with diabetes and hypertension, we found a significantly higher incidence of fatal and nonfatal myocardial infarction among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril. Since our findings are based on a secondary end point, they will require confirmation.",1998.0,0,1
2304,9488243,The natriuretic effect of nifedipine gastrointestinal therapeutic system remains despite the presence of mild-to-moderate renal failure.,C Campo; O Garcia-Vallejo; V Barrios; V Lahera; M Manero; E Esteban; J L Rodicio; L M Ruilope,"Calcium channel blockers facilitate the renal excretion of sodium and this effect is maintained during chronic administration of these drugs. However, it is unknown whether this natriuretic effect remains despite the presence of a decreased renal function. To compare the natriuretic capacity of nifedipine gastrointestinal therapeutic system (GITS) and lisinopril in patients with mild-to-moderate chronic renal failure. An open-label, randomized, comparative study was conducted to compare the natriuretic capacity of nifedipine GITS and lisinopril in the presence of mild-to-moderate renal failure (creatinine clearance 30-80 ml/min). After a wash-out period of 4 weeks an intravenous saline infusion (30 ml/kg of body weight of isotonic saline in 4 h) was performed and repeated after 4 weeks of active therapy. Two sex- and age-matched groups of hypertensive patients (n = 25) were included in the study. Renal failure was diagnosed as secondary to nephrosclerosis in all the patients. A significant increase in the renal capacity to excrete the sodium load was observed in patients receiving nifedipine GITS (n = 11) but not in those taking lisinopril (n = 13). Both drugs controlled blood pressure to a similar extent. No changes were observed in body weight, glomerular filtration rate and renal plasma flow (measured as inulin and paraaminohippurate clearances). A significant drop was observed in urinary albumin excretion after lisinopril, but not after nifedipine. Heart rate was higher in nifedipine group. The natriuretic capacity of nifedipine GITS remains despite the presence of mild-to-moderate chronic renal failure. Such an effect takes place in the absence of changes in renal hemodynamics, suggesting that it is caused by a direct tubular effect.",1998.0,0,0
2305,9489068,Cardiac amyloidosis and the use of diuretic and ACE inhibitor therapy in severe heart failure.,K L Nash; S O Brij; G J Clesham,"The underlying cause of heart failure should be established, where possible. In particular the failure to respond to diuretic and vasodilator therapy requires careful evaluation.",1998.0,0,0
2306,9489071,Fosinopril national survey: a post-marketing surveillance study of fosinopril (Staril) in general practice in the UK.,C Edwards; D A Blowers; G M Pover,"This open, non-comparative, PMS study of fosinopril (Staril) involved 12,067 hypertensive patients assessed at baseline and after two and six months of treatment; 10,791 patients provided evaluable data with 5.2 months average treatment totalling 4667 patient-years. Adverse events were reported in 24% of patients, the most common being mild-to-moderate cough (6.05%). Events considered possibly related to fosinopril were reported in 15% of patients, the frequency being lower in younger patients, males and those receiving fosinopril monotherapy. Patient well-being improved during the study. At the end of the study, most patients were taking fosinopril 10 mg once daily. Mean reductions in systolic and diastolic blood pressures were -11.0% and -11.7%, respectively; 71.3% of patients were 'responders'. No important differences were observed between subgroups. This study found fosinopril to be effective, well tolerated in a broad range of hypertensive patients, and with no previously unrecognised adverse events reported.",1998.0,0,0
2307,9489970,Effect of angiotensin-converting enzyme inhibitor dosing interval on functional parameters in patients with chronic heart failure.,H Krum; J Karrasch; A Hamer; D Hare; L G Howes; B Jackson; P Leslie,,1998.0,0,0
2308,9495661,Does lowering the blood pressure improve the mood? Quality-of-life results from the Hypertension Optimal Treatment (HOT) study.,I Wiklund; K Halling; T Rydén-Bergsten; A Fletcher,"Nine-hundred-and-twenty-two hypertensive patients were included in a substudy to the Hypertension Optimal Treatment study, which aimed to investigate the impact on quality of life of lowering the pressure and of intensified therapy. Seven-hundred-and-eighty-one patients completed both baseline and follow-up questionnaires (intention-to-treat population), while 610 patients were included in a per protocol analysis. Patients were randomized to three diastolic BP levels (DBPs), i.e. < or =90 mmHg, < or =85 mmHg and < or =80 mmHg. Two self-administered validated questionnaires, the Psychological General Well-Being index and the Subjective Symptoms Assessment Profile (SSA-P) were completed at baseline and after 6 months. The lower the DBP achieved, the greater the improvement in well-being (p < 0.05). The increase in well-being from baseline to 6 months was significant in target groups < or =80 mmHg (p < 0.01) and < or =85 mmHg (p < 0.05). The SSA-P domains, cardiac symptoms and dizziness improved in all groups but the sex life score deteriorated in the < or =80 and < or =85 mmHg groups in male patients. In all target groups, headaches were reduced (p < 0.001), while swollen ankles (p < 0.001) and dry cough in the < or =80 mmHg group (p < 0.001) increased. Although more intensive antihypertensive therapy is associated with a slight increase in subjective symptoms, it is nonetheless still associated with improvements in patients' well-being.",1998.0,0,0
2309,9495662,The Captopril Prevention Project (CAPPP) in hypertension--baseline data and current status.,L Hansson; T Hedner; L Lindholm; A Niklason; K Luomanmäki; L Niskanen; J Lanke; B Dahlöf; U de Faire; C Mörlin; B E Karlberg; P O Wester; J E Björck,"The Captopril Prevention Project (CAPPP) is an ongoing intervention study conducted in 11,019 hypertensive patients in Sweden and Finland. Patients have been randomized to receive either conventional antihypertensive therapy (diuretics and/or beta-blockers) or captopril-based treatment. A prospective, randomized, open, blinded-endpoint evaluation (PROBE) study design is used to compare these two therapeutic regimens as regards cardiovascular morbidity and mortality. The rationale for the CAPPP Study are the many observations of beneficial effects of ACE inhibition, as compared to diuretics and beta-blockers, on intermediary endpoints such as insulin sensitivity, serum lipoproteins, left ventricular hypertrophy and renal function. Captopril has also been shown to be markedly effective in the treatment of left ventricular dysfunction as well as congestive heart failure. The hypothesis is that these differences might result in improved risk reduction when ACE inhibitors are used in the treatment of hypertension. The present paper describes the baseline data and the changes in blood pressure during the first year in the total cohort. During the first year the average blood pressure was reduced by 11/8 mm Hg. A number of substudies have been conducted in the CAPPP Study. In one of these insulin sensitivity was compared in a subgroup of the patients using the euglycemic insulin clamp technique. In another substudy the ACE gene was sequenced and some new polymorphisms were discovered. Several other substudies are in progress or in the planning phase. The main results of the CAPPP Study should be available by mid-1998. Some of the intended anayses of the final results as well as other planned substudies are briefly described here.",1998.0,0,0
2310,9498655,"Renal autoregulation is normal in newly diagnosed, normotensive, NIDDM patients.",J P New; S M Marshall; R W Bilous,"Abnormalities of renal autoregulation with glomerular hyperfiltration and raised intraglomerular pressure have been suggested as important factors in the initiation and development of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibition appears to have a specific reno-protective role in diabetic nephropathy, possibly by reducing intraglomerular pressure. The acute effects of ACE inhibition on renal haemodynamics in normotensive, non-insulin-dependent diabetes mellitus (NIDDM) have not been previously reported. We measured simultaneous glomerular filtration rate (GFR) and renal plasma flow (RPF) in 29 (4 female) subjects, mean age 52 years (range 27-70), using 51Cr EDTA and 125I Hippuran. Clearances were corrected to 1.73 m(-2). All patients were normotensive (blood pressure < 75th centile for age and sex), newly diagnosed (< 30 days), taking no antihypertensive or hypoglycaemic medication. Subjects were randomly allocated (double blind) to receive the ACE inhibitor trandolapril 4mg day(-1) (H) (hypotensive dose), trandolapril 0.5 mg day(-1)(L) (non-hypotensive dose) or placebo (P) for 10 days after which renal haemodynamics were remeasured. For all subjects baseline GFR, RPF and filtration fraction (FF) were 97+/-21 ml min(-1) mean+/-SD, 439+/-120 ml min(-1) and 22.3+/-2.9 % respectively. Glomerular hyperfiltration (GFR> 120 ml min[-1]) was only demonstrated in 3 subjects (10.3 %). In group H mean arterial pressure (103+/-8 vs 93+/-9 mmHg, p < 0.001) and FF (23.8+/-2.3 vs 20.0+/-4.0%, p = 0.03) fell while RPF increased (376+/-111 vs 426+/-60 ml min(-1), p = 0.02), there was no significant change in GFR. No significant change in mean arterial pressure, GFR, RPF or FF occurred in groups P and L. These studies suggest that in newly diagnosed normotensive NIDDM subjects normal renal autoregulation occurs and glomerular hyperfiltration is uncommon.",1998.0,0,0
2311,9503167,Radiotherapy to inhibit coronary restenosis: kind of a light at the end of the tunnel?,P S Teirstein,,1998.0,0,0
2312,9504354,Double-blind crossover study of the interaction between perindopril and amlodipine on blood pressure and hormones related to fluid and electrolyte balance in patients with essential hypertension.,G S Stokes; J C Monaghan; K Berman; M Ryan; D J Campbell,"This study was to investigate the interaction between low doses of perindopril (2 mg daily) and amlodipine (2.5 mg daily) on ambulatory blood pressure (BP), clinic BP, serum angiotensin-converting enzyme (ACE), plasma levels of renin (PRA), angiotensin II (Ang II), aldosterone, and atrial natriuretic peptide (alpha-h ANP) in subjects with essential hypertension. The study design was a parallel, two-period, placebo-controlled, double-blind crossover design, with 11 subjects receiving perindopril and 10 receiving amlodipine during the run-in phase. The addition of amlodipine to perindopril had no effect on ambulatory BP, whereas the addition of perindopril to amlodipine reduced both systolic (P = 0.027) and diastolic (P = 0.049) ambulatory BP. By contrast, the opposite result was obtained for clinic BP at trough, whereby the addition of amlodipine to perindopril reduced erect systolic BP (P = 0.036) and both supine and erect diastolic BP (P = 0.038) whereas the addition of perindopril to amlodipine was without effect. The addition of perindopril to amlodipine decreased serum ACE by 72% and increased PRA two-fold, without change in plasma levels of Ang II, aldosterone or alpha-h ANP. The addition of amlodipine to perindopril increased plasma aldosterone 1.7-fold but did not affect serum ACE, PRA, Ang II, or alpha-h ANP. These interactions between perindopril and amlodipine may have been conditioned by the specific effects of the therapy first given, as well as by the different circumstances of BP measurement (ambulatory vs clinic).",1998.0,0,0
2313,9504446,Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension.,W C Cushman; J D Cohen; R P Jones; T C Marbury; R B Rhoades; L K Smith,"The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation (ER) (E/D) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension. The trial design was a multicenter, randomized, double blind, placebo controlled, parallel group, 12 week treatment phase, followed by a 36 week, open label phase. A total of 891 patients with sitting diastolic blood pressure (SiDBP) between 95 and 115 mm Hg were randomly assigned to enalapril 5 mg, diltiazem ER 120 mg, diltiazem ER 180 mg, enalapril 5 mg/diltiazem ER 120 mg (E5/D120), enalapril 5 mg/ diltiazem ER 180 mg (E5/D180), or placebo. In the open label phase, 562 patients received the fixed combination, titrated as needed to control SiDBP < 90 mm Hg. Efficacy was determined with trough (24 +/- 2 h postdose) sitting blood pressure measurements at week 12 and at the end of the open label part of the study. Safety was evaluated based on patient symptoms, clinical laboratories, and electrocardiograms (ECG). E5/D120 and E5/D180 significantly reduced trough SiDBP (-7.6 and -8.3 mm Hg, respectively; P < .05) versus their monotherapies. E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure (-7.9 and -9.0, respectively; P < .05) versus both diltiazem ER monotherapies. All active treatments significantly decreased SiDBP and SiSBP versus placebo. E/D effectively lowered SiDBP and SiSBP during the open label extension. No significant difference was seen among treatment groups for the overall incidence of adverse events. The most common drug related adverse events were headache, edema/swelling, dizziness, asthenia/fatigue, cough, rash, and impotence. The event frequency for the combinations were similar to those seen with the monotherapies. Fixed combinations of E/D were generally well tolerated, with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension.",1998.0,0,0
2314,9504938,"The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators.",H Krum; R J Viskoper; Y Lacourciere; M Budde; V Charlon,"Endothelin is a powerful vasoconstrictor peptide derived from the endothelium. We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by studying the effect of an endothelin-receptor antagonist, bosentan. We studied 293 patients with mild-to-moderate essential hypertension. After a placebo run-in period of four to six weeks, patients were randomly assigned to receive one of four oral doses of bosentan (100, 500, or 1000 mg once daily or 1000 mg twice daily), placebo, or the angiotensin-converting-enzyme inhibitor enalapril (20 mg once daily) for four weeks. Blood pressure was measured before and after treatment. As compared with placebo, bosentan resulted in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg (an absolute reduction of 5.7 mm Hg at each dose), which was similar to the reduction with enalapril (5.8 mm Hg). There were no significant changes in heart rate. Bosentan did not result in activation of the sympathetic nervous system (as determined by measurement of the plasma norepinephrine level) or the renin-angiotensin system (as determined by measurements of plasma renin activity and angiotensin II levels). An endothelin-receptor antagonist, bosentan, significantly lowered blood pressure in patients with essential hypertension, suggesting that endothelin may contribute to elevated blood pressure in such patients. The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation.",1998.0,0,0
2315,9506325,Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement.,W D Hager; B R Davis; A Riba; L A Moye; C C Wun; J L Rouleau; G A Lamas; M A Pfeffer,"As a result of randomized controlled trials with calcium channel blockers after myocardial infarction, concern has developed that these agents are associated with an increased risk of cardiovascular events, particularly in the presence of left ventricular dysfunction. To test the hypothesis that calcium channel blockers increase cardiovascular events in such patients, the incidence of all-cause mortality, cardiovascular death, severe heart failure, and recurrent infarction was examined in 940 patients taking calcium channel blockers and 1180 not taking them 24 hours before randomization to placebo or captopril in the Survival and Ventricular Enlargement (SAVE) Trial. All patients had an ejection fraction < or =40%. Relative risks for calcium channel blocker users versus nonusers and the 95% confidence intervals were computed with univariate and multivariate Cox regressions. Adjustments were made for differences in baseline covariates. For all causes of mortality, the relative risk for calcium channel blocker users versus nonusers was 0.96, with the 95% confidence interval of 0.78 to 1.17. In the SAVE placebo and captopril groups, the relative risks for the development of severe heart failure among the calcium channel block users versus nonusers were 0.95 and 1.23, with the 95% confidence interval of 0.72 to 1.25 and 0.88 to 1.71, respectively. A similar neutral result held for patients with and without a history of hypertension. Furthermore, calcium channel blockers did not alter the benefit of the angiotensin converting enzyme inhibitor, captopril. This analysis of the nonrandomized clinical use of calcium channel blockers in the postmyocardial infarction population with left ventricular dysfunction did not identify either a clinical deterioration or improvement with respect to subsequent cardiovascular events.",1998.0,0,0
2316,9506330,"Administration of thrombolytic therapy to 17,944 patients with acute myocardial infarction: the GISSI-3 database.",M Bobbio; S Bergerone; A P Maggioni; R Malacrida; M G Franzosi; S Barlera; G Tognoni; GISSI-3 Investigators,"There is growing interest in assessing therapy for acute myocardial infarction. Because thrombolysis was not a study therapy in the GISSI-3 trial, the decision about thrombolysis was left to the responsible physicians. We evaluated the data on thrombolytic therapy among patients with acute myocardial infarction enrolled in the GISSI-3 trial to study the relation between rate of prescription and the characteristics of patients and participating coronary care units. Complete clinical data were available for 17,944 patients randomized between June 1991 and July 1993 from 200 coronary care units in Italy. Demographic and clinical information were obtained for each patient, and each coronary care unit was classified according to patient volume, level of technology, and wide geographic area in which it was located. A multivariate logistic regression was performed with administration of thrombolytic therapy as the dependent variable and previously defined clinical and structural variables as independent variables. The most important factor in administration of thrombolytic therapy was that less than 6 hours elapse from symptom onset to hospital admission (odds ratio [OR] 14.05; 95% confidence interval [CI] 12.3 to 16.0). Next were location of coronary care unit in southern Italy (OR 1.81; 95% CI 1.62 to 2.01), presence of ST elevation at entrance electrocardiogram ECG (OR 1.47; 95% CI 1.35 to 1.61), absence of previous myocardial infarction (OR 1.35; 95% CI 1.22 to 1.49), and presence of catheterization laboratory or cardiac surgery program or both in the same hospital (OR 1.24; 95% CI 1.14 to 1.35). Coronary care units with high or low patient volume did not show different rates of administration of thrombolytic agents. The GISSI-3 experience confirmed a high rate of prescription of thrombolytic therapy to patients admitted within 6 hours of symptom onset and those with ST-segment elevation on entrance electrocardiogram. It demonstrated that patients admitted to coronary care units with catheterization laboratories or cardiac programs or both have higher chances of receiving thrombolytic treatment than those admitted to hospitals without these capabilities.",1998.0,0,0
2317,9509495,Polydipsia in chronic psychiatric patients: therapeutic trials of clonidine and enalapril.,R M Greendyke; A J Bernhardt; H E Tasbas; K S Lewandowski,"A six month long double-blind, placebo-controlled, crossover design pharmacological study was conducted on 14 chronically psychotic, institutionalized patients who suffered from chronic water abuse (""psychogenic polydipsia""). Effects of clonidine and enalapril administered separately and individually were assessed for possible beneficial effects on both physiological parameters such as diurnal weight gain, urine output, and serum sodium levels and on signs of delirium as measured by neurobehavioral testing. Improvement, particularly in tests reflecting fluid consumption, was found with either or both drugs in approximately 60% of test subjects, although no behavioral improvement was demonstrated. As a result of evidence for delayed and carry-over effects the authors recommend that future studies employ phases longer than one month and/or include washout periods.",1998.0,0,0
2318,9510492,"Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine.",F Cacciapuoti; A Capasso; G Mirra; A De Nicola; F Minicucci; S Gentile,"This perspective study was performed to demonstrate the prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril, in hypertensives of recent onset. Thirty-four hypertensive patients, treated with ramipril (group I), and 32 controls who received another frequently employed drug (the calcium channel-antagonist, felodipine (group II), were evaluated. Neither of two groups received any anti-hypertensive drug and did not suffer from left ventricular hypertrophy. All selected patients underwent M-mode echocardiography for measuring the following parameters: diastolic diameter of left ventricle, (DDLV); systolic diameter of left ventricle (SDLV); inter-ventricular septum (IVS); thickness of the posterior wall (PW); and left ventricular mass index (LVMI). Two anti-hypertensive drugs reduce systemic hypertension the same way. But, in hypertensives receiving ramipril (group I), the echocardiographic parameters of the left ventricle increased non-significantly. On the other hand, in those treated with felodipine (II group), these parameters significantly changed. The mechanisms of non-increase in cardiac and non-cardiac proteins, due to the ACE-inhibitors, are illustrated.",1998.0,0,0
2319,9513915,Acute interstitial nephritis.,D M Michel; C J Kelly,,1998.0,0,0
2320,9514183,Antihypertensive effectiveness of a very low fixed-dose combination of moexipril and hydrochlorothiazide.,S G Chrysant; M Stimpel,"The antihypertensive and metabolic effects of a fixed combination of very low dose of moexipril (MO), an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (HCTZ) were tested in a multicenter, placebo (PBO) controlled, double-blind, parallel study of men (M) and women (W) with mild to moderate essential hypertension. After 4 weeks of PBO treatment, 223 patients with sitting diastolic blood pressure (SDBP) of 95-114 mm Hg and sitting systolic blood pressure (SSBP) < or =200 mm Hg, inclusive, were randomized to PBO (114 patients: M, 56; W, 58) and MO/HCTZ 3.75/6.25 mg (109 patients: M, 58; W, 51) given once daily and followed up for 12 weeks. The fixed combination MO/HCTZ, 3.75/6.25 mg, reduced SSBP/SDBP -7.6/-7.6 mm Hg (M, -8.5/-8.0; W, -6.3/-7.0), versus PBO, +0.2/-3.9 mm Hg (M, -1.9/-3.4; W, +1.1/-4.4); p < 0.05. Also, 54% of patients receiving MO/HCTZ, 3.75/6.25 mg/day, had good blood pressure response (SDBP < or =90 mm Hg, or > or =10 mm Hg decrease from baseline), versus 28% for PBO (p < 0.001). The clinical and metabolic side effects were minor and not different between MO/HCTZ and PBO. The results of this study indicate (a) a once-daily very low dose fixed combination of MO/HCTZ is effective and well tolerated by men and women with mild to moderate essential hypertension; (b) it is almost devoid of clinical and metabolic side effects; and (c) the safety profile was similar in men and women.",1998.0,0,0
2321,9519205,Low-grade fever after prosthetic valve insertion and captopril therapy: an iatrogenic cause.,M C Bialas; H Varley; H G Shetty; P A Routledge,,1998.0,0,0
2322,9524014,Therapeutic benefits of cilazapril in patients with syndrome X.,I Nalbantgil; R Onder; A Altintig; S Nalbantgil; B Kiliçcioglu; B Boydak; H Yilmaz,"Although the pathophysiology of syndrome X (angina pectoris, positive ECG test findings and normal coronary arteriogram) is unclear, it is generally accepted that intracellular metabolic changes resulting from abnormal constriction of prearteriolar vessels due to endothelium-dependent vasodilation abnormalities may play a role in the pathogenesis. We established the effect of long-term treatment with cilazapril, an angiotensin-converting enzyme inhibitor, which prevents the effect of angiotensin II in the tonic control of vascular resistance. 18 patients (15 women and 3 men, mean age 43.2 +/- 4.6 years) with syndrome X were included in this study. A randomized double-blind crossover placebo-controlled trial was done. After a 1-week washout period, patients received either cilazapril 2 x 2.5 mg or placebo for 3 weeks, followed by 3 weeks of the other therapy. At the end of two periods, an exercise ECG test (modified Bruce protocol) was employed. The magnitude of ST segment depression was significantly decreased during treatment with cilazapril compared with placebo. On the other hand, total exercise time and time to 1 mm ST segment depression were significantly prolonged by cilazapril. However, rate pressure products were not significantly different at peak exercise at or at 1 mm of ST segment depression during both therapies. Cilazapril exerted a beneficial therapeutic effect in cases with syndrome X. The possible mechanism of this effect may be a modulation of coronary tone at the microcirculation level.",2000.0,0,0
2323,9524044,Short-term effects of withdrawing angiotensin converting enzyme inhibitor therapy on home self-measured blood pressure in hypertensive patients.,L Vaur; G Bobrie; C Dutrey-Dupagne; I Dubroca; B Vaisse; M B d'Yvoire; F Elkik; G Chatellier; J Menard,"The aim of this study was to compare blood pressure rise after interruption of two angiotensin converting enzyme (ACE) inhibitors in hypertensive patients. After a 2-week placebo run-in period, hypertensive patients were treated with either trandolapril 2 mg once daily or perindopril 4 mg once daily for 4 weeks in a double-blind design. A placebo was then administered for 1 week. Three periods of 1-week home self-measured blood pressure (SMBP) were programmed: end of placebo run-in period, end of treatment period, and final withdrawal placebo period. Every day, three consecutive measurements were requested both in the evening and in the morning. Individual reversion to baseline BP level was studied in the subgroup of patients responding to therapy (evening diastolic SMBP decrease > or =6 mm Hg). The ratio (R) of mean post-drug DBP lowering (residual effect) over evening on-drug DBP lowering (full effect) was used to study reversion to baseline. Patients exhibiting a lower value than the median of this ratio were called Reverters, whereas others were called Nonreverters. One hundred-nineteen patients entered the analysis. During the treatment period, mean SMBP decreased significantly, from 150 +/- 14/97 +/- 7 mm Hg to 139 +/- 15/91 +/- 9 mm Hg (all P < .001). The on-drug BP level was similar in the evening in the two treatment groups. However, both systolic and diastolic morning SMBP levels were significantly lower in the trandolapril group. After drug discontinuation, the mean BP level significantly rose to 144 +/- 14/94 +/- 9 mm Hg (all P = .01) but remained lower than the baseline BP values (P = .003 for SBP and P = .002 for DBP). The post-drug BP level was significantly lower in the trandolapril group than in the perindopril group. Seventy-four patients were responders to therapy. In this subgroup, the median of the R ratio used to analyze reversion to baseline after drug discontinuation was 44%. Nonreverters were characterized by a sustained on-drug BP decrease, compared to Reverters. We therefore conclude that ACE inhibitor treatment withdrawal is accompanied by a rapid rise in BP (within 48 h), followed by a 5-day BP plateau that is lower than the initial level. Reverters to baseline after drug discontinuation were more likely to be insufficiently controlled during therapy, particularly in the morning. The longer duration of action of trandolapril was associated with a lower BP level during both the morning during the active treatment phase and the 1-week posttreatment phase.",1998.0,0,0
2324,9527037,Gastrointestinal side effects of ramipril in peritoneal dialysis patients.,S Riley; P A Rutherford,,1998.0,0,0
2325,9530537,"ACE inhibitor-induced angioedema. Incidence, prevention and management.",W Vleeming; J G van Amsterdam; B H Stricker; D J de Wildt,"Available information from 1980 to 1997 on angiotensin converting enzyme (ACE) inhibitor-induced angioedema and its underlying mechanisms are summarised and discussed. The incidence of angioedema is low (0.1 to 0.2%) but can be considered as a potentially life-threatening adverse effect of ACE inhibitor therapy. This adverse effect of ACE inhibitors, irrespective of the chemical structure, can occur early in treatment as well as after prolonged exposure for up to several years. The estimate incidence is quite underestimated. The actual incidence can be far higher because of poorly recognised presentation of angioedema as a consequence of its late onset in combination with usually long term therapy. Also, a spontaneous reporting bias can contribute to an actual higher incidence of this phenomenon. The incidence can be even higher (up to 3-fold) in certain risk groups, for instance Black Americans. Treatment includes immediate withdrawal of the ACE inhibitor and acute symptomatic supportive therapy followed by immediate (and long term) alternative therapy with other classes of drugs to manage hypertension and/or heart failure. Preclinical and clinical studies for the elucidation of the underlying mechanism(s) of ACE inhibitor-associated angioedema have not generated definite conclusions. It is suggested that immunological processes and several mediator systems (bradykinin, histamine, substance P and prostaglandins) are involved in the pathogenesis of angioedema. A great part of all reviewed reports suggest a relationship between ACE inhibitor-induced angioedema and increased levels of (tissue) bradykinin. However, no conclusive evidence of the role of bradykinin in angioedema has been found and an exclusive role of bradykinin seems unlikely. So far, no clear-cut evidence for an immune-mediated pathogenesis has been found. In addition, ACE gene polymorphism and some enzyme deficiencies are proposed to be involved in ACE inhibitor-induced angioedema. Progress in pharmacogenetic and molecular biological research should throw more light on a possible genetic component in the pathogenesis of ACE inhibitor-associated angioedema.",1998.0,0,0
2326,9533423,Effects of combination therapy with an angiotensin converting enzyme inhibitor and thiazide diuretic on insulin action in essential hypertension.,S J Hunter; R Harper; C N Ennis; E Crothers; B Sheridan; G D Johnston; A B Atkinson; P M Bell,"To determine whether combination of an angiotensin converting enzyme inhibitor with a high dose of thiazide diuretic avoids adverse metabolic consequences of thiazide diuretics. Double-blind randomized crossover study of two 12-week treatment periods with captopril (up to 100 mg/day) either alone or in combination with 5 mg bendrofluazide given after a 6-week placebo run-in period. Treatment periods were separated by a 6-week placebo washout period. Outpatient clinics in greater Belfast. Fifteen white non-diabetic essential hypertensives (seven male) aged < 65 years recruited from general practices in greater Belfast. Systolic and diastolic blood pressures and peripheral and hepatic insulin action. Two patients failed to complete the study. Blood pressure was lowered (139/89+/-18/7 mmHg combination versus 160/97+/-21/7 mmHg captopril; P < 0.001). Fasting insulin level was raised (7.9+/-3.6 mU/l combination versus 6.2+/-3.2 mU/l baseline; P < 0.001). There were no differences between treatments for glucose, urate, cholesterol and triglyceride levels. Serum potassium level was lowered (3.8+/-0.4 mmol/l combination versus 4.2+/-0.4 mmol/l captopril, P < 0.05). Postabsorptive endogenous glucose production was raised (10.8+/-1.7 micromol/kg per min combination versus 10.0+/-1.5 micromol/kg per min captopril; P < 0.01) and was greater than baseline (9.7+/-2.1 micromol/kg per min, P < 0.05). Suppression of glucose production by insulin was similar with both treatments. Exogenous glucose infusion rates required to maintain euglycaemia did not differ (32.4+/-7.6 micromol/kg per min captopril, 32.7+/-6.2 micromol/kg per min combination, 31.5+/-7.2 micromol/kg per min baseline). Combination therapy increased glucose production (compared with captopril alone), indicating hepatic insulin resistance. It cannot be assumed that combined preparations with angiotensin converting enzyme inhibitors will ameliorate adverse effects of high doses of thiazide diuretics on insulin action.",1998.0,0,0
2327,9535416,Three candidate genes and angiotensin-converting enzyme inhibitor-related cough: a pharmacogenetic analysis.,R Y Zee; V S Rao; R Z Paster; C S Sweet; K Lindpaintner,"Unexplained, persistent cough limits the use of angiotensin-converting enzyme (ACE) inhibitors in a significant number of patients. It has been speculated that occurrence of this adverse effect is genetically predetermined; in particular, variants of the genes encoding ACE, chymase, and B2-bradykinin receptor have been implicated. To investigate this question, we determined genotypes for common polymorphisms for these three genes in subjects with a history of ACE inhibitor-related cough. Specificity of the adverse effect was confirmed by a blinded, double-crossover design protocol in which subjects were rechallenged with either lisinopril or placebo. In 99 case subjects and 70 control subjects (who failed to develop cough on rechallenge with ACE inhibitor) thus selected, frequencies for the ACE D and I alleles were 0.56 and 0.44 (cases) and 0.56 and 0.44 (controls), respectively; frequencies for chymase A and B alleles (absence/presence of BstXI site) were 0.56 and 0.44 (cases) and 0.46 and 0.54 (controls), respectively; frequencies for B2-bradykinin receptor + and - alleles (presence/absence of a 21 to 29 nonanucleotide sequence) were 0.52 and 0.48 (cases) and 0.53 and 0.47 (controls), respectively. All observed genotype frequencies were in Hardy-Weinberg equilibrium. There was no evidence for association between genotype at either gene examined and cough (adjusted for gender and age). Our data indicate that common genetic variants of ACE, chymase, and B2-bradykinin receptor do not explain the occurrence of ACE inhibitor-related cough.",1998.0,0,0
2328,9536102,Acute and chronic kidney disease.,W W Brown; P G Schmitz,"The presentation of many renal diseases in older adults is remarkably similar to that in younger patients, although the symptoms and clinical findings are frequently attributed to diseases of aging. Since older patients often respond to treatment as well as younger patients do, they deserve a thorough investigation, including renal biopsy when indicated. It is important to base decisions regarding access to evaluation and treatment, quality of life, and initiation of termination of dialysis on strong moral and ethical grounds.",1998.0,0,0
2329,9537353,Delayed profound thrombocytopenia after c7E3 Fab (abciximab) therapy.,L A Jenkins; S Lau; M Crawford; Y K Keung,,1998.0,0,0
2330,9538979,Effects of lisinopril and nifedipine on the progression to overt albuminuria in IDDM patients with incipient nephropathy and normal blood pressure. The Italian Microalbuminuria Study Group in IDDM.,G Crepaldi; Q Carta; G Deferrari; R Mangili; R Navalesi; F Santeusanio; A Spalluto; A Vanasia; G M Villa; R Nosadini,"Intervention trials on renal function in IDDM patients with microalbuminuria (MA) should adopt the rate of decline of glomerular filtration rate (GFR) as an outcome measure. However, normotensive IDDM patients with MA show no change in GFR over a follow-up period of 10 years. Thus, in the present study, we used the cumulative incidence of progression to albuminuria (albumin excretion rate [AER] > 200 micrograms/min) from MA as the primary endpoint and the yearly increase in AER at a rate of 50% above baseline as the secondary end-point of renal function. Ninety-two normotensive IDDM patients underwent double-blind, double-dummy treatment with either lisinopril or slow-release nifedipine in comparison with placebo. Ten patients discontinued the study during the 3-year follow-up period. During the 3-year follow-up period, 7 of 34 placebo-treated (20.6%), 2 of 32 lisinopril-treated (6.3%), and 2 of 26 nifedipine-treated (7.7%) patients progressed to clinical albuminuria (Fisher's exact test, P < 0.03). Time-to-event analysis indicated a reduction in the risk of progression to macroalbuminuria of 58.1% (95% CI 27.8-68.4%) in the 32 patients on lisinopril (P < 0.02) and of 62.5% (95% CI 32.5-73.4%) in the 26 patients on nifedipine (P < 0.02) after adjustment for mean blood pressure, glycated hemoglobin, and baseline AER in comparison with the 34 patients on placebo. Baseline AER was 71 micrograms/min (range: 20.7-187.3) in progressors and 73 micrograms/min (range: 20.2-174.1) in nonprogressors (NS). The percentage of patients who showed a > 50% yearly increase of AER above baseline values was significantly lower in the lisinopril group (13 of 32, 40.6%, P < 0.02), but not in the nifedipine group (15 of 26, 57.7%), than in the placebo group (23 of 34, 67.6%). The lisinopril group had significantly lower blood pressure values during follow-up than either the nifedipine (P < 0.05) or the placebo (P < 0.01) group. Our data show that both lisinopril and nifedipine are effective in delaying the occurrence of macroalbuminuria in normotensive IDDM patients with MA. As overt proteinuria strongly predicts end-stage renal failure, both treatments appear capable of preventing such a complication in normotensive IDDM patients with MA. However, lisinopril appears more powerful in slowing the course of nephropathy.",1998.0,0,0
2331,9540001,"American Diabetes Association annual meeting, 1997, and the Teczem Consultant Meeting. Diabetic nephropathy.",Z T Bloomgarden,,1998.0,0,0
2332,9542575,"A randomized, double-blind comparison of the antihypertensive efficacy and safety of once-daily losartan compared to twice-daily captopril in mild to moderate essential hypertension.",A Roca-Cusachs; W Oigman; L Lepe; R Cifkova; Y A Karpov; D W Harron,"The antihypertensive efficacy and safety of losartan, a specific and selective angiotensin II (AII) receptor antagonist, was compared to captopril in patients with mild or moderate essential hypertension. This multinational, randomized trial consisted of a 4-week single-blind, placebo baseline period followed by a 12-week double-blind, parallel comparison of once-daily administration of losartan 50 mg or twice-daily administration of captopril 25 mg. After 6 weeks of treatment, the daily dosage was doubled in patients whose sitting diastolic blood pressure (SiDBP) remained > or = 90 mm Hg. Patients with essential hypertension having a mean trough SiDBP of 95-115 mm Hg after the placebo baseline period were randomized to losartan (N = 192) or captopril (N = 204) treatment. The primary efficacy variable was the mean change from baseline to Week 12 in trough SiDBP. Safety was assessed by recording spontaneously reported or observed adverse experiences and clinical laboratory measurements. After 12 weeks, both treatments produced clinically important reductions in trough SiDBP and sitting systolic blood pressure (SiSBP). These mean reductions (SiDBP, SiSBP) were significantly greater in the losartan group (-11.5 and -15.4 mm Hg, respectively) than in the captopril group (-9.3 and -12.2 mm Hg, respectively) (p = 0.010 for diastolic and p = 0.023 for systolic). The percentage of patients exhibiting an excellent (trough SiDBP < 90 mm Hg) or good (trough SiDBP > 90 mm Hg, with decrease of > or = 10 mm Hg) antihypertensive response to losartan and captopril therapy at Week 12 was comparable (60.0% and 54.7%, respectively). The percentage of patients reporting a clinical adverse experience considered drug-related by the investigator was 13% in the captopril group and 10% in the losartan group. The incidence of drug-related cough was 2.6% in the losartan group and 4.4% in the captopril group. Once daily administration of losartan 50 to 100 mg is an effective treatment for patients with essential mild to moderate hypertension. The antihypertensive efficacy of losartan 50/100 mg is significantly greater than that of twice daily captopril 25/50 mg. Both treatments were generally well-tolerated. The number of patients with the side effect of cough was higher following captopril.",1998.0,0,0
2333,9542705,Polypharmacy: a case report and new protocol for management.,R D Lee,"Polypharmacy is an important issue in primary care, yet few data are available concerning its prevalence, complications, and management in clinical medicine. The following case illustrates the clinical perils of polypharmacy and serves as a point for critical discussion. MEDLINE was searched, using the key word ""polypharmacy,"" from 1994 to the present. A case report of polypharmacy is described, and a novel protocol for the management of polypharmacy is proposed. Polypharmacy can lead to unnecessary expense, wasted time, and embarrassment on the part of the patient and confusion and mismanagement on the part of the physician. The literature reveals controversy surrounding the definition of polypharmacy and reflects the considerable morbidity and expense associated with polypharmacy. Finally, the SAIL protocol shows that physicians need to keep in mind simplicity, adverse effects, indications, and a precise list of all medications to manage appropriately a patient's drug regimen. Polypharmacy is associated with morbidity and iatrogenic complications. The SAIL protocol can be a useful tool in the management of this entity. More research needs to be done on the prevalence, complications, and management of polypharmacy.",1998.0,0,0
2334,9544866,Little effect of ordinary antihypertensive therapy on nocturnal high blood pressure in patients with sleep disordered breathing.,L H Pelttari; E K Hietanen; T T Salo; M J Kataja; I M Kantola,"The antihypertensive effects of four different antihypertensive medications (beta-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM). Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM. Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD+/-14) mm Hg with atenolol, 7 (SD+/-10) mm Hg with isradipine SRO, 3 mm Hg (SD+/-14) with HCTZ, and 6 (SD+/-15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50. Negative correlation was observed between the apnea time and the mean systolic 24-h (r = -0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = -0.590, P = NS). Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.",1998.0,0,0
2335,9544873,Effects of verapamil and trandolapril in the treatment of hypertension. Trandolapril Study Group.,F Messerli; W H Frishman; W J Elliott,"The combination of an angiotensin converting enzyme inhibitor with a calcium antagonist has become a common way of treating patients with essential hypertension who respond insufficiently to monotherapy. This double-blind, randomized, parallel, placebo-controlled, multicenter, outpatient study evaluated the antihypertensive efficacy and safety of a calcium antagonist (verapamil SR) and an angiotensin converting enzyme inhibitor (trandolapril) in patients with mild-to-moderate (stages I and II) essential hypertension. Six hundred thirty-one patients were enrolled in this 10-week study. After a 4-week single-blind placebo phase, patients received one of the following daily dosage regimens in a double-blind fashion for 6 weeks: placebo, 4 mg of trandolapril, 240 mg of verapamil SR, or a combination of 4 mg of trandolapril and 240 mg of verapamil SR. Trough sitting diastolic blood pressure was lowered by 4.5 mm Hg, 4.3 mm Hg, and 8.1 mm Hg more than placebo in the trandolapril, verapamil SR, and combination groups, respectively. In the combination group, sitting diastolic blood pressure was significantly lowered (P < .01) by 3.6 mm Hg more than in the trandolapril group and by 3.8 mm Hg more than in the verapamil SR group. An analysis of the trough-to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and 0.67, for the 4-mg trandolapril and the combination groups, respectively, at end point. The overall incidence of adverse reactions was similar for all treatment groups. In this study the combination of an angiotensin converting enzyme inhibitor and calcium antagonist was well tolerated and more effective than either agent administered alone for the treatment of mild-to-moderate essential hypertension.",1998.0,0,0
2336,9547443,Effects of angiotensin-converting enzyme inhibitor on plasma B-type natriuretic peptide levels in patients with acute myocardial infarction.,Y Mizuno; H Yasue; S Oshima; M Yoshimura; H Ogawa; E Morita; T Saito; S Yamashita; K Noda; H Sumida; T Motoyama; H Soejima; K Nakao,"Plasma levels of B-type natriuretic peptide (BNP) are markedly increased in patients with heart failure and acute myocardial infarction. The changes in plasma BNP levels in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors have not been examined well. This study was designed to examine the effects of early angiotensin-converting enzyme inhibitor therapy on plasma BNP levels in patients with acute myocardial infarction. We measured the plasma levels of B-type natriuretic peptide over the time course for 2 weeks in 30 patients with acute myocardial infarction in whom either imidapril (n = 15) or placebo (n = 15) was given at random immediately after admission. Plasma BNP levels increased and reached a peak of 192 +/- 28 pg/ML 16 hours after administration; thereafter, the levels decreased and then again increased, forming the second peak of 217 +/- 38 pg/ML on the fifth day (biphasic pattern). On the other hand, plasma BNP levels increased and reached a peak level of 190 +/- 22 pg/ML 16 hours after admission and then decreased from 2 days after admission until the second week in the imidapril group (monophasic pattern). Left ventricular ejection fraction measured in the second week was significantly higher in the imidapril group than in the control group (62.2 +/- 1.1% vs 51.2 +/- 3.6%, P < .01). It is concluded that plasma BNP levels followed a monophasic pattern after imidapril treatment, whereas a biphasic pattern was followed after placebo, and that plasma BNP levels constitute a marker of ventricular dysfunction in the treatment of acute myocardial infarction with angiotensin-converting enzyme inhibitors.",1998.0,0,0
2337,9549634,Clinical utility of long-term enalapril/diltiazem ER in stage 3-4 essential hypertension. Long-term Use of Enalapril/Diltiazem ER in Stage 3-4 Hypertension Group.,S G Chrysant; H Gavras; A L Niederman; T C Marbury; R Goldstein,"The use of angiotensin converting enzyme inhibitors and calcium channel blockers, as monotherapies and in combination, is common in the management of hypertension. Clinical studies have documented the augmentation of blood pressure reduction when these agents are combined compared with the individual agents, in short-term studies. In the present investigation, 93 patients with stage 3-4 essential hypertension, who successfully completed a short-term double-blind study, participated in a 40-week open-label treatment phase. The patients were maintained on their previous doses of enalapril/diltiazem ER (E/D) with or without additional antihypertensive medications. Doses of medication could be adjusted as necessary for blood pressure control. Of the 93 patients, 68% were male and 82% were white; they averaged 52.7 years of age and had a baseline mean sitting blood pressure (SiBP) of 167/111 mmHg. The use of E/D alone (n = 14) reduced mean SiBP by 14.5/14.4 mmHg from baseline, whereas the use of E/ D with other agents (n = 79) decreased it by 27/20.5 mmHg from baseline. E/D alone or in combination with other drugs was well-tolerated, and no serious adverse events were noted. This long-term open-label study demonstrated that the E/D combination alone or with the addition of other antihypertensive drugs was effective, safe, and well-tolerated after prolonged administration.",1998.0,0,0
2338,9551877,Relationship between salt and blood pressure in hypertensive patients on chronic ACE-inhibition.,H Herlitz; B Dahlöf; O Jonsson; P Friberg,"We investigated the effect of a 4-day oral salt load (150 mmol NaCl extra per day) on blood pressure, erythrocyte sodium transport and the activity in the renin-angiotensin system in six males with primary hypertension, who had attained normotension on chronic enalapril treatment for 4 years. The design was a placebo-controlled, randomized, two-way cross over, double-blind study, i.e. each patient served as his own control. Intracellular erythrocyte sodium and potassium content were measured by flame photomometry. The increase in the intracellular sodium concentration during 1 h in 37 degrees C incubation of whole-blood with ouabain (compared with no-ouabain) was measured to determine the rate of active sodium efflux. 24-h blood pressure registration was performed with Space-lab equipment (SL 90202) before and at the end of the salt load. Left ventricular morphology was evaluated with echocardiography and the minimal vascular resistance of the hand vascular bed with water plethysmography at baseline and after 4 years on enalapril. Four years' enalapril treatment caused a significant decrease in blood pressure, left ventricular mass and minimal vascular resistance. During the 4-day salt load average 24-h blood pressure was significantly elevated, 129+/-3/85+/-2 mmHg as compared to 124+/-2/82+/-2 mmHg during placebo treatment (p=0.025). The change (delta) in MAP during high salt intake showed a negative relationship to delta-sodium efflux rate constant (r=-0.65, p=0.047). No significant relationship was found between the blood pressure response to the salt load and structural cardiovascular changes. In conclusion, a short-term oral salt load in hypertensive patients on chronic enalapril treatment caused a blood pressure rise, which was related to cellular sodium transport but not to structural cardiovascular changes.",1998.0,0,0
2339,9554816,Inhibitory effect of enalapril on neurally mediated syncope in elderly patients.,C Y Zeng; Z Zhu; G Liu; X Wang; D He; H Wang; C Yang; J Tan,"A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.",1998.0,0,0
2340,9555769,Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study.,F Chiarella; E Santoro; S Domenicucci; A Maggioni; C Vecchio,"Left ventricular (LV) thrombosis can be found in patients with acute myocardial infarction (AMI). No wide multicenter trial on AMI has provided information about LV thrombosis until now. The protocol of the GISSI-3 study included the search for the presence of LV thrombosis in patients from 200 coronary care units that did not specifically focus on LV thrombosis. We examined the GISSI-3 database results related to 8,326 patients at low to medium risk for LV thrombi in which a predischarge echocardiogram (9 +/- 5 days) was available. LV thrombosis was found in 427 patients (5.1%): 292 of 2,544 patients (11.5%) with anterior AMI and in 135 of 5,782 patients (2.3%) with AMI in other sites (p <0.0001). The incidence of LV thrombosis was higher in patients with ejection fraction < or = 40% (151 of 1,432 [10.5%] vs 276 of 6,894 [4%]; p <0.0001) both in the total population and in the subgroup with anterior AMI (106 of 597 [17.8%] vs 186 of 1,947 [9.6%]; p <0.0001). Multivariate analysis showed that only the Killip class > I and early intravenous beta-blocker administration were independently associated with higher LV thrombosis risk in the subgroup of patients with anterior AMI (odds ratio 1.75, 95% confidence interval 1.28 to 2.39; odds ratio 1.32, 95% confidence interval 1.02 to 1.72, respectively). In patients with anterior AMI, oral beta-blocker therapy given or not given after early intravenous beta-blocker administration does not influence the occurrence of LV thrombosis. The rate of LV thrombosis was similar in patients treated or not treated with nitrates and lisinopril both in the total population and in patients with anterior and nonanterior AMI. In conclusion, in the GISSI-3 population at low to medium risk for LV thrombi, the highest rate of occurrence of LV thrombosis was found among patients with anterior AMI and an ejection fraction < 40%. Killip class > I and the early intravenous beta-blocker administration were the only variables independently associated with a higher predischarge incidence of LV thrombosis after anterior AMI.",1998.0,0,0
2341,9556644,Calcium channel antagonists: morbidity and mortality--what's the evidence?,R J Straka; A L Swanson; D Parra,"Recent studies have shown an association between the use of calcium channel antagonists for the treatment of hypertension and an increased risk of myocardial infarction, gastrointestinal hemorrhage and cancer. The interpretation of the results of these studies and their application to clinical practice requires an understanding of study design constraints, conflicting results and limitations in extrapolating study findings to other dosage strengths, formulations or agents within the calcium channel antagonist class. A review and critique of these studies provides background information on the controversial subject of using calcium channel antagonists for the treatment of hypertension. Despite the limitations of these studies, clinicians may want to select other classes of agents, including diuretics and beta blockers, as first-line therapy until the morbidity and mortality effects related to the use of calcium channel antagonists are clearly known.",2000.0,0,0
2342,9556832,Medical treatment of migraine: from mechanisms of action to contraindications.,F Higelin; J M Annoni,"Management of migraine patients with or without aura must include appropriate medication to treat the attack and long-term preventive therapy, especially if the frequency of the attacks is greater than 2-4 per month. In both cases the choice of treatment depends on its efficacy and side effects. With regard to acute drug therapy, group studies do not suggest that ergot derivatives and sumatriptan are superior to simple analgesics and anti-inflammatory drugs, particularly if a prokinetic agent is added. These new substances are indicated for severe attacks refractory to more conventional therapy. Chronic drug abuse may induce drug-induced or rebound headaches. As regards long-term prophylaxis, group studies suggest that calcium antagonists and 5-HT-influencing drugs are superior concerning attacks frequency to beta-blocking agents, but involve very frequent side effects (weight gain and somnolence). Interesting preliminary results have also been reported with valproate and enalapril, which will confirmation by controlled studies. Finally, the choice of drug must take into account the patient's comorbidities (cardiovascular diseases, asthma, diabetes etc).",1998.0,0,0
2343,9557932,Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.,A Pechère-Bertschi; J Nussberger; L Decosterd; C Armagnac; J Sissmann; M Bouroudian; H R Brunner; M Burnier,"To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily. Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study. After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy. Treatment and administration assignments were double-blind. Twenty-four-hour ambulatory blood pressure was monitored before and after 6 and 12 weeks of therapy. Renal hemodynamics were determined on the first day of drug administration and 12 and 24 h after the last dose during chronic treatment. Administration of each antihypertensive agent induced a renal vasodilatation with no significant change in glomerular filtration rate. However, the time course appeared to differ: irbesartan had no significant acute effect 4 h after the first dose, but during chronic administration a renal vasodilatory response was found 12 and 24 h after the dose; enalapril was effective acutely and 12 h after administration, but no residual effect was found 24 h after the dose. Both antihypertensive agents lowered mean ambulatory blood pressure effectively, with no significant difference between treatments or between administration schedules (morning versus evening). Irbesartan and enalapril have comparable effects on blood pressure and renal hemodynamics in hypertensive patients with normal renal functioning. However, the time profiles of the renal effects appear to differ, which might be important for long-term renoprotective effects.",1998.0,0,0
2344,9562008,Regression of radial artery wall hypertrophy and improvement of carotid artery compliance after long-term antihypertensive treatment in elderly patients.,X Girerd; C Giannattasio; C Moulin; M Safar; G Mancia; S Laurent,"The present study was designed to assess whether a diuretic- or an angiotensin-converting enzyme inhibitor-based treatment can reduce arterial wall hypertrophy of a distal muscular medium-sized artery--the radial artery--and the stiffness of a proximal large elastic artery--the common carotid artery. Large-artery wall thickness and stiffness are increased during sustained essential hypertension and contribute to the increased risk of complications. Whether antihypertensive treatment can normalize the wall hypertrophy of conducting arteries has not yet been determined. Seventy-seven elderly hypertensive patients were randomized to receive 9 months of double-blind treatment with perindopril (2 to 8 mg/day) or the diuretic combination of hydrochlorothiazide (12.5 to 50 mg/day) plus amiloride (1.25 to 5 mg/day) after a 1-month placebo washout period. If systolic blood pressure remained at >160 mm Hg after 5 months, chlorthalidone or atenolol was added, respectively. Arterial variables, including radial artery mass and common carotid artery compliance, were calculated from noninvasive measurements of internal diameter and wall thickness with the use of high resolution echo-tracking systems at baseline and after 5 and 9 months. During treatment, blood pressure and arterial variables changed to the same extent in both groups. After a 9-month treatment, systolic, diastolic and pulse pressures and radial artery wall thickness, mass and thickness/radius ratio decreased significantly (p < 0.01), whereas carotid compliance increased (p < 0.001). The decrease in radial artery thickness/radius ratio after a 9-month treatment was significantly related to the reduction in pulse pressure (p < 0.01), whereas the improvement in carotid compliance was related to the reduction in mean arterial pressure (p < 0.01). In healthy subjects and untreated hypertensive patients, radial artery diameter, wall thickness and thickness/radius ratio and carotid artery compliance did not change significantly during a 9-month observation period. These results indicate that in elderly hypertensive patients, both angiotensin-converting enzyme inhibitor- and diuretic combination-based treatments can reduce radial artery wall hypertrophy and improve carotid artery compliance.",1998.0,0,0
2345,9562649,Hemodynamic performances in patients treated with sotalol after electrical cardioversion of atrial fibrillation.,G A Dan; A Gonţa,"The negative inotropic effect of nearly all antiarrhythmic drugs, especially important in patients with impaired left ventricular function, represents a major drawback of medical therapy. The aim of this study is to evaluate the atrial and ventricular function and the exercise capacity in patients with mild heart failure treated with d,l-sotalol after electrical conversion of atrial fibrillation. The study included patients with persistent atrial fibrillation (for more than 2 weeks but less than 1 year) and mild heart failure (< or = class II NYHA). All patients had comparable basal echocardiographic findings, and received captopril. After successful cardioversion the patients were randomized in two groups: group 1 treated with sotalol (mean dose 240 mg q.d., max. 320 mg) and group 2--without sotalol. The drop-out criterion was the failure to maintain sinus rhythm. Finally, in the study remained 17 patients (10 men, 7 women, aged 41-60 years); group 1 included 10 patients and group 2-7 patients. They were assessed by quantitative echocardiography + Doppler and by standard ecg exercise test at less than 1 month but more than 2 weeks, and at 1, 3, and 6 months. When first evaluated (2 weeks-1 month), peak A wave velocity and atrial filling ratio were higher in group 2 than in group 1 (37 +/- 10 cm/s vs 20 +/- 5 cm/s and 23% +/- 7 vs 13% +/- 5, respectively) and group 1 had also a lower exercise tolerance (80 +/- 25 W vs 110 +/- 10 W). There were no significant differences between groups 1 and 2 in left atrial and left ventricular dimensions, ejection fraction and E wave deceleration time. After 1 month there were no significant differences in Doppler characteristics, echocardiographic parameters and exercise tolerance between the two groups. Group 1 remained at a lower heart rate and had a lower maximal double product (17250 mmHg/min vs 22100 mmHg/min) corresponding to a lower cardiac work. At 3 and 6 months there were no significant changes in all characteristics between the two groups. In conclusion, sotalol seems to be a well tolerated antiarrhythmic agent in patients with mild heart failure, after conversion of persistent atrial fibrillation. In this setting: 1. Sotalol could reversibly amplify the effect of atrial stunning after electrical cardioversion of atrial fibrillation, but this effect is brief. 2. Sotalol has no relevant negative inotropic effect, at least not in association with captopril. 3. Sotalol improves the effort capacity.",1998.0,0,0
2346,9562936,"Patterns of angiotensin-converting enzyme inhibitor prescriptions, educational interventions, and outcomes among hospitalized patients with heart failure.",M M McDermott; P Lee; S Mehta; M Gheorghiade,"Among hospitalized patients with heart failure, we describe characteristics associated with prescription of angiotensin-converting enzyme (ACE) inhibitors in the doses recommended by clinical practice guidelines. We also describe the impact of ACE inhibitor prescriptions, increases in ACE inhibitor dose, and nonpharmacologic educational interventions on readmission-free survival rates. We hypothesize that care by a cardiologist physician and higher mean arterial blood pressure on admission are associated with receipt of optimal ACE inhibitor doses. We hypothesize that receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are associated with superior readmission-free survival. Between January 1, 1992, and December 31, 1993, medical records were reviewed for consecutively hospitalized patients with a principal diagnosis of heart failure at an academic medical center. Documented instructions and medications prescribed at discharge were abstracted. Deaths and readmissions through December 31, 1994, were identified with the National Death Index and the study institution's administrative data base, respectively. During 1992 and 1993, 387 patients were discharged alive from hospitalization for heart failure. Among patients discharged on enalapril or captopril, 18% received doses recommended by heart failure clinical practice guidelines. Patients discharged on a recommended ACE inhibitor dose were more likely to be African-American and had lower sodium levels and higher mean arterial pressures than patients discharged on lower ACE inhibitor doses. In survival analyses, an increase in ACE inhibitor dose was associated with improved readmission-free survival, independent of left ventricular systolic function type. Receipt of an ACE inhibitor at discharge was also associated with superior readmission-free survival, while nonpharmacologic educational instructions were not associated with improved outcomes. Interventions are needed to improve the frequency with which ACE inhibitors are prescribed at recommended doses to hospitalized patients with heart failure. We conclude that among these patients, receipt of an ACE inhibitor at discharge and an increase in ACE inhibitor dose during hospitalization are each associated with measurable effects on readmission-free survival, while provision of educational instructions as currently practiced is not associated with better outcomes.",1998.0,0,0
2347,9562938,Influence of tissue affinity of angiotensin-converting enzyme inhibitors on left ventricular remodeling after myocardial infarction.,M Konermann; C Altmann; F Laschewski; W Josephs; H J Odenthal; E Horstmann; B Sanner,"The demonstration of local renin-angiotension systems has raised the question of whether angiotensin-converting enzyme (ACE) inhibitors with different tissue affinities differ with regard to their effects on postinfarction remodeling. The study was undertaken to investigate the influence of ACE inhibitors with different tissue affinity on morphology and function of the infarcted left ventricle. In all, 52 patients (17 women, 35 men, 38-73 years) with large acute myocardial infarction were randomized to receive either 25-75 mg/day captopril or 10-20 mg/day fosinopril beginning on the Day 7 after infarction. Of these, 28 had anterior and 24 had posterior wall infarctions. Infarct size was determined by the creatine kinase integral method. Fifty patients were examined by cinemagnetic resonance imaging (CMRI) 1 and 26 weeks after infarction. The following parameters were determined: left ventricular end-diastolic and end-systolic volume index (LVEDVI, LVESVI), ejection fraction (LVEF), infarct weight, and muscle mass (LVMM). The volume-to-mass ratio (VMR) was calculated and the clinical status according to the guidelines of the New York Heart Association (NYHA) was documented at each examination time. The results were compared with those of a historical sample without ACE-inhibitor therapy examined in an identical manner (n = 31, 10 women, 21 men, 36-75 years). LVEDVI and LVESVI increased in the first 6 months after infarction by 24.9 and 36.6%, respectively, in the historical sample; by 11.0 and 7.8%, respectively, under captopril; and by 13.1 and 10.7%, respectively, under fosinopril. LVEF decreased by 14.9% in the untreated sample, by 3.7% under captopril and by 5.0% under fosinopril. Infarct weight and LVMM increased by 12.7 and 15.3%, respectively, without ACE inhibition, by 5.7 and 10.1%, respectively, in patients treated with captopril, and by 6.1 and 9.3%, respectively, in patients treated with fosinopril. The VMR increased by 7.4% in the historical sample, by 3.5% in the captopril group, and by 1.8% in the fosinopril group. The NYHA clinical status improved by 18.2% without ACE inhibition, by 42.9% in the captopril group, and by 26.3% in the fosinopril group. The differences between the two ACE-inhibitor groups and the reference group were all significant, while the differences between the captopril group and the fosinopril group were significant only for VMR (p < 0.01) and NYHA class (p < 0.05). Both captopril and fosinopril have a comparable positive influence on postinfarction remodeling and on clinical status. Lipophilicity and tissue affinity do not seem to play a clinically important role in ACE-inhibitor therapy after infarction.",1998.0,0,1
2348,9563995,North of England evidence based development project: guideline for angiotensin converting enzyme inhibitors in primary care management of adults with symptomatic heart failure.,M Eccles; N Freemantle; J Mason,,1998.0,0,0
2349,9567598,Effect of antihypertensives on plasma potassium in end stage renal disease: a retrospective study.,M Tripathi; S Kaushik; A Gaur; V Kher,"The antihypertensive drug therapy and the peri-operative plasma potassium trend in end stage renal disease (ESRD) patients undergoing renal transplant were analysed. Out of consecutive 107 live related donor renal transplant, complete data available for 74 patients between June 1991 and March 1993, were entered in proforma and analysed. On the basis of antihypertensive or no antihypertensive drugs prescribed, patients were grouped in 6 categories. Group I patients taking no antihypertensives were taken as control. All patients were comparable for their age, sex, weight, immunosuppressive therapy, anaesthetic and fluid management during surgery. At the time of induction of anaesthesia, patients taking atenolol (plasma K+ levels being 5.34 +/- 0.75 mmol/l in group II and 5.44 +/- 0.63 mmol/l in group III) or captopril (serum K+ level being 5.05 +/- 0.94 mmol/l in group V) in combination with nifedipine and with or without clonidine had significant hyperkalaemia than the patient without antihypertensives (serum K+ level being 4.49 +/- 0.71 mmol/l). Patients, on these two antihypertensives, frequently needed active treatment of alarming hyperkalaemia (blood K+ more than 5 mmol/l and tall 'T' wave in lead II) and cardiac arrhythmias. In conclusion, ESRD patients taking atenolol or captopril are needed to be frequently monitored for blood potassium levels and it would be advisable to avoid these drugs to control hypertension in ESRD patients, especially, when scheduled for renal transplantation.",1998.0,0,0
2350,9568453,Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. The NETWORK Investigators.,,"Angiotensin converting-enzyme (ACE) inhibitors used for the treatment of heart failure relieve symptoms, increase exercise performance, reduce hospital admissions and prolong life. The large survival studies have used higher doses of ACE inhibitors than those commonly used in clinical practice. NETWORK was set up to compare the effect of dose on the clinical outcome of ACE inhibition. 1532 patients with heart failure drawn from primary care (n = 619) and hospital sources (n = 913) were randomized to receive enalapril 2.5 mg twice daily (n = 506). 5 mg twice daily (n = 510) or 10 mg twice daily (n = 516). The mean age was 70 years and 65% were male. Coronary heart disease was the cause of heart failure in 71%. Sixty-five percent were in NYHA class II and 35% in class III or IV. The mean left ventricular end-diastolic diameter was 59 (SD 11) mm. The incidence of the primary end-point of death, heart failure related hospitalization or worsening heart failure was assessed after follow-up of each patient for 24 weeks. The number of patients reaching the primary end-point was 62 (12.3%) in the 2.5 mg twice daily group, 66 (12.9%) in the 5 mg twice daily group and 76 (14.7%) in the 10 mg twice daily group. Deaths in each group were 21 (4.2%), 17 (3.3%) and 15 (2.9%), respectively. There were no significant differences in the results between the three groups. The crude relative risk for the combined end-point in the 10 mg twice daily group compared to the 2.5 mg twice daily group was 1.20 (95% CI 0.88 to 1.64). NETWORK did not demonstrate a relationship between dose of enalapril and clinical outcome in patients with heart failure selected from both primary care and hospital practice.",1998.0,0,1
2351,9568701,,,,,0,0
2352,9571349,Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM.,P Tatti; M Pahor; R P Byington; P Di Mauro; R Guarisco; G Strollo; F Strollo,"ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism. The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension. Prospectively defined cardiovascular events were assessed as secondary outcomes. Inclusion criteria included a diagnosis of NIDDM and hypertension (systolic blood pressure of > 140 mmHg or diastolic blood pressure of > 90 mmHg). Exclusion criteria included a history of coronary heart disease or stroke, serum creatinine > 1.5 mg/dl, albuminuria > 40 micrograms/min, and use of lipid-lowering drugs, aspirin, or antihypertensive agents other than beta-blockers or diuretics. A total of 380 hypertensive diabetics were randomly assigned to open-label fosinopril (20 mg/day) or amlodipine (10 mg/day) and followed for up to 3.5 years. If blood pressure was not controlled, the other study drug was added. Both treatments were effective in lowering blood pressure. At the end of follow-up, between the two groups there was no significant difference in total serum cholesterol, HDL cholesterol, HbA1c, fasting serum glucose, or plasma insulin. The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infarction, stroke, or hospitalized angina than those receiving amlodipine (14/189 vs. 27/191; hazards ratio = 0.49, 95% CI = 0.26-0.95). Fosinopril and amlodipine had similar effects on biochemical measures, but the patients randomized to fosinopril had a significantly lower risk of major vascular events, compared with the patients randomized to amlodipine.",1998.0,0,0
2353,9571355,Effects of perindopril and carvedilol on endothelium-dependent vascular functions in patients with diabetes and hypertension.,D Giugliano; R Marfella; R Acampora; R Giunta; L Coppola; F D'Onofrio,"To compare the effects of the ACE inhibitor perindopril and the beta-blocker carvedilol on blood pressure and endothelial functions in NIDDM patients with hypertension. We conducted a double-blind randomized trial in 26 patients with NIDDM and mild hypertension. A 4-week run-in placebo period preceded the active 12-week treatment with perindopril (4-8 mg daily) or carvedilol (25-50 mg daily). Endothelial functions were assessed by evaluating the hemodynamic (mean blood pressure, leg blood flow) and rheological (platelet aggregation, blood viscosity, and blood filterability) responses to an intravenous bolus of 3 g L-arginine, the natural precursor of nitric oxide. Both perindopril and carvedilol significantly reduced mean blood pressure (P < 0.001) and increased leg blood flow (P < 0.05) to the same extent; blood filterability remained unchanged in both perindopril- and carvedilol-treated groups. Carvedilol reduced platelet aggregation and blood viscosity significantly (P < 0.05) but perindopril did not. Before treatment, the hemodynamic and rheologic responses to L-arginine were significantly lower in patients (P < 0.05-0.01) than in 20 nondiabetic nonhypertensive control subjects. After 12 weeks of treatment, both drugs normalized the hemodynamic responses to L-arginine. Platelet aggregation response to L-arginine was ameliorated by carvedilol and remained unchanged in the perindopril group. At the doses used, both drugs effectively reduce blood pressure and normalize the hemodynamic responses to L-arginine. The implications of the ameliorated endothelial function for the poor cardiovascular outlook of the NIDDM hypertensive patient need further assessment.",1998.0,0,0
2354,9571359,Hypertension and diabetes and the Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET). More ammunition against surrogate end points.,R M Califf; C B Granger,,1998.0,0,0
2355,9573498,Regional differences in the characteristics and treatment of patients participating in an international heart failure trial. The Assessment of Treatment with Lisinopril and Survival (ATLAS) Trial Investigators.,B M Massie; J G Cleland; P W Armstrong; J D Horowitz; M Packer; P A Poole-Wilson; L Ryden; R Lars,"This study was designed to determine regional differences in patient characteristics and medication use among patients entered into an international heart failure trial. Data for this analysis were derived from the Assessment of Treatment with Lisinopril and Survival Study (ATLAS), a prospective randomized comparison of high- and low-dose therapy with lisinopril in patients with New York Heart Association class II, III, or IV chronic heart failure, which enrolled 3164 patients in 291 centers in 19 countries on 3 continents. Information was collected at baseline concerning patient demographics, etiology of heart failure, accompanying conditions, prior revascularization procedures, and medication use. The primary findings were a lower incidence of ischemic cardiomyopathy in southern and western Europe, more frequent diabetes in North America, and a greater use of coronary revascularization in the United States and Canada. There was substantial variation in medication use, particularly with regard to digoxin, anticoagulants, and amiodarone. Although there is considerable overlap in guidelines concerning the treatment of heart failure issued by authorities in Europe and North America, there are significant regional variations in medication use. Some, but not all, of these differences can be explained by differences in patient characteristics.",1998.0,0,0
2356,9573535,"Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. ""Gruppo Italiano di Studi Epidemiologici in Nefrologia"" (GISEN).",P Ruggenenti; A Perna; L Mosconi; R Pisoni; G Remuzzi,"We investigated the predictors of the rate of glomerular filtration rate decline (delta GFR) and progression to end-stage renal failure (ESRF) in the 352 patients with proteinuric non-diabetic chronic nephropathies [urinary protein excretion rate (UProt) > or = 1 g/24 hr, creatinine clearance 20 to 70 ml/min/1.73 m2] enrolled in the Ramipril Efficacy In Nephropathy (REIN) study. Overall the GFR declined linearly by 0.46 +/- 0.05 ml/min/1.73 m2/month (mean rate +/- SEM) over a median follow-up of 23 months (range 3 to 64 months), and progression to ESRF was 17.3%. Using multivariate analysis, higher UProt and mean arterial pressure (MAP) independently correlated with a faster delta GFR (P = 0.0001 and P = 0.0002, respectively) and progression to ESRF (P = 0.0001 and P = 0.003, respectively). Mean UProt and systolic blood pressure during follow-up were the only time-dependent covariates that significantly correlated with delta GFR (P = 0.005 and P = 0.003, respectively) and ESRF (P = 0.006 and P = 0.0001, respectively). After stratification for baseline UProt, patients in the lowest tertile (UProt < 1.9 g/24 hr) had the slowest delta GFR (0.16 +/- 0.07 ml/min/1.73 m2/month) and progression to ESRF (4.3%) as compared with patients in the middle tertile (UProt 2.0 to 3.8 g/24hr; delta GFR, 0.55 +/- 0.09 ml/min/1.73 m2/month, P = 0.0002; ESRF, 15.3%, P = 0.0001) and in the highest tertile (UProt 3.9 to 18.8 g/24 hr; delta GFR, 0.70 +/- 0.11 ml/min/1.73 m2/month, P = 0.0001; ESRF, 32.5%, P = 0.0001). Both delta GFR (P = 0.01) and progression to ESRF (P = 0.01) significantly differed even between the middle and the highest tertiles. On the contrary, stratification in tertiles of baseline MAP failed to segregate subgroups of patients into different risk levels. Patients with the highest proteinuria and blood pressure were those with the fastest progression (delta GFR, 0.91 +/- 0.23; ESRF 34.7%). Of interest, at each level of baseline MAP, a higher proteinuria was associated with a faster delta GFR and progression to ESRF. On the other hand, at each level of proteinuria, a faster delta GFR was associated with MAP only in the highest tertile (> 112 mm Hg) and the risk of ESRF was independent of the MAP. Thus, in chronic nephropathies proteinuria is the best independent predictor of both disease progression and ESRF. Arterial hypertension may contribute to the acceleration of renal injury associated with enhanced traffic of plasma proteins. Antihypertensive drugs that most effectively limit protein traffic at comparable levels of blood pressure are those that most effectively slow disease progression and delay or prevent ESRF in proteinuric chronic nephropathies.",1998.0,0,0
2357,9576119,Influence of race and dietary salt on the antihypertensive efficacy of an angiotensin-converting enzyme inhibitor or a calcium channel antagonist in salt-sensitive hypertensives.,M R Weir; S G Chrysant; D A McCarron; M Canossa-Terris; J D Cohen; P A Gunter; A J Lewin; R F Mennella; L W Kirkegaard; J H Hamilton; M H Weinberger; A B Weder,"Dietary salt restriction is a recommended adjunct with antihypertensive therapy. There may be racial differences in blood pressure response to salt restriction while on antihypertensive therapy. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial (black, n=96; Hispanic, n=63; white, n=232). Participants were initially preselected for stage I to III hypertension and then further selected for salt sensitivity (> or = 5 mm Hg increase in diastolic blood pressure after 3 weeks of low salt [< or = 88 mmol/d Na+] and high salt [>190 mmol/d Na+] diet). We compared the antihypertensive effect of an angiotensin-converting enzyme inhibitor (enalapril 5 or 20 mg BID) or a calcium channel antagonist (isradipine 5 or 10 mg BID) during alternating periods of high and low salt intake. The main outcome measure was blood pressure change and absolute blood pressure level achieved with therapy. During the high salt diet (314.7+/-107.5 mmol/d urinary Na+) there was greater downward change in blood pressure with both enalapril and isradipine compared with the low salt diet (90.1+/-50.8 mmol/d Na+); however, the absolute blood pressure achieved in all races was consistently lower on a low salt diet for both agents. Black, white, and Hispanic isradipine-treated salt-sensitive hypertensives demonstrated a smaller difference between high and low salt diets (black, -3.6/-1.6 mmHg; white, -6.2/-3.9 mmHg; Hispanic, -8.1/-5.3 mm Hg) than did enalapril-treated patients (black, -9.0/-5.3 mm Hg; white, -11.8/-7.0 mm Hg; Hispanic, -11.1/-5.6 mm Hg). On the low salt diet, blacks, whites, and Hispanics had similar blood pressure control with enalapril and isradipine. On the high salt diet, blacks had better blood pressure control with isradipine than with enalapril, whereas there was no difference in the blood pressure control in whites and Hispanics treated with either drug. Dietary salt reduction helps reduce blood pressure in salt-sensitive hypertensive blacks, whites, and Hispanics treated with enalapril or isradipine. These data demonstrate that controlling for salt sensitivity diminishes race-related differences in antihypertensive activity.",1998.0,0,0
2358,9576406,,,,,0,0
2359,9577944,Effects of cardiac versus circulatory angiotensin-converting enzyme inhibition on left ventricular diastolic function and coronary blood flow in hypertrophic obstructive cardiomyopathy.,M Kyriakidis; F Triposkiadis; J Dernellis; A E Androulakis; P Mellas; G A Kelepeshis; J E Gialafos,"Left ventricular (LV) diastolic function and coronary flow are impaired in hypertrophic obstructive cardiomyopathy (HOCM). This study was designed to evaluate the impact of cardiac and circulatory ACE inhibition on such derangements. Twenty patients with HOCM underwent cardiac ACE inhibition with intracoronary (IC) enalaprilat (0.05 mg/min infused into the left anterior descending coronary artery for 15 minutes) followed by circulatory ACE inhibition with 25 mg sublingual (SL) captopril. Contrast ventriculography, pressure, and coronary flow measurements were performed at baseline, after IC enalaprilat infusion, and 45 minutes after SL captopril. Heart rate was not affected by the respective interventions (75+/-11 versus 76+/-13 versus 75+/-10 bpm; P=NS), whereas mean aortic pressure dropped slightly after IC enalaprilat and significantly after SL captopril (90+/-8 versus 85+/-10 versus 74+/-9 mm Hg; P<.05). Compared with baseline, IC enalaprilat resulted in a decrease in LV end-diastolic pressure (17.6+/-5.9 versus 14.4+/-4.9 mm Hg; P<.05), time constant of isovolumic LV pressure relaxation (tauG) (69+/-9 versus 52+/-10 ms; P<.05), and outflow gradient (45.2+/-6.9 versus 24.4+/-3.7 mm Hg; P<.05) and in an increase in coronary blood flow (107+/-10 versus 127+/-12 mL/min; P<.05) and coronary flow reserve (2.2+/-0.4 versus 2.6+/-0.3; P<.05). After SL captopril, tauG was prolonged (60+/-13 ms; P<.05 versus IC enalaprilat), and LV outflow gradient, coronary blood flow, and coronary flow reserve values returned to baseline (45.5+/-5.3 mm Hg, 107+/-12 mL/min, and 2.2+/-0.5, respectively; P=NS versus baseline). Activation of the cardiac renin-angiotensin system contributes to LV diastolic dysfunction as well as to the decreased coronary blood flow and coronary flow reserve in HOCM. Cardiac ACE inhibition restores and circulatory ACE inhibition aggravates the above derangements.",1998.0,0,0
2360,9577953,Angiotensin-converting enzyme inhibitors.,N J Brown; D E Vaughan,"ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.",1998.0,0,0
2361,9578185,Single dose and steady state pharmacokinetics and pharmacodynamics of the ACE-inhibitor imidapril in hypertensive patients.,S Harder; P A Thürmann; W Ungethüm,"To investigate the pharmacokinetic profile of the ACE-inhibitor imidapril in 10 hypertensive patients after a first single dose (10 mg) and after 28 days therapy with imidapril 10 mg once daily. Cmax, tmax, t1/2 and AUC of imidapril and imidaprilat were obtained. ACE-activity and arterial blood pressure during imidapril were corrected by a preceding placebo-investigation. The AUC of imidapril was 140 (43 s.d.) ng ml(-1) h after the first dose and 123 (34 s.d.) ng ml(-1) h at steady state. AUC of the active moiety imidaprilat averaged 211 (101 s.d.) ng ml(-1) h after the first dose and 240 (55 s.d.) ng ml(-1) h at the steady state investigation. Maximal ACE-inhibition was 75% after the single dose as well as at steady state. ACE inhibition before drug intake at day 28 (i.e. trough) was 50%. The (placebo-corrected) maximal drop in diastolic blood pressure after imidapril was 22 mm Hg after the first dose and 25 mmHg at steady state. Exploratory analysis of imidaprilat plasma concentration vs effect profiles suggests a hyperbolic concentration effect relationship where data of the single dose contribute to the ascending part of an Emax-curve, whereas the plateau around Emax is maintained at steady state. In this group of hypertensive patients, the pharmacokinetic profile and the drop in ACE-activity as well as in blood pressure seen after a single dose of imidapril and at steady state were similar. The initial response to a test dose might therefore predict the response during chronic dosing.",1998.0,0,0
2362,9579768,"Assessment of the acute arterial effects of converting enzyme inhibition in essential hypertension: a double-blind, comparative and crossover study.",J Topouchian; A M Brisac; B Pannier; E Vicaut; M Safar; R Asmar,"In subjects with essential hypertension, angiotensin-converting enzyme (ACE) inhibition increases arterial diameter, compliance and distensibility of peripheral muscular arteries in association with blood pressure reduction. Whether pulse pressure amplification is modified by ACE inhibition and whether changes in compliance and distensibility are due to a drug effect on the arterial wall, to the blood pressure reduction or to a combination of both factors, is largely ignored. In a randomised, double-blind crossover trial, we used the ACE inhibitor quinapril as a marker to evaluate the changes in: pulse pressure amplification (applanation tonometry), carotid compliance and distensibility (echo-tracking technique), and aortic distensibility (measured from pulse wave velocity). Quinapril decreased in the same extent carotid and brachial pulse pressure, thus causing a resetting of pulse pressure amplification toward normal values. Carotid compliance and distensibility as well as aortic distensibility increased significantly. Based on three-way analysis of variance, it was shown that, whereas the changes in carotid stiffness were exclusively due to blood pressure reduction and not to a drug-induced relaxation of the arterial wall, the changes in aortic distensibility were due to the combination of both factors. Thus, using an atraumatic non-invasive procedure, it was possible to show that: (i) ACE inhibition is able to maintain pulse pressure amplification, an important factor contributing to reduce the afterload of the heart; and (ii) ACE inhibition alters the hypertensive arterial wall in a very heterogeneous manner, with a maximal drug effect on muscular large arteries like the abdominal aorta, and not on elastic arteries like the carotid artery and the thoracic aorta.",1998.0,0,0
2363,9579769,Renin status does not predict the anti-hypertensive response to angiotensin-converting enzyme inhibition in African-Americans. Trandolapril Multicenter Study Group.,M R Weir; E Saunders,"The angiotensin-converting enzyme (ACE) inhibitor trandolapril, a non-sulfhydryl prodrug which is hydrolysed into trandolaprilat, was studied in 322 hypertensives of African-American descent using a double-blind, randomised, placebo-controlled, parallel study design. Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day trandolapril, an analysis of drug effect on trough blood pressure (BP) stratified by age, gender, weight, pre-treatment plasma renin activity, and trandolaprilat concentration was performed. Two mg was the lowest effective trandolapril dose, whereas doses above 4 mg did not significantly reduce trough BP. Reduction in BP did not correlate with trough plasma trandolaprilat concentration. Pre-treatment plasma renin activity was not a reliable indicator of anti-hypertensive response, as similar reductions in BP occurred even in patients with the lowest renin levels. There were no observable differences based on age, gender or measurements of the renin-angiotensin-aldosterone axis. In conclusion, neither age, gender or plasma renin activity influenced anti-hypertensive response to angiotensin-converting enzyme inhibition in African-Americans.",1998.0,0,0
2364,9579771,"A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension.",A Mimran; L Ruilope; L Kerwin; M Nys; D Owens; K Kassler-Taub; M Osbakken,"To compare the anti-hypertensive efficacy, safety, and tolerability of irbesartan with those of the full dose range of enalapril in patients with mild-to-moderate hypertension. A total of 200 patients were randomised to irbesartan 75 mg or enalapril 10 mg (once daily). Doses were doubled at Weeks 4 and/or 8 if seated diastolic blood pressure (DBP) was > or = 90 mm Hg. Trough blood pressure was measured after completion of a 4- to 5-week placebo lead-in period and again after 2, 4, 8, and 12 weeks of treatment. Efficacy was evaluated by determining the change from baseline in trough seated blood pressure and the proportion of patients normalised (seated DBP <90 mm Hg) at Week 12. Safety and tolerability were assessed by adverse events reported by physicians, by patients in response to a specific-symptoms questionnaire, by open-ended questioning of patients by physicians, and by clinical laboratory evaluations. Both treatments significantly lowered blood pressure with no significant difference in efficacy between treatment groups. At Week 12, the percentage of patients titrated to either enalapril 40 mg or irbesartan 300 mg was 24% and 28%, respectively. The frequency of overall adverse events was similar in both groups. The incidence of cough in the enalapril and irbesartan groups was 17% and 10%, respectively. In contrast to other AII receptor antagonists, there was no change in uric acid concentrations with irbesartan. Irbesartan was as effective as the full dose range of enalapril. Irbesartan also demonstrated an excellent tolerability profile.",1998.0,0,0
2365,9581728,"Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.",M J Mullen; P Clarkson; A E Donald; H Thomson; S A Thorne; A J Powe; T Furuno; T Bull; J E Deanfield,"We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.",1998.0,0,0
2366,9589245,Beneficial impact of ramipril on left ventricular hypertrophy in normotensive nonalbuminuric NIDDM patients.,F S Nielsen; A Sato; S Ali; L Tarnow; U M Smidt; J Kastrup; H H Parving,"To evaluate the effect of the ACE inhibitor ramipril as compared with placebo on left ventricular mass index (LVMI) in normotensive, nonalbuminuric NIDDM patients with left ventricular hypertrophy (LVH). Patients with NIDDM are characterized by excessive cardiovascular morbidity and mortality, and LVH, an independent risk factor for cardiac events, is often present in NIDDM patients. A total of 38 normotensive, nonalbuminuric (albuminuria < 100 mg/24 h) NIDDM patients with LVH (LVMI > 131 g/m2 in men and > 100 g/m2 in women) were enrolled in a 6-month randomized, double-blind parallel group study to compare the effects of ramipril (5 mg/day) with placebo on LVMI (echocardiography, Vingmed CFM725, Diasonics Sonotron), QTc dispersion determined as the interlead variation in QTc interval on standard electrocardiogram (ECG), and 24-h ambulatory blood pressure (A&D TM2420, Tokyo, Japan). A total of 16 ramipril (10 men, 60 +/- 9 years [mean +/- SD]) and 15 placebo-treated (8 men, 55 +/- 10 years) patients completed the study, and their data are presented. Ambulatory blood pressure was almost identical at baseline (132/76 +/- 3/1 vs. 133/74 +/- 5/2 mmHg [mean +/- SEM]) and remained stable during follow-up (134/76 +/- 3/1 vs. 136/74 +/- 6/2 mmHg) in the ramipril and placebo group, respectively. LVMI was comparable at baseline (137.1 +/- 7.0 vs. 129.6 +/- 3.7 g/m2) in the ramipril and placebo group, respectively, and decreased significantly more in the ramipril group as compared with the placebo group (17.6 +/- 3.0 vs. 5.7 +/- 4.6 g/m2, respectively, 11.9 [0.7-23.1] g/m2, mean difference [95% CI]; P = 0.037). QTc dispersion was comparable at baseline (60.2 [5.5] vs. 64.1 [6.5] ms) and did not change significantly during follow-up: -2.5 [7.0] vs. -12.2 [9.5] ms; mean difference 9.8 (-14.2 to 33.8 ms) in the ramipril and placebo group, respectively. Ramipril induces regression of LVH in normotensive, nonalbuminuric NIDDM patients, independent of reduction in systemic blood pressure.",1998.0,0,0
2367,9591932,Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with chronic renal failure.,J F Hoogkamer; C H Kleinbloesem; A Nokhodian; M J Ouwerkerk; G Lankhaar; W Ungethüm; W Kirch,"An open study on the single dose and steady-state pharmacokinetics of imidapril, a novel prodrug-type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite imidaprilat was conducted in eight patients with moderate chronic renal failure [mean creatinine clearance (CL(CR)) 64 ml x min(-1); range 42-77 ml x min(-1)], eight patients with severe chronic renal failure (mean CL(CR), 18 ml x min(-1); range 11-29 ml x min(-1)) and eight healthy volunteers with normal renal function. Subjects received an oral dose of 10 mg imidapril once per day for 7 days. No statistical differences of either maximum concentration (Cmax) or the area under the curve (AUC) were found between patients with moderate renal failure and healthy subjects. However, Cmax and AUC for both imidapril and imidaprilat were significantly higher in patients with severe renal impairment than in healthy volunteers. There were no clinically relevant differences among the three subject groups with regard to total urinary excretion of both imidapril and imidaprilat. The smallest imidapril dose which is clinically effective should be used in patients with severe renal insufficiency.",1998.0,0,0
2368,9594263,Secondary prevention of cardiac events following myocardial infarction: effects of atenolol and enalapril. Beijing Collaborative Study Group.,N Wu; Z Fan,"To investigate the actions of beta-blocker (atenolol) and ACE inhibitor (enalapril) for the secondary prevention of the main cardiac complications after acute myocardial infarction (AMI). 1106 cases of AMI from 7 hospitals in the Beijing area were collected and were divided randomly into three groups: control (group C), atenolol (group A), and enalapril (group E). Drugs for investigation were administered 2-4 weeks after the onset of AMI, and the subjects were followed up for a median period of 19 months. All patients were given aspirin 50 mg/day. The end points of observation were cardiac events and non-cardiac events. Cardiac events included sudden cardiac death (SCD), heart failure death, total cardiac deaths, and myocardial re-infarction. The clinical conditions of the three groups were compatible. Sixty-six cardiac events (6.0%) occurred. Comparing with group C, the rate of SCD decreased significantly by 68% in group A after atenolol treatment for 28 months. Both atenolol and enalapril significantly increased left ventricular ejection fraction (LVEF), whereas in group C the LVEF did not change during the follow-up period. There was obvious decreasing tendency of the survival curve in group C, compared with the other two groups. Totally drugs decrease one cardiac death 0/00/month. But the rate of myocardial re-infarction was the same in the three groups. No serious side effects on blood pressure or heart rate were observed. Both atenolol and enalapril (domestic products) are beneficial to the secondary prevention of SCD and heart failure death after AMI, but not to re-infarction. Both drugs should be continued for a prolonged period to be effective. Drugs given 2-4 weeks after acute stage are also effective, with no serious side effects.",1998.0,0,1
2369,9595286,Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.,T Kinugawa; K Ogino; M Kato; Y Furuse; M Shimoyama; M Mori; A Endo; T Kato; H Omodani; S Osaki; H Miyakoda; I Hisatome; C Shigemasa,"1. Treatment with spironolactone is reported to be useful when combined with loop diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effects of additive spironolactone on exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at rest and after peak exercise in nine patients with CHF (six idiopathic and three ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7 +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive single daily dose of 25 mg of spironolactone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P < 0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/- 2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/- 313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/- 11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and AII were insignificantly increased, and ANP was insignificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormones to return toward pretreatment values. 4. In conclusion, chronic additive treatment with spironolactone was associated with neurohormonal activation both at rest and during exercise without changing the exercise capacity of patients with mild CHF who were already on loop diuretics and ACE inhibitor therapy.",1998.0,0,0
2370,9602958,"Cough-challenge trial with a new angiotensin-converting enzyme inhibitor, imidapril.",H Shionoiri; I Takasaki; K Minamisawa; S Ueda; M Kihara; K Shindo; S Hiroto; K Sugimoto; H Himeno; M Naruse; I Nagamochi; G Yasuda,"This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.",1998.0,0,0
2371,9604795,,,,,0,0
2372,9604941,Effects of aspirin on angiotensin-converting enzyme inhibition and left ventricular dilation one year after acute myocardial infarction.,M Oosterga; R L Anthonio; P J de Kam; J H Kingma; H J Crijns; W H van Gilst,"There are conflicting reports on the interaction of aspirin with angiotensin-converting enzyme inhibitors in heart failure and systemic hypertension. A post hoc analysis of the Captopril and Thrombolysis Study (CATS) study was conducted. At randomization, 94 patients (31.5%) took aspirin. In patients who took aspirin, the cumulative alpha-hydroxy butyrate dehydrogenase release was 1,151 +/- 132 IU/L in patients randomized to captopril compared with 1,401 +/- 136 IU/L in patients randomized to placebo (difference -250 +/- 189 [95% confidence interval (CI) -620 to 120]). This difference was comparable to the difference in patients who did not use aspirin (-199 +/- 147 [95% CI -488 to 897]). One year after acute myocardial infarction, an increase in left ventricular end-diastolic volume index of 2.2 +/- 3.0 ml/m2 in captopril-treated and 1.9 +/- 2.9 ml/m2 in placebo-treated patients was observed in patients who took aspirin (difference 0.4 +/- 4.2 [95% CI -8.2 to 8.9]). This difference was also comparable to the difference in patients who did not take aspirin (2.2 +/- 3.8 [95% CI -5.2 to 9.7]). One year after acute myocardial infarction, patients who did take aspirin had a mean change in LV end-diastolic volume index of 2.1 +/- 2.1 ml/m2 compared with 8.4 +/- 1.9 ml/m2 in patients who did not use aspirin (p = 0.02). Thus, aspirin does not attenuate the acute and long-term effects of angiotensin-converting enzyme inhibition after acute myocardial infarction, but independently reduces LV dilation after myocardial infarction.",1998.0,0,0
2373,9607375,"Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy.",M J Roman; M H Alderman; T G Pickering; R Pini; J O Keating; J E Sealey; R B Devereux,"Diuretic-based therapy is less effective in reducing the cardiac complications of hypertension than the risk of stroke and may be less effective in reducing left ventricular (LV) mass than is therapy with angiotensin converting enzyme (ACE) inhibition. In view of the strong association of LV hypertrophy with cardiovascular risk, this study was designed to compare the impact of therapy with a diuretic and ACE inhibition on cardiac and vascular structure. Fifty essential hypertensives (74% male, 88% nonwhite) participated in a double-blind study for 6 months and were randomized to either ramipril or hydrochlorothiazide (HCTZ). Echocardiography, carotid ultrasonography, and ambulatory blood pressure (BP) monitoring were performed at baseline and 3 and 6 months after initiation of therapy. The 22 ramipril patients were comparable to the 28 HCTZ patients at baseline in age, race, and 24-h BP. Although HCTZ resulted in a greater reduction in 24-h BP, only treatment with ramipril resulted in a decrease in LV mass (193 to 179 g, P < .005, v 184 to 182 g, P = NS), attributable to a reduction in wall thicknesses but not in chamber diameter. In multivariate analysis, both change in BP and treatment group were independent predictors of change in LV mass. Importantly, although neither drug reduced carotid artery cross-sectional area, relative wall thickness increased due to a tendency for vessel diameter to decrease and wall thickness to increase, particularly in the diuretic group. Ramipril caused a sustained fall in plasma angiotensin II, whereas HCTZ increased angiotensin II levels. Although diuretic therapy was more effective in lowering ambulatory BP in this predominantly nonwhite population, only therapy with ACE inhibition was associated with regression of LV mass. Vascular geometry was altered consistent with the reduction in distending pressure resulting in vascular remodelling.",1998.0,0,0
2374,9607389,Insulin receptor number in arterial hypertension: response to treatment with fosinopril or atenolol.,T Makris; P Krespi; F Triposkiadis; V Votteas; A Hatzizaharias; M Kyriakidis,"Human insulin receptor (hINR) number and its response to medical treatment was evaluated in 14 male controls and 40 male hypertensive patients. Twenty patients treated with fosinopril (10 to 20 mg daily orally) comprised Group A and 20 treated with atenolol (25 to 50 mg daily orally) Group B. The hINR number (receptors x 10(3)/red cell) was greater in controls compared to untreated patients (8.22+/-2.4 v 5.53+/-1.27, P < .001). After 6 months of treatment the hINR number increased in Group A (5.73+/-1.47 v 7.5+/-2.06, P < .001) and remained unchanged (5.35+/-1.09 v 5.5+/-1.31, P = NS) in Group B. Thus, hINR number is decreased in hypertension and, in contrast to atenolol, fosinopril treatment is associated with an increase in hINR number, suggesting a favorable effect on glucose metabolism.",1998.0,0,0
2375,9610531,"Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial.",J J Mahmarian; L A Moyé; D A Chinoy; R F Sequeira; G B Habib; W J Henry; A Jain; B R Chaitman; C S Weng; H Morales-Ballejo; C M Pratt,"Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.",1998.0,0,0
2376,9610981,Angioedema.,E S Nadel; D F Brown,,1998.0,0,0
2377,9613870,Special topics in pediatric hypertension.,L G Feld; J E Springate; W R Waz,"This review emphasizes four major areas of pediatric hypertension. Because hypertension is the most common reason student athletes fail the sports pre-participation examinations, we have attempted to provide a rationale approach to the decision process to permit a hypertensive child to partake in leisure and competitive sports. Without question, obesity is a major reason for referral for hypertension to a pediatric nephrologist. The work-up should be directed to diet control and an exercise program to achieve sustained weight reduction. Hypertension associated with chronic renal failure and renal disease secondary to insulin-dependent diabetes mellitus is a major problem in pediatric and adult nephrology. With adequate control of systemic blood pressure, progressive decline in renal function may be delayed. By understanding these common areas of associated pediatric hypertension, a more systematic approach to the evaluation and treatment can be achieved.",1998.0,0,0
2378,9617599,Moexipril. A review of its use in the management of essential hypertension.,R N Brogden; L R Wiseman,"Moexipril is a prodrug which is hydrolysed after oral administration to its active metabolite moexiprilat, an inhibitor of the angiotensin converting enzyme (ACE). Once daily administration of moexipril 7.5 or 15 mg effectively reduces blood pressure in patients with essential hypertension (including the elderly and postmenopausal women with this condition). In double-blind randomised comparative studies, moexipril 7.5 to 15 mg once daily showed similar efficacy to other antihypertensive agents, including captopril, hydrochlorothiazide, atenolol, metoprolol, sustained release verapamil and nitrendipine. Combined therapy with hydrochlorothiazide and moexipril had a significantly greater antihypertensive effect than either agent alone. Moexipril is well tolerated by the majority of patients and compares well in this respect with other antihypertensive agents. Its tolerability profile appears to be characteristic of ACE inhibitors as a class (the most common adverse events being headache, symptoms of upper respiratory tract infection and cough). Moexipril generally had no clinically significant effect on lipid, glucose or electrolyte metabolism or haematological parameters, and, in particular, it was not associated with any significant changes in lipid or glucose metabolism in postmenopausal women (with or without hormone replacement therapy). Once daily moexipril is a useful agent for the treatment of essential hypertension, which compares well with currently available options in terms of clinical efficacy and tolerability. In addition, clinical experience to date supports its use in postmenopausal women.",1998.0,0,0
2379,9620114,Potential angiotensin-converting enzyme inhibitor-epoetin alfa interaction in patients receiving chronic hemodialysis.,M H Schwenk; A Q Jumani; C R Rosenberg; J E Kulogowski; C Charytan; B S Spinowitz,"We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (+/- SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 +/- 2575, 5800 +/- 2026, and 5660 +/- 2285 U 3 times/week (p=0.56), and mean differences were -212 U for 0-3 months (95% CI -1310 to 886) and -713 U for 0-12 months (95% CI -2142 to 716). Mean +/- SD hematocrits were 30.5 +/- 3.9%, 31.6 +/- 3.2%, and 34.2 +/- 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0-3 months (95% CI -1.41 to 4.81) and 3.85% for zero-12 months (95% CI 0.71-7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.",1998.0,0,0
2380,9621290,Leucine turnover in patients with nephrotic syndrome: evidence suggesting body protein conservation.,V S Lim; M Wolfson; K E Yarasheski; M J Flanigan; J D Kopple,"Whole-body leucine flux was measured in eight patients with nephrotic syndrome and in five healthy subjects by primed-constant infusion of L-[1-13C leucine]. Plasma enrichment of 13C leucine and 13C alpha-keto-isocaproate (13C KIC) was measured by gas chromatography/mass spectrometry, and expired 13CO2 was measured by isotope ration mass spectrometry. Leucine kinetics, calculated from the primary pool enrichment [13C leucine], showed no difference between the nephrotic patients and the control subjects. Kinetics derived from the reciprocal pool [1-13C KIC] enrichment, however, showed that leucine turnover rates were reduced in the nephrotic patients. The values (mumol/kg per h, means +/- SD) comparing the patients and the control subjects are as follows: rate of leucine release from protein degradation, 99 +/- 6 and 117 +/- 12 (P = 0.007); leucine oxidation rate, 15 +/- 7 and 22 +/- 3 (P = 0.04); rate of leucine incorporation into body protein [S], 84 +/- 10 and 95 +/- 6 (P = 0.04); protein turnover rate, 3.99 +/- 0.49 and 4.72 +/- 0.25 g/kg per d (P = 0.007). Nitrogen balance, measured only in the nephrotic patients, showed a mean positive balance of 0.5 g/d. In the nephrotic and control subjects, protein intake levels were 0.84 +/- 0.16 and 1.17 +/- 0.18 g/kg per d (P = 0.002), respectively, and energy intake levels were 33.3 +/- 8.5 and 33.9 +/- 2.4 kcal/kg per d, respectively. Linear correlations between leucine turnover rates and protein intake were highly significant. This study found that nephrotic patients given a modestly protein-restricted diet were able to maintain positive nitrogen balance. Moreover, leucine flux measurements showed downregulation of protein degradation and amino acid oxidation, reflecting appropriate adaptation to a lower protein intake.",1998.0,0,0
2381,9625684,"Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial.",M Ravid; D Brosh; Z Levi; Y Bar-Dayan; D Ravid; R Rachmani,"Angiotensin-converting enzyme (ACE) inhibitors attenuate the decline in renal function in diabetic patients with microalbuminuria. However, no data are available on the use of ACE inhibitors to prevent the decrease in renal function in normotensive, normoalbuminuric patients with type 2 diabetes. To evaluate the effect of prolonged ACE inhibition on renal function and albuminuria in patients with type 2 diabetes. Randomized, double-blind, placebo-controlled trial with 6-year follow-up. Eight outpatient clinics coordinated by a department of medicine in a university hospital. 156 patients in whom type 2 diabetes was diagnosed after 40 years of age who had a baseline mean blood pressure less than 107 mm Hg and albuminuria (albumin excretion < or = 30 mg/24 h). Enalapril, 10 mg/d, or placebo. Degree of albuminuria at 24 hours, creatinine clearance, blood pressure, and hemoglobin A1c values. Enalapril therapy decreased albumin excretion from a mean +/- SD of 11.6 +/- 7 mg/24 h to 9.7 +/- 6 mg/24 h at 2 years. This was followed by a gradual increase to 15.8 +/- 8 mg/24 h at 6 years. In the placebo group, albumin excretion increased from 10.8 +/- 8 mg/24 h to 26.5 +/- 10 mg/24 h at 6 years (P = 0.001 for enalapril compared with placebo). Transition to microalbuminuria occurred in 15 of 79 (19%) placebo recipients and 5 of 77 (6.5%) enalapril recipients. Enalapril treatment resulted in an absolute risk reduction of 12.5% (95% CI, 2% to 23%; P = 0.042) for development of microalbuminuria. After 6 years, creatinine clearance decreased from 1.78 +/- 0.13 mL/s to 1.63 +/- 0.12 mL/s (mean decrease, 0.025 mL/s per year) in enalapril recipients and from 1.81 +/- 0.15 mL/s to 1.57 +/- 0.17 mL/s (mean decrease, 0.04 mL/s per year) in placebo recipients (P = 0.040). Hemoglobin A1c values decreased modestly in both groups. Mean blood pressure remained normal (< 107 mm Hg) in all patients. Enalapril attenuated the decline in renal function and reduced the extent of albuminuria in normotensive, normoalbuminuric patients with type 2 diabetes. Further research is needed to determine whether this treatment forestalls the development of overt nephropathy.",2000.0,0,0
2382,9631869,"Indications for ACE inhibitors in the early treatment of acute myocardial infarction: systematic overview of individual data from 100,000 patients in randomized trials. ACE Inhibitor Myocardial Infarction Collaborative Group.",,"Several large-scale trials have demonstrated improved survival with ACE-inhibitor therapy started during acute myocardial infarction. A systematic overview was conducted to resolve uncertainties regarding time of initiation, time course of effect, and identification of patients in whom the benefits or the risks may be greater. This overview aimed to include individual data from all randomized trials involving more than 1000 patients in which ACE-inhibitor treatment was started in the acute phase (0 to 36 hours) of myocardial infarction and continued for a short time (4 to 6 weeks). Data were available for 98,496 patients from 4 eligible trials, and the results were consistent among the trials. Thirty-day mortality was 7.1% among patients allocated to ACE inhibitors and 7.6% among control subjects, corresponding to a 7% (SD, 2%) proportional reduction (95% CI, 2% to 11%; 2P<0.004). This represented avoidance of approximately 5 (SD, 2) deaths per 1000 patients, with most of the benefit observed within the first week. The proportional benefit was similar in patients at different underlying risk. The absolute benefit was particularly large in some high-risk groups (ie, Killip class 2 to 3, heart rate > or = 100 bpm at entry) and in anterior MI. ACE-inhibitor therapy also reduced the incidence of nonfatal cardiac failure (14.6% versus 15.2%, 2P=0.01) but was associated with an excess of persistent hypotension (17.6% versus 9.3%, 2P<0.01) and renal dysfunction (1.3% versus 0.6%, 2P<0.01). These results support the use of ACE inhibitors early in the treatment of acute MI, either to a wide range of patients or selectively in patients with anterior MI and in those at increased risk of death.",1998.0,0,0
2383,9631978,Efficacy of low-dose combination of bisoprolol/hydrochlorothiazide compared with amlodipine and enalapril in men and women with essential hypertension.,V Papademetriou; L M Prisant; J M Neutel; M R Weir,The efficacy of the low-dose combination of bisoprolol/hydrochlorothiazide was compared with amlodipine and enalapril. The low-dose combination was found to be at least as effective as amlodipine and more effective than enalapril in both men and women.,1998.0,0,0
2384,9631980,"Effect of benazepril on complex ventricular arrhythmias in older patients with congestive heart failure, prior myocardial infarction, and normal left ventricular ejection fraction.",W S Aronow; A D Mercando; S Epstein,"Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior myocardial infarction, normal left ventricular ejection fraction, and > or = 30 ventricular premature complexes per hour detected by 24-hour ambulatory electrocardiograms, and who were treated with diuretics, were randomized to treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30 patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory electrocardiograms showed that compared with no benazepril, benazepril caused no significant reduction in the number of ventricular premature complexes per hour or in the number of runs of ventricular tachycardia per 24 hours.",1998.0,0,0
2385,9638391,The ELITE Study. What are its implications for the drug treatment of heart failure? Evaluation of Losartan in the Elderly Study.,W S Aronow,"Angiotensin II type 1 (AT1) receptor antagonists inhibit the renin-angiotensin system more completely than ACE inhibitors, and do not increase bradykinin levels as ACE inhibitors do. ACE inhibitors have been proven to increase survival and improve quality of life in patients with congestive heart failure (CHF). At the 48-week follow-up of the Evaluation of Losartan in the Elderly (ELITE) Study, the AT1 receptor antagonist losartan (at a dosage of 50 mg/day) was found to be superior to captopril 50 mg 3 times daily in terms of its effects on total mortality, total mortality and/or hospitalisation for CHF, and hospitalisation for any reason. Hospitalisation for CHF was the same for both drugs. Adverse effects occurred in 12 and 21% of those receiving losartan and captopril, respectively. Cough, rash, angioedema or taste disturbances/reduced appetite prompted the cessation of drug treatment in 0 and 7% of those receiving losartan and captopril, respectively. Until additional data are available, this author recommends that elderly patients with CHF and an abnormal or normal left ventricular ejection fraction, and who are unable to tolerate ACE inhibitors, should receive losartan 50 mg/day.",1998.0,0,1
2386,9639376,Inhibition of neutral endopeptidase causes vasoconstriction of human resistance vessels in vivo.,C J Ferro; J C Spratt; W G Haynes; D J Webb,"Neutral endopeptidase (NEP) degrades vasoactive peptides, including the natriuretic peptides, angiotensin II, and endothelin-1. Systemic inhibition of NEP does not consistently lower blood pressure, even though it increases natriuretic peptide concentrations and causes natriuresis and diuresis. We therefore investigated the direct effects of local inhibition of NEP on forearm resistance vessel tone. Four separate studies were performed, each with 90-minute drug infusions. In the first study, 10 healthy subjects received a brachial artery infusion of the NEP inhibitor candoxatrilat (125 nmol/min), which caused a slowly progressive forearm vasoconstriction (12+/-2%; P=0.001). In a second two-phase study, 6 healthy subjects received, 4 hours after enalapril (20 mg) or placebo, an intra-arterial infusion of the NEP inhibitor thiorphan (30 nmol/min). Thiorphan caused similar degrees of local forearm vasoconstriction (P=0.6) after pretreatment with both placebo (13+/-1%, P=0.006) and enalapril (17+/-6%, P=0.05). In a third three-phase study, 8 healthy subjects received intra-arterial thiorphan (30 nmol/min), the endothelin ETA antagonist BQ-123 (100 nmol/min), and both combined. Thiorphan caused local forearm vasoconstriction (13+/-1%, P=0.0001); BQ-123 caused local vasodilatation (33+/-3%, P=0.0001). Combined thiorphan and BQ-123 caused vasodilatation (32+/-1%, P=0.0001) similar to BQ-123 alone (P=0.98). In a fourth study, 6 hypertensive patients (blood pressure >160/100 mm Hg) received intra-arterial thiorphan (30 nmol/min). Thiorphan caused a slowly progressive forearm vasoconstriction (10+/-2%, P=0.0001). Inhibition of local NEP causes vasoconstriction in forearm resistance vessels of both healthy volunteers and patients with hypertension. The lack of effect of ACE inhibition on the vasoconstriction produced by thiorphan and its absence during concomitant ETA receptor blockade suggest that it is mediated by endothelin-1 and not angiotensin II. These findings may help to explain the failure of systemic NEP inhibition to lower blood pressure.",1998.0,0,0
2387,9642527,Drug-induced lichen planus.,P Ellgehausen; P Elsner; G Burg,,1998.0,0,0
2388,9642529,Drug-induced scleroderma and sclerodermiform conditions.,U F Haustein; B Haupt,,1998.0,0,0
2389,9642532,Drug-induced linear immunoglobulin-A bullous dermatosis.,M Camilleri; J L Pace,,1998.0,0,0
2390,9642533,Drug-induced pemphigus.,S Brenner; A Bialy-Golan; V Ruocco,,1998.0,0,0
2391,9643274,"Antihypertensive treatment in postmenopausal women: results from a prospective, randomized, double-blind, controlled study comparing an ACE inhibitor (moexipril) with a diuretic (hydrochlorothiazide).",M Stimpel; B Koch; S Oparil,"The present study was designed to compare the safety and efficacy of the new angiotensin-converting enzyme inhibitor moexipril with that of hydrochlorothiazide (HCTZ) in postmenopausal women with mild-to-moderate hypertension. After a 4-week single-blind placebo period, 97 postmenopausal hypertensive women (42-74 years of age) with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg were randomized to receive either once daily moexipril 15 mg or HCTZ 25 mg for a 12-week double-blind treatment period. At study endpoint, HCTZ caused significantly greater increases from baseline in serum uric acid levels than did moexipril (0.8 +/- 0.1 vs. 0.1 +/- 0.1 mg/dl, p < 0.01). Furthermore, 12-week treatment with HCTZ resulted in significant increases in glucose (+11.0 +/- 4.1 mg/dl) and total cholesterol/HDL ratio (+0.3 +/- 0.1 mg/dl) and a significant decrease in HDL (-3.2 +/- 0.7 mg/dl). In contrast, moexipril treatment was not associated with significant changes in any metabolic parameter. Both drugs efficiently lowered SDBP with reductions of -10.0 +/- 1.3 and -11.8 +/- 1.1 mm Hg in the moexipril and HCTZ group, respectively. Clinical adverse events were reported by a greater percentage of HCTZ patients (53%) than moexipril patients (40%), with headache and rhinitis as the most frequent events. The results indicate that moexipril was better tolerated than HCTZ in postmenopausal women and did not adversely affect metabolic parameters. Both drugs were effective in lowering blood pressure.",2000.0,0,0
2392,9643276,Limitation of left ventricular hypertrophy and dysfunction by ACE inhibition after anterior Q-wave myocardial infarction.,B I Jugdutt; D P Humen,"To determine whether limitation of left ventricular (LV) hypertrophy with angiotensin-converting enzyme inhibition after myocardial infarction (MI) is associated with improved systolic and diastolic function, quantitative two-dimensional echocardiograms and Doppler of 40 patients, who were randomized on day 3 after a first Q-wave anterior MI to receive therapy with captopril (12.5 mg t.i.d.) or placebo for 6 weeks, were analyzed for LV volumes (Simpson's rule) and mass (3D reconstruction), remodeling parameters and peak early (E) and late (A) transmitral flow velocities and deceleration times (DT) at 3 days, 6 weeks, 6 months and 1 year. Compared to placebo over 1 year, captopril limited (p < 0.001) the increase in diastolic volume and mass, increased LV ejection fraction and diastolic E/A ratio, and decreased DT, the frequency of E and A reversal, infarct expansion and aneurysm frequency but volume/ mass ratio was unchanged. Captopril over the first 6 weeks after a first Q-wave anterior MI limited LV remodeling and hypertrophy and improved both systolic and diastolic function up to 1 year.",2000.0,0,0
2393,9643277,Long-term effects on cardiac output and peripheral resistance in patients treated with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study Group. Cooperative New Scandinavian Enalapril Survival Study.,M Edner; K Caidahl; V V Bonarjee; D W Nilsen; S Carstensen; J Berning,"In the Cooperative New Scandinavian Enalapril Survival Study (CONSENSUS II), in which enalapril treatment was initiated intravenously within 24 h after acute myocardial infarction, there was a neutral effect on 6-month mortality, whereas a beneficial effect on the progression of congestive heart failure was noted. We studied the effect of enalapril on left ventricular systolic function in terms of cardiac output and mean acceleration time measured by pulsed-wave Doppler in the left ventricular outflow tract and peripheral resistance. Early angiotensin-converting enzyme inhibition after acute myocardial infarction did not result in a general improvement of cardiac output. However, a small increase in cardiac output was observed in a subgroup of enalapril-treated patients with ejection fraction > or = 45%, probably due to a reduction in peripheral resistance in these patients.",2000.0,0,0
2394,9648079,Free pentosidine and neopterin as markers of progression rate in diabetic nephropathy. Collaborative Study Group.,M F Weiss; R A Rodby; A C Justice; D E Hricik,"Patients with diabetic nephropathy experience a progressive and usually inexorable decline in renal function. The presence of the structurally defined advanced glycation end product (AGE) pentosidine on tissue and circulating proteins has been correlated with the severity of diabetic complications. To delineate a role for this AGE in the progression of diabetic nephropathy, glycohemoglobin and free and protein-bound pentosidine were measured in baseline stored serum and urine from a subgroup of patients with diabetes mellitus and proteinuria originally followed by the Collaborative Study Group Trial. To delineate a potential role for an immune-activation response to AGEs, the inflammatory markers, interleukin-6 (IL-6), C-reactive protein (CRP), and the monocyte activation marker marker neopterin were also measured at baseline. The patients chosen represented 67 subjects whose creatinine levels had ""doubled"" over the course of the study whether or not they later were treated with captopril, and 67 paired ""non-doublers."" Baseline disease activity, as manifested by glycohemoglobin, serum creatinine and degree of proteinuria was equal in the two groups, as was protein-bound pentosidine and the immune-markers IL-6 and CRP. At baseline the ""doublers"" as compared to the ""non-doublers"" had elevated serum levels of free pentosidine and neopterin. Baseline increases in these two parameters were also associated with an increased rate of ""doubling"" of serum creatinine by the proportional hazards method. Differences in individual responsiveness to AGEs, as manifested by either the production of free pentosidine or its release from a protein-bound form, and by evidence of monocyte/macrophage activation, are associated with progression of diabetic nephropathy.",1998.0,0,0
2395,9649912,Divergent cardiac response to exercise in essential hypertension vs. normotension and the effect of enalapril.,N Gadsbøll; S Rasmussen; B H Jensen; A Leth; J Giese; P F Høilund-Carlsen,"The aims of this study were to examine (1) the cardiac response to exercise in essential hypertension and (2) the effect of long-term enalapril treatment on cardiac reserve. Ten normotensive control subjects and 15 patients with moderate, essential hypertension underwent radionuclide ventriculography during graded, supine exercise (0 W-50 W-100 W). The hypertensive patients were studied during monotherapy using hydrochlorothiazide and 3 and 12 months after supplementation with enalapril 10-40 mg o.d. During exercise, the control subjects demonstrated a 17% increase in left ventricular ejection fraction (LVEF) mediated by a 30% decrease in end-systolic volume, a small increase in stroke volume and a minor biphasic (increase-decrease) change in end-diastolic volume. In the hypertensive patients, both the end-diastolic and the end-systolic volume increased substantially with no increase in LVEF, although stroke volume increased by 33%. Long-term therapy with enalapril induced only a minor change towards a more normal pattern of cardiac response to exercise. The hypertensive patients increased their stroke volume during exercise by recruiting preload reserve instead of increasing contractility. Long-term treatment with enalapril had little, if any, effect on this abnormal cardiac response.",1998.0,0,0
2396,9650536,Use of angiotensin-converting enzyme inhibitors as monotherapy and in combination with diuretics and calcium channel blockers.,A Cheng; W H Frishman,"Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in medical therapy since their discovery about two decades ago. This family of drug has grown tremendously since the introduction of captopril in 1981. There are currently more than 14 ACE inhibitors in the world and 9 are available in the United States. Although these agents share many similarities, they differ in their pharmacokinetic properties, approved indications, and cost. This paper provides guidance for selection of ACE inhibitors by examining the pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost of these agents. Combination products of ACE inhibitors with either diuretics or calcium channel blockers also are reviewed.",1998.0,0,0
2397,9657538,Effects of amlodipine and lisinopril on left ventricular mass and diastolic function in previously untreated patients with mild to moderate diastolic hypertension.,F W Beltman; W F Heesen; A J Smit; J F May; P A de Graeff; T K Havinga; F H Schuurman; E van der Veur; K I Lie; B Meyboom-de Jong,"The aim of the study was to compare the effects of two long-acting antihypertensive agents, the calcium-antagonist amlodipine and the ACE inhibitor lisinopril, on left ventricular mass and diastolic filling in patients with mild to moderate diastolic hypertension from primary care centres. It is a 1-year prospective, double-blind, randomized, parallel group, comparative study. Patients between 25 and 75 years of age with untreated hypertension with elevated diastolic blood pressure (> or = 95 mmHg) on three occasions (twice on the first visit and once only on the second and third visits) were recruited from a population survey. After 4 weeks placebo run-in 71 patients were randomized to dosages of amlodipine 5-10 mg or lisinopril 10-20 mg, which were titrated on the basis of the effects on blood pressure. Fifty-nine patients completed the study period. Primary endpoints were left ventricular mass index and early to atrial peak filling velocity. Office and ambulatory blood pressure and other echocardiographic measurements were considered secondary. Decrease in blood pressure was equal for both treatment regimens. A statistically significant decrease in left ventricular mass index in both treatment groups was observed: -11.0 g/m2 (95% CI: -6.0, -16.1) in the amlodipine group and -12.6 g/m2 (95% CI: -8.2, -17.0) in the lisinopril group. The higher the baseline value of left ventricular mass before treatment, the more the decrease after treatment. Early to atrial peak filling velocity did not change significantly within the treatment groups: +0.07 (95% CI: -0.01, +0.15) in the amlodipine group and +0.01 (95% CI: -0.06, +0.08) in the lisinopril group. However, analysis of time measurements of the early peak showed significant changes for both treatment groups. No significant differences in primary and secondary endpoints between treatment groups were found. Twelve patients did not complete the study, seven in amlodipine and five in lisinopril, basically due to adverse events. The effects of amlodipine and lisinopril on left ventricular mass and early to atrial filling peak velocity after 1 year of treatment in patients with previously untreated mild to moderate hypertension are similar. Further studies are recommended, particularly with a larger sample size and a follow-up of longer duration.",1998.0,0,0
2398,9657539,Regression of left ventricular wall thickness during ACE-inhibitor treatment of essential hypertension is associated with an increase in insulin mediated skeletal muscle blood flow.,P E Andersson; L Lind; B Andrén; A Hänni; R Reneland; C Berne; H Lithell,"Left ventricular hypertrophy (LVH) has been associated with insulin resistance, a condition with an impaired insulin-mediated vasodilation in skeletal muscle. ACE-inhibitors have been reported to be superior to most other antihypertensive drugs in inducing a regression of LVH. In a double-blind study with parallel groups, 50 patients with essential hypertension were randomized to treatment with either fosinopril (20 mg o.d.) or atenolol (50 mg o.d.) for 12-16 weeks. Left ventricle wall thickness (LVWT, defined as the sum of interventricular septum and posterior wall), diastolic function (represented by the ratio between the E-wave and the A-wave of mitral blood flow) and femoral artery blood flow (FBF) were evaluated using ultrasonic measurements. FBF was measured at normoinsulinemia and after 2 h of euglycemic hyperinsulinemia. Before treatment, the insulin-induced increase in FBF was inversely related to the LVWT (r = -0.52, p < 0.02). The reduction in ambulatory 24-h SBP/DBP was 13/9 mmHg for fosinopril and 15/14 for atenolol, ambulatory DBP being significantly more reduced by atenolol (p = 0.03 for difference in treatment effect). However, only fosinopril treatment resulted in a significant reduction in LVWT (from 20.5 mm to 19.4 mm, p < 0.05). The degree of reduction in LVWT was related to the increase in FBF in the fosinopril group (r = -0.45, p < 0.05). For fosinopril (but not for atenolol), there was a positive relationship between the change in E/A ratio and the change in femoral artery stroke volume (r = 0.80, p < 0.01). Impaired insulin-induced stimulation of leg blood flow was related to an increased LVWT. Furthermore, during fosinopril treatment, regression of LVWT was associated with enhanced skeletal muscle blood flow during hyperinsulinemia. This indicates that impaired peripheral blood flow (and thereby increased afterload) may be a possible mechanism explaining the previously found association between insulin resistance and cardiovascular hypertrophy.",1998.0,0,0
2399,9657623,Vagal cardiac activity in essential hypertension: the effects of metoprolol and ramipril.,R K Vesalainen; I M Kantola; K E Airaksinen; K U Tahvanainen; T J Kaila,"Cardiovascular parasympathetic activity is attenuated in essential hypertension. Both beta-adrenoceptor antagonists and angiotensin converting enzyme inhibitors have been reported to increase vagal modulation of heart rate and baroreflex sensitivity, but the relations between the antihypertensive and vagal cardiac effects of these drugs have remained unclear in essential hypertension. In the present study we evaluated the effects of a 4-week crossover monotherapy with metoprolol and ramipril on spectrum analysis indices of heart rate variability in the supine rest and head-up tilted positions, baroreflex sensitivity (phenylephrine method), and 24-h ambulatory blood pressure (BP) in 12 formerly untreated stage 1-2 essential hypertensive patients. Compared to the pretreatment values, both drugs decreased BP similarly and significantly. However, the drugs showed different effects on cardiac vagal activity: metoprolol increased significantly mean R-R interval, R-R interval total, and high-frequency variability at supine rest and baroreflex sensitivity, but ramipril did not significantly affect these variables. The metoprolol-induced decrease in ambulatory BP correlated with the prolongation of the R-R interval and the increase of high-frequency variability at supine rest. The present data show that 4-week treatment with metoprolol increases tonic and reflex vagal cardiac activity, whereas ramipril does not affect vagal cardiac control in essential hypertension. Increase in vagal activity may contribute to the BP-lowering effect of metoprolol in hypertensive patients.",1998.0,0,0
2400,9657627,Effects of an ACE inhibitor and a calcium channel blocker on cardiovascular autonomic nervous system and carotid distensibility in patients with mild to moderate hypertension.,H Tomiyama; Y Kimura; Y Sakuma; K Shiojima; A Yamamoto; I Saito; Y Ishikawa; H Yoshida; S Morita; N Doba,"We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 +/- 1.9 --> 5.6 +/- 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 +/- 0.8 --> 2.5 +/- 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.",1998.0,0,0
2401,9661803,"Long-term therapy with an ACE inhibitor, temocapril, reduces microalbuminuria in essential hypertension.",H Shionoiri; K Sugimoto; T Kosaka; E Kita; H Oda; T Ushikubo; T Goto; I Takasaki; G Yasuda,"The present study was conducted to prospectively evaluate whether a new ACE inhibitor, temocapril, could modify urinary microalbumin excretion rate (UAE) in a group of hypertensive outpatients who had no evidence of renal impairment. Sixty-three outpatients (32 men and 31 women; mean age, 59.9 +/- 1.5 yr) with essential hypertension entered the study, all having been treated for at least 6 mo with dihydropyridine calcium-channel blockers (CCBs: nitrendipine, nisoldipine, or amlodipine). Their blood pressures (BPs) had been controlled to adequate levels with the CCBs. None had overt proteinuria (determined by Albustix) or abnormal serum creatinine levels. After 3 mo of baseline observation under the previous treatment, the subjects were randomly divided into two groups. In group A (n = 31), the previously used CCBs were switched to temocapril, 2 to 4 mg once daily for 12 mo, and BP was controlled at a level equivalent to that during CCB treatment. In group B (n = 32), the subjects were maintained on their previous treatment for a further 12 mo. The effect of temocapril on BP appeared to be clinically similar to that of the previously used CCBs, but it significantly decreased UAE as compared with the previous therapy. In group A, UAE decreased significantly (p < 0.01) from the baseline value of 38.9 +/- 5.1 mg/g creatinine (Cr) to 22.2 +/- 4.2 and 25.3 +/- 5.6 mg/g Cr at the 6th and 12th months of temocapril therapy, respectively. In contrast, in group B UAE was unchanged (baseline 39.8 +/- 6.6 mg/g Cr; 6 mo, 44.6 +/- 6.8; 12 mo, 45.9 +/- 7.7). In group A, 17 of 31 patients (54.8%) had abnormal UAE levels (> or = 29.5 mg/g Cr) during previous therapy with CCBs, but 6 mo after switching to temocapril 25 of these patients (80.6%) had normal UAE (< 29.5 mg/g Cr). In group B, 15 of 32 patients (46.9%) had abnormal UAE levels during the observation period, and these abnormal UAE levels remained unchanged; 17 of the 32 patients (53.1%) had abnormal UAE levels after a further 6 mo of continued CCBs therapy. We conclude that long-term therapy with temocapril may provide renal protection by reducing UAE even in hypertensive patients with no evidence of renal impairment.",1998.0,0,0
2402,9663368,"Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group.",A H Gradman; N R Cutler; P J Davis; J A Robbins; R J Weiss; B C Wood; E L Michelson,"A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.",1998.0,0,0
2403,9663811,Determinants of the blood pressure response to the first dose of ACE inhibitor in mild to moderate congestive heart failure.,L Murray; I B Squire; J L Reid; K R Lees,"To investigate the relationship in patients with heart failure between BP response to the first dose of ACE inhibitor and (1) plasma drug concentration and (2) baseline clinical and laboratory variables. We studied individual placebo-corrected BP responses to initiation of treatment with one of a number ACE inhibitor preparations in 132 patients with mild to moderate CHF. Various pharmacokinetic/pharmacodynamic models were compared. We assessed the strength of association between baseline physiological and laboratory variables and the BP response as assessed directly from the AUC(0,10 h) and indirectly from the slope of the PK/PD relationship. Predictive models for response variables were developing using regression analysis. BP response was primarily related to plasma drug concentration. The association between the fall in BP and baseline variables was weak. The strongest single predictor of BP response was baseline mean arterial pressure (r2 = 5.8%, P = 0.02). The best combinations of predictor variables contained mean arterial pressure, plasma renin activity, creatinine concentration and age (r2 = 14.4%, P = 0.37). When the choice of ACE inhibitor was added, the predictive power of the model increased (r = 23.6%, P < 0.01) but left the majority of the variability in response unexplained. The first-dose blood pressure response to ACE inhibition cannot be accurately predicted from baseline pathophysiological variables in patients with mild to moderate CHF. The choice of ACE inhibitor accounts for a small proportion of the variability in response but wide inter-individual variability exists in the response to each treatment.",1998.0,0,0
2404,9663912,Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study. Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation.,S Omboni; G Parati; P Palatini; A Vanasia; M L Muiesan; C Cuspidi; G Mancia,"To assess whether modifications in the nighttime blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension. The analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular hypertrophy involved in the SAMPLE study. For each patient, ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index were performed at the end of a 4-week wash-out pretreatment period, after 3 and 12 months of treatment with lisinopril or with lisinopril plus hydrochlorothiazide and after a final 4-week placebo period. For each ambulatory blood pressure monitoring the 24 h average, daytime average (0600-2400 h), night-time average (2400-0600 h) and day-night difference was computed. The percentages of dipper and non-dipper patients (i.e. the patients with night blood pressure falls greater and less than 10% of the daytime average, respectively) were also computed. The reproducibility of the day-night difference was low, both for comparison of the pretreatment and final placebo periods (n = 170) and for comparison of the third and the 12th month of treatment (n = 180). The reproducibility of the dipper-non-dipper dichotomy was also low, 35-40% of patients becoming non-dippers if they were dippers and vice versa, both with and without treatment The changes in left ventricular mass index after 12 months of treatment were significantly (P<0.01) related to the changes in 24 h, daytime and night-time blood pressure (r always > 0.33), but this was not the case for the treatment-induced modification of the day-night difference (r= -0.03 and -0.008 for systolic and diastolic blood pressures, respectively). Our results show that day-night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time. It also provides the first prospective evidence that treatment-induced changes in day-night blood pressure difference are not related to treatment-induced regression of left ventricular mass index, thus having a limited clinical significance.",1998.0,0,0
2405,9671045,Acute hyponatremic encephalopathy after a cerebrovascular accident.,N A Moussa; A R Osman; T M Yahya,"A 66-year-old hypertensive male with acute intracerebral hemorrhage developed acute hyponatremic coma 3 days after the addition of enalapril and a combination of amiloride and a thiazide diuretic to his hypotensive regimen. The patient recovered consciousness and serum sodium normalized 2 days after fluid restriction and withdrawal of both medications. Three weeks later, upon inadvertent reinstitution of enalapril and indapamide, severe hyponatremic encephalopathy promptly recurred; recovery was again rapid following fluid restriction and withdrawal of both medications. This temporal relationship establishes the thiazide diuretic or the angiotensin converting enzyme inhibitor or both as the cause of the profound symptomatic hyponatremia in this patient. Results of simultaneous serum and urine osmolality assays on several occasions were consistent with a decrease in free water clearance, a result of either increased antidiuretic hormone (ADH) secretion or potentiation of its peripheral action, and thiazide-induced natriuresis. The use of a thiazide diuretic in the presence of either of these aberrations of ADH homeostasis most likely explains the profound and rapid development of hyponatremia. Drug-induced disturbances in serum osmolality are a potentially reversible cause of deterioration of the mental state in a patient with an acute cerebrovascular accident.",1998.0,0,0
2406,9672278,Why deny ACE inhibitors to patients with aortic stenosis?,N L Cox; A R Abdul-Hamid; G P Mulley,,1998.0,0,0
2407,9674632,"Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.",Y Higashi; T Oshima; S Sasaki; Y Nakano; M Kambe; H Matsuura; G Kajiyama,"Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.",1998.0,0,0
2408,9679720,Effect of single-drug therapy on reduction of left atrial size in mild to moderate hypertension: comparison of six antihypertensive agents.,J S Gottdiener; D J Reda; D W Williams; B J Materson; W Cushman; R J Anderson,"Cardiac effects of hypertension include increased left ventricular (LV) mass and LV hypertrophy, as well as increased left atrial size, a predictor of stroke and atrial fibrillation. Although literature on reduction of LV mass with antihypertensive therapy is extensive, little information is available on effects of treatment on left atrial size. Patients with mild to moderate hypertension (diastolic blood pressure 95 to 109 mm Hg) were randomly allocated to treatment with atenolol, captopril, clonidine, diltiazem, hydrochlorothiazide, or prazosin in a double-masked trial. Two-dimensional targeted M-mode echocardiography was used to assess left atrial size and LV mass at baseline, 8 weeks, and 1 and 2 years. Longitudinal analysis examined changes in left atrial size from the baseline study, statistically adjusting for age, race, pretreatment left atrial size and LV mass, and serial measurements of systolic blood pressure, body weight, urinary sodium excretion, and physical activity score. Without adjustment for covariates, only hydrochlorothiazide was associated with decreases in left atrial size from baseline at 8 weeks (-1.0 +/- 5.2 mm; P=0.052), 1 year (-2.0 +/- 5.1 mm; P=0.02), and 2 years (4.6+/-7.2 mm; P=0.002). After adjustment for effects of covariates, patients with normal left atrial size had greater reduction (-3.3 mm) in left atrial size at 2 years with hydrochlorothiazide than with any other drug. For patients with left atrial enlargement, left atrial size decreased significantly with hydrochlorothiazide, atenolol, clonidine, and diltiazem at 1 year and with all treatments at 2 years. However, reduction at 2 years was greater with hydrochlorothiazide than with captopril or prazosin. Antihypertensive drugs differ in their effects on left atrial size. Hydrochlorothiazide was associated with greater overall reduction of left atrial size than other drugs effective for the treatment of hypertension. Reduction of left atrial size with therapy is in part independent of factors known to influence left atrial size, including LV mass and reduction of LV mass with treatment. The clinical benefit of reducing left atrial size with antihypertensive treatment remains to be determined.",1998.0,0,0
2409,9681661,"Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.",T Kinugawa; M Kato; M Mori; A Endo; T Kato; T Hamada; N Noguchi; H Omodani; S Osaki; K Ogino; H Miyakoda; I Hisatome; C Shigemasa,"Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate. Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)). Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate. These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.",1998.0,0,0
2410,9690951,"Perindopril postmarketing surveillance: a 12 month study in 47,351 hypertensive patients.",C Speirs; F Wagniart; L Poggi,"To gain information on serious adverse events in a large number of patients exposed to perindopril. Four thousand seven hundred and eighty-eight general practitioners throughout France collaborated in the recruitment of 47,351 patients for a 12 month postmarketing study. Data collection was undertaken by company representatives under the supervision of nine regional medical officers. Computerised data entry was performed by six pharmaceutical officers. Serious adverse events were later individually reviewed medically. Withdrawals due to adverse events occurred in 6.1% of female and 3.2% of males patients. The ascertainment of adverse events in this study approved satisfactory, as shown by the reported incidence of cough, which was 11.3% in women and 7.8% in men, this being compatible with the best estimates of the true incidence of cough during ACE-inhibitor therapy. Serious adverse reactions-anaphylaxis and blood dyscrasias-were rare. This study successfully followed a large cohort of patients treated with perindopril and failed to demonstrate any unexpected hazards.",1998.0,0,0
2411,9696956,A Bayesian neural network method for adverse drug reaction signal generation.,A Bate; M Lindquist; I R Edwards; S Olsson; R Orre; A Lansner; R M De Freitas,"The database of adverse drug reactions (ADRs) held by the Uppsala Monitoring Centre on behalf of the 47 countries of the World Health Organization (WHO) Collaborating Programme for International Drug Monitoring contains nearly two million reports. It is the largest database of this sort in the world, and about 35,000 new reports are added quarterly. The task of trying to find new drug-ADR signals has been carried out by an expert panel, but with such a large volume of material the task is daunting. We have developed a flexible, automated procedure to find new signals with known probability difference from the background data. Data mining, using various computational approaches, has been applied in a variety of disciplines. A Bayesian confidence propagation neural network (BCPNN) has been developed which can manage large data sets, is robust in handling incomplete data, and may be used with complex variables. Using information theory, such a tool is ideal for finding drug-ADR combinations with other variables, which are highly associated compared to the generality of the stored data, or a section of the stored data. The method is transparent for easy checking and flexible for different kinds of search. Using the BCPNN, some time scan examples are given which show the power of the technique to find signals early (captopril-coughing) and to avoid false positives where a common drug and ADRs occur in the database (digoxin-acne; digoxin-rash). A routine application of the BCPNN to a quarterly update is also tested, showing that 1004 suspected drug-ADR combinations reached the 97.5% confidence level of difference from the generality. Of these, 307 were potentially serious ADRs, and of these 53 related to new drugs. Twelve of the latter were not recorded in the CD editions of The physician's Desk Reference or Martindale's Extra Pharmacopoea and did not appear in Reactions Weekly online. The results indicate that the BCPNN can be used in the detection of significant signals from the data set of the WHO Programme on International Drug Monitoring. The BCPNN will be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs.",1998.0,0,0
2412,9699935,"Gender differences in baseline variables, therapies and outcomes in Chinese patients with acute myocardial infarction.",P H Chu; C W Chiang; N J Cheng; Y L Ko; C J Chang; W J Chen; C T Kuo; T S Hsu; Y S Lee,"We prospectively studied the gender differences of baseline variables, therapies, and outcomes among a cohort of 369 Chinese patients with acute myocardial infarction from 1990 to 1995. There were 277 male and 92 female patients. The male gender had a younger mean (+/-SD) age (61.5+/-10.7 vs. 67.1+/-11.7 years, P<0.0001). Hypercholesterolemia (201.2+/-44.2 vs. 187.5+/-43.7 mg/dl, P=0.0111) and obesity (25.0 vs. 15.9%, P=0.0494) were more prominent in the female. Smoking was more prevalent in the male (78.3 vs. 18.5%, P<0.0001). The male group also had more frequent use of thrombolytic agents (19.1 vs. 9.8%, P=0.0377), beta-blockers (61.7 vs. 47.8%, P=0.0191) and heparin (25.3 vs. 12.0%, P=0.0075); but less use of angiotensin-converting enzyme inhibitors (6.9 vs. 15.2%, P=0.0149). The condition on admission was worse in the female group (Killip classification (1.5+/-0.9 vs. 1.9+/-1.0, P=0.0022), myocardial failure (8.7 vs. 2.9%, P=0.0178) and cardiomegaly (65.2 vs. 53.1%, P=0.0419). During a follow-up duration of 26.4+/-24.1 and 22.9+/-23.9 months respectively, the mortality rate was lower in the male (19.5 vs. 30.4%, P=0.0288). However after adjustment for the effect of age, the differences in Killip classification, myocardial failure, cardiomegaly and mortality became insignificant.",1998.0,0,0
2413,9701103,Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly.,J A Staessen; R Fagard; L Thijs; H Celis; W H Birkenhäger; C J Bulpitt; P W de Leeuw; A E Fletcher; M R Babarskiene; F Forette; J Kocemba; T Laks; G Leonetti; C Nachev; J C Petrie; J Tuomilehto; H Vanhanen; J Webster; Y Yodfat; A Zanchetti,"In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.",1998.0,0,0
2414,9702445,Long-term lisinopril therapy reduces exercise-induced albuminuria in normoalbuminuric normotensive IDDM patients.,J A Tuominen; P Ebeling; V A Koivisto,"To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate. A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 +/- 3 years, BMI 24.5 +/- 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 +/- 2 years, BMI 24.4 +/- 0.9 kg/m2). Overnight and exercise-induced urinary albumin excretion rate was measured at baseline and after 1 and 2 years of treatment. Two patients in the placebo group and none in the lisinopril group developed microalbuminuria. In the lisinopril group, the exercise-induced urinary albumin excretion rate diminished 46% after the 1st year (P = 0.059) and 66% (P < 0.01) after the 2nd year. However, it remained unchanged in the control group. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were similar at baseline and after 1 year, but at 2 years, sBP was 13 mmHg lower (P = 0.03) and dBP was 9 mmHg lower (P = 0.052) in the lisinopril group as compared with the control group. The dBP decreased significantly at 1 and 2 years in the lisinopril group, while there was no significant change in the sBP. In the whole group at baseline, the overnight albumin excretion rate correlated with HbA1c (r = 0.50, P < 0.01) and the duration of diabetes (r = 0.39, P < 0.05), and sBP correlated with both the overnight (r = 0.42, P < 0.05) and the exercise-induced (r = 0.48, P < 0.05) albumin excretion rate. Glycemic control and blood pressure are directly related to the overnight albumin excretion rate also in normotensive normoalbuminuric IDDM patients. Lisinopril treatment reduces the exercise-induced urinary albumin excretion rate in such patients. These data suggest a protective effect of lisinopril against the development of microalbuminuria.",1998.0,0,0
2415,9704248,Comparative tolerability profile of hypertensive crisis treatments.,E Grossman; A N Ironi; F H Messerli,"Hypertensive crisis is defined as a severe elevation in BP and is classified as either urgency or emergency. In hypertensive urgency there is no end-organ injury and no evidence that acute BP lowering is beneficial. Indeed, rapid uncontrolled pressure reduction may be harmful. Therefore, in hypertensive urgencies BP should be lowered gradually over 24 to 48 hours using oral antihypertensives. When the cause of transient BP elevations is easily identified, appropriate treatment should be given. When the cause is unknown, an oral antihypertensive should be given. The efficacy of available treatments appear similar; however, the underlying pathophysiological and clinical findings, mechanism of action and potential for adverse effects should guide choice. Captopril should be avoided in patients with bilateral renal artery stenosis or unilateral renal artery stenosis in patients with a solitary kidney. Nifedipine and other dihydropyridines increase heart rate whereas clonidine, beta-blockers and labetalol tend to decrease it. This is particularly important in patients with ischaemic heart disease. Labetalol and beta-blockers are contraindicated in patients with bronchospasm and bradycardia or heart blocks. Clonidine should be avoided if mental acuity is desired. In hypertensive emergency there is an immediate threat to the integrity of the cardiovascular system. BP should be immediately reduced to avoid further end organ damage. Sodium nitroprusside is the most popular agent. Nitroglycerin (glyceryl trinitrate) is preferred when there is acute coronary insufficiency. A beta-blocker may be added in some patients. Loop diuretics, nitroglycerin and sodium nitroprusside are effective in patients with concomitant pulmonary oedema. Enalaprilat is also theoretically helpful, especially when the renin system might be activated. Initial treatment of aortic dissection involves rapid, controlled titration of arterial pressure to normal levels using intravenous sodium nitroprusside and a beta-blocker. If beta-blockers are contraindicated, urapidil or trimetaphan camsilate are alternatives. Hydralazine is the drug of choice for patients with eclampsia. Labetalol, urapidil or calcium antagonists are possible alternatives if hydralazine fails or is contraindicated. For patients with catecholamine-induced crises, an alpha-blocker such as phentolamine should be given; labetalol or sodium nitroprusside with beta-blockers are alternatives. There are few, if any, comparative or randomised trials providing definitive conclusions about the efficacy and safety of comparative agents. Some investigators recommend decreasing the diastolic BP to no less than 100 to 110 mm Hg. A reasonable approach for most patients with hypertensive emergencies is to lower the mean arterial pressure by 25% over the initial 2 to 4 hours with the most specific antihypertensive regimen.",1998.0,0,0
2416,9704681,Short- and long-term effects of early fosinopril administration in patients with acute anterior myocardial infarction undergoing intravenous thrombolysis: results from the Fosinopril in Acute Myocardial Infarction Study. FAMIS Working Party.,C Borghi; P Marino; P Zardini; B Magnani; S Collatina; E Ambrosioni,"Angiotensin-converting enzyme inhibitors are used in patients who have myocardial infarction with left ventricular (LV) dysfunction. Few data are available in patients whose LV function is within the normal range. The Fosinopril in Acute Myocardial Infarction Study was a 2-year, randomized, double-blind, placebo-controlled, multicenter study of 285 patients with anterior acute myocardial infarction and was designed to investigate the effects of the early (<9 hours) administration of fosinopril and thrombolysis on (1) changes in echocardiographically evaluated LV volumes at 3 months and (2) long-term occurrence of death and congestive heart failure. LV volumes were normal at baseline in more than 70% of patients and were comparable between groups both at baseline and after 3 months of treatment. Fosinopril-treated patients showed a 30% reduction in the 2-year combined prevalence of death or moderate-to-severe congestive heart failure (New York Heart Association class III-IV) despite having a worse clinical profile at baseline. The benefit of fosinopril was confirmed both in patients without congestive heart failure at admission and in those with ejection fraction >40% at baseline. Moreover, the incidence of significant ventricular arrhythmias was lower in the fosinopril group (0.8% vs 6.0%, p < 0.02). The results of the Fosinopril in Acute Myocardial Infarction Study suggest that early treatment with fosinopril can benefit patients with acute myocardial infarction in addition to a prevention of LV remodeling.",1998.0,1,1
2417,9704689,Changes in left ventricular mass and volumes in patients receiving angiotensin-converting enzyme inhibitor therapy for left ventricular dysfunction after Q-wave myocardial infarction.,R E Foster; D B Johnson; F Barilla; G G Blackwell; R Orr; M Roney; A W Stanley; G M Pohost; L J Dell'Italia,"We evaluated global and segmental left ventricular (LV) mass and LV mass/volume ratio in patients with LV dysfunction receiving angiotensin-converting enzyme (ACE) inhibitor therapy after acute myocardial infarction (MI). ACE inhibitors attenuate LV dilatation and compensatory hypertrophy after acute MI in animal models. However, LV remodeling in patients after acute MI has been largely defined on the basis of changes in chamber volume alone. Twenty-nine patients with LV ejection fraction <40% received the ACE inhibitor ramipril (range 2.5 to 20 mg/day) within 5 days of their first Q-wave MI. Magnetic resonance imaging was performed at baseline and at 3 months, providing global and regional LV volumes and mass from summated serial short-axis slices. Mean arterial blood pressure was unchanged from baseline to 3-month follow-up (89 +/- 10 to 92 +/- 17 mm Hg). LV mass decreased (90 +/- 25 to 77 +/- 21 gm/m2, p < 0.0005) as LV end-diastolic volumes increased (65 +/- 13 to 73 +/- 22 ml/m2, p < 0.01). Global LV mass to volume ratio decreased from 1.40 +/- 0.28 to 1.08 +/- 0.18 gm/ml (p < 0.0001), as did circumferential wall thickness to volume ratio of noninfarcted myocardium at the base of the LV (0.06 +/- 0.02 to 0.05 +/- 0.02 mm/ml, p < 0.001). LV ejection fraction increased from 35 +/- 6 to 40 +/- 9% (p < 0.001) in the presence of an increase in calculated end-systolic wall stress (185 +/- 57 to 227 +/- 54 gm/cm2, p < 0.01). ACE inhibitor therapy was associated with improved LV function in the face of a decrease in mass to volume ratio of the LV as well as a decrease in wall thickness to volume ratio of noninfarcted myocardium. Whether ACE inhibitor therapy had direct or indirect effects on these changes in LV mass and function are open questions that require further investigation.",2001.0,0,0
2418,9705044,Differences between amlodipine and lisinopril in control of clinic and twenty-four hour ambulatory blood pressures.,A R Lorimer; D Lyons; G Fowler; J C Petrie; M T Rothman,"The anti-hypertensive efficacy of once-daily amlodipine (up to 10 mg) and lisinopril (up to 20 mg) were compared in terms of clinic and ambulatory blood pressure (BP) control, in an observer-blind, two-period crossover study. Following a 4-week placebo run-in period, patients underwent two active treatment phases each lasting 12 weeks and separated by a 4-week washout period. Sixty patients with a supine diastolic BP between 90 and 120 mm Hg were included, irrespective of whether or not they had received previous anti-hypertensive medication. Amlodipine reduced supine systolic and diastolic clinic BP significantly more than lisinopril (-20+/-2/-14+/-1 vs -11 3/-7+/-1 mm Hg; P=0.02/ P=0.001) 24 h post-dose. Clinic standing diastolic BP was also significantly reduced with amlodipine compared with lisinopril (P=0.05). Both drugs produced control of mean ambulatory BP relative to baseline over 24 h. Amlodipine showed more consistent control of BP over the 24-h period in contrast to lisinopril which exerted its greatest effect during the daytime.",1998.0,0,0
2419,9710178,Secondary prevention of coronary heart disease.,A M Zafari; N K Wenger,"Despite the significant reduction in cardiovascular mortality during the past three decades, atherosclerotic coronary heart disease (CHD) remains the leading cause of death and disability in the United States. Randomized clinical trials in patients with CHD have provided convincing evidence that risk factor modification is beneficial in decreasing all-cause mortality and cardiovascular morbidity and mortality. Multifactorial coronary risk reduction provides the most substantial benefit. Coronary risk reduction is associated with a decrease in cardiovascular-related hospital admissions, a reduced need for myocardial revascularization procedures, and an improved quality of life for the patients so treated. Control of coronary risk factors is an integral component of the optimal care of the patient with CHD.",1998.0,0,0
2420,9715782,Nocturnal reduction of blood pressure and the antihypertensive response to a diuretic or angiotensin converting enzyme inhibitor in obese hypertensive patients. TROPHY Study Group.,M R Weir; E Reisin; B Falkner; H G Hutchinson; L Sha; M L Tuck,"During a 12-week, multicenter study to evaluate the efficacy and safety of lisinopril and hydrochlorothiazide (HCTZ) for the treatment of obesity-related hypertension, ambulatory blood pressure (ABP) monitoring was performed both at baseline and at study completion in 124 patients. Patients were randomized to three groups: placebo, lisinopril (10, 20, or 40 mg/day), or HCTZ (12.5, 25, or 50 mg/day). All groups were matched with regard to sex, race, age, body mass index, and waist/hip ratio. The primary analysis of ABP data revealed that both lisinopril and HCTZ effectively lowered mean 24-h systolic (SBP) and diastolic (DBP) blood pressure compared with placebo, (mean change from baseline SBP/DBP: -12.0/-8.2, -10.6/-5.5, and -0.3/-0.5 mm Hg, respectively); however, lisinopril lowered DBP better than HCTZ (P < .05). Secondary analyses of groups revealed that men responded better to lisinopril than HCTZ (-11.9/-7.3 v -6.6/-3.5 mm Hg, respectively), whereas women responded well to both drugs. White patients responded better to lisinopril than HCTZ, whereas black patients showed a significant response to HCTZ only. Response to treatment was also influenced by patient classification of 24-h blood pressure profiles, ie, ""dipper"" or ""nondipper."" Overall, the majority of obese hypertensives were nondippers. Nondippers (n = 82) responded well to both drugs (-10.4/-6.9 v -12.5/-5.7 mm Hg, P < .05 v placebo), whereas dippers (n = 42) responded to lisinopril (-11.7/ -9.4 mm Hg, P < .05 v placebo and HCTZ), but not HCTZ (-5.6/-4.1 mm Hg, P = NS v placebo). Results of 24-h ABP data show that both lisinopril and HCTZ are effective therapies for obesity-related hypertension and that response to treatment is influenced by sex, race, and dipper/nondipper status.",1998.0,0,0
2421,9723415,Losartan versus ramipril in the treatment of postrenal transplant erythrocytosis.,L Hortal; A Fernández; N Vega; J C Rodríguez; A Losada; M Lorenzo; C Plaza; L Palop,,1998.0,0,0
2422,9723827,Start of therapy with the angiotensin II antagonist losartan after immediate switch from pretreatment with an ACE inhibitor.,J Scholze; M Stapff,"To evaluate initial blood pressure effects of the angiotensin II antagonist losartan (L) immediately after switching from an ACE inhibitor (captopril, C). Two-phase multicentre randomized study in 177 outpatients with mild to moderate essential hypertension. For 6 weeks all patients received 25 mg C twice daily. Then they were randomized double-blind to switch for another 6 weeks to 50 mg L once daily (n=110) or to maintain C (n=55). On the first day of the switch they underwent ambulatory blood pressure measurement (ABPM). Within 12 h of first dose, 31% of patients who switched to L had two consecutive systolic BP readings of 30 mmHg below their individual baseline value compared with 24% of patients who stayed on C. In 3% of patients with L and in 6% of the C patients systolic BP readings less than 100 mmHg were recorded within 12 h of first dose. The differences were not statistically significant. There were no clinical symptoms attributable to initial hypotension. During the 6 weeks double-blind therapy, 9% of L patients experienced at least one adverse event, compared with 16% of patients with C. In this study the angiotensin II antagonist losartan was effective and generally well tolerated when administered immediately after pretreatment with an ACE inhibitor.",1998.0,0,0
2423,9725973,Acute pancreatitis following lisinopril rechallenge.,T Gershon; J S Olshaker,"Acute pancreatitis has many causes, the most common being biliary tract disease and alcoholism. Other etiologic categories are abdominal trauma; postoperative, including endoscopic retrograde cholangiopancreatography; metabolic, including hypercalcemia and hypertriglyceridemia; Infectious; idiopathic; and drug-induced. The drugs most strongly associated with pancreatitis are sulfonamides, thiazides, furosemide, estrogens, and tetracycline. Approximately 100 cases of pancreatitis induced by angiotensin-converting enzyme inhibitor have been reported to the US Food and Drug Administration, of which about 20 involved lisinopril. We report a case of pancreatitis occurring only 3 hours after intake of lisinopril by a man without other risk factors for the illness. The patient had experienced a similar but less severe reaction to this medication 3 months earlier. This case probably represents the first time a patient was rechallenged with lisinopril and had a more significant adverse reaction.",1998.0,0,0
2424,9726242,Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.,G Penno; N Chaturvedi; P J Talmud; P Cotroneo; A Manto; M Nannipieri; L A Luong; J H Fuller,"We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.",1998.0,0,0
2425,9727545,"Acute hemodynamic interaction of aspirin and ticlopidine with enalapril: results of a double-blind, randomized comparative trial.",C Spaulding; B Charbonnier; A Cohen-Solal; Y Juillière; E P Kromer; K Benhamda; R Cador; S Weber,"Coprescription of aspirin and ACE inhibitors is frequent in heart failure caused by coronary artery disease. Negative interaction between aspirin and enalapril has been reported, presumably through inhibition by aspirin of ACE inhibitor-induced prostaglandin synthesis. Ticlopidine is a potent antiplatelet agent without interaction with prostaglandin synthesis. The objective of this study was to compare the influence of a coadministration of ticlopidine or aspirin on the hemodynamic effects of an ACE inhibitor (enalapril) in patients with chronic heart failure. Twenty patients with severe heart failure were enrolled in a double-blind comparative trial and allocated to ticlopidine (500 mg daily, 12 patients) or aspirin (325 mg daily, 8 patients). Hemodynamic evaluation was performed after 7 days of treatment, every hour for 4 hours after an oral administration of 10 mg of enalapril. Significant reductions in systemic vascular resistance were observed in the ticlopidine group, in contrast to no significant decrease in the aspirin group. A significant (P=0.03) time-by-treatment interaction indicated significant aspirin-enalapril drug interaction. Total pulmonary resistance decreased significantly in both groups, with no difference between patients assigned to aspirin or ticlopidine. Enalapril reduced systemic vascular resistance more effectively when given in combination with ticlopidine than with aspirin. In contrast, the reduction in total pulmonary resistance is similar when enalapril is administered in combination with aspirin or ticlopidine. Negative aspirin-enalapril interaction on prostaglandin synthesis presumably alters vasodilatation in systemic vessels, whereas prostaglandin-independent actions of ACE inhibition such as pulmonary arterial vasodilatation are maintained.",2000.0,0,0
2426,9732337,Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group.,,"To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of <150/85 mm Hg (with the use of an angiotensin converting enzyme inhibitor captopril or a beta blocker atenolol as main treatment) with less tight control aiming at a blood pressure of <180/105 mm Hg. 20 hospital based clinics in England, Scotland, and Northern Ireland. 1148 hypertensive patients with type 2 diabetes (mean age 56, mean blood pressure at entry 160/94 mm Hg); 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years. Predefined clinical end points, fatal and non-fatal, related to diabetes, deaths related to diabetes, and all cause mortality. Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography. Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control (144/82 mm Hg) compared with the group assigned to less tight control (154/87 mm Hg) (P<0.0001). Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24% in diabetes related end points (95% confidence interval 8% to 38%) (P=0.0046), 32% in deaths related to diabetes (6% to 51%) (P=0.019), 44% in strokes (11% to 65%) (P=0.013), and 37% in microvascular end points (11% to 56%) (P=0.0092), predominantly owing to a reduced risk of retinal photocoagulation. There was a non-significant reduction in all cause mortality. After nine years of follow up the group assigned to tight blood pressure control also had a 34% reduction in risk in the proportion of patients with deterioration of retinopathy by two steps (99% confidence interval 11% to 50%) (P=0.0004) and a 47% reduced risk (7% to 70%) (P=0.004) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study (ETDRS) chart. After nine years of follow up 29% of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures. Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinically important reduction in the risk of deaths related to diabetes, complications related to diabetes, progression of diabetic retinopathy, and deterioration in visual acuity.",1998.0,0,0
2427,9732338,Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group.,,"To determine whether tight control of blood pressure with either a beta blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes. Randomised controlled trial comparing an angiotensin converting enzyme inhibitor (captopril) with a beta blocker (atenolol) in patients with type 2 diabetes aiming at a blood pressure of <150/<85 mm Hg. 20 hospital based clinics in England, Scotland, and Northern Ireland. 1148 hypertensive patients with type 2 diabetes (mean age 56 years, mean blood pressure 160/94 mm Hg). Of the 758 patients allocated to tight control of blood pressure, 400 were allocated to captopril and 358 to atenolol. 390 patients were allocated to less tight control of blood pressure. Predefined clinical end points, fatal and non-fatal, related to diabetes, death related to diabetes, and all cause mortality. Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography. Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively, with a similar proportion of patients (27% and 31%) requiring three or more antihypertensive treatments. More patients in the captopril group than the atenolol group took the allocated treatment: at their last clinic visit, 78% of those allocated captopril and 65% of those allocated atenolol were taking the drug (P<0.0001). Captopril and atenolol were equally effective in reducing the risk of macrovascular end points. Similar proportions of patients in the two groups showed deterioration in retinopathy by two grades after nine years (31% in the captopril group and 37% in the atenolol group) and developed clinical grade albuminuria >=300 mg/l (5% and 9%). The proportion of patients with hypoglycaemic attacks was not different between groups, but mean weight gain in the atenolol group was greater (3.4 kg v 1.6 kg). Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications. This study provided no evidence that either drug has any specific beneficial or deleterious effect, suggesting that blood pressure reduction in itself may be more important than the treatment used.",1998.0,0,0
2428,9732339,Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. UK Prospective Diabetes Study Group.,,"To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. 20 hospital based clinics in England, Scotland, and Northern Ireland. 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to pound1049 (costs and effects discounted at 6% per year) and pound434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was pound720 (costs and effects discounted at 6% per year) and pound291 (costs discounted at 6% per year and effects not discounted). Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.",1998.0,0,0
2429,9733228,Accelerated cholesteryl ester transfer in patients with essential hypertension and the effect of ramipril treatment.,J D Bagdade; X Q Liu; W F Buchanan; J Hafner; R Rosenson,"Although the transfer of cholesteryl ester (CE) from high-density lipoprotein (HDL) to the apolipoprotein B-containing lipoproteins (very-low-density lipoproteins + low-density lipoproteins) has been shown to be abnormally increased in a number of conditions associated with increased cardiovascular risk, it has not been studied in patients with essential hypertension (EH). To determine whether subjects with EH have increased CE transport, CE transfer (CET) was estimated isotopically and lipoprotein lipid and phospholipid composition determined in a group of 14 untreated normolipidemic (triglycerides 116+/-46, cholesterol 185+/-30, HDL 38+/-10 mg/dl) otherwise healthy ethnically diverse EH subjects. CET was significantly increased in EH subjects compared to a similar group of normotensive controls (EH: k = 0.27+/- 0.09 vs. control k = 0.11+/-0.02: P < 0.01). Lipoprotein concentration and composition were comparable in the two groups and closely resembled that of an age- and sex-matched reference group. The abnormal increase in CET persisted (k = 0.25+/-0.12) after 3 months of treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril without a change in either plasma or lipoprotein lipids. Thus, CET is increased in normolipidemic subjects with EH and is not affected by the ACE inhibitor ramipril.",1998.0,0,0
2430,9734886,Plasma bradykinin in angio-oedema.,J Nussberger; M Cugno; C Amstutz; M Cicardi; A Pellacani; A Agostoni,"Bradykinin is believed to be the main mediator of symptoms in hereditary (HA) and acquired (AA) angio-oedema due to C1 esterase inhibitor deficiency, as well as in angio-oedema that complicates treatment with inhibitors of angiotensin-converting enzyme (ACE). Difficulties in the measurement of kinin concentrations, however, have so far precluded the demonstration of an incontrovertible change in plasma bradykinin concentrations in these disorders. By developing a reliable assay we have been able to follow bradykinin concentrations during attacks and during remission in HA and in AA, and also in a patient treated with an ACE-inhibitor. Liquid-phase extraction, high-performance liquid chromatography, and RIA were used for specific measurement of plasma bradykinin concentrations in 22 patients with HA and in 22 healthy volunteers of similar age and sex distribution. Four patients with AA and one hypertensive patient treated with the ACE inhibitor captopril were also studied. Among the healthy volunteers plasma bradykinin concentration was inversely proportional to age. The geometric mean plasma bradykinin concentration in the healthy volunteers was 2.2 fmol/mL (SD 2.2), compared with 3.9 fmol/mL (3.7) among patients with HA during remission (p=0.095). Bradykinin was also high in the patients with AA (10.4 fmol/mL [1.6]). During acute attacks of oedema, in both HA and AA, plasma bradykinin rose to two to 12 times the upper limit of normal. Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations. In the patient receiving the ACE-inhibitor captopril, bradykinin concentration was very high at 47 fmol/mL during an acute attack of angio-oedema, but normal at 3.2 fmol/mL in remission after withdrawal of the drug. A sensitive method for measurement of plasma bradykinin provided the means to show that concentrations of this peptide decrease with age in healthy people. Although the differences between patients in remission and healthy controls did not reach statistical significance, there were substantial rises in bradykinin during acute attacks of hereditary, acquired, or captopril-induced angio-oedema.",1998.0,0,0
2431,9736816,"Effect of an alpha-adrenergic blocker, and ACE inhibitor and hydrochlorothiazide on blood pressure and on renal function in type 2 diabetic patients with hypertension and albuminuria. A randomized cross-over study.",R Rachmani; Z Levi; I Slavachevsky; E Half-Onn; M Ravid,"alpha-Adrenergic blockers are potential alternative antihypertensive agents for diabetic patients. Data on their relative efficacy and their effect on kidney function and albuminuria are very limited however. 76 patients with diabetes type 2, hypertension (>/=140/90 mm Hg) and albuminuria (>/=30 mg/24 h) were randomized into three groups to receive cilazapril (2.5-10 mg), doxazosin (2-8 mg) or both. Patients of the first and second groups received a single agent for 4 months, the agents were then crossed for an additional period of 4 months followed by the addition of hydrochlorothiazide (25 mg) for a third 4-month period. Blood pressure was monitored monthly, creatinine clearance and HbA1c were measured before and at the end of each treatment period. Patients of the third group received reduced doses of cilazapril and doxazosin for 4 months. Hydrochlorothiazide was then added for the subsequent 4 months. There was a significant decline in blood pressure values during the first period in all groups. Cilazapril: systolic blood pressure (SBP) 160 +/- 6 to 149 +/- 5 mm Hg; diastolic blood pressure (DBP): 101 +/- 3 to 94 +/- 3 mm Hg (p = 0.001). Albuminuria declined from 350 +/- 105 to 205 +/- 96 mg/24 h (p = 0.001), creatinine clearance (CrCl) was unchanged. Doxazosin: SBP: 160 +/- 7 to 151 +/- 6 mm Hg; DBP: 97 +/- 4 to 90 +/- 4 mm Hg (p = 0.001). Albuminuria 373 +/- 121 to 322 +/- 107 mg/24 h (p = 0.065) and CrCl 87 +/- 7 to 91 +/- 6 ml/min. The combination of both agents at half doses was equipotent or superior to either drug alone. Cross-over of cilazapril and doxazosin reproduced the hypotensive effect and reversed the antialbuminuric effect. The addition of hydrochlorothiazide resulted in a further decline of 6-14 mm Hg in SBP and 3-11 mm Hg in DPB.",2000.0,0,0
2432,9740480,Valsartan in heart failure patients previously untreated with an ACE inhibitor.,V P Mazayev; I G Fomina; E N Kazakov; V A Sulimov; T V Zvereva; V A Lyusov; V A Orlov; L I Olbinskaya; T D Bolshakova; J Sullivan; D O Spormann,"To evaluate the effect on cardiac hemodynamic parameters of valsartan in patients with chronic stable congestive heart failure previously untreated with ACE inhibitors. After a 2 to 4 week run-in period, 116 adult outpatients were randomized to receive valsartan 40, 80 or 160 mg twice daily, the ACE inhibitor lisinopril 5/10 mg once daily, or placebo. At baseline and after 28 days of treatment, cardiac hemodynamic parameters were measured. Tolerability was assessed by adverse events and by any changes in systolic or diastolic blood pressure, body weight, heart rate, and routine laboratory parameters. For the 12 hour time point (trough), all doses of valsartan reduced mean pulmonary capillary wedge pressure (statistically significant for valsartan 40 mg and 160 mg), decreased systemic vascular resistance (statistically significant for all three valsartan doses and for lisinopril at peak and trough), and increased cardiac output (statistically significant for all three valsartan doses at peak, and for 80 and 160 mg at trough). There were no clinically relevant effects on any safety parameters. Valsartan has beneficial effects on cardiac hemodynamics, and is generally well tolerated in patients with congestive heart failure not taking ACE inhibitors.",1998.0,0,1
2433,9740604,Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension.,J A Staessen; L Thijs; R H Fagard; W H Birkenhäger; G Arabidze; S Babeanu; B Gil-Extremera; C J Bulpitt; C Davidson; P W de Leeuw; A D Efstratopoulos; A E Fletcher; R Fogari; M Jääskivi; K Kawecka-Jaszcz; C Nachev; J C Petrie; M L Seux; J Tuomilehto; J Webster; Y Yodfat,"In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P</=0. 01) in total mortality (40%), stroke (59%), and all cardiovascular end points (39%). Among the control patients, 863 used only the first-line placebo. Compared with this subgroup, patients receiving monotherapy with nitrendipine showed a nearly 50% (P</=0.004) reduction of all types of end points, including total and cardiovascular mortality. The full relative benefit from nitrendipine was seen as early as 6 months after randomization. To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias, the 1327 patients remaining on monotherapy with nitrendipine were matched by gender, age, previous cardiovascular complications, and systolic blood pressure at entry with an equal number of placebo patients. In this analysis, nitrendipine reduced (P</=0.05) cardiovascular mortality by 41%, all cardiovascular end points by 33%, and fatal and nonfatal cardiac end points by 33%. Despite the limitations inherent in post hoc analyses, the present findings suggest that the calcium channel blocker nitrendipine, given as a single antihypertensive medication, prevents cardiovascular complications in older patients with isolated systolic hypertension.",1998.0,0,0
2434,9740606,Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study.,S Omboni; R Fogari; P Palatini; A Rappelli; G Mancia,"The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r<0.42). Furthermore, the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average, trough, and peak blood pressures but not with the T/Ps. This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis. In patients with a T/P >/=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.",1998.0,0,0
2435,9741512,"Superiority of ""triple"" drug therapy in heart failure: insights from the PROVED and RADIANCE trials. Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin. Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme.",J B Young; M Gheorghiade; B F Uretsky; J H Patterson; K F Adams,"We sought to study the efficacy of ""triple"" therapy with digoxin, diuretic and angiotensin-converting enzyme inhibitor (ACEI) compared to other combinations of these drugs in patients with symptomatic left ventricular systolic dysfunction. Controversy continues concerning the role of combining digoxin with diuretic and ACEI in the initial management of patients with heart failure. The study utilized data from two studies of digoxin efficacy: Prospective Randomized Study of Ventricular Function and Efficacy of Digoxin (PROVED) and Randomized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme (RADIANCE). Worsening heart failure defined as augmentation of heart failure therapy or an emergency room visit or hospitalization for increased heart failure was the main outcome measure. A total of 266 patients comprising the four treatment groups of the combined PROVED (diuretic alone or digoxin and diuretic) and RADIANCE (ACEI and diuretic, or digoxin, diuretic and ACEI) trials were analyzed. Worsening heart failure occurred in only 4 of the 85 patients who continued digoxin, diuretic and ACEI therapy (4.7%) compared to 18 of the 42 patients (19%) on digoxin and diuretic therapy (p=0.009), to 23 of the 93 patients (25%) on ACEI and diuretic therapy (p=0.001) and to 18 of the 46 patients (39%) on diuretic alone (p < 0.001). Life table and multivariate analysis also demonstrated that worsening heart failure was least likely in patients treated with triple therapy (p < 0.01 vs. all other groups). Pending definitive, prospective clinical trials, our results argue for triple therapy as the initial management of patients with symptomatic heart failure due to systolic dysfunction.",2001.0,0,0
2436,9741513,Triple drug therapy--what is next?,S Goldstein,,1998.0,0,0
2437,9741514,Atrial fibrillation is associated with an increased risk for mortality and heart failure progression in patients with asymptomatic and symptomatic left ventricular systolic dysfunction: a retrospective analysis of the SOLVD trials. Studies of Left Ventricular Dysfunction.,D L Dries; D V Exner; B J Gersh; M J Domanski; M A Waclawiw; L W Stevenson,"This study undertook to determine if the presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular dysfunction was associated with increased mortality and, if so, whether the increase could be attributed to progressive heart failure or arrhythmic death. Atrial fibrillation is a common condition in heart failure with the potential to impact hemodynamics and progression of left ventricular systolic dysfunction as well as the electrophysiologic substrate for arrhythmias. The available data do not conclusively define the effect of atrial fibrillation on prognosis in heart failure. A retrospective analysis of the Studies of Left Ventricular Dysfunction Prevention and Treatment Trials was conducted that compared patients with atrial fibrillation to those in sinus rhythm at baseline for the risk of all-cause mortality, progressive pump-failure death and arrhythmic death. The patients with atrial fibrillation at baseline, compared to those in sinus rhythm, had greater all-cause mortality (34% vs. 23%, p < 0.001), death attributed to pump-failure (16.7% vs. 9.4%, p < 0.001) and were more likely to reach the composite end point of death or hospitalization for heart failure (45% vs. 33%, p < 0.001), but there was no significant difference between the groups in arrhythmic deaths. After multivariate analysis, atrial fibrillation remained significantly associated with all-cause mortality (relative risk [RR] 1.34, 95% confidence interval [CI] 1.12 to 1.62, p=0.002), progressive pump-failure death (RR 1.42, 95% CI 1.09 to 1.85, p=0.01), the composite end point of death or hospitalization for heart failure (RR 1.26, 95% CI 1.03 to 1.42, p=0.02), but not arrhythmic death (RR 1.13; 95% CI 0.75 to 1.71; p=0.55). The presence of atrial fibrillation in patients with asymptomatic and symptomatic left ventricular systolic dysfunction is associated with an increased risk for all-cause mortality, largely explained by an increased risk for pump-failure death. These data suggest that atrial fibrillation is associated with progression of left ventricular systolic dysfunction.",1998.0,0,0
2438,9752816,Influences of educational interventions and adverse news about calcium-channel blockers on first-line prescribing of antihypertensive drugs to elderly people in British Columbia.,M Maclure; C Dormuth; T Naumann; J McCormack; R Rangno; C Whiteside; J M Wright,"The way in which dissemination of evidence changes medical practice needs to be better understood. Controversy about calcium-channel blockers (CCB) in the past 3 years has provided a natural experiment, enabling assessment of the impact of media stories, a national warning letter, a teleconference, small group workshops, and newsletters on first-line prescribing of antihypertensive drugs. We included all physicians (4403) in British Columbia who prescribed a thiazide diuretic, beta-blocker, inhibitor of angiotensin-converting enzyme (ACE), or CCB as the first antihypertensive agent for 36,507 residents aged 66 years and over, with no previous or concurrent sign of underlying cardiovascular disease. We used a database covering all prescriptions to elderly people to measure the change in proportion of newly treated patients who received each class of drug as first-line therapy. We used a matched cohort design for assessment of the teleconference and workshops, a randomised community design for the newsletters, and time-series analysis for the media impacts. The proportion of patients who received a CCB as first-line therapy declined gradually from 22% in early 1994 to 15% in late 1996. This proportion was not affected by two waves of adverse news about CCBs in 1995, but fell by 5% for 5 months and by 3% for 1 month after two waves in 1996. The proportion of patients who received either a CCB or an ACE inhibitor as first-line therapy, contrary to guidelines, was still 42% overall in 1996. The workshops and newsletters were followed by shifts from first-line CCB to first-line thiazide prescribing. Changes in prescribing practices occur gradually with the accumulation of small impacts from educational interventions and lay media attention.",1998.0,0,0
2439,9752891,Ambulatory blood pressure and urinary albumin excretion in diabetic (non-insulin-dependent and insulin-dependent) hypertensive patients: relationships at baseline and after treatment by the angiotensin converting enzyme inhibitor trandolapril.,B Bauduceau; N Genès; B Chamontin; L Vaur; M Renault; S Etienne; M Marre,"The aim of the present study was to examine the relationships between ambulatory blood pressure (ABPM) and urinary albumin excretion (UAE) in diabetic (non-insulin dependent [NIDDM] and insulin-dependent [IDDM]) hypertensives at baseline and after treatment by an angiotensin converting enzyme (ACE) inhibitor. After a 3-week placebo period, patients were treated for 16 weeks with trandolapril, 2 to 4 mg/day. The UAE and blood pressure (mercury sphygmomanometer and 24-h ABPM) were measured at baseline and repeated on trandolapril. Predictive factors of abnormal UAE (24-h UAE > or = 30 mg) were determined using univariate and multivariate analysis (logistic regression). Predictors of UAE decrease were also searched. One hundred seventy-one patients entered the analysis. Baseline office BP was 164+/-14 / 97+/-6 mm Hg and 24-h BP was 142+/-17 / 83+/-10 mm Hg. Seventy-four patients (43%) had UAE > or = 30 mg. Independent risk factors for abnormal UAE were nighttime diastolic BP (odds ratio [OR] = 4.1, confidence interval [CI] = 2.0 to 8.6, P = .0001), diabetes duration (OR = 2.4, CI = 1.1 to 5.0, P = .025), and presence of retinopathy (OR = 3.2, CI = 1.0 to 10.0, P = .047). Conversely, office BP level was not significantly related to UAE. On treatment, office BP levels decreased to 143+/-13 / 82+/-8 mm Hg (P < .0001) and 24-h BP levels to 134+/-17 / 78+/-9 mm Hg (P < .0001). In the abnormal UAE group, UAE significantly decreased from 76 to 50 mg/day (P = .006). After treatment, independent predictive factors of abnormal UAE were: on-drug fasting plasma glucose (OR = 3.5, CI = 1.7 to 7.4, P = .0009) and on-drug nighttime diastolic BP (OR = 3.5, CI = 1.7 to 7.4, P = .001). The only predictor of UAE decrease was a 24-h systolic BP decrease (OR = 2.3, CI = 1.3 to 4.3, P = .007). We conclude that in diabetic hypertensives with abnormal UAE, trandolapril exhibited a sustained 24-h antihypertensive effect and provided a consistent reduction of microalbuminuria. This study confirmed the superiority of ABPM over clinical BP to predict target organ damage.",1998.0,0,0
2440,9752892,"Comparison between the effects of amlodipine and lisinopril on proteinuria in nondiabetic renal failure: a double-blind, randomized prospective study.",J J Janssen; R O Gans; J van der Meulen; R Pijpers; P M ter Wee,"Double-blind, randomized controlled studies of longer than 1 week in duration comparing the antiproteinuric potential of long-acting dihydropyridine calcium channel blockers with that of angiotensin converting enzyme (ACE) inhibitors are lacking. Therefore, we performed such a study in patients with nondiabetic renal disease and proteinuria. After a 4-week wash-out period in which patients did not use any medication known to affect proteinuria, 21 patients were randomized in a double-blind fashion to receive either the calcium channel blocker amlodipine (Amlo, 5 to 10 mg) or the ACE-inhibitor lisinopril (Lis, 5 to 10 mg). Throughout the 16-week study period, blood pressure, creatinine clearances, and proteinuria were measured every 2 weeks. In addition, device-measured blood pressure and renal hemodynamic studies were performed at the start and end of the study. Systolic blood pressure fell in the Lis group from 163+/-7 (SEM) to 140+/-8 mm Hg (P < .01) and from 157+/-10 to 147+/-6 mm Hg in the Amlo group; diastolic blood pressure fell from 101+/-3 to 86+/-7 mm Hg in the Lis group and from 98+/-3 to 91+/-2 mm Hg in the Amlo group. Renal hemodynamics were not affected by amlodipine treatment, whereas a fall in glomerular filtration rate (GFR) was seen in lisinopril-treated patients (from 55+/-11 to 50+/-10 mL/min; P < .01). Amlodipine did not significantly affect proteinuria. Lisinopril induced a decline in the protein-creatinine ratio with a maximal effect reached after 12 to 16 weeks of therapy (from 0.39+/-0.17 to 0.26 +/-0.11 g/mmol; P < .009). In conclusion, we could not demonstrate an antiproteinuric effect of the long-acting dihydropyridine calcium channel blocker amlodipine, whereas therapy with the ACE-inhibitor lisinopril resulted in a decrease in proteinuria. Amlodipine did not affect renal hemodynamics, whereas lisinopril induced a fall in GFR.",1998.0,0,0
2441,9752894,Fixed low-dose perindopril-indapamide combination in hypertensive patients with chronic renal failure.,A Meyrier; M Dratwa; J Sennesael; V Lachaud-Pettiti,"The angiotensin converting enzyme inhibitor perindopril and the diuretic indapamide have been shown to be effective antihypertensive agents in patients with chronic renal failure. A fixed low-dose combination of these two agents has been proposed in the treatment of hypertension. We evaluated this combination in 26 patients with mild to moderate essential hypertension and mild to severe chronic renal failure that did not require dialysis. This was a multicenter, open trial consisting of a 2-week single-blind placebo washout period followed by 12 weeks of active treatment. At week 0, the patients received 2 mg perindopril/0.625 mg indapamide once a day or every other day, with the possibility of dosage adjustment to perindopril 4 mg/indapamide 1.25 mg at week 2, week 4, or week 8. A pharmacokinetic analysis using a population pharmacokinetic approach was performed at week 8. Twenty-three patients completed the 12-week study, at which time 14 patients were receiving 2 mg perindopril/0.625 mg indapamide daily, three were receiving 2 mg perindopril/0.625 mg indapamide every other day, and six perindopril 4 mg/indapamide 1.25 mg. Blood pressure readings (supine) decreased from 170.4+/-19.2 / 101.5+/-6.7 mm Hg before active treatment to 146.5+/-19.7 / 86.5+/-10.6 mm Hg at the end of treatment (P < .0001). Pharmacokinetic analysis showed that for indapamide and perindoprilat (the active metabolite of perindopril) the area under the curve (AUC24) increased with the severity of renal failure. No interaction was noted between the two drugs. Mean serum creatinine and sodium and serum potassium levels remained stable during the study. Impairment of renal function occurred in one patient and was considered unrelated to treatment. We conclude that a fixed low-dose perindopril-indapamide combination as first-line treatment has a good safety/efficacy ratio in hypertensive patients with chronic renal failure.",1998.0,0,0
2442,9754589,Angiotensin-converting enzyme gene expression in skeletal muscle in patients with chronic heart failure.,M Schaufelberger; H Drexler; E Schieffer; K Swedberg,"Skeletal muscle factors may influence functional limitation in patients with heart failure. The renin-angiotensin system is activated in chronic heart failure. Treatment with angiotensin-converting enzyme (ACE) inhibitors improve symptoms and prognosis. The goal of this study was to quantify and localize skeletal muscle ACE-mRNA in patients with chronic heart failure and in control subjects, and to elucidate skeletal muscle fiber area and capillary density. Biopsies from the lateral vastus muscle were taken from 9 patients before and after treatment with enalapril and in 10 control subjects. ACE-mRNA was quantified with reverse transcription polymerase chain reaction. Immunohistochemistry was used to localize ACE within skeletal muscle. No difference in ACE-mRNA transcripts between patients and control subjects was detected, nor did ACE gene expression change after treatment with enalapril. The number of ACE-mRNA transcripts was related to muscle fiber area, whereas an inverse relationship between the number of ACE transcripts and capillary density was found. ACE was detected in the endothelial cells of capillaries in skeletal muscle. ACE is expressed in skeletal muscle and is confined to endothelial cells. The close relationship between capillary density and number of ACE transcripts indicate that activation of the renin-angiotensin system has an impact on capillary growth.",1998.0,0,0
2443,9758323,Frequency of hospitalization after exposure to known drug-drug interactions in a Medicaid population.,R A Hamilton; L L Briceland; M H Andritz,"A matched-pair case-control analysis of Medicaid claims was performed to determine the risks of hospitalization associated with drug-drug interactions. Patients were hospitalized and controls were not. They were randomly matched based on contemporaneous eligibility for Medicaid benefits. Odds ratios for hospitalization in patients exposed to known drug-drug interactions were compared with those in patients exposed to one of the interacting agents. When confidence intervals did not overlap, the odds ratio was considered to be significantly increased. Odds ratios were significantly increased for many interacting drug pairs, and were associated with commonly recognized interactions as well as less widely recognized ones. Cimetidine interactions achieved significance only with theophylline. In the Medicaid population, exposure to a number of drug-drug interactions was associated with a significantly increased risk of hospitalization.",1998.0,0,0
2444,9759984,"Captopril, but not nifedipine, improves endothelium-dependent vasodilation in hypertensive patients.",J Millgård; A Hägg; M Sarabi; L Lind,"The present study aimed to investigate the influence of the angiotensin-converting enzyme (ACE)-inhibitor captopril and the Ca-antagonist nifedipine on endothelium-dependent vasodilation (EDV) in the forearm of hypertensive patients. Twenty-three middle-aged untreated hypertensive patients underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium-nitroprusside (SNP, evaluating EIDV), before and 1 h after intake of either captopril (25 mg) or nifedipine (10 mg) in a randomised, double-blind fashion. A matched normotensive control group was investigated at baseline conditions only. Five of the hypertensives were also evaluated after 3 months of treatment with captopril 25 mg twice daily in an open pilot study. First, the vasodilation induced by methacholine (MCh), but not SNP, was significantly attenuated in the hypertensive patients compared to the normotensive controls (P < 0.001 at MCh 4 microg/min). Second, although the two drugs induced a similar decline in blood pressure (BP) 1 h after administration (-11 to 10 mm Hg/-8 to 7 mm Hg), captopril significantly potentiated the vasodilator response to MCh (+32+/-13%, MCh 4 micr og/min, P < 0.01) but not SNP, while nifedipine did not significantly alter the response to either MCh or SNP. The improvement in vasodilator response to MCh induced by captopril was closely related to the reduction in BP (r = 0.72, P < 0.01). Third, in the pilot study, 3 months of captopril treatment induced a significant potentiation of the vasodilator response to MCh (+34+/-17%, MCh 4 microg/min, P < 0.05) in parallel with a significant BP reduction (-22+/-24/13+/-13 mm Hg, P < 0.05), while the response to SNP was unchanged. In conclusion, the present study confirmed that essential hypertension is associated with a defect in EDV. Furthermore, an improvement in EDV was seen in hypertensive patients shortly after administration of captopril, but not nifedipine. In addition, a significant beneficial effect on EDV was seen in a small pilot study during long-term treatment with captopril.",1998.0,0,0
2445,9759987,The direct costs to the NHS of discontinuing and switching prescriptions for hypertension.,D Hughes; A McGuire,"There is much evidence to suggest that the treatment of hypertension reduces the risk of cardiovascular diseases and that it is cost-effective in most patients. However, the effectiveness of treatment relies on compliance and maintenance of treatment. Each pharmacological agent differs in terms of side effects. The existence of side effects can result in poor compliance and switching between treatments. A number of studies have reported high discontinuation rates for anti-hypertensive therapies. This potentially imposes costs on the health service. The aim of this study is to use the MEDIPLUS data set to consider the cost arising from switching and discontinuation of therapy. The analysis will assess the resource costs in terms of extra GP visits and hospitalisations arising from individuals switching and discontinuing treatments. The total costs of hypertension were estimated to be around 76.5 m pound sterling per annum, of which 26.9 m pound sterling can be attributed to patients who switch or discontinue therapy.",1998.0,0,0
2446,9760271,"Role of drug disposition in drug hypersensitivity: a chemical, molecular, and clinical perspective.",B K Park; M Pirmohamed; N R Kitteringham,,1998.0,0,0
2447,9764049,Angiotensin II receptor antagonists for heart failure.,A D Struthers,,1998.0,0,0
2448,9764148,The use of skin testing in the investigation of cutaneous adverse drug reactions.,A Barbaud; S Reichert-Penetrat; P Tréchot; M A Jacquin-Petit; A Ehlinger; V Noirez; G C Faure; J L Schmutz; M C Béné,"Skin testing with the suspected compound has been reported to be helpful in determining the cause of cutaneous adverse drug reactions (ADRs), but the value and specificity of these tests need to be determined. In this study, 72 patients with presumed drug eruptions (27 maculopapular, 18 urticarial, seven erythrodermic, nine eczematous, four photosensitivity, three fixed drug eruptions, three with pruritus and one with acute generalized exanthematous pustulosis) were assessed. All had drug patch tests; 46 also had prick tests and 30 had intradermal tests (performed on hospitalized patients using a sterile solution of the suspected drug, diluted sequentially) with immediate and delayed readings. Among these patients, 52 (72%) had a positive skin test reaction, 43%, 24% and 67% in patch, prick and intradermal skin tests, respectively. The results of skin tests varied with the drug tested and with the clinical type of cutaneous ADR, as a significantly higher number of positive patch tests was observed in maculopapular rashes than in urticarial reactions (P = 0.001). This study supports the value of careful sequential drug skin testing in establishing the cause of cutaneous ADR. Guidelines are proposed for performing these tests, and these include the use of appropriate negative control patients to avoid false-positive results.",1998.0,0,0
2449,9772413,"Oral captopril versus placebo among 14,962 patients with suspected acute myocardial infarction: a multicenter, randomized, double-blind, placebo controlled clinical trial. Chinese Cardiac Study (CCS-1) Collaborative Group.",,"To assess the efficacy of captopril on mortality and morbidity after acute myocardial infarction (AMI). A total of 14,962 patients entering 650 hospitals from 30 provinces and autonomous regions of China up to 36 hours (mean 16.6 +/- 10.2 hours) after the onset of suspected acute myocardial infarction (MI) with no clear contraindications or indications to the study treatments (in particular, no persistent hypotension or hypovolemia due to long-term use of large dose of diuretics) were randomized to use either 4 weeks of oral captopril (6.25 mg initial dose, 12.5 mg 2 hours later, and then 12.5 mg three times daily) or matching placebo. Captopril was associated with a non-significant reduction in 4-week mortality (9.12% vs 9.74%; P = 0.20); but incidence of heart failure was significantly reduced among captopril group (17.0% vs 18.7%; P = 0.01). The combined end point (death + heart failure) was 1680 (21.5%) in captopril group and 1733 (23.1%) in placebo group (P = 0.02). Anterior wall infarction of captopril treated group was found to have lower mortality (8.6% vs 10.2%, P = 0.02). Captopril treated group with a heart rate (HR) > or = 60/min at entry showed significantly lower mortality than placebo group (9.2% vs 10.7%; P = 0.01). There was a significant excess of hypotension, mostly after the start of treatment, but no evidence of any adverse effect on early mortality. The angiotensin converting enzyme inhibitors (CEI) therapy started early in acute MI prevents about 6 deaths per 1000 treated, and about 15 deaths due to heart failure per 1000 in the 1st 4 weeks with greater benefits. In anterior myocardial infarction group it prevents 16 deaths per 1000 with nearly no benefit for the inferior infarction group. Due to the parasympathetic mimic effect, CEI should be used carefully in inferior infarction patients especially when HR is slow or heart block and hypotension are present.",1998.0,1,1
2450,9773137,The effect of i.v. enalaprilat in chronically treated hypertensive patients during cardiac surgery.,W H Schuetz; K H Lindner; M Georgieff; S Mueller; F Oertel; P Radermacher; A Gauss,"Angiotensin-converting enzyme (ACE) inhibitors are well established as long-term antihypertensives and have also been proved useful in hypertensive emergencies. Therefore, we investigated whether intraoperative i.v. enalaprilat may reduce the incidence of perioperative hypertensive reactions in coronary artery bypass grafting (CABG). Thirty-eight male patients chronically treated for arterial hypertension and scheduled for CABG randomly and double-blindly received either enalaprilat 30 micrograms.kg-1 or NaCl 0.9% at the time of skin incision. Intraoperatively, increases of mean arterial pressure (MAP) > 85 mmHg or > 80 mmHg during cardiopulmonary bypass (CPB) were treated by an urapidil bolus. The total intraoperative amount of urapidil was documented for both groups. Systemic and pulmonary hemodynamics as well as the plasma levels of epinephrine, norepinephrine, arginine vasopressin and renin were measured intraoperatively and up to 2 h after admission to the intensive care unit. Mean arterial pressure, cardiac index and systemic vascular resistance did not differ between the enalaprilat and the control group. Renin plasma levels significantly increased after infusion of enalaprilat and did not change in the placebo group. Catecholamine and arginine vasopressin plasma levels increased significantly during CPB and remained high in the postoperative period without any intergroup difference. The same amount of urapidil had to be given in the two groups to maintain MAP below the defined limit. We conclude that infusing 30 micrograms.kg-1 enalaprilat in patients chronically treated for arterial hypertension does not prevent hypertensive reactions during CABG.",1998.0,0,0
2451,9773316,Worsening of head-up tilt test response during chronic beta-blocker therapy in patients treated for neurally mediated syncope.,A Gardini; G Benedini; C Proto,"The prognosis of patients with neurally mediated syncope and asystolic response at tilt test is controversial and there is no consensus regarding their management. Many patients seem to benefit from beta-blockers and their effectiveness has been assessed with repeated tilt tests in asystolic patients as well. However, little is known about the long-term effects of beta-blockers. Preliminary data and isolated reports suggest that in some cases, these agents may actually worsen the clinical outcome or the tilt test response. Three patients are described who experienced worsening of tilt test response with prolonged asystole (19.9, 9 and 5.5 sec respectively) during chronic treatment with beta-blockers in the absence of spontaneous symptoms. At discharge, one patient received a dual-chamber pace-maker combined with metoprolol, another one continued to take metoprolol and enalapril. The third patient refused any further medication. During follow-up (8, 11, 13 months respectively), they were symptom-free. The clinical and prognostic significance of this response is not clear and needs further investigation.",1998.0,0,0
2452,9773753,Diabetes and risk of adverse events with calcium antagonists.,H H Parving; P Rossing,,1998.0,0,0
2453,9776426,Aphtous ulcers of the mouth associated with losartan.,E Goffin; J M Pochet; P Lejuste; J F De Plaen,,1998.0,0,0
2454,9777817,Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.,R A Preston; B J Materson; D J Reda; D W Williams; R J Hamburger; W C Cushman; R J Anderson,"Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. Fifteen Veterans Affairs hypertension centers. A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.",2001.0,0,0
2455,9778071,Differential effects of fosinopril and enalapril in patients with mild to moderate chronic heart failure. Fosinopril in Heart Failure Study Investigators.,F Zannad; Z Chati; M Guest; F Plat,"To investigate the efficacy and safety of fosinopril in the treatment of chronic heart failure (CHF), patients with mild to moderate CHF and left ventricular ejection fractions <40% were randomly assigned in a double-blind manner to receive fosinopril 5 to 20 mg every day (n = 122) or enalapril 5 to 20 mg every day (n = 132) for 1 year. The event-free survival time was longer (1.6 vs 1.0 months, P= .032) and the total rate of hospitalizations plus deaths was smaller with fosinopril than with enalapril (19.7% vs 25.0%, P= .028). There was consistently better symptom improvement with fosinopril (P< .05). The incidence of orthostatic hypotension was lower in the fosinopril group (1.6% vs 7.6%, P< .05). Fosinopril 5 to 20 mg every day was more effective in improving symptoms and delaying events related to worsening of CHF and produced less orthostatic hypotension than enalapril 5 to 20 mg every day.",1998.0,1,1
2456,9781723,Influence of angiotensin-converting enzyme inhibitor enalaprilat on endothelial-derived substances in the critically ill.,J Boldt; M Papsdorf; B Kumle; S Piper; G Hempelmann,"To assess the effects of the angiotensin-converting enzyme inhibitor enalaprilat on endothelial cells in septic patients. Prospective, randomized, placebo-controlled, blinded study. Clinical investigation on a surgical intensive care unit of a university hospital. Forty surgical septic patients (noncardiac/nonneurosurgical patients). After inclusion in the study and after baseline data were obtained, either 0.25 mg/hr (enalaprilat group, n = 20) or saline solution as placebo (control group, n = 20) was continuously given and continued throughout the following 5 days. Extensive hemodynamic monitoring was carried out in all patients. Plasma concentrations of endothelin-1, angiotensin II, soluble thrombomodulin, and soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and granule membrane protein-140) were measured from arterial blood samples. All measurements were carried out before the start of the infusion (""baseline"" values) and daily during the following 5 days. All endothelial-derived substances (thrombomodulin, endothelin-1, and all soluble adhesion molecules) were similarly increased beyond normal in both group. Endothelin-1 increased only in the untreated control patients (from 6.9 +/- 0.7 to 14.3 +/- 1.4 mg/mL). Soluble thrombomodulin increased in the untreated control patients (from 58 +/- 9 to 79 +/- 14 ng/mL [p < .05]), but significantly decreased in the enalaprilat-treated patients. Soluble adhesion molecules increased in the untreated control group (endothelial leukocyte adhesion molecule from 92 +/- 14 to 192 +/- 29 ng/mL; intercellular adhesion molecule-1 from 480 +/- 110 to 850 +/- 119 ng/ mL) and returned almost to normal values in the enalaprilat patients. The survival rate did not differ significantly between the two groups. Control patients developed severe sepsis and septic shock more often than the enalaprilat-treated group. The complex pathogenesis of endothelial function abnormalities in sepsis may offer a large number of pharmacologic interventions. Administration of the angiotensin-converting enzyme inhibitor enalaprilat resulted in a reduced release of soluble endothelial-derived substances into the circulating blood, which may indicate an improved endothelial function. The specific actions of enalaprilat on the endothelium have to be elucidated in further studies.",1998.0,0,0
2457,9781930,ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients.,R Fogari; A Zoppi; P Lazzari; P Preti; A Mugellini; L Corradi; P Lusardi,"The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.",1998.0,0,0
2458,9783490,Tailoring anti-hypertensive treatment in the elderly.,S Bonapace; C Rajkumar; C J Bulpitt,"The treatment of hypertension in the elderly has to take into account co-existing pathology. However, the benefit from treatment are large in terms owing to the frequency of cardiovascular events in the elderly. The benefits observed in randomised controlled trials are reviewed together with the adverse effects of the individual treatments. The optimal use of anti-hypertensive treatment is considered in light of any concomitant disease; for example beta-blockers or calcium channel blockers when angina is present and the avoidance of diuretics in the presence of gout. Important hazardous drug interactions are also discussed. It is concluded that diuretics are still the first choice in uncomplicated hypertension and the least expensive. However the place of anti-hypertensive treatment is not established in those over the age of 80 years.",1998.0,0,0
2459,9783492,PROGRESS: Perindopril pROtection aGainst REcurrent Stroke Study: status in March 1997. PROGRESS Management Committee.,,"The study has been designed to assess the efficacy of blood pressure (BP) reduction in the prevention of stroke in patients with a history of ischaemic stroke, haemorrhagic stroke, or transient ischaemic attack. A randomised, double-blind, placebo-controlled, international, multicentre trial of the angiotensin-converting enzyme (ACE) inhibitor perindopril, alone or in combination with the diuretic indapamide, in the secondary prevention of stroke and other major cardiovascular events. A total of 6000 normotensive or hypertensive patients with a history of stroke or transient cerebral ischaemia within the previous 5 years will be included in the study. The study is being conducted in over 160 centres located in seven regions: Australia and New Zealand; The People's Republic of China; France and Belgium; Italy; Japan; Sweden; and the United Kingdom. The primary study outcome is the total number of strokes defined by WHO criteria. Secondary outcomes include fatal and disabling strokes, total number of cardiovascular events and deaths, cognitive function, disability, and dependency. A minimum of 4 years' follow-up is planned. By 27 March 1997, 173 local clinical centres had been registered in seven regions. A total of 5268 patients (64% with a history of hypertension or baseline BPs above 95 mm Hg [diastolic] or 160 mm Hg [systolic]) had been randomly assigned to active treatment or placebo. After 6 months' follow-up the difference in BP between treatment and control groups was 10.2/4.5 mm Hg (systolic/diastolic). Sixty-three strokes (two fatal) and 20 myocardial infarctions (four fatal) had been recorded. The viability of the study is now assured, with almost 90% of 6000 patients recruited. ACE therapy with perindopril is well tolerated in the studied population. The BP differences between control and treatment groups and the event rates recorded to date suggest that the study will achieve its primary objectives.",1998.0,0,0
2460,9783501,The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial.,I P Villarosa; G L Bakris,,1998.0,0,0
2461,9786602,Calcium channel blockers shorten the periodicity of ultradian variation in blood pressure in patients with essential hypertension.,H Kawamura; H Mitsubayashi; T Saito; K Kanmatsuse; N Saito,"We studied ultradian and circadian variations in blood pressure (BP) in patients with essential hypertension who were receiving antihypertensive agents. No patient had previously received antihypertensive agents before this study began. After a 2-wk control period, we performed ambulatory blood pressure monitoring (ABPM) in 86 patients with essential hypertension (WHO stages I or II). The patients were then given a long-acting angiotensin converting enzyme inhibitor (ACEI) (captopril or imidapril), a beta-receptor blocker (arotinolol or bisoprolol), or a calcium channel blocker (nisoldipine or benidipine) twice daily to control BP. We evaluated the patients' BP once every 2 wk to ensure optimal control. After 12 wk, ultradian and circadian variations in BP were analyzed by the maximum entropy method (MEM). All antihypertensive agents decreased office systolic BP (SBP), office diastolic BP (DBP), 24-h SBP, and 24-h DBP. ACEI did not change office, 24-h, daytime, or nighttime pulse rate (PR). Arotinolol and bisoprolol decreased 24-h PR. All antihypertensive agents decreased 24-h, daytime, and nighttime pressure rate product. MEM showed that no antihypertensive agent affected the circadian variation in the 1st peak (24-h periodicity) of SBP, DBP, or PR. However, calcium channel blockers shortened the periodicity of circadian variations in the 2nd peak (12-h periodicity) of SBP and the 3rd peak (8 to 6 h periodicity) of SBP. Therefore, ultradian variations in BP should be carefully monitored in hypertensive patients treated with calcium channel blockers.",1998.0,0,0
2462,9787950,Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage.,V Lufft; V Kliem; A Hamkens; J S Bleck; U Eisenberger; R Petersen; G Ehlerding; H Maschek; R Pichlmayr; R Brunkhorst,"Angiotensin converting enzyme (ACE) inhibitors have been successfully used for treatment of proteinuria after renal transplantation (RTx). Factors possibly responsible for the great inter-patient variance of the antiproteinuric effect (APE) have not yet been investigated in renal-transplanted patients. 28 patients after RTx with a persistent proteinuria of more than 1.25 g/d were treated prospectively with does of fosinopril (10-15 mg/d) which were not effective on systemic arterial blood pressure. Prior to initiation of fosinopril, renal graft biopsy was performed in all patients and renal graft artery stenosis was excluded by duplex ultrasound. Serum creatinine and proteinuria were measured prior to, as well as 3 and 8 months after initiation of ACE inhibition, mean arterial pressure was controlled via 24-h measurement and repeated spot measurements. Reduction of proteinuria was correlated with renal histology, serum creatinine, creatinine clearance, mean arterial blood pressure, sodium excretion before therapy and the relative changes of these parameters during therapy respectively. Therapy had to be stopped in 8/28 patients due to side effects including rise of serum creatinine (n = 4). Three patients were excluded due to non-compliance. In the remaining patients (n = 17) proteinuria was reduced from 2.94 +/- 1.66 to 1.82 +/- 1.39 and 2.48 +/- 3.05 g/d after 3 and 8 months respectively, in the mean +/- SD. There was a significant inverse correlation between the APE and the extent of benign nephrosclerosis, interstitial fibrosis and tubular atrophy. No correlation of the APE to any of the other parameters could be demonstrated. Fosinopril can be administered effectively in a subgroup of proteinuric renal transplant recipients. However, because of a high proportion of patients developing side effects, careful monitoring is obligatory. Our results show that the lesser the degree of chronic morphological injury, the greater is the antiproteinuric effect. Thus, the degree of pre-existing histologically proven damage of the graft may serve as an indicator for the antiproteinuric efficacy of ACE inhibitor therapy after RTx.",1998.0,0,0
2463,9788454,Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy.,P Ruggenenti; A Perna; G Gherardi; F Gaspari; R Benini; G Remuzzi,"The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study. 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat. During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0] vs 23.8 [9.4] mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy. In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (> or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.",1998.0,0,0
2464,9788828,Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition.,G Vescovo; L Dalla Libera; F Serafini; C Leprotti; L Facchin; M Volterrani; C Ceconi; G B Ambrosio,"In congestive heart failure, fatigue-resistant, oxidative, slow type I fibers are decreased in leg skeletal muscle, contributing to exercise capacity (EC) limitation. The mechanisms by which ACE inhibitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal muscle composition toward type I fibers. Eight patients with congestive heart failure, NYHA classes I through IV, were treated for 6 months with enalapril (E) 20 mg/d, and another 8 with losartan (L) 50 mg/d. EC was assessed with maximal cardiopulmonary exercise testing at baseline and after treatment. Myosin heavy chain (MHC) composition of the gastrocnemius was studied after electrophoretic separation of slow MHC1, fast oxidative MHC2a, and fast glycolytic MHC2b isoforms from needle microbiopsies obtained at baseline and after 6 months. EC improved in both groups. Peak V(O2) increased from 21.0+/-4.7 to 27.6+/-4.3 mL . kg-1 . min -1 (P=0.011) in the L group and from 17.5+/-5.0 to 25.0+/-5.5 mL . kg-1 . min -1 (P=0.014) in the E group. Similarly, ventilatory threshold changed from 15.0+/-4.0 to 19.9+/-4.9 mL (P=0. 049) with L and from 12.0+/-1.9 to 15.4+/-3.5 mL (P=0.039) with E. MCH1 increased from 61.2+/-11.2% to 75.4+/-7.6% with L (P=0.012) and from 60.6+/-13.1% to 80.1+/-10.9% (P=0.006) with E. Similarly, MHC2a decreased from 21.20+/-9.5% to 12.9+/-4.4% (P=0.05) with L and from 19.9+/-7.8% to 11.8+/-7.9% (P=0.06) with E. MHC2b changed from 17. 5+/-6.5% to 11.7+/-5.2% (P=0.07) with L and from 19.5+/-6.4% to 8. 1+/-4.6% (P=0.0015) with E. There was a significant correlation between net changes in MHC1 and absolute changes in peak V(O2) (r2=0.29, P=0.029) and a trend to significance for MHC2a and 2b. Six months' treatment with L and with E produces an improvement in EC of similar magnitude. These changes are accompanied by a reshift of MHCs of leg skeletal muscle toward the slow, more fatigue-resistant isoforms. Magnitude of MHC1 changes correlates with the net peak V(O2) gain, which suggests that improved EC may be caused by favorable biochemical changes occurring in the skeletal muscle.",1998.0,0,0
2465,9792263,Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients.,D A Duprez; M L De Buyzere; E R Rietzschel; Y Taes; D L Clement; D Morgan; J N Cohn,"The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by non-invasive mathematical lumped-parameter modelling of the compliance of the arterial system. Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml x mmHg(-1), P<0.01) and distal (C2, 0.050 +/- 0.011 ml x mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml x mmHg(-1); C2, 0.054 +/- 0.006 ml x mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= - 0.795, P=0.002) and standing (r= - 0.628, P=0.029) positions. In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.",1998.0,0,0
2466,9793599,ACE inhibitor- versus angiotensin II blocker-induced cough and angioedema.,G B Pylypchuk,"To compare the tolerability of angiotensin-converting enzyme (ACE) inhibitors with that of angiotensin II (AII)-receptor blockers and the incidence of cough and angioedema associated with their use through review of published data. References were identified through a MEDLINE search of articles published between January 1975 and April 1997. Bibliographies of pertinent references were also reviewed. Results of placebo-controlled and comparative trials of the AII blockers demonstrate that they are at least as effective as ACE inhibitors for hypertension, but exhibit an incidence of cough and absent or rare angioedema like that of placebo. In the 10 comparative trials described, all reported a lower incidence of cough with AII blockers than with ACE inhibitors. Angioedema was not reported in the comparative trials described.",1998.0,0,0
2467,9793603,Losartan as an alternative to ACE inhibitors in patients with renal dysfunction.,Z N Esmail; P S Loewen,"Losartan-induced acute renal failure may occur in patients sensitive to reduced renal plasma flow. Such patients include those with bilateral renal artery stenosis, severe congestive heart failure, and severe sodium and volume depletion because their renal function is often angiotensin-dependent. Theoretically, both ACE inhibitors and losartan could adversely affect renal function in such sensitive patients. The ELITE trial showed a 10.5% incidence of losartan-induced renal dysfunction in elderly patients with congestive heart failure with no known underlying renal dysfunction, an incidence identical to that for captopril. A review of the literature revealed no controlled trials that specifically address whether losartan can be used as an alternative in patients in whom renal dysfunction associated with losartan have been published and an additional case report was identified from a local adverse drug reaction monitoring program. There were two cases of patients who developed renal dysfunction while receiving ACE inhibitors and then losartan. We found only one published case in which losartan was used without deterioration in renal function in patients who developed renal dysfunction while taking an ACE inhibitor, although underreporting of such cases would be expected. There was one case of renal dysfunction with losartan after a lack of renal dysfunction while the patient was taking an ACE inhibitor. The remaining three reports are of patients who developed renal dysfunction while taking losartan with no antecedent ACE inhibitor use. All case reports describe renal deterioration that was reversible upon discontinuation of the inciting agent, whether an ACE inhibitor or losartan. All but two patients (personal communication, Barbara Cadario) had underlying renal pathology. Although there is a paucity of published literature and the clinical experience of some may suggest otherwise, there is currently no evidence (with the exception of 1 case report) to suggest that losartan is any better tolerated than ACE inhibitors from the standpoint of renal toxicity. Available evidence suggests that this is equally true in patients with and without underlying renal dysfunction. Furthermore, case reports suggest that, as with ACE inhibitors, losartan should be avoided in patients with bilateral renal artery stenosis and in patients with unilateral renal artery stenosis in a solitary kidney. In patients with underlying renal dysfunction, regardless of whether they tolerate ACE inhibitors, losartan may be used if deemed necessary. Renal function should be monitored and losartan should be stopped if evidence of renal dysfunction becomes apparent, since several case reports and a randomized trial suggest that losartan may cause the same negative renal effects as ACE inhibitors.",1998.0,0,0
2468,9794352,Effects of candesartan cilexetil in patients with systemic hypertension. Candesartan Cilexetil Study Investigators.,M Reif; W B White; T C Fagan; S Oparil; T L Flanagan; D T Edwards; D J Cushing; E L Michelson,"The objectives of this double-blind, multicenter, randomized, parallel-arm, placebo-controlled study were to evaluate the dose-related efficacy, tolerability, and safety of candesartan cilexetil, a potent, AT1 selective, long-acting angiotensin II receptor blocker, in 365 adult patients with systemic hypertension and mean sitting diastolic blood pressure (BP) of 95 to 114 mm Hg. Patients received either placebo or candesartan cilexetil 2, 4, 8, 16, or 32 mg once daily for 8 weeks. All doses of candesartan cilexetil reduced trough (24 hours after treatment) sitting diastolic and systolic BP significantly compared with placebo (p < 0.005). A significant (p < or = 0.0001) dose response was evident, with greater decreases in BP at higher doses. Mean changes in BP were -10.7/-7.8 mm Hg and -12.6/-10.2 mm Hg in the 16- and 32-mg groups, respectively, versus -0.3/-2.6 mm Hg in the placebo group. The 16- and 32-mg doses were consistently significantly superior to placebo in antihypertensive effect with regard to all BP measurements, including peak (6 hours after treatment), trough, sitting, and standing measurements of diastolic and systolic BP. Responder rates (trough sitting diastolic BP < 90 or > or = 10 mm Hg BP decrease) were 54% and 64% for the 16- and 32-mg groups, respectively. Tolerability and safety profiles were similar to placebo at all doses. In conclusion, candesartan cilexetil administered once daily effectively reduces BP in a dose-related manner while maintaining safety and tolerability; doses of 16 and 32 mg are most effective for treatment of hypertension.",1998.0,0,0
2469,9797181,Effects of nitrendipine and enalapril on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension.,T A Gerritsen; A A Bak; R P Stolk; J J Jonker; D E Grobbee,"To compare the effects of a calcium antagonist (nitrendipine) and an angiotensin converting enzyme inhibitor (enalapril) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension. A double-blind randomized, placebo-controlled trial. General practitioners referred patients to the trial physician. The study population comprised 121 patients with non-insulin-dependent diabetes mellitus. Inclusion criteria for blood pressure were diastolic blood pressure 90-115 mmHg and systolic blood pressure < or = 200 mmHg, while subjects were not being administered blood-pressure-lowering drugs for 3 weeks. Patients were randomly allocated to receive nitrendipine (n = 40), enalapril (n = 40) or placebo (n = 41). The treatment period was 48 weeks. The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment. The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly. Left ventricular mass was measured by M-mode echocardiography. Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures. During 48 weeks left ventricular mass index decreased by 5% for patients in the nitrendipine group (decrease by 12 g/m2, 95% confidence interval 1-23), remained about the same for patients in the enalapril group (decrease by 1 g/m2, 95% confidence interval decrease by 10 to increase by 9) and increased by 9% for patients in the placebo group (increase by 9 g/m2, 95% confidence interval 2-16). These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension reduces left ventricular mass index. Enalapril appears not to induce regression, but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo.",1998.0,0,0
2470,9797199,Centralized echocardiogram quality control in a multicenter study of regression of left ventricular hypertrophy in hypertension.,P Gosse; D Guez; P Guéret; O Dubourg; A Beauchet; A de Cordoüe; S Barrandon,"To test the feasibility and utility of instituting centralized echocardiographic quality control during a multicenter study of regression of left ventricular hypertrophy in hypertension. The LIVE (Left Ventricular Hypertrophy: Indapamide Versus Enalapril) study is an ongoing multicenter, double-blind, controlled study of regression of echocardiographic left ventricular mass index in hypertensive patients with left ventricular hypertrophy (left ventricular mass indexes > 100 g/m2 for women and > 120 g/m2 for men) treated for 1 year with 1.5 mg indapamide sustained-release coated tablets versus 20 mg enalapril. A centralized evaluation committee has validated a prestudy sample echocardiogram from each center, and is now reviewing all videotapes recorded during this study for quality control; final results will be based on a further randomized blinded analysis by this centralized evaluation committee. Since December 1994, 878 patients have been preselected (videoechocardiographic recordings sent for assessment), 645 selected (videoechocardiographic recordings validated), and 576 randomly allocated to treatment. After preliminary quality control, 27% (233) of baseline echocardiograms were rejected by our centralized evaluation committee, and 22% (142) of postinclusion echocardiographic measurements had to be repeated, mainly because they were of poor echogenic quality. Analysis of approved baseline echocardiograms for the first 274 randomly allocated patients with digitized data showed that there was a significant correlation between centralized evaluation committee and investigator calculations of left ventricular mass index (r = 0.76, P < 0.001), with consistently higher values for investigator calculations, independently of level of left ventricular mass index (correlation between difference and mean of investigator and centralized evaluation committee measurements, r = 0.08, P = 0.28). The mean difference was 8 +/- 20 g/m2 (P < 0.001). Early results of the LIVE study quality control showed that real-time 'live', centralized echocardiographic reading was not only feasible, but also useful for avoiding unquantifiable echocardiograms and overestimation of left ventricular mass index. Thus, real-time, centralized echocardiographic quality control should be recommended for multicenter studies of regression of left ventricular hypertrophy.",1998.0,0,0
2471,9797501,Adult Schönlein-Henoch purpura after enalapril.,R Gonçalves; H Cortez Pinto; F Serejo; F Ramalho,,1998.0,0,0
2472,9799034,Factors influencing reduction in blood pressure and left ventricular mass in hypertensive type-1 diabetic patients using captopril or doxazosin for 6 months.,E Gerdts; E Svarstad; S Aanderud; O L Myking; P Lund-Johansen; P Omvik,"The effect of doxazosin versus captopril on blood pressure, albuminuria, and left ventricular mass was studied in 33 hypertensive type-1 diabetic patients randomized to 6 months treatment with captopril (17 patients, mean daily dose 100 mg) or doxazosin (16 patients, mean daily dose 9 mg). Casual and 24-h ambulatory blood pressure (24hBP) were reduced from 163/95 to 144/83 mm Hg and 152/86 to 145/81 mm Hg, respectively, in the captopril group, and from 160/93 to 145/86 mm Hg and 156/86 to 147/79 mm Hg in the doxazosin group (all P < .05). The achieved 24hBP on treatment was positively associated with pretreatment levels of glycosylated hemoglobin (HbA1c) and plasma atrial natriuretic peptide (r = 0.53 and 0.59, respectively, both P < .01). Albuminuria did not change significantly in either group. Left ventricular hypertrophy was present in 13 patients (7 in the captopril and 6 in the doxazosin group). Left ventricular mass was reduced by an average of 27% and 23%, respectively, in these patients (both P < .01), but did not change significantly in patients without left ventricular hypertrophy. The reduction in left ventricular mass was positively associated with the presence of baseline left ventricular hypertrophy and inversely with dietary sodium intake and achieved casual blood pressure on treatment (R2 = 0.59, P < .001). We conclude that doxazosin and captopril used for 6 months are equally effective in reducing blood pressure and left ventricular hypertrophy in hypertensive type-1 diabetic patients; the antihypertensive effect is closely related to glycemic control; and dietary sodium intake and achieved casual blood pressure after treatment are independent determinants of the reduction in left ventricular mass seen in these patients.",1998.0,0,0
2473,9799042,Sexual function in hypertensive males treated with lisinopril or atenolol: a cross-over study.,R Fogari; A Zoppi; L Corradi; A Mugellini; L Poletti; P Lusardi,"To evaluate the effect of antihypertensive treatment on sexual activity, 90 hypertensive men, aged 40 to 49 years, all married and without history of sexual dysfunction were treated with 100 mg of atenolol or 20 mg of lisinopril for 16 weeks, according to a double-blind, randomized, cross-over design. During the first month of therapy, sexual activity, assessed as number of sexual intercourse episodes per month, significantly declined with both atenolol (from 7.8 +/- 4.3 to 4.5 +/- 2.8, P < .01 v placebo) and lisinopril (from 7.1 +/- 4.0 to 5.0 +/- 2.5, P < .05 v placebo). Ongoing with the treatment, sexual activity tended toward recovery in the lisinopril (7.7 +/- 4.0 sexual intercourse episodes per month, P = NS v placebo), but not in the atenolol group (4.2 +/- 2.8, P < .01 v placebo), with a statistically significant difference between the two drugs (P < .01). The percentage of patients who complained of sexual dysfunction symptoms was significantly higher in the atenolol- than in the lisinopril-treated group (17% v 3%, P < .05). These findings suggest that atenolol induces a chronic worsening of sexual activity, whereas lisinopril causes only a temporary decline.",1998.0,0,0
2474,9799047,Study of supplemental oral l-arginine in hypertensives treated with enalapril + hydrochlorothiazide.,V Pezza; F Bernardini; E Pezza; B Pezza; M Curione,,1998.0,0,0
2475,9800739,Risk of morbidity from renovascular disease in elderly patients with congestive cardiac failure.,P MacDowall; P A Kalra; D J O'Donoghue; S Waldek; H Mamtora; K Brown,"Renovasular disease commonly affects elderly people. Elderly patients with heart failure are routinely treated with angiotensin-converting-enzyme (ACE) inhibitors, which may increase risk of renal dysfunction. We investigated the frequency of renovascular disease among elderly people with heart failure. From the local population of Salford, UK, we recruited 86 patients with heart failure with a mean age of 77.5 (SD 5.6) years, who were admitted as acute emergencies or who attended general medical clinics. We selected patients by intention to treat with ACE inhibitors. We used captopril renography to screen for renovascular disease. All patients with abnormal renograms underwent magnetic-resonance angiography of the renal arteries as well as 40% of patients with normal renograms as negative controls. Magnetic-resonance angiography showed severe renovascular disease (>50% renal-artery stenosis or occlusion) in 29 (34%) patients. Captopril renography had an estimated sensitivity of 78.8% (95% CI 72.7-97.8) and specificity of 94.3% (67.6-97.3) for detection of renovascular disease. The estimated positive predictive value of captopril renography was 89.7% and the negative predictive value was 87.5%. Patients with renovascular disease had worse renal function (mean creatinine 201 [SD 56] vs 136 [40] pmol/L, p<0.001), were older (mean age 80.7 [5.6] vs 76.8 [5.3] years, p<0.01), and were more likely than patients without renovascular disease to have peripheral arterial disease. Some elderly patients with occult renovascular disease on ACE inhibitors will be at risk of developing uraemia. Renal function should be closely monitored to detect any deterioration early.",1998.0,0,0
2476,9802141,"The Angiotensin Converting Enzyme Inhibition Post Revascularization Study (APRES). Effects of ramipril in patients with reduced left ventricular function. Rationale, design, methods, baseline characteristics and first-year experience.",L Kjøller-Hansen; R Steffensen; P Grande,"Invasive revascularization improves prognosis, functional status and quality of life in patients with severe angina pectoris and impaired left ventricular function, and treatment with ACE-I reduces the development of cardiac events and left ventricular dysfunction in patients without or with mild angina pectoris. However, the effects of a combined treatment strategy with invasive revascularization and subsequent long-term ACE-I therapy in patients with limiting angina pectoris and impaired left ventricular function have not previously been investigated. APRES is a long-term, prospective, randomized double-blind study that evaluates the effects of ramipril 10 mg o.d. on the long-term development of cardiac events, left ventricular function, functional status and quality of life following invasive revascularization in patients without recent AMI or clinical heart failure and with preoperative ejection fraction in the range 0.30-0.50. The rationale, design and power of APRES and the choice and relevance of outcome measures are discussed. Based on experience and results from the first year of the study for screening procedure, inclusion rate, patient compliance, reproducibility analyses and the magnitude of outcome measures, we conclude that the study is feasible and safe. The included patients match with the target population, the outcome measures seem appropriate and the power considerations valid for the majority of the outcome measures.",1998.0,0,0
2477,9802273,Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial.,F Forette; M L Seux; J A Staessen; L Thijs; W H Birkenhäger; M R Babarskiene; S Babeanu; A Bossini; B Gil-Extremera; X Girerd; T Laks; E Lilov; V Moisseyev; J Tuomilehto; H Vanhanen; J Webster; Y Yodfat; R Fagard,"Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia. Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score. Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference). In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.",1998.0,0,0
2478,9803197,Treatment of hypertension: insights from the JNC-VI report.,N M Kaplan,"The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) provides updated guidelines for the treatment of hypertension. Antihypertensive drug therapy may be initiated either after a trial of lifestyle modifications or immediately after the diagnosis is made, depending on the patient's other cardiovascular risk factors and the presence of clinical cardiovascular disease. In general, therapy may begin with diuretics or beta-adrenergic blockers in patients under age 65, unless a concomitant condition warrants another, more tailored choice. Low dosages should be used initially, but if the blood pressure is not successfully reduced to 140/90 mm Hg or below, another drug should be added or should replace the initial choice. General principles of therapy include the use of once-a-day formulations and combination drugs as well as cost considerations.",1998.0,0,0
2479,9803242,A new paradigm for funding cardiovascular-outcome research in general practice. The Second Australian National Blood Pressure Study. ANBP2 Management Committee.,C M Reid; L M Wing; D H Graham,,1998.0,0,0
2480,9806660,"Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses' health study.",K B Michels; B A Rosner; A M Walker; M J Stampfer; J E Manson; G A Colditz; C H Hennekens; W C Willett,"Some studies have suggested that the use of calcium channel blockers may increase the risk of cancer. A possible association of the use of calcium channel blockers with cancer incidence and cancer mortality was addressed using data from the Nurses' Health Study. In this study, a total of 18,635 female nurses reported regularly taking at least 1 of 4 cardiovascular medications in 1988: diuretics, beta-blockers, calcium channel blockers, and/or angiotensin-converting enzyme (ACE) inhibitors. Cancer incidence and cancer deaths were ascertained until 1994. During 6 years of follow-up, 852 women were newly diagnosed with cancer and 335 women died of cancer. Women who reported the use of calcium channel blockers had no increased risk of newly diagnosed cancer compared with those taking other cardiovascular drugs (relative risk=1.02; 95% CI 0.83-1.26). The relative risk of dying from cancer associated with the self-reported use of calcium channel blockers was 1.25 (95% CI 0.91-1.72). Relative risks were adjusted for the following self-reported factors: age; weight; height; cholesterol level; systolic and diastolic blood pressure; smoking; alcohol intake; physical activity; menopausal status; postmenopausal hormone use; aspirin use; and history of diabetes, cancer, stroke, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina, and hypertension. Regarding site specific cancer incidence and mortality, only lung cancer incidence was somewhat increased (RR=1.61; 95% CI 0.88-2.96). These data suggest no important increase in overall cancer incidence or cancer mortality related to the self-reported use of calcium channel blockers.",2000.0,0,0
2481,9807055,,,,,0,0
2482,9808096,"Effects of dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibition, and blood pressure control on chronic, nondiabetic nephropathies. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN).",P Ruggenenti; A Perna; R Benini; G Remuzzi,"Dihydropyridine-type calcium channel blockers (dihydropyridine CCB) adversely affect renal function in diabetes. The effects of dihydropyridine CCB on 24-h urinary protein excretion rate and GFR decline (deltaGFR) were prospectively evaluated in 117 nondiabetic patients with chronic, proteinuric nephropathies enrolled in the Ramipril Efficacy in Nephropathy study and randomized to angiotensin-converting enzyme inhibition (ACEI) or placebo plus conventional antihypertensive therapy. Sixty-three percent of patients were treated with dihydropyridine CCB. During follow-up, CCB-treated compared with no CCB patients had higher proteinuria (mean+/-SEM: 4.8+/-0.2 g/24 h versus 4.2+/-0.2 g/24 h, respectively, P = 0.015) and mean arterial BP (MAP). The difference in proteinuria was significant in the placebo group (5.1+/-0.2 g/24 h versus 4.3+/-0.3 g/24 h, P = 0.02), but not in the ACEI group (4.4+/-0.2 g/24 h versus 4.1+/-0.2 g/24 h). Of note, CCB-treated patients had significantly less proteinuria (P = 0.028) in the ACEI group compared with placebo. CCB-treated versus no CCB patients had a faster deltaGFR in the overall study population and in the placebo group, but not in the Ramipril group. Proteinuria was comparable in CCBtreated and no CCB patients for MAP < or = 100 mmHg, but was higher in CCB-treated patients for MAP >100 mmHg. Similarly, proteinuria was comparable in the placebo and in the ACEI group for MAP < or = 100 mmHg, but was higher in the placebo group for MAP >100 mmHg. In CCB- and placebo-treated patients, a linear correlation (P = 0.006 for both groups) was found between proteinuria and MAP values. MAP, proteinuria, and deltaGFR in patients given nifedipine versus those given other dihydropyridine CCB were comparable. Thus, in nondiabetic proteinuric nephropathies, dihydropyridine CCB may have an adverse effect on renal protein handling that depends on the severity of hypertension and is minimized by ACEI therapy or tight BP control. ACE inhibitors may electively limit proteinuria in patients on dihydropyridine CCB treatment and/or with uncontrolled hypertension.",1998.0,0,0
2483,9809930,Rationale and design of the International Verapamil SR/Trandolapril Study (INVEST): an Internet-based randomized trial in coronary artery disease patients with hypertension.,C J Pepine; E Handberg-Thurmond; R G Marks; M Conlon; R Cooper-DeHoff; P Volkers; P Zellig,"The primary objective of the International Verapamil SR/Trandolapril Study (INVEST) is to compare the risk for adverse outcomes (all-cause mortality, nonfatal myocardial infarction [MI] or nonfatal stroke) in hypertensive patients with coronary artery disease (CAD) treated with either a calcium antagonist-based or a noncalcium antagonist-based strategy. Treatment recommendations for hypertension include initial therapy with a diuretic or beta-adrenergic blocking agent, for which reductions in morbidity and mortality are documented from randomized trials but are less than expected from epidemiologic data. For this reason, recent attention has focused on calcium antagonists or angiotensin-converting enzyme inhibitors. While these agents reduce blood pressure, outcome data from large randomized trials are lacking, but some case-control data, dominated by short-acting dihydropyridines, suggest an increased risk of cardiovascular events. These studies had methodologic limitations and did not differentiate among calcium antagonist types and formulations. Several studies differentiating among calcium antagonist types and an overview of published randomized trials show no increased risk with verapamil and suggestion for benefit in CAD patients. A total of 27,000 CAD patients with hypertension will be randomized at 1,500 primary care sites to receive either a calcium antagonist-based (verapamil) or beta-blocker/diuretic-based (atenolol/hydrochlorothiazide) antihypertensive care strategy. The study uses a novel, electronic ""paper-less"" system for direct on-screen data entry, randomization and drug distribution from a mail pharmacy linked to the coordination center via the Internet. Contract negotiations with the United States and international sites are ongoing. Patients being enrolled are predominantly elderly (72% aged 60 years or older) men (54%), with either an abnormal coronary angiogram or prior MI (71%). In addition to hypertension, CAD and elderly age, most patients (89%) have one or more associated conditions (diabetes, dyslipidemia, smoking, cerebral or peripheral vascular disease, etc.) contributing to increased risk for adverse outcome. While 26% have diabetes, most of these are noninsulin dependent. Using the protocol strategies, target blood pressures (according to JNC VI) have been reached in 58% at the fourth visit, and as expected most (89%) are requiring multiple antihypertensive drugs. The design and baseline characteristics of the initial patients recruited for a prospective, randomized, international, multicenter study comparing two therapeutic strategies to control hypertension in CAD patients are described.",1998.0,0,0
2484,9810784,Effect of the angiotensin-converting enzyme inhibitor enalapril on post-transplant erythrocytosis.,S Marubayashi; H Yamamoto; S Shibata; Y Fudaba; Y Miyata; K Fukuma; K Okada; T Hinoi; M Ikeda; T Maeda; Y Oshiro; K Dohi,"Post-transplant erythrocytosis (PTE) is increasingly recognized as a complication of kidney transplantation. In this study we report the effect of the angiotesin-converting enzyme (ACE) inhibitor enalapril on hematocrit (Ht) and erythropoietin in four patients with PTE. Four renal allograft recipients with Ht greater than 51% were studied. Treatment was initiated with enalapril administered orally at a dose of 2.5 mg/day. All the patients had an increase of hemoglobin (Hb) (17.7 +/- 0.64 g/dl), Ht (54.5 +/- 1.29%) and red blood cell count (RBC) (584 +/- 19.2 x 10(4)/microliter). All patients responded to enalapril in 8 weeks with a significant decrease of Hb, Ht, and RBC. In one patient, the downward trend was more rapid and sustained, and treatment had to be discontinued to prevent the development of anemia. Serum erythropoietin showed normal in all four patients and remained unchanged during the study, even after discontinuation of enalapril treatment. Serum creatinine remained relatively stable throughout the study. These results suggest that PTE may not be dependent upon circulating erythropoietin and that enalapril treatment may be an effective treatment of PTE without renal dysfunction.",1998.0,0,0
2485,9811387,"Effect of enalapril on proteinuria, phosphaturia, and calciuria in insulin-dependent diabetes.",H Yüksel; S Darcan; C Kabasakal; A Cura; S Mir; E Mavi,"Elevated urinary calcium and phosphate excretion have been observed in children with insulin-dependent diabetes mellitus (IDDM). This may be related to a defect in tubular reabsorption. It is well known that converting enzyme inhibition decreases microalbuminuria and may prevent or retard diabetic nephropathy. We investigated whether enalapril also improves the defect in calcium and phosphate reabsorption. We studied 16 children and young adults (age 12-21 years) with IDDM and persistent microalbuminuria before and during 12 weeks of enalapril treatment. Before treatment microalbuminuria, urinary calcium excretion, and fractional tubular phosphorus reabsorption (TPR) were 153+/-53 microg/min, 5.5+/-0.9 mg/kg per day, and 71.4+/-3.6%, respectively. At the end of the 12th week, microalbuminuria had decreased to 20.3+/-7.9 microg/min and calcium excretion to 3.3+/-0.4 mg/kg per day (P<0.01), while the TPR increased to 80.1+/-3.8% (NS). The renal threshold phosphate concentration increased from 1.8+/-0.15 to 2.92+/-0.23 mg/dl (P<0.01). The fasting serum glucose and hemoglobin Alc levels did not change significantly during the study. Systolic and diastolic blood pressures were 120.4+/-2.2 / 79.3+/-1.4 mm Hg and 110.5+/-1.8 / 71.3+/-0.9 mm Hg before and after 12 weeks, respectively. We conclude that enalapril treatment improves not only microalbuminuria but also abnormal calcium and phosphate excretion in microalbuminuric children with IDDM.",1998.0,0,0
2486,9812081,"Randomized, double-blind, placebo-controlled trial of oral enalapril in patients with neurally mediated syncope.",C Zeng; Z Zhu; G Liu; W Hu; X Wang; C Yang; H Wang; D He; J Tan,"The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS. Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril. This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.",2000.0,0,0
2487,9812933,"Initiating angiotensin converting enzyme inhibitors in mild to moderate heart failure in general practice: randomised, placebo controlled trial.",M Lough; J Cleland; J Langan; A Cowley; A Wade,,1998.0,0,1
2488,9814627,Combination of enalapril and low-dose thiazide reduces normoalbuminuria in essential hypertension.,S Nielsen; J Dollerup; B Nielsen; C E Mogensen,"To examine the effect of the combination of enalapril with a very low dose of hydrochlorothiazide versus atenolol on urinary albumin excretion in normoalbuminuric patients with mild to moderate essential hypertension. A secondary objective was to compare the effects of the two regimens in patients with different levels of albuminuria. A 12 weeks, randomized, double-blind, double-dummy, multicenter, comparative study with two parallel groups. General practices in Denmark and Finland. The subjects comprised 174 patients with mild to moderate essential hypertension, normal serum creatinine and no proteinuria. Enalapril/hydrochlorothiazide (20/6 mg) daily or atenolol (50 mg) daily. Urinary albumin: creatinine ratio and blood pressure. At baseline, normoalbuminuria was found in 74 and 85 patients in the enalapril/hydrochlorothiazide and atenolol groups, respectively. Blood pressure was reduced similarly by both treatments. The ratio of urinary albumin to creatinine in normoalbuminuric patients was significantly reduced during treatment with enalapril/hydrochlorothiazide at 20/6 mg (from geometic mean x/divided by antilog SD of 0.53 x/divided by 1.77 to 0.47 x/divided by 1.58 mg/mmol, P=0.02) but was unchanged during atenolol treatment (0.55 x/divided by 1.74 and 0.58 x/divided by 1.87 mg/mmol). The difference between the two treatments was statistically significant (P=0.03) and was predominantly achieved through a reduction of albuminuria in the upper-normal range during enalapril/hydrochlorothiazide treatment. Therapy with enalapril/hydrochlorothiazide at 20/6 mg and atenolol at 50 mg once daily reduced blood pressure similarly in patients with essential hypertension. Suppression of urinary albumin excretion within the normoalbuminuric range was observed during treatment with enalapril/hydrochlorothiazide at 20/6 mg.",1998.0,0,0
2489,9817475,"Usefulness of losartan, captopril, and furosemide in preventing nitrate tolerance and improving control of unstable angina pectoris.",G Cotter; E Metzkor-Cotter; E Kaluski; A Blatt; I Litinsky; Y Baumohl; Y Moshkovitz; Z Vered; R Zaidenstein; A Golik,"Sixty consecutive normotensive patients with unstable angina pectoris, who were on continuous intravenous isosorbide dinitrate (ISDN) treatment and had not previously received angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, or diuretics were randomly assigned to treatment groups receiving intravenous ISDN for 72 hours. No additional treatment was given to group A (n = 15). Captopril, in a test dose of 6.25 mg, and followed by 12.5 mg 3 times daily for 24 hours and 25 mg 3 times daily for the next 24 hours, was given to group B (n = 15). The same dose of captopril plus 40 mg of furosemide in the morning were given to group C (n = 15). Losartan, in a single dose of 25 mg/day and increased to 50 mg after 24 hours was given to group D (n = 15). Nitrate tolerance was evaluated at 24-hour intervals at trough levels of each of the drugs by administering intravenous ISDN (1 mg bolus dose every 4 minutes) and recording the total ISDN test dose required to decrease the mean arterial blood pressure by > or =10%. Treatment with continuous ISDN only (group A) induced nitrate tolerance. The ISDN (mean +/- SD) test dose was 3.5 +/- 1.8 mg at baseline, increasing to 4.9 +/- 2.4 mg at 24 hours, and 8.0 +/- 3.0 mg at 48 hours. The addition of increasing doses of captopril to the continuous ISDN treatment (group B) completely prevented nitrate tolerance. Losartan, however, did not attenuate nitrate tolerance at 24 hours and attenuated it only partially at 48 hours. The addition of furosemide to captopril had no further effect on nitrate tolerance. Of 15 patients in group A (ISDN only), 4 (27%) experienced recurrent ischemic events requiring urgent coronary catheterization. No such events were recorded in group B (captopril), but did occur in 1 patient in each of group C (captopril plus furosemide) and D (losartan) (p = 0.083). Thus, the addition of captopril to the ISDN treatment regimen prevented tolerance to nitrates and improved angina control with apparent safety. Losartan also decreased nitrate tolerance, although to a lesser extent, and also improved angina control. The addition of furosemide to captopril conferred no further benefit.",1998.0,0,0
2490,9819786,Comparison between moexipril and atenolol in obese postmenopausal women with hypertension.,M Stimpel; B Koch; M A Weber,"The present study investigated the effect of the new ACE-inhibitor moexipril versus the beta 1-adrenergic blocker atenolol on metabolic parameters, adverse events (AEs) and sitting systolic (SSBP) and sitting diastolic blood pressure (SDBP) in obese postmenopausal women with hypertension (stage I and II). After a 4-week placebo run-in phase, 116 obese, postmenopausal women with primary hypertension were randomised into two treatment groups receiving once daily dosages of either moexipril 7.5 mg or atenolol 25 mg initially (mean age: 57 +/- 7 years in both groups; mean weight: 94 kg in the moexipril group and 89 kg in the atenolol group, corresponding to a body mass index (BMI) of 35.2 kg/m2 and 34.1 kg/m2 in both groups, respectively). After 4 and 8 weeks, the dosages were uptitrated to moexipril 15 mg, or if necessary to moexipril 15 mg/hydrochlorothiazide (HCTZ) 25 mg, or to atenolol 50 mg and atenolol 50 mg/HCTZ 25 mg, in patients whose blood pressure was not sufficiently controlled. At endpoint, metabolic parameters (total cholesterol, triglycerides, LDL, HDL, glucose, insulin) were not significantly altered in either treatment group. Most frequent adverse events under monotherapy (moexipril/atenolol) were asthenia (5.3/13.0%), headache (13.2/21.7%), cough (7.9/6.5%), pharyngitis (21.1/8.7%) and peripheral oedema (5.3/13.0%). Overall at least one AE was reported in 66% of the patients treated with moexipril and in 78% of those treated with atenolol. Reduction of SSBP/SDBP at endpoint was 14.7 +/- 1.9/10.0 +/- 1.1 and 8.7 +/- 1.9/8.4 +/- 1.1 mmHg after treatment with moexipril and atenolol, respectively. The results showed that moexipril and atenolol are equally effective in reducing blood pressure without adversely affecting blood lipids and carbohydrate metabolism.",1998.0,0,0
2491,9820991,Results of transmyocardial laser revascularization in non-revascularizable coronary artery disease after 3 years follow-up [ssee comments].,H Nägele; H M Stubbe; C Nienaber; W Rödiger,"Transmyocardial laser revascularization is a new therapeutic option for end-stage coronary artery disease if no other cardiological or cardiosurgical intervention is possible. Data are few on how patients fare after more than 1 year follow-up. From a total of 157 patients who were suggested for transmyocardial laser therapy in the years 1995-1997, 126 were judged to have non-revascularizable coronary artery disease (mean age 61.9 +/- 14 years, 80% men, mean left ventricular ejection fraction 46.2 +/- 17.1%). Sixty-six patients had a good clinical response to intensification of the antianginal therapy and were therefore treated further medically. In 60 patients with refractory angina, sole transmyocardial laser revascularization without cardiopulmonary bypass or additional grafts was performed. The transmyocardial laser revascularization group was 32% female; 78.3% patients had had bypass operations; the mean left ventricular ejection fraction was 53.6 +/- 15%. Eighty five percent of the transmyocardial laser revascularization patients had demonstrable ischaemic regions, as visualized by dipyridamol-MIBI scintigraphy. The percentage of patients with some hibernating myocardium in positron emission tomography studies was 70%. Good early relief of angina symptoms was experienced by patients who had undergone laser treatment. After 3 months the Canadian Cardiovascular Society class fell from 3.31 +/- 0.51 to 1.84 +/- 0.77 in 49 patients (P < 0.0001), but increased in the total group to 2.02 +/- 0.92 after 6 months (n = 47), to 2.26 +/- 0.99 after 1 year (n = 42), to 2.47 +/- 1.11 after 2 years (n = 38) and to 2.58 +/- 0.9 after 3 years (n = 19). MIBI/positron emission tomography data at rest and after 6 months was worse in patients in whom pre- and postoperative studies were complete (n = 22). The peri-operative mortality was 12% (n = 7: peri-operative myocardial infarction, low output syndrome, arrhythmia). Mortality after 1 and 3 years was 23% and 30%, respectively. The risk of transmyocardial laser revascularization was significantly elevated in patients with left ventricular ejection fraction < 40%. Late deaths (n = 9) were due to sudden arrhythmias or pump failure. There was a high rate of cardiac events and reinterventions in the transmyocardial laser revascularization group, including percutaneous transluminal coronary angioplasty in newly developed lesions (n = 7), valve replacement (n = 2), need for intermittent urokinase therapy (n = 5) and heart transplantation (n = 2). Fifty percent of patients with non-revascularizable coronary artery disease submitted for transmyocardial laser revascularization can be stabilized medically. Transmyocardial laser revascularization led to a rapid early relief of symptoms, but with a trend towards worsening over time and showed a high peri-operative risk (> 10%) dependent on the pre-operative ejection fraction. Our data were in contrast to other published reports on the more beneficial effects of transmyocardial laser revascularization and should lead to further investigation of this experimental method. Transmyocardial laser revascularization should only be performed after failure of maximal anti-anginal therapy, and should be avoided when the left ventricular ejection fraction is < 40%.",1998.0,0,0
2492,9820992,Differences in the treatment of coronary heart disease between countries as revealed in the Scandinavian Simvastatin Survival Study (4S),O Faergeman; J Kjekshus; T Cook; K Pyörälä; L Wilhelmsen; G Thorgeirsson; T R Pedersen,"To assess differences in treatment of ischaemic heart disease in the Scandinavian countries. The Scandinavian Simvastatin Survival Study (4S) lasted 5.4 years and showed that death rates in 4444 patients with coronary heart disease were 30% lower in those treated with simvastatin to lower serum cholesterol than in those given placebo. Apart from this main result, the 4S provided detailed information on rates of death and other manifestations of coronary heart disease, as well as on use of non-lipid forms of therapy. There were substantial differences in 4S placebo group rates of mortality, coronary deaths and major coronary events between countries. Surgical and medical therapy varied importantly between countries. Major inter-country differences in rates of death and myocardial infarction in patients with coronary heart disease were likely to be due to a composite of differences in baseline characteristics including smoking. They occurred in a setting of very uneven exploitation of the potential for improving survival of patients with ischaemic heart disease.",1998.0,0,0
2493,9820995,Two-year time course and significance of neurohumoral activation in the Survival and Ventricular Enlargement (SAVE) Study.,P Vantrimpont; J L Rouleau; A Ciampi; F Harel; J de Champlain; D Bichet; L A Moyé; M Pfeffer,"To describe the temporal evolution of neurohumoral activation in survivors of myocardial infarction with left ventricular dysfunction who are initially asymptomatic and to relate this to prognosis. Patients in the neurohumoral substudy (n = 534) of the Survival and Ventricular Enlargement (SAVE) study had their neurohormones measured at baseline, 3, 12 and 24 months post-infarction, were followed 38 +/- 7 months and had these values related to prognosis. All patients had a left ventricular ejection fraction < or = 40% early post-infarction. Atrial natriuretic peptide, aldosterone, norepinephrine and plasma renin activity decreased progressively over time. Patients with events had a persistent increase in these neurohormones with those dying within the first 24 months of follow-up having the greatest increase. Treatment with captopril affected only plasma renin activity (increase) and aldosterone (decrease). For patients who remained asymptomatic for the first 3 months post-infarction (n = 471), by multivariate analyses (all neurohormones together with non-neurohumoral risk factors), 3-month plasma atrial natriuretic peptide and aldosterone were the most closely related to the development of severe heart failure or to the combined end-points (cardiovascular death, myocardial infarction, or severe heart failure). No neurohormone was related to recurrent myocardial infarction or to cardiovascular mortality. When the last neurohormone measured prior to an event was considered along with non-neurohumoral risk factors (adjusted univariate), atrial natriuretic peptide, aldosterone, norepinephrine and epinephrine were associated with prognosis indicating that a time-dependent analysis identified a closer relationship between neurohormones and events than that identified by 3-month values. However, by multivariate analyses atrial natriuretic peptide was the only neurohormone associated with an event, being associated with the development of severe heart failure (P < 0.001) and the combined end-points (P = 0.022). However, when neurohormones were considered as binary variables, activated or non-activated (defined as > 1.96 SD above the mean of age-matched controls), an association between activation of norepinephrine prior to recurrent myocardial infarction (P < 0.001) and combined end-points (P < 0.01) and between activation of aldosterone and severe heart failure (P < 0.05) was identified. Neurohumoral activation decreases progressively post-infarction, but only in patients with a good prognosis. In patients with a left ventricular ejection fraction < or = 40% and asymptomatic post-infarction plasma atrial natriuretic peptide at 3 months, aldosterone levels appeared to be the neurohormones most closely associated with prognosis. Increased levels of atrial natriuretic peptide, aldosterone and norepinephrine appear to be temporally most closely associated with events.",1998.0,0,0
2494,9821850,Benazepril causes in hypertension a greater reduction in left ventricular mass than does nitrendipine: a randomized study using magnetic resonance imaging.,C Gaudio; G Tanzilli; F M Ferri; S Villatico Campbell; F Bertocchi; M Motolese; P P Campa,"To assess the comparative effects of benazepril and nitrendipine monotherapies on left ventricular mass index (LVMI) in hypertensive patients with echocardiographically determined left ventricular hypertrophy, patients with diastolic blood pressure (BP) > or = 100 mm Hg were randomized to benazepril, 10 mg, or nitrendipine, 20 mg, both given once or twice daily. After 4 weeks, only the responders (diastolic BP <90 mm Hg) entered a 5-month maintenance period. At baseline, and after 3 and 6 months, LVMI was blindly estimated by means of magnetic resonance imaging (MRI) and, for comparison, by means of echocardiography. Of the 50 randomized patients, three were excluded from the study as nonresponders after 4 weeks; moreover, two patients taking benazepril and one taking nitrendipine discontinued the treatment after 2 months for adverse effects. Both monotherapies reduced systolic and diastolic BP to a similar extent. After 3 months, MRI-estimated LVMI decreased by 21.5 g/m2 in the benazepril and 8.8 g/m2 in the nitrendipine group, with an adjusted mean difference between the two groups of 11.1 g/m2 (95% CI, 7.3-14.8 g/m2; p = 0.0001). After 6 months, it decreased by 23.6 g/m2 and 10.0 g/m2, respectively, with an adjusted mean difference of 11.3 g/m2 (95% CI, 7.5-15.5; p = 0.0001) in favor of benazepril. In conclusion, despite a similar antihypertensive effect, benazepril led to a greater reduction in MRI-measured LVMI than did nitrendipine (-16.2% vs. -7.2%) in hypertensive patients with left ventricular hypertrophy.",1998.0,0,0
2495,9824003,Captopril reduces the VE/VCO2 ratio in myocardial infarction patients with low ejection fraction.,T R McConnell; F J Menapace; L H Hartley; M A Pfeffer,"To determine whether captopril (CAP) therapy had an effect on the minute ventilation/carbon dioxide output (VE/VCO2) ratio at submaximal levels of exercise in asymptomatic patients with reduced left ventricular function after myocardial infarction. Double blinded, randomized, prospective, repeated measures. One hundred thirty-five patients with left ventricular ejection fractions of < 40% were randomly assigned to a treatment group (CAP; n = 62) or a placebo group (PLC; n = 73). Subjects had cycle ergometer exercise tests at 2 to 6 months (T1), 10 to 14 months (T2), and > 22 months (T3) postmyocardial infarction. Oxygen uptake (VO2), VCO2, and VE were measured throughout each exercise test. Dependent variables were peak VO2 (VO2peak), the ventilatory anaerobic threshold (VAT), and the VE/VCO2 ratio measured at 30 W and at 75% VO2peak. VO2peak and VAT did not differ as a result of treatment (CAP vs PLC; p = 0.92 and 0.80) or over time (T1 vs T2 vs T3; p = 0.51 and 0.07). VE/VCO2 was significantly lower for CAP at 30 W (p = 0.05) and, although lower at 75% VO2peak, did not obtain statistical significance (p = 0.22). The between group differences were larger at T2 and T3 when compared with T1. CAP resulted in a reduced VE/VCO2 ratio during submaximal exercise. The reduced ventilation may permit patients to perform their normal activities of daily living at a lower perception of difficulty, reduce symptoms, and provide an improved quality of life.",2001.0,0,0
2496,9824192,Simultaneous mucosal and small bowel angioedema due to captopril.,S H Smoger; M A Sayed,"Although angiotensin-converting enzyme inhibitors (ACEIs) are well-known causes of orofacial angioedema, angioedema from these agents involving the bowel is not often considered. We report a case of simultaneous onset of small bowel and orofacial angioedema due to captopril. A 61-year-old black man with hypertension, coronary artery disease, and congestive heart failure had been treated with captopril for 5 years. He had sudden swelling of the lips, face, and tongue, followed by nausea, emesis, abdominal pain, and diarrhea. Other medications included aspirin, indomethacin, allopurinol, colchicine, and nifedipine. Examination showed swelling of the tongue, buccal mucosa, and neck; he also had midabdominal tenderness but no respiratory distress. Laboratory data were normal. A C1-esterase inhibitor level was normal. An ileus pattern was present on abdominal x-ray film. Angioedema was diagnosed, and all signs and symptoms resolved in 24 hours after captopril was discontinued. Clinicians need to be vigilant for bowel involvement from ACEI angioedema.",1998.0,0,0
2497,9825192,Treatment with ramipril improves systolic function even in patients with mild systolic dysfunction and symptoms of heart failure after acute myocardial infarction.,O Kongstad-Rasmussen; P Blomstrand; M Broqvist; U Dahlström; B Wranne,"Clinical signs of heart failure such as pulmonary rales and dyspnea, ventricular dysfunction, and ventricular arrhythmia are independent predictors of a poor prognosis after acute myocardial infarction (AMI). The study aimed to assess the effect of ramipril treatment on mildly depressed left ventricular (LV) systolic function, assessed by atrioventricular (AV) plane displacement in patients with congestive heart failure after AMI. The study was a substudy in the Acute Infarction Ramipril Efficacy Study, a double-blind, randomized, place-bo-controlled trial of ramipril versus placebo in patients with symptoms of heart failure after AMI. In all, 56 patients were included in the main study, 4 refused to participate in the substudy, and 4 were excluded for logistical reasons. Echocardiography was performed at entry and after 6 months. Patients who underwent coronary artery bypass grafting during the follow-up period were excluded. At baseline, the patients had modest LV dysfunction, and mean AV plane displacement of 9.7 mm. During follow-up, AV plane displacement increased in ramipril-treated patients from 9.5 to 10.9 mm (p < 0.01). No statistically significant changes were seen in the placebo group. Ramipril improves LV systolic function in patients with clinical signs of heart failure and only modest systolic dysfunction after AMI. Measurement of AV plane displacement is a simple and reproducible method for detection of small changes in systolic function and may be used instead of ejection fraction in patients with poor image quality.",1998.0,0,0
2498,9826312,Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure.,G Sütsch; W Kiowski; X W Yan; P Hunziker; S Christen; W Strobel; J H Kim; P Rickenbacher; O Bertel,"The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. Thirty-six men (mean age+/-SD, 55+/-8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4+/-4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], -13.9% [-16.0% to -11.7%]), pulmonary artery mean (-12.9% [-17. 4% to -8.3%]) and capillary wedge (-14.5% [-20.5% to -8.5%]) pressures, and right atrial pressure (-20.2% [-29.4% to -11.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (-24.2% [-28.1% to -20.3%]) and pulmonary (-19.9% [-28.4% to -11.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15. 2% [10.8% to 19.6%]) and systemic (-9.3% [-12.3% to -6.4%]) and pulmonary (-9.7% [-16.3% to -3.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged. Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.",1998.0,0,0
2499,9829158,Candesartan cilexetil. A review of its use in essential hypertension.,K J McClellan; K L Goa,"Candesartan cilexetil is completely converted to the nonpeptide angiotensin II receptor blocker candesartan during absorption from the gastrointestinal tract. Candesartan selectively blocks and dissociates slowly from the angiotensin II subtype 1 (AT1) receptor which mediates most of the known activities of angiotensin II. When administered once daily, oral candesartan cilexetil 8 to 32 mg dose-dependently and effectively reduces blood pressure in patients with mild to moderate essential hypertension. In comparative studies, candesartan cilexetil 8 mg/day was as effective as usual therapeutic dosages of enalapril, losartan potassium, hydrochlorothiazide and amlodipine. One study showed candesartan cilexetil 16 mg/day to be more effective than losartan potassium 50 mg/day. Furthermore, the combination of candesartan cilexetil with either hydrochlorothiazide or amlodipine resulted in additive antihypertensive effects. Preliminary evidence suggests that the blood pressure-lowering effects of candesartan cilexetil are associated with the prevention or improvement of end-organ damage in patients with hypertension. However, this requires further confirmation in clinical studies. Candesartan cilexetil improves insulin sensitivity in patients with hypertension and does not affect glucose homeostasis or the serum lipid profile in those with coexisting type 2 (non-insulin-dependent) diabetes mellitus. Candesartan cilexetil is well tolerated in patients with hypertension. Pooled data indicate that the tolerability profile of the drug is not significantly different from that of placebo, with headache being the most commonly reported event. Adverse events are not dose related and are mostly mild to moderate in severity. Candesartan cilexetil is better tolerated than enalapril, primarily because of a reduced incidence of cough, and was not associated with the hypokalaemia or hyperuricaemia seen with hydrochlorothiazide in a study in patients aged > or = 75 years. The drug has an adverse events profile similar to that of losartan potassium in patients with mild to moderate hypertension. once daily candesartan cilexetil is effective and well tolerated when used once daily (as monotherapy or in combination with other antihypertensive agents) in patients with mild, moderate or severe hypertension. Initially, however, the drug is likely to be used as an alternative to other agents in patients not responding to or intolerant of their current drug therapy.",1998.0,0,0
2500,9829159,Trandolapril. An update of its pharmacology and therapeutic use in cardiovascular disorders.,D C Peters; S Noble; G L Plosker,"Trandolapril is an orally administered angiotensin converting enzyme (ACE) inhibitor that has been used in the treatment of patients with hypertension and congestive heart failure (CHF), and after myocardial infarction (MI). Trandolapril is a nonsulfhydryl prodrug that is hydrolysed to the active diacid trandolaprilat. Trandolapril 2 mg once daily provides effective control of blood pressure (BP) over 24 hours in patients with mild to moderate hypertension, with a trough/peak ratio of BP reduction (as determined by 24-hour ambulatory monitoring) consistently > or = 50%. Trandolapril has similar antihypertensive efficacy to enalapril as indicated by several clinical trials. Combined therapy with trandolapril and sustained-release verapamil has a significantly greater antihypertensive effect than either agent alone. Only limited data are available on the use of trandolapril in patients with CHF, although ACE inhibitors as a class are recommended as first line therapy in such patients. In the Trandolapril Cardiac Evaluation (TRACE) study, trandolapril 1 to 4 mg once daily resulted in an early and long term reduction in all-cause mortality, including cardiovascular mortality, in patients with left ventricular (LV) dysfunction after an MI. Trandolapril therapy was commenced a mean 4.5 days after acute MI and continued for 24 to 50 months. At study end, the relative risk of death from any cause with trandolapril versus placebo was 0.78 (p = 0.001). The tolerability profile of trandolapril is similar to that of other ACE inhibitors. Most adverse events are mild and transient in nature, and include cough, asthenia, dizziness, headache and nausea. Trandolapril has no adverse effect on lipid or carbohydrate metabolism. trandolapril has a favourable pharmacological profile and an antihypertensive efficacy at least comparable to that of other ACE inhibitors. The pharmacological characteristics of trandolapril allow it to provide good 24-hour control of BP with once-daily administration. Trandolapril has also demonstrated some efficacy in a small number of patients with CHF. In addition, trandolapril provides long term protection against all-cause mortality in patients with LV dysfunction after MI. The results of the Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) study will determine its potential as a cardioprotective agent in patients with coronary artery disease and preserved LV function. Thus, trandolapril represents an effective, well-tolerated and convenient treatment option for patients with mild to moderate hypertension or LV systolic dysfunction after MI.",1998.0,0,0
2501,9829449,Use of losartan in the treatment of hypertensive patients with a history of cough induced by angiotensin-converting enzyme inhibitors.,R Z Paster; D B Snavely; A R Sweet; R A Draper; A I Goldberg; B A Soffer; C S Sweet,"The objective of this study was to determine the incidence of dry cough in hypertensive patients with a history of angiotensin-converting enzyme (ACE) inhibitor-induced cough after treatment with losartan (an angiotensin II-receptor antagonist), lisinopril (an ACE inhibitor), or placebo. One hundred patients from 16 outpatient treatment centers in the United States were included in this double-masked, randomized, parallel-group, active- and placebo-controlled study, with stratification according to sex. After a challenge phase with lisinopril and a placebo washout phase, patients were randomly allocated to receive losartan 50 mg once daily, lisinopril 20 mg once daily, or placebo for a maximum of 8 weeks. The primary efficacy end point of the study was the presence or absence of dry cough during the double-masked period, as rated by the patient at each visit using a validated symptom assessment questionnaire. A secondary end point was the frequency of dry cough, as measured at each visit using a visual analogue scale (VAS). The incidence of dry cough was significantly higher in the lisinopril group than in the losartan and placebo groups (87.5% vs 36.7% and 31.4%, respectively) at the end of the double-masked treatment period; there was no statistically significant difference between the losartan and placebo groups. Mean VAS scores showed that patients treated with lisinopril rated themselves as having a significantly higher frequency of cough than did patients treated with losartan or placebo (4.0 vs 1.2 and 1.5, respectively). Again, the difference between the losartan and placebo groups was not statistically significant. All treatments were otherwise well tolerated, and no serious clinical or laboratory adverse events were reported during the double-masked phase of the study. These results demonstrate that the incidence, severity, and frequency of dry cough in patients with a history of ACE inhibitor-induced dry cough are significantly lower in those treated with losartan than in those treated with lisinopril and are similar to the incidence, severity, and frequency of dry cough in those receiving placebo.",1998.0,0,0
2502,9830787,Results of the ATLAS study. High or low doses of ACE inhibitors for heart failure?,R E Hobbs,"In a large, randomized study, patients with heart failure who received a large daily dose of an angiotensin-converting inhibitor had a trend toward a lower mortality rate than did patients who received a low daily dose. Moreover, the hospitalization rate was lower in the high-dose group, and the side-effect profile was the same in both groups. Physicians should try to give maximal doses to achieve optimum benefit in this patient population.",1998.0,0,0
2503,9831696,,,,,0,0
2504,9832115,Effects of high-dose lisinopril-isosorbide dinitrate on severe mitral regurgitation and heart failure remodeling.,A B Levine; C Muller; T B Levine,"In long-term, 1-year follow-up, uptitration of angiotensin-converting enzyme inhibitor and nitrate therapy over established doses can further improve severe functional mitral regurgitation in patients with dilated cardiomyopathy due to a reversal of heart failure-related left ventricular remodeling. With marked left ventricular enlargement, >6.8 cm end-diastolic diameter, heart failure remodeling may be irreversible and resistant to further medical intervention.",1998.0,0,0
2505,9833600,Comparative effects of lisinopril and losartan on insulin sensitivity in the treatment of non diabetic hypertensive patients.,R Fogari; A Zoppi; L Corradi; P Lazzari; A Mugellini; P Lusardi,"The aim of this study was to compare the effects of the ACE-inhibitor lisinopril and the angiotensin II receptor antagonist losartan on insulin sensitivity in the treatment of non diabetic hypertensives. Twenty-five non diabetic subjects with mild to moderate hypertension, 11 females and 14 males, aged 44-63 years, after a 4-week wash-out period on placebo, were randomized to receive lisinopril 20 mg once daily or losartan 50 mg once daily for 6 weeks. Following another 4-week wash-out period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the active treatment periods, blood pressure (BP) was measured (by standard mercury sphygmomanometer, Korotkoff I and V) and insulin sensitivity was assessed by the euglycaemic hyperinsulinaemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both lisinopril and losartan significantly reduced SBP (by a mean of 20.2 and 17.2 mmHg, respectively) and DBP (by a mean of 15.2 and 12.3 mmHg, respectively), with no difference between the two treatments. GIR, used as an indicator of insulin sensitivity, was significantly increased by lisinopril (+1.5 mg min(-1) kg(-1), P<0.05 vs baseline) but not by losartan (+0.42 mg min(-1) kig(-1), NS), the difference between the two drugs being statistically significant (P<0.05). TGR was increased by lisinopril (+7.3 g, P<0.05 vs baseline), whereas losartan did not significantly modify it (+1.9 g, NS). In conclusion, with all cautions due to an absence in this study of a randomized placebo phase, our findings suggest that lisinopril improved insulin sensitivity whereas losartan did not affect it.",1998.0,0,0
2506,9839057,Do calcium channel blockers increase the risk of myocardial infarction in hypertensive patients with diabetes mellitus?,L Park; C P Por; M F Evans,,1998.0,0,0
2507,9839101,Isradipine in prediabetic hypertensive subjects.,R P Byington; C D Furberg; T E Craven; M Pahor; J R Sowers,"Investigators from the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) previously reported that the isradipine group had a higher incidence of cardiovascular disease (CVD) events than the diuretic group. The ultimate objective of the analyses presented here was to assess how indices of glycemia (specifically, serum glucose, serum insulin, and HbA1c) might have influenced the effects of the two agents on blood pressure control and CVD events. Inclusion criteria included men and women > or = 40 years of age with ultrasonographically confirmed carotid atherosclerosis and a diastolic blood pressure of > 90 mmHg. Although insulin-dependent diabetic patients were excluded, the three glycemia indices had wide enough ranges to include patients who may be classified as prediabetic. A total of 883 patients were randomized either to the dihydropyridine calcium antagonist (CA) isradipine (2.5-5 mg twice a day) or to the diuretic hydrochlorothiazide (12.5-25 mg twice a day) and followed in double-blind fashion for 3 years. Both treatment groups had achieved comparable control of diastolic blood pressure, and there were no statistically significant differences in any of the glycemia indices, either at baseline or during follow-up. However, the excess isradipine events were noted to be clustered among those patients with elevated baseline levels of HbA1c who also experienced greater blood pressure reductions during follow-up. The increased cardiovascular risk associated with dihydropyridine CAs in prediabetic patients may be an explanation for the overall CA debate.",1998.0,0,0
2508,9842405,Long-term effect of converting enzyme inhibition on circadian sympathetic and parasympathetic modulation in patients with diabetic autonomic neuropathy.,V G Athyros; T P Didangelos; D T Karamitsos; A A Papageorgiou; H Boudoulas; A G Kontopoulos,"Autonomic nervous system function in patients with diabetes mellitus (DM), especially those with diabetic autonomic neuropathy (DAN), displays an abnormal circadian pattern compared to normal subjects; this probably plays an important role in the onset of acute cardiovascular syndromes, which display a similar pattern of occurrence with a blunted late morning peak, and an increase of episodes during the night, in comparison to non-diabetic subjects. This study was undertaken to investigate the effect of an angiotensin-converting enzyme inhibitor, quinapril, on the circadian pattern of heart rate variability (HRV), a reliable index of sympathovagal interactions, in patients with definite DAN. Normalised HRV frequency domain indices [high frequency power (HFP), reflecting vagal tone, low frequency power (LFP), reflecting both vagal and sympathetic (predominantly) modulation, and their ratio (LFP/HFP), indicative of sympathovagal balance] were assessed in 60 patients with DAN at baseline and one year after therapy with quinapril (n = 30), or placebo (n = 30) on a 24-hour 2-channel electrocardiogram with a solid state Holter monitor. Normal subjects (n = 30) and patients with DM without DAN (n = 30), were used as controls. The baseline circadian variation of fractional normalised power in DAN patients was abolished, with pronounced dominance of LFP over HFP during the whole 24-hour period. After one year of treatment, quinapril increased HFP, decreased LFP and improved their ratio, in the morning (07.00 a.m. to 15.00 p.m.) and night (23.00 p.m. to 07.00 a.m.) time intervals, with maximal effect in the night time interval (HFP = 20%, LFP = -8%, LFP/HFP = -31%; for all comparisons p < 0.05 vs baseline values and p < 0.001 vs one year of placebo). Quinapril increased HFP and decreased LFP as well as their ratio, all indicative of sympathetic predominance reduction, in patients with DAN at time intervals these indices were most adversely affected (morning and night). Since autonomic function is an important contributor in the pathogenesis of acute coronary events, malignant arrhythmias and sudden cardiac death, improvement of indices related to autonomic function in DAN patients in these time intervals may prove beneficial in clinical practice.",1998.0,0,0
2509,9848785,The antiproteinuric effect of angiotensin antagonism in human IgA nephropathy is potentiated by indomethacin.,N Perico; A Remuzzi; F Sangalli; N Azzollini; M Mister; P Ruggenenti; G Remuzzi,"Evidence is available from animal and human studies that protein traffic through the glomerular capillary has a pathogenetic role in subsequent renal damage and that angiotensin-converting enzyme (ACE) inhibitors appear superior to other drugs in lowering proteinuria and the rate of renal function decline. This study compares the effect of ACE inhibition or angiotensin II (AngII) receptor blockade on urinary protein excretion and renal hemodynamics in 20 patients with IgA glomerulonephritis randomized to receive enalapril (20 mg/d) or irbesartan (100 mg/d) for 28 d in a double-blind study with two parallel groups. This study also evaluated whether addition of indomethacin (75 mg twice a day) to each of the two treatments resulted in a more potent antiproteinuric effect. Enalapril alone reduced total protein excretion (61% change from baseline) and fractional clearance of albumin without changes in GFR and minor elevation in renal plasma flow. Also, patients randomized to receive the AngII receptor antagonist irbesartan for 28 d had lower proteinuria (55% change from baseline) and fractional clearance of albumin at the end of the treatment period with similar renal hemodynamic changes. When indomethacin was added to enalapril treatment, a further significant reduction in urinary proteins and fractional albumin clearance was observed. In patients given irbesartan, the addition of indomethacin further reduced proteinuria and fractional clearance of albumin. The combined therapy with enalapril or irbesartan and indomethacin did not significantly affect GFR and renal plasma flow compared with baseline. These findings indicate that in patients with IgA glomerulonephritis the antiproteinuric effect of blocking AngII activity by either ACE inhibitors or AngII receptor antagonists is potentiated by indomethacin, an effect that occurred without impairment of renal function.",1998.0,0,0
2510,9853182,The impact of beta-receptor blocker addition to high-dose angiotensin-converting enzyme inhibitor-nitrate therapy in heart failure.,T B Levine; A B Levine; S J Keteyian; B Narins,"The natural history of heart failure is one of continued worsening of cardiac function. Beta-receptor blocker therapy has been effective in improving clinical status and left ventricular function in patients with heart failure. Similarly, high doses of angiotensin-converting enzyme (ACE) inhibitors with nitrates partially reverse the ventricular remodeling of heart failure. We tested the hypothesis that beta-blocker therapy added to high-dose ACE inhibitor-nitrates would potentiate the reversal of heart failure. Thirteen patients, aged 52 +/- 8 years, with moderate to severe heart failure, 12 of whom were referred for transplant consideration, with heart failure duration of 4.8 +/- 2.2 years, were prospectively followed for 12 months. Baseline echocardiographic ejection fraction was 19 +/- 8%, and presenting New York Heart Association class was 2.9 +/- 0.7. Angiotensin-converting enzyme inhibitors and nitrates were uptitrated over 6 months to a final dose of lisinopril 53 +/- 31 mg/day, and isosorbide dinitrate 217 +/- 213 mg/day. At 6 months, beta-blocker therapy with atenolol was initiated and titrated to a final dose of 46 +/- 23 mg/day. Two-dimensional Doppler echocardiography and metabolic stress testing were performed at baseline, at 6 months on lisinopril-nitrates only, and at 12 months on combined ACE inhibitor-nitrate and beta-blocker therapy. New York Heart Association classification improved from 2.9 +/- 0.7 to 1.8 +/- 0.8 on lisinopril-nitrates (p < 0.05), and to 1.5 +/- 0.5 with the addition of beta blockade (p = NS). On follow-up, peak oxygen consumption rose from 17 +/- 7 ml O2/kg/min at baseline to 21 +/- 5 ml O2/kg/min at 6 months on lisinopril-nitrates (p = 0.06) without further change on beta blockade. Ejection fraction rose from 19 +/- 8 to 33 +/- 14% on lisinopril-nitrates at 6 months (p = 0.005) and to 36 +/- 18% on beta blockade at 12 months (p = NS). High-dose ACE inhibitor-nitrate therapy significantly improved patient clinical status and left ventricular systolic function in heart failure. The addition of beta-receptor blockade over and above high-dose ACE inhibitor-nitrates was well tolerated but had no further impact on symptomatic status, exercise tolerance, or left ventricular systolic function. The potential for pharmacologic reversal of heart failure remodeling may be finite despite the use of complementary therapies. Larger placebo-controlled and randomized trials of beta-receptor blockade added to high-dose ACE inhibitor-nitrate therapy are needed to confirm these observations.",1998.0,0,0
2511,9854116,A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators.,J N Cohn; S O Goldstein; B H Greenberg; B H Lorell; R C Bourge; B E Jaski; S O Gottlieb; F McGrew; D L DeMets; B G White,"Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.",2001.0,0,0
2512,9856366,Captopril does not improve insulin action in essential hypertension: a double-blind placebo-controlled study.,M I Wiggam; S J Hunter; A B Atkinson; C N Ennis; J S Henry; J N Browne; B Sheridan; P M Bell,"To compare the effect of captopril with that of placebo on peripheral and hepatic insulin action in essential hypertension, in light of evidence that insulin resistance is associated with cardiovascular risk. Randomized, double-blind, placebo-controlled, crossover trial, with 8 week treatment periods of captopril and placebo preceded and separated by 6 weeks of placebo. Belfast teaching hospital. Eighteen Caucasian nondiabetic patients (10 males), aged under 65 years, with essential hypertension, recruited from general practices in the greater Belfast area. Captopril at 50 mg twice a day or placebo twice a day for two 8 week treatment periods. Peripheral and hepatic insulin sensitivity assessed by glucose clamps. Fourteen patients completed the study. Mean (+/- SEM) levels of fasting glucose, fasting insulin and postabsorptive hepatic glucose production were similar after captopril and placebo (5.4+/-0.1 versus 5.4+/-0.1 mmol/l, 10.6+/-2.2 versus 9.5+/-1.1 mU/l, 11.2+/-0.6 versus 11.0+/-0.5 mmol/kg per min, respectively). During hyperinsulinaemia, hepatic glucose production was suppressed to comparable levels after both treatments (4.8+/-0.6 versus 4.3+/-0.6 mmol/kg per min) and exogenous glucose infusion rates required to maintain euglycaemia were also similar (30.0+/-2.6 versus 30.3+/-2.6 mmol/kg per min). Captopril therapy in uncomplicated essential hypertension has no effect on peripheral or hepatic insulin sensitivity.",1998.0,0,0
2513,9856370,"The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension.",G Parati; S Omboni; D Rizzoni; E Agabiti-Rosei; G Mancia,"To introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment. In 174 patients with essential hypertension and left ventricular hypertrophy, enrolled in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE), aged 20-65 years, we measured clinic blood pressure, 24 h ambulatory blood pressure and the left ventricular mass index (echocardiography) before and after treatment with lisinopril at 20 mg with the addition of 12.5 or 25 mg hydrochlorothiazide as needed to reach a sufficient blood pressure reduction. The following parameters were computed for systolic and diastolic ambulatory blood pressure: (1) hourly and 24 h blood pressure averages (+/- SD) at baseline and after 3 and 12 months of treatment; (2) hourly blood pressure changes from baseline after 3 and 12 months of treatment, and their average (+/- SD) over 24 h; (3) the trough : peak ratio after 3 and 12 months of treatment; and (4) the smoothness index after 3 and 12 months of treatment Similar calculations were also performed at the end of a final study month during which active treatment was withdrawn and placebo was substituted (n = 164). The smoothness index for systolic and diastolic ambulatory blood pressure computed after 3 months of treatment was more closely related to its corresponding values after 12 months of treatment than the trough : peak ratio values computed after the same time periods were (r = 0.68 versus 0.38 for systolic and 0.68 versus 0.42 for diastolic blood pressure, respectively). The smoothness index showed an inverse correlation with the 24 h standard deviation of systolic and diastolic blood pressure (r = -0.25 and -0.16, P < 0.01 and < 0.05, respectively, for 12 months of treatment), while the trough : peak ratio did not (r = -0.01 to -0.12, NS). A treatment-induced reduction in the left ventricular mass index was related to the smoothness index for systolic and diastolic blood pressure (r = -0.35 and -0.32, P< 0.001 with 12 months of treatment), but not to the corresponding trough : peak ratios. The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak ratio.",1998.0,0,0
2514,9856958,Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1.,N J Brown; M A Agirbasli; G H Williams; W R Litchfield; D E Vaughan,"Increased plasma renin activity (PRA) has been associated with an increased risk of myocardial infarction (MI), whereas angiotensin-converting enzyme (ACE) inhibition appears to reduce the risk of recurrent MI in patients with left ventricular dysfunction. These observations may be partially explained by an interaction between the renin-angiotensin system (RAS) and fibrinolytic system. To test this hypothesis, we examined the effect of salt depletion on tissue-type plasminogen activator (tPA) antigen and plasminogen activator inhibitor-1 (PAI-1) activity and antigen in normotensive subjects in the presence and absence of quinapril (40 mg BID). Under low (10 mmol/d) and high (200 mmol/d) salt conditions there was significant diurnal variation in PAI-1 antigen and activity and tPA antigen. Morning (8 AM through 2 PM) PAI-1 antigen levels were significantly higher during low salt intake compared with high salt intake conditions (ANOVA, F=5.8, P=0.048). PAI-1 antigen correlated with aldosterone (r=0.56, P<10(-7)) during low salt intake. ACE inhibition significantly decreased 24-hour (ANOVA for 24 hours, F=6. 7, P=0.04) and morning (F=24, P=0.002) PAI-1 antigen and PAI-1 activity (F=6.48, P=0.038) but did not alter tPA antigen. Thus, the mean morning PAI-1 antigen concentration was significantly higher during low salt intake than during either high salt intake or low salt intake and concomitant ACE inhibition (22.7+/-4.6 versus 16. 1+/-3.3 and 16.3+/-3.7 ng/mL, respectively; P<0.05). This study provides evidence of a direct functional link between the RAS and fibrinolytic system in humans. The data suggest that ACE inhibition has the potential to reduce the incidence of thrombotic cardiovascular events by blunting the morning peak in PAI-1.",1998.0,0,0
2515,9857856,"High- versus low-dose ACE inhibition in chronic heart failure: a double-blind, placebo-controlled study of imidapril.",D J van Veldhuisen; S Genth-Zotz; J Brouwer; F Boomsma; T Netzer; A J Man In 'T Veld; Y M Pinto; K I Lie; H J Crijns,"To determine dose-related clinical and neurohumoral effects of angiotensin-converting enzyme (ACE) inhibitors in patients with chronic heart failure (CHF), we conducted a double-blind, placebo-controlled, randomized study of three doses (2.5 mg, 5 mg and 10 mg) of the long-acting ACE inhibitor imidapril. The ACE inhibitors have become a cornerstone in the treatment of CHF, but whether high doses are more effective than low doses has not been fully elucidated, nor have the mechanisms involved in such a dose-related effect. In a parallel group comparison, the effects of three doses of imidapril were examined. We studied 244 patients with mild to moderate CHF (New York Heart Association class II-III: +/-80%/20%), who were stable on digoxin and diuretics. Patients were treated for 12 weeks, and the main end points were exercise capacity and plasma neurohormones. At baseline, the four treatment groups were well-matched for demographic variables. Of the 244 patients, 25 dropped out: 3 patients died, and 9 developed progressive CHF (3/182 patients on imidapril vs. 6/62 patients on placebo, p < 0.05). Exercise time increased 45 s in the 10-mg group (p = 0.02 vs. placebo), but it did not significantly change in the 5-mg (+16 s), and 2.5-mg (+11 s) imidapril group, compared to placebo (+3 s). Physical working capacity also increased in a dose-related manner. Plasma brain and atrial natriuretic peptide decreased (p < 0.05 for linear trend), while (nor)epinephrine, aldosterone and endothelin were not significantly affected. Renin increased in a dose-related manner, but plasma ACE activity was suppressed similarly (+/-60%) on all three doses. Already within 3 months after treatment initiation, high-dose ACE inhibition (with imidapril) is superior to low-dose. This is reflected by a more pronounced effect on exercise capacity and some of the neurohormones, but it does not appear to be related to the extent of suppression of plasma ACE.",1998.0,0,0
2516,9857924,A placebo-controlled study of growth hormone in patients with congestive heart failure.,J Isgaard; C H Bergh; K Caidahl; M Lomsky; A Hjalmarson; B A Bengtsson,"Experimental data in heart failure models and an open trial of seven patients with idiopathic dilated cardiomyopathy have suggested beneficial effects of growth hormone on cardiac function. The aim of the present study was to evaluate growth hormone effects on cardiac function in a placebo-controlled study. Twenty two patients with congestive heart failure of different aetiologies in NYHA II and III and an echocardiographic ejection fraction <0.45 were studied in a 3 month double-blind placebo-controlled study with growth hormone added to optimal heart failure therapy. Patients received either placebo (n=11) or recombinant human growth hormone (n=11) in an initial dose of 0.1 IU x kg(-1) week(-1) for 1 week, and thereafter 0.25 IU x kg(-1) week(-1) for the rest of the treatment period. Cardiac function was assessed by equilibrium radionuclide angiography and Doppler echocardiography. Functional capacity was evaluated by computerized bicycle exercise electrocardiography. Recombinant human growth hormone had no significant effect on systolic or diastolic cardiac function, exercise capacity or neuroendocrine activation. In addition, there was no overall improvement in functional class or dyspnoea grade. Insulin-like growth factor-I significantly increased demonstrating that the growth hormone had an endocrine effect. This is the first double-blind and placebo-controlled study of the administration, over 3 months, of recombinant human growth hormone in patients with congestive heart failure of different aetiologies. The treatment was safe and without serious side effects. However, no beneficial effects on cardiac function or structure could be detected.",1998.0,0,0
2517,9861898,,,,,0,0
2518,9869017,Comparison of active treatment and placebo in older Chinese patients with isolated systolic hypertension. Systolic Hypertension in China (Syst-China) Collaborative Group.,L Liu; J G Wang; L Gong; G Liu; J A Staessen,"Isolated systolic hypertension occurs in around 8% of Chinese people aged 60 years or older. In 1988, the Systolic Hypertension in China (Syst-China) Collaborative Group started to investigate whether active treatment could reduce the incidence of stroke and other cardiovascular complications in older patients with isolated systolic hypertension. All patients were initially started on masked placebo. After stratification for centre, sex and previous cardiovascular complications, alternate patients (n=1253) were assigned nitrendipine at 10-40 mg daily, with the addition of captopril at 12.5-50.0 mg daily or hydrochlorothiazide at 12.5-50.0 mg daily, or both, if a sufficient blood pressure fall was not obtained. In the remaining 1141 control patients, matching placebos were administered similarly. At entry, sitting blood pressure averaged 170.5 mmHg systolic and 86.0 mmHg diastolic, age averaged 66.5 years and total serum cholesterol was 5.1 mmol/l. After 2 years of follow-up, sitting systolic and diastolic blood pressures had fallen by 10.9 mmHg and 1.9 mmHg in the placebo group and by 20.0 mmHg and 5.0 mmHg in the active treatment group. The intergroup differences were 9.1 mmHg systolic (95% confidence interval 7.6-10.7 mmHg ) and 3.2 mmHg diastolic (95% confidence interval 2.4-4.0). Active treatment reduced total strokes by 38% (from 20.8 to 13.0 endpoints per 1000 patient-years, P=0.01), all-cause mortality by 39% (from 28.4 to 17.4 endpoints per 1000 patient-years, P=0.003), cardiovascular mortality by 39% (from 15.2 to 9.4 endpoints per 1000 patient-years, P=0.03), stroke mortality by 58% (from 6.9 to 2.9 endpoints per 1000 patient-years, P=0.02), and ail fatal and nonfatal cardiovascular endpoints by 37% (from 33.3 to 21.4 endpoints per 1000 patient-years, P=0.004). Antihypertensive treatment prevents stroke and other cardiovascular complications in older Chinese patients with isolated systolic hypertension. Treatment of 1000 Chinese patients for 5 years could prevent 55 deaths, 39 strokes or 59 major cardiovascular endpoints.",1998.0,0,0
2519,9869506,Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure.,L O'Toole; M Stewart; P Padfield; K Channer,"There is marked interindividual variation in serum and tissue angiotensin-converting enzyme (ACE) levels for which the insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene is a marker. ACE inhibitors have important effects on morbidity and mortality in heart failure. The influence of this polymorphism on the response to ACE inhibitors in patients with heart failure is not known. We studied response by ACE genotype of 34 subjects in a randomised, double-blind, crossover study comparing 6 weeks of lisinopril (10 mg, o.d.) or captopril (25 mg, t.d.s.) on 24-h blood pressure (BP) profile and on renal function in patients with symptomatic heart failure [mean left ventricular ejection fraction (LVEF), 24%]. Glomerular filtration rate (GFR), 99mTc diethylenetriaminepentaacetic acid (DTPA), and ambulatory 24-h mean arterial pressure (MAP; Spacelabs 90207) were assessed at the beginning and end of treatment periods. There was a significant relation between ACE genotype and change in MAP with captopril (mm Hg; DD group, -0.5; ID, -4.7; II, -7.4; p = 0.02) but not to lisinopril (mm Hg DD, -6.0; ID, -6.6; II, -7.4; p = 0.89) in these patients. There was no significant relation between genotype and change in GFR with captopril (percentage change from baseline: DD, +7.9; ID, +13.1; II, -0.6; p = 0.45) or lisinopril (percentage change from baseline: DD, -0.1; ID, -3.0; II, -13.3; p = 0.39), but the decline in renal function tended to be greatest in II subjects. Whereas the results are not conclusive, there may be a significant interaction between ACE genotype and response to ACE inhibitors in patients with heart failure.",1998.0,0,0
2520,9870118,Do intensive blood pressure lowering and low-dose ASA help our hypertensive patients?,M F Evans,,1998.0,0,0
2521,9872248,Effect of angiotensin-converting-enzyme (ACE) inhibitor trandolapril on human diabetic neuropathy: randomised double-blind controlled trial.,R A Malik; S Williamson; C Abbott; A L Carrington; J Iqbal; W Schady; A J Boulton,"Diabetes is a common cause of polyneuropathy. The development and progression of nephropathy, retinopathy, and neuropathy are closely related. Angiotensin-converting enzyme (ACE) inhibitors delay progression of both nephropathy and retinopathy. We investigated the effect of ACE inhibition on diabetic neuropathy. We recruited 41 normotensive patients with type I or type II diabetes and mild neuropathy into a randomised double-blind placebo-controlled trial. Changes in the neuropathy symptom and deficit scores, vibration-perception threshold, peripheral-nerve electrophysiology, and cardiovascular autonomic function, were assessed at 6 and 12 months. The primary endpoint was the change in peroneal nerve motor conduction velocity. We found no significant difference at baseline for age, HbA1c, blood pressure, or severity of neuropathy between two groups. There was no change in HbA1c over the treatment period. Peroneal motor nerve conduction velocity (p=0.03) and M-wave amplitude (p=0.03) increased, and the F-wave latency (p=0.03) decreased and sural nerve action potential amplitude increased (p=0.04) significantly after 12 months of treatment with trandolapril compared with placebo. Vibration-perception threshold, autonomic function, and the neuropathy symptom and deficit score showed no improvement in either group. The ACE inhibitor trandolapril may improve peripheral neuropathy in normotensive patients with diabetes. Larger clinical trials are needed to confirm these data before changes to clinical practice can be advocated.",1999.0,0,1
2522,9874028,Cutaneous reaction to captopril with positive patch test and lack of cross-sensitivity to enalapril and benazepril.,M Lluch-Bernal; A Novalbos; A Umpierrez; E Figueredo; C Bombin; J Sastre,,1999.0,0,0
2523,9880125,,,,,0,0
2524,9880204,Vasodilator therapy of hypertensive acute left ventricular failure: comparison of captopril-prazosin with hydralazine-isosorbide dinitrate.,A Q Adigun; O E Ajayi; G G Sofowora; A A Ajayi,"A prospective study to evaluate and compare the cardiorespiratory effects and clinical efficacy of the Neurohormonal inhibitors (Captopril 50 mg+prazosin 1 mg only) and direct arteriolar and venular dilators (Intravenous hydralazine 30 mg+oral isosorbide dinitrate 30 mg) used as vasodilator therapy, was undertaken in a randomized, single blind study in 17 Nigerian patients with hypertensive acute left ventricular failure. Both vasodilator regimes separately and significantly reduced the systolic and diastolic blood pressures (P<0.001 ANOVA), heart rate (P<0.001 ANOVA), and the respiratory rate (P<0.05 ANOVA), the double product, but increased the peak expiratory flow rate (P<0.05 ANOVA). However, the neurohormonal antagonists, captopril and prazosin (n=9) caused a statistically significantly greater reduction in heart rate (P<0.05 ANOVA) respiratory rate (P<0.05 ANOVA) and induced a significantly greater increase in the self-paced exercise capacity, 24 h after initiation of treatment, (P<0.02) compared to the hydralazine and isosorbide dinitrate combination (n=8). Five of the nine patients on the neurohormonal antagonist therapy were ambulant at 24 h, compared to none of the eight patients receiving conventional venular and arteriolar dilators hydralazine and isosorbide dinitrate (chi2=5.84 dfi P<0.05). There was a significant inverse correlation between the systolic blood pressure heart rate product, and the distance covered during symptom limited self paced exercise capacity (r=-0.58, P=0.0146 ANOVA). One of eight patients in the hydralazine+isosorbide nitrate combination died, but there was no mortality in the captopril+prazosin group. These findings collectively suggest that captopril+prazosin combination may be a superior vasodilator therapy compared to hydralazine-isosorbide dinitrate, in hypertensive acute pulmonary oedema.",1999.0,0,0
2525,9883711,Why beta-blockers are good for some patients with hypertension: a case study of a hypertensive patient with adrenergic paroxysmal atrial fibrillation.,G Y Lip; D G Beevers,,1999.0,0,0
2526,9884016,Heart failure: a diagnostic and therapeutic dilemma in elderly patients.,N D Gillespie; D Darbar; A D Struthers; M E McMurdo,,1999.0,0,0
2527,9884431,Angiotensin-converting enzyme inhibitors but not angiotensin II AT 1 receptor antagonists affect erythropoiesis in patients with anemia of end-stage renal disease.,H Schiffl; S M Lang,,2000.0,0,0
2528,9885106,Treatment of advanced heart failure in a young man with familial cardiomyopathy.,E K Massin,We report the case of a young man with familial cardiomyopathy whose symptoms became difficult to control as his myopathy worsened. He had persistent cardiac arrhythmias and was intolerant of angiotensin-converting enzyme inhibitor therapy. His case illustrates the difficulties that can be encountered in treating patients with advanced heart failure.,1999.0,0,0
2529,9886714,,,,,0,0
2530,9886723,Candoxatril improves exercise capacity in patients with chronic heart failure receiving angiotensin converting enzyme inhibition.,D E Newby; T McDonagh; P F Currie; D B Northridge; N A Boon; H J Dargie,"To assess the effect of candoxatril, a novel neutral endopeptidase inhibitor, on exercise capacity, clinical status and quality of life in patients with mild to moderate chronic heart failure receiving angiotensin converting enzyme inhibition. Patients were recruited from 16 centres throughout the United Kingdom. Following a 4-week single-blind placebo 'run-in' phase of weekly exercise tests, patients underwent double-blind randomization to receive either candoxatril (100 mg twice daily) or placebo for the next 84 days. Patients were then reassessed every 28 days. Of 110 patients randomized, 56 received candoxatril and 54 placebo. Over the study period, the overall improvement in mean total exercise time in the candoxatril group in comparison to the placebo group was 34.1 s (P=0.02: 95% confidence interval: 5.1 to 63.0). There were no significant changes in functional class, clinical status or quality of life scores between the two groups. There was a trend for a small reduction in blood pressure in the candoxatril group. Candoxatril confers an improvement in exercise capacity in patients with chronic heart failure who are receiving maintenance angiotensin converting enzyme inhibitor therapy.",1999.0,0,0
2531,9886725,Failure of an ACE inhibitor to improve exercise tolerance. A randomized study of trandolapril. Trandolapril study group.,J R Hampton; A J Cowley; A M Wnuk-Wojnar,"There has been conflicting evidence of the effect of angiotensin-converting enzyme (ACE) inhibitors on exercise tolerance. Meta-analysis of published results has suggested that a beneficial effect of ACE inhibitors is demonstrated if a trial design is adequate. Multicentre International Trial. In a double-blind, randomized, multicentre trial, 292 patients with moderate (New York Heart Association Grades II and III) heart failure were treated with trandolapril or placebo in addition to diuretics, and followed for 16 weeks. Exercise tolerance on a treadmill was assessed at baseline and after 4, 8, 12 and 16 weeks of treatment. Both a modified Bruce and a modified Naughton protocol were used. Exercise tolerance improved in both treatment groups, with no significant benefit from trandolapril treatment. Trandolapril does not improve exercise tolerance as measured by treadmill testing.",2000.0,0,0
2532,9886905,Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).,M J Brown; A Castaigne; P W de Leeuw; G Mancia; T Rosenthal; L M Ruilope,"To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). To determine the success of single and combination therapy in achieving target blood pressures in such a population. INSIGHT is a double-blind, prospective outcome trial comparing the efficacy of the calcium channel blocker, nifedipine GITS, and the thiazide, co-amilozide, in preventing myocardial infarction and stroke. We recruited 2996 men and 3454 women, aged 55-80 years, with blood pressure during placebo run-in >150/95 mmHg or isolated systolic blood pressure >160 mmHg from nine countries. Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide (hydrochlorothiazide 25 mg/amiloride 5 mg) once daily was performed by minimization rather than randomization to balance additional risk factors. This was followed by four optional increases in treatment: dose-doubling of the primary drug, addition of atenolol 25/50 mg or enalapril 5/10 mg, and then any other hypotensive drug excluding calcium blockers or diuretics. Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg. Blood pressure at randomization was 172+/-15 / 99+/-9 mmHg. Thirteen per cent of the patients were previously untreated. The proportions of each additional risk factors were: smoking > 10/day, 29%; cholesterol > 6.43 mmol/l, 52%; family history of premature myocardial infarction or stroke, 21%; diabetes mellitus 20%; left ventricular hypertrophy, 10%; previous myocardial infarction, other presentations of coronary heart disease, and peripheral vascular disease, each 6%; proteinuria, 3%. Fifty-five per cent of patients had one additional risk factor, whereas 33%, 9% and 3% had two, three or more additional risk factors, respectively. The blood pressure (and falls in blood pressure) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg (33+/-15 / 17+/-9) in the 5226 patients still on randomized treatment The numbers requiring the four treatment increments were, respectively, 1591, 780, 597 and 294, meaning that almost 70% of patients on randomized treatment in INSIGHT are receiving only the primary drug. At one year, 69% of patients had a blood pressure < or = 140/90 mmHg. INSIGHT is one of the first double-blind comparisons of active antihypertensive treatments, requiring high-risk patients to achieve sufficient power. Despite this requirement, it is possible to achieve good blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents.",1999.0,0,0
2533,9892479,Angiotensin converting enzyme inhibitor therapy in severe postcardiotomy dysfunction: a prospective randomized study.,S Sirivella; I Gielchinsky; V Parsonnet,"Occurrence of severe postcardiotomy dysfunction requiring prolonged postoperative support with intra-aortic balloon counterpulsation (IABP) and inotropes, complicating surgery for coronary artery disease and valvular heart disease carries important hospital morbidity and mortality. This study evaluated the impact of angiotensin converting enzyme inhibitor (captopril) therapy in these patients in the early postoperative period. During a 5-year period, 298 patients with prolonged diminished cardiac output required support (> 48 to 72 hours) with IABP plus two or three inotropes. This cohort was randomized to two groups, group A (195 patients) who were continued on IABP and inotropes alone and group B (103 patients) who were given an angiotensin converting enzyme (ACE) inhibitor, captopril 48 to 72 hours postoperatively and continued on IABP and inotropes. Tissue perfusion and hemodynamic parameters improved (p < 0.0001) in group B with early termination of IABP (duration of support mean 86 hours in group B vs 169 hours in group A) and inotropes. Peak improvement in tissue perfusion and hemodynamic parameters correlated with decreased serum angiotensin converting enzyme levels. Hospital mortality occurred in 31% of patients in group A and 14.5% in group B. Morbidity complications developed in 37% of patients in group A and 20% in group B. The average length of hospital stay in group A was 27 days and 17 days in group B. Cardiac, pulmonary, infective, gastrointestinal, renal, and neurological complications were common in both groups. Administration of ACE inhibitors in the early postoperative period to patients with severe postcardiotomy dysfunction caused improvement in tissue perfusion with decreases in mortality, morbidity, and length of hospital stay. These drugs, by effectively limiting physiological effects induced by renin angiotensin-aldosterone axis and other mechanisms, caused recovery of stunned myocardium. More randomized trials are needed before recommending these drugs for routine use in similar patients.",1999.0,0,0
2534,9893735,Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension.,L T Dijkhorst-Oei; J J Beutler; E S Stroes; H A Koomans; T J Rabelink,"Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.",1999.0,0,0
2535,9894621,Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction.,Y Moriyama; H Ogawa; S Oshima; H Arai; K Takazoe; H Shimomura; N Hirai; H Suefuji; H Soejima; K Nishiyama; K Misumi; H Yasue,"An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.",1999.0,0,0
2536,9928746,Target organ involvement in hypertensive patients in Eastern Sudan.,A A Hussain; A G Elzubier; M E Ahmed,"Hypertension has become a major cause of cardiovascular morbidity and mortality in both the developed and the developing nations. In a cross-sectional study we assessed the state of blood pressure (BP) control and the pattern of target organ complications in 198 Sudanese patients treated in a teaching hospital in Kassala town in Eastern Sudan, (mean age 53 years, 76% women). Excellent BP control (BP <140/90 mm Hg) was achieved in 46% of the patients. Stage 2 or Stage 3 target organ involvement, particularly albuminuria and ischaemic heart disease, were detected in one-third of the patients. These complications were found to be related to both the severity and the duration of hypertension as well as to the frequency of cigarette smoking. Factors such as poor compliance, adverse socioeconomic status, as well as obesity and cigarette smoking may account for poor BP control and hence the development of hypertensive complications. We conclude that optimal BP control is not yet achieved in the majority of hypertensives in the Sudan. Reasons for this failure should be identified and corrected in order to avoid hypertensive target organ damage.",1999.0,0,0
2537,9928752,Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive patients with type II diabetes and impaired renal function.,R Fogari; A Zoppi; L Corradi; A Mugellini; P Lazzari; P Preti; P Lusardi,"The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion (UAE) in hypertensive patients with type II non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. A 2-year, prospective, randomised study was conducted on 51 men with a diastolic blood pressure (DBP) > or =95 and < or =105 mm Hg, stable NIDDM, serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE >300 and <2000 mg/24 h. After a 3-month preliminary observation period, during which patients began a low-protein, low-sodium diet, and a subsequent 4-week run-in period on placebo, patients were randomly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years. Both drugs similarly reduced BP without affecting glucose homeostasis. In the ramipril group UAE significantly decreased after only 3 months of treatment, whereas in the nitrendipine group a significant although lesser reduction in UAE was observed only after 1 year. During the second year the UAE% change was not statistically different between the two treatments. Serum creatinine and creatinine clearance showed no significant change with both drugs. The progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups. In conclusion both ramipril and nitrendipine were associated with a decrease in UAE although such a reduction was earlier and more marked with ramipril. The decline of renal function did not differ significantly between the two treatments.",1999.0,0,0
2538,9928753,Improved efficacy with maintained tolerability in the treatment of primary hypertension. Comparison between the felodipine-metoprolol combination tablet and monotherapy with enalapril. Swedish Multicentre Group.,O K Andersson,"In this multicentre, double-blind, parallel-group study, 120 out-patients with mild to moderate primary hypertension were randomised, after a 4-week single-blind placebo run-in period, to a combination tablet of felodipine-metoprolol 5/50 mg (Logimax, Mobloc, Astra) once daily or enalapril 10 mg once daily. If blood pressure (BP) remained suboptimally controlled after 4 weeks (supine diastolic BP >90 mm Hg 24-h post dose), the dose was doubled for a further 4 weeks. After 8 weeks felodipine-metoprolol reduced supine BP significantly more than enalapril (19.7/12.0 mmHg and 11.1/7.2 mm Hg, respectively). The mean differences in change in BP between treatments were 8.6/4.8 mm Hg in favour of felodipine-metoprolol (P = 0.001/P <0.001). A statistically significant difference to the advantage of felodipine-metoprolol was also seen in standing BP. Even though the dose was increased in a larger proportion of patients in the enalapril group (61%) than in the felodipine-metoprolol group (40%), fewer enalapril-treated patients achieved adequate BP control (41% vs 63% on felodipine-metoprolol, P <0.05). Both treatments were well tolerated. Three patients treated with felodipine-metoprolol and four with enalapril discontinued treatment due to adverse events. A similar number of patients reported adverse events in each treatment group. In conclusion, a combination tablet of felodipine-metoprolol 5/50-10/100 mg once daily reduced BP more effectively than enalapril 10-20 mg once daily 24 h post dose. The result was expected, but a more important observation was that both treatments were tolerated to a similar degree. Obviously, a considerable BP reduction may be well tolerated, as was the main purpose to demonstrate in this study.",1999.0,0,0
2539,9928754,Verapamil SR/trandolapril combination therapy for the elderly hypertensive patient. German VeraTran Hypertension Study Group.,H Holzgreve; D Compagnone; P Zilles,"A total of 254 elderly hypertensive patients (71 men and 183 women aged between 63 and 92 years, diastolic blood pressure (DBP) 95-115 mm Hg inclusive) were treated with the fixed combination of verapamil SR/trandolapril following a 4-week single-blind placebo run-in period. Treatment was started with a response dependent 3-step dose titration period. All patients were initiated at dose step 1 (verapamil SR/trandolapril 120/0.5 mg o.d.) and if not normalised (DBP <90 mm Hg) titrated at 4-weekly intervals over dose step 2 (verapamil SR/trandolapril 180/1 mg o.d.) to dose step 3 (verapamil SR/trandolapril 180/2 mg o.d.) during the first 12 weeks. After 3 months of treatment all patients not normalised were excluded from further participation in the study. The total duration of the treatment period was 6 months. Routine safety investigations were performed prior, during and on completion of the treatment period. Verapamil SR/trandolapril was highly effective in reducing blood pressure. At individual last visit during active treatment (also taking the non-responders into account), the mean reduction in SBP/DBP was 21.9/17.1 mm Hg (95% CI 19.8-24.1/16.1-18.1 mm Hg), with most of this reduction occurring during the first 3 months of treatment. After 6 months, 81.9% of the patients enrolled showed normalisation of DBP (<90 mm Hg) and 85% were responders (normalisation and/or reduction in DBP by at least 10 mm Hg). Normalisation and responder rates appeared to be comparable when stratified by age subgroups (63-69, 70-79 and > or =80 years) and were all greater than 80%. Verapamil SR/trandolapril was very well tolerated and there was no evidence of any clinically relevant changes in routine laboratory safety variables or resting ECG. In conclusion, the fixed dose combination of verapamil SR/trandolapril is an effective and safe alternative treatment for the elderly hypertensive patient.",1999.0,0,0
2540,9935020,Effects of early captopril administration after thrombolysis on regional wall motion in relation to infarct artery blood flow.,J K French; D J Amos; B F Williams; D B Cross; J M Elliott; H H Hart; M G Williams; R M Norris; N G Ashton; R M Whitlock; S C McLaughlin; H D White,"To determine whether early administration of captopril lessens infarct zone regional wall motion abnormalities when infarct artery blood flow is abnormal. The interaction between angiotensin-converting enzyme (ACE) inhibitor therapy, ventricular function and infarct artery blood flow has not been well described. A total of 493 patients aged < or = 75 years with first infarctions, presenting within 4 h of symptom onset, were randomized to receive 6.25 mg captopril, increasing to 50 mg t.d.s. or a matching placebo 2.1+/-0.4 h after commencing intravenous streptokinase (1.5 x 10(6) U over 30 to 60 min). Trial therapy was stopped 48 h prior to angiography at 3 weeks, to determine regional wall motion and infarct artery flow. There were no differences in ejection fractions or end-systolic volumes between patients randomized to receive captopril and those randomized to receive a placebo. Among patients with anterior infarction (n = 216), randomization to captopril resulted in fewer hypokinetic chords (40+/-13; vs. 44+/-13; p=0.028) and a trend toward fewer chords >2 SD below normal (26+/-17 vs. 30+/-17; p=0.052) in the infarct zone. In patients randomized to receive captopril who had anterior infarction and Thrombolysis in Myocardial Infarction (TIMI) 0-2, flow there were fewer hypokinetic chords (44+/-12 vs. 50+/-9; p=0.043) and a trend toward fewer chords >2 SD below normal (33+/-15 vs. 39+/-13; p=0.057). Patients receiving captopril who had anterior infarction and corrected TIMI frame counts > 27 had fewer hypokinetic chords (42+/-13 vs. 46+/-12; p=0.015) and fewer chords >2 SD below normal (27+/-17 vs. 32+/-17; p= 0.047). Captopril had no effect in patients with inferior infarction. There were 20 late cardiac deaths (median follow-up 4 years) in the captopril group and 35 in the placebo group (p=0.036). Randomization to receive captopril 2 h after streptokinase improved regional wall motion at 3 weeks. The greatest benefit was seen in patients with anterior infarction particularly when infarct artery blood flow is reduced.",1999.0,0,0
2541,9987043,The extent of regional wall motion abnormalities identifies patients at risk of extensive left ventricular remodeling: implications for the design of post myocardial infarction trials.,L Zanolla; P Marino; G Golia; M Anselmi; P Zardini; C Borghi; E Ambrosioni,"The FAMIS (Fosinopril in Acute Myocardial Infarction Study) was a multicenter, placebo-controlled, double-blind trial designed to evaluate the safety and the efficacy of fosinopril in reducing left ventricular enlargement after acute anterior myocardial infarction. We evaluated the echocardiographic examinations performed during the trial in order to assess the trend of the remodeling process over time and to evaluate the role of infarct size in identifying patients at risk of progressive left ventricular dilation. A complete echocardiographic examination was performed on admission, before discharge and three months later. Patients undergoing coronary bypass surgery or PTCA had a further examination prior to the procedure. The echocardiograms were analyzed at a central laboratory, and the end-diastolic and end-systolic left ventricular volumes were computed by using a modified Simpson's rule technique. Regional wall motion was evaluated using the centerline method, analyzing the left ventricular boundary along 100 chords perpendicular to the centerline constructed midway between the end-diastolic and the end-systolic contours. A quantitative infarct-size index was then computed according to the number of chords with a fractional shortening equal to or less than 5%. Left ventricular end-diastolic and end-systolic volume index significantly increased over time (p < 0.0001); as a result, the stroke volume increased (p < 0.0001) but the ejection fraction did not change. Patients were then divided according to the three-month infarct-size index. For both end-diastolic and end-systolic volume, not only did larger infarcts had higher volumes, but there was also a greater increase from baseline to 3 months. Moreover, larger infarcts had a lower ejection fraction, with a further reduction over the three months, while smaller infarcts had higher values and an increase over time. An infarct-size index of 25 or larger allowed prospective identification at the baseline examination of patients at risk of subsequent left ventricular dilation. In conclusion, patients at greatest risk of left ventricular dilation, namely those with larger infarct size, constitute a group that is worth considering for any therapeutic effort for reducing the remodeling process. These patients could in fact benefit from therapeutic strategies aimed at the reduction of left ventricular remodeling and should be studied in clinical trials.",1999.0,0,0
2542,9988956,"Aggressive blood pressure lowering is safe, but benefit is still hard to prove.",D G Vidt; M A Pohl,"In the Hypertension Optimal Treatment (HOT) study, hypertensive patients who were randomly assigned to undergo antihypertensive treatment to achieve a goal diastolic blood pressure of 80 mm Hg or lower did not experience fewer cardiovascular events than did patients who received treatment with goal pressures of 85 or 90 mm Hg. Such aggressive antihypertensive treatment was safe and well tolerated, and did result in fewer cardiovascular events in the subset of patients with diabetes. All patients were randomly assigned to take aspirin 75 mg/day or placebo, and patients in the aspirin group had a 15% lower rate of major cardiovascular events and myocardial infarctions than did patients who received placebo. This finding establishes the efficacy of aspirin in preventing strokes and myocardial infarctions in hypertensive patients.",1999.0,0,0
2543,9990366,Increased levels of interleukin 5 are associated with the generation of eosinophilia in drug-induced hypersensitivity syndrome.,G Choquet-Kastylevsky; L Intrator; C Chenal; H Bocquet; J Revuz; J C Roujeau,"Hypersensitivity syndrome (HSS) usually refers to severe drug eruption associated with systemic symptoms and eosinophilia. Interleukin (IL)-5 regulates eosinophil counts with the help of IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF). Blood IL-5 levels have been reported to be increased in patients with eosinophilia secondary to parasitic infections or idiopathic eosinophilia, but have never been evaluated in drug-induced eosinophilia. The aim of our study was to determine whether IL-5, IL-3 and GM-CSF are involved in eosinophilia in patients with drug-induced HSS. Plasma levels of IL-3, IL-5 and GM-CSF were assayed by ELISA in seven patients with drug-induced HSS, in eight patients with cutaneous adverse drug reactions not associated with eosinophilia, and in five patients with eosinophilia unrelated to drug treatment. IL-5 levels were normal in all eight patients with drug eruptions without eosinophilia, and increased in five of the seven patients with HSS. In the latter patients, IL-5 levels peaked several days before highest eosinophil counts were noted, and returned to normal within a few days, even when eosinophilia persisted. In patients with eosinophilia unrelated to drug treatment, IL-5 levels, although significantly increased remained lower than in HSS patients. IL-3 and GM-CSF could not be detected in any group, at any time. Our results show that IL-5 is involved in drug-related eosinophilia. As IL-5 production was only involved in the early stages of the reaction, it is suggested that IL-5 mainly derives from activated lymphocytes rather than eosinophils. Our results support the clinical relevance of previous in vitro findings. Further studies are needed to test whether assays of IL-5 production by lymphocytes of patients stimulated by the suspected drug and/or its metabolites, are useful in establishing causality in drug-induced reactions associated with eosinophilia.",1999.0,0,0
2544,9990397,Severe bullous drug reactions treated successfully with cyclophosphamide.,A Trautmann; C E Klein; E Kämpgen; E B Bröcker,,1999.0,0,0