record_id,pubmedID,title,authors,abstract,year,label_included,label_abstract_screening
1,10024334,Irbesartan reduces QT dispersion in hypertensive individuals.,P O Lim; M Nys; A A Naas; A D Struthers; M Osbakken; T M MacDonald,"Angiotensin type 1 receptor antagonists have direct effects on the autonomic nervous system and myocardium. Because of this, we hypothesized that irbesartan would reduce QT dispersion to a greater degree than amlodipine, a highly selective vasodilator. To test this, we gathered electrocardiographic (ECG) data from a multinational, multicenter, randomized, double-blind parallel group study that compared the antihypertensive efficacy of irbesartan and amlodipine in elderly subjects with mild to moderate hypertension. Subjects were treated for 6 months with either drug. Hydrochlorothiazide and atenolol were added after 12 weeks if blood pressure (BP) remained uncontrolled. ECGs were obtained before randomization and at 6 months. A total of 188 subjects (118 with baseline ECGs) were randomized. We analyzed 104 subjects who had complete ECGs at baseline and after 6 months of treatment. Baseline characteristics between treatments were similar, apart from a slight imbalance in diastolic BP (irbesartan [n=53] versus amlodipine [n=51], 99.2 [SD 3. 6] versus 100.8 [3.8] mm Hg; P=0.03). There were no significant differences in BP normalization (diastolic BP <90 mm Hg) between treatments at 6 months (irbesartan versus amlodipine, 80% versus 88%; P=0.378). We found a significant reduction in QT indexes in the irbesartan group (QTc dispersion mean, -11.4 [34.5] milliseconds, P=0.02; QTc max, -12.8 [35.5] milliseconds, P=0.01), and QTc dispersion did not correlate with the change in BP. The reduction in QT indexes with amlodipine (QTc dispersion, -9.7 [35.4] milliseconds, P=0.06; QTc max, -8.6 [33.2] milliseconds, P=0.07) did not quite reach statistical significance, but there was a correlation between the change in QT indexes and changes in systolic BP. In conclusion, irbesartan improved QT dispersion, and this effect may be important in preventing sudden cardiac death in at-risk hypertensive subjects.",1999.0,0,0
2,10029786,Preterm labor.,D G Weismiller,"Preterm labor is the leading cause of perinatal morbidity and mortality in the United States. It is characterized by cervical effacement and/or dilatation and increased uterine irritability before 37 weeks of gestation. Women with a history of preterm labor are at greatest risk. Strategies for reducing the incidence of preterm labor and delivery have focused on educating both physicians and patients about the risks for preterm labor and methods of detecting preterm cervical dilatation. Methods used to predict preterm labor include weekly cervical assessment, transvaginal ultrasonography, detection of fetal fibronectin and home uterine activity monitoring. As yet, it is unclear if any of these strategies should be routinely employed. At present, management of preterm labor may include the use of tocolytic agents, corticosteroids and antibiotics.",1999.0,0,0
3,10030325,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
4,10052772,Prevalence of gingival overgrowth induced by calcium channel blockers: a community-based study.,J S Ellis; R A Seymour; J G Steele; P Robertson; T J Butler; J M Thomason,"The prevalence of gingival overgrowth induced by chronic medication with calcium channel blockers is uncertain. Although there have been several studies examining this question, the results are conflicting, with previous estimates ranging from 20% to 83%. There have been only 2 studies examining the prevalence of overgrowth induced by diltiazem and amlodipine, with estimates of 74% and 3.3%, respectively. The current study aimed to address the problems associated with these studies by examining a sample of patients taking one of 3 calcium channel blockers, who were drawn from a community-based population in northeastern England. Nine hundred eleven (911) subjects were recruited from general medical practices in the area. Of these, 442 were taking nifedipine, 181 amlodipine, and 186 diltiazem. In addition, 102 control subjects were examined. Drug and demographic data for each subject were recorded. The periodontal condition of all subjects was assessed including plaque index, papillary bleeding index, and a photograph of the anterior gingivae for subsequent analysis of overgrowth severity. More than six percent (6.3%) of subjects taking nifedipine were seen to have significant overgrowth. This overgrowth was statistically greater than the amount of overgrowth seen in either of the other 2 drug groups or the control population. The prevalence of gingival overgrowth induced by amlodipine or diltiazem was not statistically significant when compared to the control group. The severity of overgrowth within the nifedipine group was found to be related to the amount of gingival inflammation and also to the gender of the subject, with males being 3 times as likely to develop overgrowth than females. The prevalence of clinically significant overgrowth related to chronic medication with calcium channel blockers is low, i.e., 6.3% for nifedipine. Males are 3 times as likely as females to develop clinically significant overgrowth. The presence of gingival inflammation is an important cofactor for the expression of this effect.",1999.0,0,1
5,10053176,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
6,10067786,,,,,0,0
7,10069685,Long-acting lacidipine versus short-acting nifedipine in the treatment of asymptomatic acute blood pressure increase.,M Sánchez; J Sobrino; L Ribera; M J Adrián; M Torres; A Coca,"We compared antihypertensive efficacy and safety of a single administration of equipotent doses of lacidipine versus nifedipine in the hypertensive urgencies. Twenty-nine asymptomatic essential hypertensive patients (nine men, 20 women) with a mean age of 55.03+/-11.19 years and baseline diastolic blood pressure (DBP) of > or =120 mm Hg after resting 30 min, not taking antihypertensive drugs for the last 24 h, were randomized in a single-blind fashion to receive lacidipine, 4 mg (LCD, 15 patients) or short-acting nifedipine, 20 mg (NFD, 14 patients) in a single dose. Blood pressure (BP) and heart rate (HR) were taken every 30 min during the first 8 h and every 2 h until 24 h of follow-up. Baseline BP values were similar in the two groups (LCD, 222.5+/-32.8/124.6+/-8.4 mm Hg vs. NFD, 215.9+/-20.6/128+/-7.7 mm Hg; p = NS). Both drugs promoted a significant reduction of systolic blood pressure (SBP; 169.6+/-27.8 vs. 170.6+/-25.3 mm Hg) and diastolic blood pressure (DBP; 104.1+/-16 vs. 102.9+/-12.4 mm Hg) after 8 h. However, either SBP (165+/-27.3 vs. 190.6+/-18.2 mm Hg; p = 0.008) and DBP (99.9+/-12.3 vs. 117.2+/-11.4 mm Hg; p = 0.001) were significantly higher in the NFD group after 24-h dosing. Eleven patients in the LCD group had a decrease in BP >25% of the baseline value both 8 and 24 h after the dose. Although 10 patients showed the same response in the NFD group 8 h after the dose, only four patients maintained these values at 24 h. One patient treated with NFD had a transient cerebrovascular ischemic attack. No adverse effects were observed in the LCD group. We conclude that the long-acting calcium antagonist lacidipine was more effective than the short-acting nifedipine in both controlling BP and maintaining this BP reduction over 8 h in essential hypertensive patients with acute asymptomatic BP increase.",1999.0,0,0
8,10073852,"Comparison of controlled-onset, extended-release verapamil with amlodipine and amlodipine plus atenolol on exercise performance and ambulatory ischemia in patients with chronic stable angina pectoris.",W H Frishman; S Glasser; P Stone; P C Deedwania; M Johnson; T D Fakouhi,"This multicenter, randomized, double-blind, parallel group, placebo lead-in, placebo-controlled study compared the antianginal and anti-ischemic effects of once-daily bedtime dosing of controlled-onset extended-release (COER-24) verapamil to a once-daily morning dosing of amlodipine +/- atenolol in patients with chronic stable angina. A total of 551 patients with exercise-induced myocardial ischemia and evidence of coronary artery disease were randomized to a 4-week, forced-dose titration treatment period with (1) COER-24 verapamil 240 mg titrated to 480 mg at bedtime (n = 173), (2) amlodipine 5 mg titrated to 10 mg/day (n = 149), (3) amlodipine 5 mg (titrated to 10 mg) plus atenolol 50 mg/day in the A.M. (n = 154), or (4) placebo (n = 75). Treadmill exercise tolerance testing (standard Bruce protocol), and 48-hour ambulatory electrocardiographic (Holter) monitoring were performed at the end of placebo lead-in and double-blind treatment. Each active treatment significantly improved symptom-limited exercise duration and time to moderate angina (p < or = 0.01 vs placebo). For patients with baseline ischemia, amlodipine resulted in a statistically significant increase in total duration of ischemic episodes compared with placebo, whereas COER-24 verapamil and amlodipine plus atenolol resulted in statistically significant decreases compared with placebo and amlodipine. Heart rate at onset of ischemic episodes and ST product were also significantly increased with amlodipine (p < 0.05) compared with either COER-24 or amlodipine plus atenolol. COER-24 and amlodipine alone or in combination with atenolol improved exercise capacity in patients with angina pectoris. COER-24 verapamil monotherapy or amlodipine plus atenolol combination therapy were more effective than amlodipine monotherapy in decreasing ambulatory myocardial ischemia, especially during the hours of 6 A.M. to 12 noon.",1999.0,0,1
9,10080455,The Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET) and combination therapies.,M Pahor; P Tatti,,1999.0,0,1
10,10090111,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
11,10090348,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
12,10091520,[The additional efficacy of the nifedipine-diuretic combination depends on the potency of the drug administered first and not the sequence of administration. A double blind study in salt-sensitive black hypertensives].,A Damasceno; P Caupers; A Rafik; A Santos; J Polónia,"To evaluate whether the additional antihypertensive efficacy of the nifedipine-thiazide combination depends on the sequence of drug administration and whether the natriuretic effect of thiazide persists when co-administered with nifedipine. Double blind, randomised, crossover, placebo-controlled study, in 12 salt-sensitive hypertensive black patients (SSH). Evaluation of the antihypertensive (24 h ambulatory monitoring) and natriuretic effects of placebo (PL), of nifedipine-GITS (NIF, 30 mg/d) and of hydrochlorothiazide (HCTZ, 25 mg/d) given alone and in combination within two separate therapeutic sequences: PL-->NIF-->NIF + HCTZ and PL-->HCTZ-->HCTZ + NIF (1 month for each therapeutic regimen). NIF induced greater (p < 0.04) reduction of 24 h mean arterial pressure (MAP) (-15.9 +/- 1.9 mm Hg, v PL) than HCTZ (-9.0 +/- 1.3 mm Hg). The association of NIF to HCTZ induced a greater (p < 0.05) additional reduction of MAP-24 h (9.7 +/- 2.2 mm Hg) than that produced by the association of HCTZ to NIF (4.1 +/- 1.3 mm Hg). NIF alone and in combination did not modify the diuresis-natriuresis observed with the previous treatment, whereas HCTZ alone and in combination always increased diuresis (by 25%) and natriuresis (by 53%). There was a significant negative correlation (r = -0.71, p < 0.001) between blood pressure (BP) reduction induced by the drug administered first (NIF or HCTZ) and the additional BP reduction obtained by the association of the second drug. In most of the SSH the NIF-GITS was more potent than HCTZ. NIF did not modify the diuretic-natriuretic effect of PL and of HCTZ. The greater potency of NIF may explain why in most patients the combination HCTZ to NIF induced a lower hypotensive effect than that of the association of NIF to HCTZ. Independently of the sequence of the drug administration, the lower the hypotensive effect of the drug administered first the greater the additional hypotensive effect that was observed by adding the second drug.",1999.0,0,0
13,10099034,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.",1999.0,0,1
14,10099075,"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
15,10100056,Baroreflex sensitivity changes with calcium antagonist therapy in elderly subjects with isolated systolic hypertension.,M A James; H Rakicka; R B Panerai; J F Potter,"In order to study the effects of calcium-blocking therapy on cardiovascular homeostasis in elderly subjects with isolated systolic hypertension, we performed a randomised double-blind placebo-controlled crossover study of 6 weeks therapy with modified-release nifedipine or placebo. Changes with calcium-blocker treatment in clinic and 24-h blood pressure (BP), heart rate, BP variability, baroreflex sensitivity (BRS) by three methods (Valsalva manoeuvre, phenylephrine and sodium nitroprusside injection), and in baroreflex- and non-baroreflex-mediated reflexes (tilt and cold face stimulus) were studied in 14 elderly subjects (mean age [+/- SEM] 70 +/- 1 years) with sustained isolated systolic hypertension (clinic BP 179 +/- 3/85 +/- 1 mm Hg). Clinic systolic BP, but not diastolic BP, was reduced with treatment (by 14 +/- 6 mm Hg, P = 0.03, diastolic BP 4 +/- 3 mm Hg, P = 0.16). Twenty-four hour BP was also reduced by nifedipine treatment (by 18 +/- 3/9 +/- 2 mm Hg, both P < 0.001). Clinic and 24-h heart rate, and daytime BP variability, were unchanged with treatment. BRS was significantly increased during nifedipine therapy by all three measurement methods (all P < 0.05). With 60 degrees tilt during active treatment, subjects exhibited a greater heart rate increase (P < 0.01), and a reduced fall in systolic (P < 0.05) and diastolic BP (P < 0.05). Thus despite the arteriosclerosis and reductions in large artery compliance described in elderly patients with isolated systolic hypertension, clinically important improvements in clinic and ambulatory BP and some aspects of cardiovascular homeostasis can be achieved with calcium-channel blocking therapy.",1999.0,0,0
16,10100063,"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.",1999.0,0,1
17,10100066,,,,,0,1
18,10100083,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
19,10158113,Efficacy of preconditioning with intracoronary diltiazem in preventing laser-induced spasm.,M McIvor; C Undemir; J Moses; J Reddinger; J Lawson,"Laser energy produces a multitude of effects, resulting both in therapeutic tissue ablation and complications such as laser-induced spasm (LIS). LIS can occur during lasing itself or during subsequent adjunctive angioplasty. Intracoronary diltiazem (ICD) can partially reverse LIS after it occurs. To determine whether pre-treatment with ICD might prevent LIS during laser interventions, 3 groups of 50 lesions each were studied. Group 1 served as controls receiving no ICD during the procedure. Group 2 received 2.5 mg ICD before lasing. Group 3 received ICD before lasing and then a second infusion of 2.5 mg ICD after lasing but before adjunctive therapy. There were no differences in clinical characteristics of the 3 groups. Over 75% of lesions in each group were complex (B2 or C) lesions, and average lesion length was 15 mm in all 3 groups. Procedural success was > or = 94% in all groups. There was no significant difference among groups in pre-procedure artery stenosis, post-procedure stenosis, laser power used or number of laser pulses delivered. Pretreatment with ICD produced vasodilation of the minimum lumen diameter from 0.86 +/- 0.1 to 1.0 +/- 0.1 mm (p < 0.01) and was well tolerated. Control patients exhibited a 12% incidence of LIS. Group 2 had an 80% reduction of LIS during lasing (p < 0.01) but had increased LIS during adjunctive therapy with the same 12% incidence of LIS overall. Group 3 had only a 2% incidence of LIS (p < 0.01). We concluded that pretreatment with ICD significantly reduces LIS. Multiple infusions of ICD are necessary to sustain this protective effect.",1995.0,0,0
20,10172139,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.",1999.0,0,1
21,10183386,Gingival hyperplasia due to calcium antagonists.,,,1998.0,0,0
22,10189144,Incidence of cancer in postmyocardial infarction patients treated with short-acting nifedipine and diltiazem. Secondary Prevention Group.,K Kanamasa; A Kimura; M Miyataka; T Takenaka; K Ishikawa,"Recent reports suggest a possible link between nifedipine (but not diltiazem) and an increased risk of cancer in patients being treated with calcium antagonists. A total of 1054 postmyocardial infarction patients were divided randomly into those being treated with calcium antagonists (n = 566 [nifedipine, 425 patients and diltiazem, 141 patients]) and controls (no calcium antagonist; n = 488). The patients were followed for 26.3 months, and the incidences of cardiac events as well as cancer were compared among the 3 groups. Thirteen patients (2.7%) in the control group developed cancer, whereas 15 patients in the nifedipine group (3.5%; odds ratio, 1.34; 95% confidence interval [95% CI], 0.63-2.85) and 3 patients in the diltiazem group (2.1%; odds ratio, 0.89; 95% CI, 0.27-2.93) developed cancer. Diltiazem appears to present no increased risk of cancer. The incidence of cancer was slightly higher in the patients receiving nifedipine than in those not being treated with a calcium antagonist, which is consistent with earlier reports; however, this increase was not statistically significant.",2000.0,1,1
23,10192229,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
24,10192233,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
25,10195086,Cardiac risks with beta agonists.,B Lindmark,,1999.0,0,0
26,10197663,Antiischemic effects of nicardipine and nitroglycerin after coronary artery bypass grafting.,I A Apostolidou; G J Despotis; C W Hogue; N J Skubas; C A McCawley; E L Hauptmann; D G Lappas,"We assessed the efficacy of a continuous infusion of nicardipine and nitroglycerin in reducing the incidence and severity of perioperative myocardial ischemia during elective coronary artery bypass grafting procedures in a prospective, randomized, controlled study. Patients received either nicardipine infusion (0.7 to 1.4 microg x kg(-1) x min(-1); n = 30) or nitroglycerin (0.5 to 1 microg x kg(-1) x min(-1); n = 30) or neither medication (n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes (MIE) were considered to have occurred with ST-segment depressions or elevations of at least 1 mm and at least 2 mm (for both depressions or elevations), each at J + 60 ms and lasting at least 1 minute, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (p = 0.02) of the 1-mm or greater minutes per hour (3.2 +/- 1.2 minutes per hour) and eliminated the number (p = 0.02) of the 2-mm or greater minutes per hour (zero minutes per hour) when compared with control patients (17.2 +/- 5.6 minutes per hour and 0.17 minutes per hour, respectively) during the intraoperative postbypass period. Our results suggest that nicardipine lessened the severity of myocardial ischemia shortly after coronary revascularization and could be considered as an alternative to standard antiischemic therapy.",2001.0,0,0
27,10202197,,,,,0,0
28,10203199,Symptoms reported by elderly patients with isolated systolic hypertension: baseline data from the SYST-EUR trial. Systolic Hypertension in Europe.,C J Bulpitt; A E Fletcher; L Thijs; J A Staessen; R Antikainen; C Davidson; R Fagard; B Gil-Extremera; M Jääskivi; E O'Brien; P Palatini; J Tuomilehto,"To determine the symptomatic well-being of elderly persons with isolated systolic hypertension. Well-being determined during the placebo run-in period prior to entry to the Systolic Hypertension in Europe (SYST-EUR) trial. 641 People, 60 years or older with an average sitting blood pressure of 173/86 mm Hg. 33 Symptomatic complaints determined by a standard interview. The 437 women complained of 25% of the symptoms and the 204 men 21% (P<0.001). A markedly higher prevalence was observed in women compared with men for: pain in the joints of the hands (35% of women complained of this against 22% of men); 'racing heart' (33% against 17%); dry eyes (16% against 6%); blurring of vision (35% against 23%); cramps in the legs (43% against 31%); and a sore throat (15% against 7%). Nocturia was the most frequent complaint (68% in both sexes). Eight symptoms increased with age and one (rash) tended to decline. With increasing systolic pressure women also reported more headaches, unsteadiness, blurring of vision, irregular heart beat and 'racing heart' but, of these, only headaches increased with diastolic pressure. These observations were made after adjusting for age, blood sugar and body mass index (BMI) and were not observed in men. Higher blood sugars were associated with mouth ulcers, 'racing heart', blurring of vision and cramps in the legs. A higher BMI was associated with six symptoms, and a lower age of leaving education with eight. In men, alcohol consumption was related to 'racing heart', and smoking to wheezing and having a dry cough. A high level of complaint was associated with female gender, increasing age, blood sugar and BMI and a low age of leaving education.",1999.0,0,1
29,10204813,Ambulatory blood pressure profiles in essential hypertensives after treatment with a new once daily nifedipine formulation.,G Nold; C Herholz; M Sturm; R Hopf; B Lemmer,"The antihypertensive efficacy of a new controlled-release preparation of nifedipine developed for once daily administration was investigated in comparison with a standard therapy with sustained-release nifedipine given twice daily in a randomised, open crossover trial. Twenty-two patients with mild to moderate essential hypertension were enrolled. Ambulatory blood pressure monitoring (ABPM) was performed after a wash-out period and after a 3 weeks treatment with 40 mg controlled-release nifedipine once daily and 20 mg sustained-release nifedipine twice daily, respectively. ABPM data were evaluated by conventional linear analysis and by rhythm analysis. Both once daily and twice daily administration of nifedipine significantly reduced systolic blood pressure during the daytime and during the night when compared with baseline. The 24-h diastolic blood pressure was significantly decreased by both treatments, but only the once daily regimen significantly lowered both diastolic daytime and night-time means. Comparing systolic and diastolic blood pressures after both treatments, however, no significant differences were obtained. Both nifedipine treatments did neither greatly modify the circadian blood pressure pattern nor reflexly increase heart rate. In conclusion, once daily application of the controlled-release formulation of nifedipine resulted in a consistent and significant blood pressure reduction. Once daily and twice daily medications of nifedipine were about equally effective in lowering the elevated blood pressures.",1999.0,0,0
30,10213554,"Isradipine, raised glycosylated haemoglobin, and risk of cardiovascular events.",R P Byington; T E Craven; C D Furberg; M Pahor,,1999.0,0,0
31,10218748,Physical Symptoms Distress Index: a sensitive tool to evaluate the impact of pharmacological agents on quality of life.,R B Anderson; N K Hollenberg; G H Williams,"To examine whether the degree of stress associated with adverse physical side effects correlates with overall quality of life (QOL) and compliance rates. To determine if instruments used to assess QOL can detect differences between treatments that have no known central nervous system effects. This randomized, double-blind, parallel group study evaluated 180 to 480 mg of controlled onset, extended release (COER)-verapamil (n = 259) or 30 to 120 mg/d of nifedipine gastrointestinal therapeutic system (GITS) (n = 269) in men and women between 21 and 80 years of age with stages 1 to 3 hypertension. A battery of questions evaluating psychological well-being and a physical symptom distress index was administered after a 4-week placebo washout (baseline) and after 10 weeks of treatment or at dropout. Both treatments effectively lowered blood pressure, and there were no significant between-group differences in psychosocial QOL. A difference in the level of physical symptom distress was detected between treatments (P = .002; multivariate analysis of variance), with 7 significant univariate treatment effects, all favoring COER-verapamil, being noted-pedal edema, polyuria, rapid heart beat or palpitations, hives, muscle cramps, abdominal cramps, and headaches. Constipation-related distress increased significantly (P = .001) but to a similar extent with both treatments. The difference in symptom distress tended to predict compliance as there were more withdrawals in the nifedipine GITS group (n = 85) vs COER-verapamil group (n = 64) (P = .08). Patient-assessed physical symptom distress is a sensitive, simple technique to evaluate the effect of antihypertensive medications on QOL and tolerability, as shown by its ability to detect the improvement associated with COER-verapamil. Depending on the agents involved, the Physical Symptom Distress Index may more closely predict dropout rates than the traditional psychosocial instruments, as suggested by the lower dropout rate in the COER-verapamil group. Thus, in studying treatment effects on QOL, both the distress of physical symptoms and the impact of psychosocial factors should be evaluated.",1999.0,1,1
32,10220634,Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group.,H Emanuelsson; K Egstrup; K Nikus; J Ellström; T Glud; C Pater; M Scheibel; A Tisell; K J Tötterman; M Forsby,"The primary objective of this randomized, double-blind, parallel group trial was to compare the antianginal and antiischemic efficacy of a combination tablet of felodipine-metoprolol 10/100 mg once daily with both drugs given separately once daily in patients with stable effort-induced angina pectoris. The secondary objective was to compare the tolerability of the 3 treatments. The main criteria for inclusion were stable effort-induced angina pectoris for at least 2 months before the enrollment and a positive bicycle exercise test result. Patients were allocated to once-daily treatment with either felodipine-metoprolol 10/100 mg, felodipine 10 mg, or metoprolol 100 mg. The duration of active double-blind treatment was 4 weeks. There were 3 primary efficacy variables in the study; time until end of exercise, time until onset of chest discomfort, and time until 1-mm ST depression during a standardized exercise test. The number of patients randomized was 397. There was a statistically significant improvement in time until end of exercise with felodipine-metoprolol 10/100 mg compared with metoprolol 100 mg (P =.04) and felodipine 10 mg compared with metoprolol 100 mg ( P =.03). However, for time until onset of pain or time until 1-mm ST-depression there were no significant differences among the treatment groups. At highest comparable workload, ST depression was less pronounced with felodipine-metoprolol than with metoprolol alone (P =.04), and the rate-pressure product was significantly lower in the groups receiving felodipine-metoprolol and metoprolol than in the group receiving felodipine alone. The combination and metoprolol were better tolerated than felodipine alone. In stable angina pectoris, the combination felodipine-metoprolol 10/100 mg and felodipine 10 mg alone increased exercise time compared with metoprolol 100 mg. The combination tablet and metoprolol 100 mg alone showed a more favorable tolerability profile than felodipine 10 mg alone.",1999.0,0,1
33,10321444,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
34,10323641,Effects of long-acting versus short-acting calcium channel blockers among older survivors of acute myocardial infarction.,M W Gillman; D Ross-Degnan; T J McLaughlin; X Gao; D Spiegelman; E Hertzmark; L Goldman; S B Soumerai,"Recent studies have highlighted the potentially harmful effects of short-acting calcium channel blockers, especially of the dihydropyridine type, in patients with coronary heart disease. Some have argued that long-acting calcium channel blockers are safer, but few outcome data exist. The objective of the study was to compare the occurrence of adverse outcomes among recipients of long-acting versus short-acting calcium channel blockers, with dihydropyridines and non-dihydropyridines compared separately. The New Jersey Medicare population. A retrospective cohort study using linked Medicare and drug claims data. Older survivors of acute myocardial infarction (MI) occurring in 1989 and 1990. Eligible subjects had survived at least 30 days after the MI, participated in Medicare and a drug benefits program, and were prescribed a single type of either a long-acting or a short-acting calcium channel blocker within 90 days after the MI. The two outcome measures were rates of all-cause mortality and cardiac rehospitalization. Using separate Cox regression models for dihydropyridines (nifedipine, nicardipine) and non-dihydropyridines (diltiazem, verapamil), we examined these outcomes for recipients of long-acting compared with short-acting calcium channel blockers. Of the 833 patients eligible for the study, 160 were prescribed long-acting and 673 short-acting calcium channel blockers. Clinical characteristics of long-acting and short-acting users were comparable. During 2 years of follow-up, 221 deaths and 300 rehospitalizations occurred. Controlling for age, sex, race, and indicators of disease severity and comorbidity, the relative risk of dying for recipients of long-acting, compared with short-acting, dihydropyridines was .42 (95% confidence interval (CI), 0.21-0.86). For cardiac rehospitalization, the relative risk was 0.57 (95% CI, 0.34-0.94). For the long-acting versus short-acting nondihydropyridines, the adjusted relative risk of dying was 1.43 (95% CI, 0.88-2.32), and for cardiac rehospitalization, .65 (95% CI, 0.40-1.05). Use of long-acting dihydropyridine calcium channel blockers after acute MI was associated with substantially lower rates of cardiac rehospitalization and death compared with use of their short-acting counterparts. More data are needed to address the possibility that long-acting, compared with short-acting, non-dihydropyridines could decrease rehospitalization rates but increase mortality.",1999.0,1,1
35,10323823,Fortnightly review: management of hypertension in pregnancy.,L A Magee; M P Ornstein; P von Dadelszen,,1999.0,0,0
36,10335324,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
37,10336572,Combination of calcium channel blockers and beta-adrenoceptor blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. Netherlands Working Group on Cardiovascular Research (WCN).,J A Van Der Vring; M C Daniëls; N J Holwerda; P J Withagen; A Schelling; T J Cleophas; M G Hendriks,"The combination of calcium channel blockers and beta-adrenoceptor blockers is more effective for the treatment of exercise-induced angina pectoris than beta-adrenoceptor blocker monotherapy. As ischaemia in exercise-induced angina is preceded by increase in heart rate, calcium channel blockers with negative chronotropic properties may perform better for this purpose than nonchronotropic compounds. A 335 patient double-blind parallel-group study comparing 14 day treatment with amlodipine 5 and 10 mg, with diltiazem 200 and 300 mg, and mibefradil 50 and 100 mg added to baseline beta-adrenoceptor blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all significantly delayed onset of 1 mm ST-segment depression on ETT (P<0.001 for any treatment vs baseline). In addition, mibefradil, both low and high dose treatment, produced the longest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, respectively, P<0. 003 and <0.001; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, respectively, P<0.001 and <0.001). These effects were linearly correlated with the reduction in rate pressure product (RPP). Serious symptoms of dizziness occurred significantly more frequently on mibefradil (P<0.05), and 19 patients on mibefradil withdrew from trial. Calcium channel blockers with negative chronotropic properties provide greater delay of ischaemia in patients with exercise-induced angina, but the concomitant risk of intolerable dizziness attenuates this benefit.",1999.0,0,1
38,10336581,Retrospective analysis of the frequency and recognition of adverse drug reactions by means of automatically recorded laboratory signals.,I Tegeder; M Levy; U Muth-Selbach; R Oelkers; F Neumann; H Dormann; T Azaz-Livshits; M Criegee-Rieck; H T Schneider; E Hahn; K Brune; G Geisslinger,To estimate the frequency of adverse drug reactions (ADRs) identified through the use of automatic signals generated from laboratory data (ALS) in hospitalised patients. To determine the frequency of spontaneous recognition of these ADRs by the attending physicians and to assess the potential value of ALS for detection of ADRs. Laboratory results of patients hospitalised in a nine bed medical ward were automatically recorded over a period of 17 months. Values exceeding defined boundaries were used as ALS. Charts of every third patient were analysed retrospectively with regard to adverse drug related reactions and causality was evaluated as well as whether the ADR had been recognised during the period of hospitalisation. The charts and ALS of 98 patients were analysed. In 18 cases a drug-related adverse reaction was probable. Awareness to the reaction by the treating physicians was evident in 6 out of these 18 ADRs. Approximately 80% of the ADRs were considered predictable. Three ADRs were regarded as serious. Adverse drug reactions are common and often preventable. Only one third of ADRs which could have been detected through ALS were recognised by the attending physicians. An increased doctor's awareness of the frequency of drug related abnormal laboratory results by means of ALS is likely to increase the recognition rate of ADRs and might help to prevent them.,1999.0,0,0
39,10342920,Sustained-release nifedipine: new indication. Angina: safer drugs are available.,,"The efficacy of sustained-release osmotic tablets of nifedipine in the symptomatic treatment of stable angina is poorly documented.  The safety of nifedipine remains uncertain, as high-dose treatment with immediate-release preparations increased mortality in trials involving coronary patients.  In angina, nifedipine can be used only in combination with a betablocker, and only to treat patients with no recent history of myocardial infarction, or unstable angina. In stable angina with inadequate symptom control by betablockers, it is no more effective than other dihydropyridines also indicated in the treatment of angina, i.e. amlodipine and felodipine.  Furthermore, medium-term data on amlodipine are relatively reassuring. Nifedipine appears a little more effective than sustained-release nitrate derivatives, but less safe.",1999.0,0,0
40,10342928,Hypotension and coronary events on nifedipine: reassessing nifedipine safety.,,"Nifedipine administration for hypertensive emergencies can induce neurological and cardiac events due to abrupt hypotension.  Nifedipine also increase the risk of coronary events in case of unstable angina or recent myocardial infarction. In hypertensive emergencies, the potential advantages and risks of achieving a rapid fall in arterial pressure should be assessed case by case. In patients with coronary heart disease, nifedipine is contraindicated in case of recent myocardial infarction or unstable angina.  Nifedipine is only a second-line choice for stable angina, and should be combined with a betablocker.",1999.0,0,0
41,10348094,"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
42,10349897,"Meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina.",P A Heidenreich; K M McDonald; T Hastie; B Fadel; V Hagan; B K Lee; M A Hlatky,"Which drug is most effective as a first-line treatment for stable angina is not known. To compare the relative efficacy and tolerability of treatment with beta-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina. We identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies. Randomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (beta-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria. Two independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine). Rates of cardiac death and myocardial infarction were not significantly different for treatment with beta-blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P = .79). There were 0.31 (95% CI, 0.00-0.62; P = .05) fewer episodes of angina per week with beta-blockers than with calcium antagonists. beta-Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P<.001). The differences between beta-blockers and calcium antagonists were most striking for nifedipine (OR for adverse events with beta-blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few trials compared nitrates with calcium antagonists or beta-blockers to draw firm conclusions about relative efficacy. beta-Blockers provide similar clinical outcomes and are associated with fewer adverse events than calcium antagonists in randomized trials of patients who have stable angina.",2001.0,0,0
43,10355069,[Medicamentous prevention of symptomatic paroxysmal atrial fibrillation/flutter onset. Goals and design of the SOPAT Study. Executive committee of the investigators representing trial physicians].,M Patten; H P Koch; F Sonntag; B Lüderitz; T Meinertz,"The indication to treat symptomatic paroxysmal atrial fibrillation is discussed controversely. Successful medical treatment may result in the reduction of symptoms by improving hemodynamics in a reduction of thromboembolic events. However, several antiarrhythmic drugs are also known to increase the risk of proarrhythmic events. A randomized, double-blind, and placebo-controlled multicenter trial with 1000 patients to be recruited was designed to compare the effects of two antiarrhythmic drugs frequently used in Germany for the treatment of atrial fibrillation, Sotalol and the fixed combination of chinidin and verapamil (Cordichin). Patients with symptomatic paroxysmal atrial fibrillation/atrial flutter will be observed for a period of one year. The occurrence of paroxysmal atrial fibrillation is documented by transtelephonic ECG monitoring. Patients with document an ECG once daily, and recording is mandatory in case of symptoms. ECGs are transmitted to a central data base for analysis. This clinical trial is designed to answer the following questions: (1) What is the average rate of spontaneous events of symptomatic atrial fibrillation? (2) Is it possible to reduce the frequency of symptomatic events by chronic antiarrhythmic drug administration? (3) What is the long-term frequency for the occurrence of severe side-effects under antiarrhythmic medication? The primary endpoint is defined as the time to first recurrence of symptomatic arrhythmia after reaching steady-state plasma concentrations of the study medication. The trial started in November 1997 and is planned to be finished by the end of 1999.",1999.0,0,0
44,10355070,[Medicamentous prevention after electric cardioversion of chronic atrial fibrillation. Goals and design of the PAFAC Study].,T Fetsch; G Burschel; G Breithardt; R Engberding; H P Koch; J Lukl; H J Trappe; N Treese,"Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. However, despite manifold publications reflecting numerous clinical trials about treatment of AF, the management of this arrhythmia is still under controversial discussion, in daily clinical work as well as in research. The present study concentrates on three major questions: 1. How frequent are recurrences of AF in long-term follow-up? Most of the previous studies used the occurrence of symptoms as a surrogate parameter for recurrences of AF, despite the expected high rate of asymptomatic relapses. In the present study a daily transtelephonic ECG transmission enables a rhythm monitoring independent of symptoms. 2. Is the frequency of AF recurrences significantly reduced by antiarrhythmic medication? A direct comparison of class I and III antiarrhythmic drugs, which still are most frequently used for this indication, and of placebo will answer this question. 3. How safe is the long-term treatment for the prevention of AF recurrences with special respect to proarrhythmic effects? The daily transtelephonic ECG transmission enables a quantitative and qualitative monitoring of tachy- and bradyarrhythmias independent of symptoms. Additionally, the daily analysis of ECG measures may detect parameters predicting subsequent life threatening arrhythmias. The study design provides a prospective, randomised, double-blind, placebo controlled, multicenter parallel group comparison. In Germany and in the Czech Republic about 90 hospitals will include 900 patients with documented chronic AF, age 18 to 80 years, if they are eligible for electrical cardioversion without concomitant antiarrhythmic drug therapy and if they are anticoagulated for at least three weeks prior to inclusion. Neither the size of the left atrium nor the duration of chronic AF are exclusion criteria. A few hours after successful electrical cardioversion the patients are randomised either to sotalol (2 x 160 mg) or quinidine + verapamil (3 x 160 mg + 3 x 80 mg) or placebo. Starting at the day after cardioversion, the patient is asked to record and transmit electrocardiograms of one minute duration at least once a day using his personal transtelephonic ECG recording unit (Tele-ECG recorder, credit card size), in case of symptoms as often as necessary. The ECGs can be transmitted at any time by any regular phone without additional equipment using a toll free number. A custom made, computer based, fully automated receiving centre is handling the patient calls interactively with voice control, including a voice recording of the patient's symptoms. The ECG tracings and the patient's voice messages are subsequently computer based analysed by experienced technicians. All ECG measures are stored in a database. In case of AF recurrence, any other relevant arrhythmia or additional abnormalities (e.g. QT prolongation) the correspondent hospital is immediately informed by fax. In case of AF recurrence, a subsequent Holter recording discriminates in paroxysmal and permanent AF. Study medication is ended if either permanent AF or the third episode of paroxysmal AF are detected or after 12 months of follow-up. Regular follow-up visits are performed monthly. Major endpoints are the time to first recurrence of AF or the time to death, secondary parameters are the number of AF recurrences, the time to end of medication and AF related symptoms. The recruitment started in the last days of 1996. Until the end of June 1998, 424 patients have been randomised. It is expected to end recruitment in spring 1999 and to close the study in spring 2000. Final results will be available in summer 2000.",1999.0,0,0
45,10362225,ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina).,R J Gibbons; K Chatterjee; J Daley; J S Douglas; S D Fihn; J M Gardin; M A Grunwald; D Levy; B W Lytle; R A O'Rourke; W P Schafer; S V Williams; J L Ritchie; M D Cheitlin; K A Eagle; T J Gardner; A Garson; R O Russell; T J Ryan; S C Smith,,2001.0,0,0
46,10373236,Update on the systolic hypertension in Europe (Syst-Eur) trial. The Syst-Eur Investigators.,J A Staessen; L Thijs; W H Birkenhäger; C J Bulpitt; R Fagard,,1999.0,0,1
47,10378820,Combination of calcium channel blockers and beta blockers for patients with exercise-induced angina pectoris: a double-blind parallel-group comparison of different classes of calcium channel blockers. The Netherlands Working Group on Cardiovascular Research (WCN).,J A van der Vring; M C Daniëls; N J Holwerda; P J Withagen; A Schelling; T J Cleophas; M G Hendriks,"The combination of calcium channel blockers and beta blockers is more effective for the treatment of exercise-induced angina pectoris than beta blocker monotherapy. Since ischemia in exercise-induced angina is essentially preceded by an increase in heart rate, calcium channel blockers with negative chronotropic property may perform better for this purpose than nonchronotropic compounds. A 335-patient, 10-week, double-blind, parallel-group comparison of amlodipine 5 and 10 mg, diltiazem XR 200 and 300 mg, and mibefradil 50 and 100 mg treatment added to baseline beta blocker treatment was performed. Exercise testing (ETT) was performed by bicycle ergometry. Although none of the calcium channel blockers improved duration of exercise or amount of workload, all of them significantly delayed onset of 1 mm ST segment depression on ETT (p<0.001 for any treatment versus baseline). In addition, mibefradil, both low- and high-dose treatment, produced the largest delays (low dose: different from diltiazem and amlodipine by 24.1 and 29.8 s, p<0.003 and <0.001, respectively; high dose: different from diltiazem and amlodipine by 33.7 and 37.0 s, p<0.001 and <0.001, respectively). These effects were linearly correlated to the amount of rate pressure product (RPP) reduction. Serious symptoms of dizziness likewise occurred significantly more frequently with mibefradil (p<0.05) and led 19 patients taking mibefradil to withdraw from the trial. The authors conclude that calcium channel blockers with negative chronotropic property provide better delay of ischemia in patients with exercise-induced angina but that the concomitant risk of intolerable dizziness largely reduces this benefit.",1999.0,0,1
48,10389531,"[Lowering of diastolic blood pressure < or = 90 mmHg should not be attempted, except in type 2 diabetics; the 'Hypertension optimal treatment' (HOT) trial].",H Wesseling,"Recently the 'Hypertension optimal treatment' (HOT) study was reported. In this study 18,790 patients with diastolic blood pressure between 100 and 115 mmHg were randomly assigned target pressures of < or = 90, < or = 85 and < or = 80 mmHg respectively, and treated with a felodipine-based antihypertensive regimen. In all three groups an impressive fall in both diastolic and systolic blood pressures, and as a consequence very few major cardiovascular events (the primary endpoint of the study) were observed, but there was no difference in endpoint scores among the three groups. Type 2 diabetic patients fared substantially better than non-diabetic patients and they are likely to profit if their diastolic pressure is decreased below 80 mmHg. In the remaining patients rigorous maintenance of present-day standards (diastolic pressure < or = 90 mmHg) is advised. The addition of 75 mg aspirin 1 dd resulted in a modest but significant reduction of major cardiovascular events, but at the cost of increased gastrointestinal bleedings.",1999.0,0,0
49,10394257,Comparison of bisoprolol and verapamil in hypertension: influence on left ventricular mass and function--a pilot study.,P Gosse; V Gressin; P Clerson; P Lemetayer; J Clémenty,"The objective of this study was to test the influence of bisoprolol and verapamil on left ventricular filling in hypertensive patients in a 6 month randomized, double-blind trial in 54 hypertensive patients not previously treated with beta-blockers or calcium inhibitors. After administration of placebo for 14 days, an M echocardiogram of the left ventricle was recorded to determine left ventricular mass. Blood flow was evaluated by pulsed Doppler sonography. After randomization into two groups, one group received 10 mg of bisoprolol and the other 240 mg of verapamil LP in a single dose in the morning. After 2 months' treatment, the patients whose blood pressure was not well controlled were given a diuretic. Echo-Doppler was performed again by the same operator after 4-10 days on active treatment, after 6 months and after a subsequent 2 weeks of placebo for the patients treated with a single drug. The reduction in blood pressure was comparable in the two treated groups, but there was no significant decrease in left ventricular mass. Left ventricular filling was improved only in the patients receiving bisoprolol. The effect was observed immediately after the first administration and throughout the 6 months' treatment period declining slowly during the placebo wash-out. This effect appeared to be independent of any alteration in heart rate and was thought to be a specific action of this drug.",1999.0,0,0
50,10403616,Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients.,M Petretta; V Canonico; A Madrid; M Mickiewicz; L Spinelli; F Marciano; A Vetrano; A Signorini; D Bonaduce,"We evaluated the effect of two calcium channel blockers, verapamil and felodipine, on heart rate variability in hypertensive patients. Time and frequency domain measures of heart rate variability were obtained from 24 h Holter recording in 25 previously untreated hypertensive patients without left ventricular hypertrophy, before and after 3 months of verapamil slow-release treatment (240 mg once daily) or felodipine extended-release treatment (10 mg once daily). Blood pressure values decreased with both drugs. Measures of heart rate variability, comparable at baseline in the two groups, were unchanged after felodipine. After verapamil, the average RR interval, the square root of the mean of the squared differences between all adjacent normal RR intervals (r-MSSD) and the percentage of differences between all adjacent normal RR intervals > 50 ms (pNN50), measures of vagal modulation of heart rate, increased (from 735 +/- 67 to 827 +/- 84 ms, P < 0.001; from 30 +/- 10 to 44 +/- 15 ms, P < 0.001; and from 3 +/- 2 to 7 +/- 6%, P < 0.01, respectively) and were higher than after felodipine. The coefficient of variation, a measure that compensates for heart rate effects, increased only after verapamil (from 5.8 +/- 1.3% to 6.6 +/- 1.0%; P < 0.05). High frequency power and its coefficient of component variance, both representing the vagal modulation of heart rate, increased after verapamil (from 5.33 +/- 0.29 to 5.80 +/- 0.27 In units, P < 0.001 and from 1.9 +/- 0.3 to 2.2 +/- 0.25%; P < 0.05). Finally, the low to high frequency power ratio, an indicator of sympathovagal balance, with a high value suggesting a sympathetic predominance, decreased after verapamil (from 2.16 +/- 0.41 to 1.36 +/- 0.35; P < 0.001), confirming the improvement in vagal modulation of heart rate. In hypertensive patients, despite a comparable anti-hypertensive effect, verapamil, but not felodipine, has favourable effect on cardiac autonomic control.",1999.0,0,0
51,10411366,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
52,10412882,Prolonged antihypertensive effect of amlodipine: a prospective double-blind randomized study.,P Biston; C Mélot; J P Degaute; D Clement; A Quoidbach,"Amlodipine is a calcium antagonist with a long elimination half-life (35 to 50 h) allowing a once daily dosing in the treatment of hypertension. This randomized, double-blind study was performed to assess the residual antihypertensive effect of amlodipine 5 mg O.D. 3 days after discontinuing therapy in previously well-controlled mild to moderate hypertensive patients. Blood pressure (BP) was evaluated by conventional (OBP) and by ambulatory blood pressure monitoring (ABPM). Amlodipine 5 mg OD administered during a 6-week period, significantly reduced both OBP and ABPM mean values (p < 0.05), whereas no change in heart rate was observed. At the end of the active treatment period, adequately controlled patients were randomized either to amlodipine 5 mg OD (group A) or amlodipine for 12 days followed by a 3-day period on placebo. After this double-blind treatment phase, group P exhibited no significant increase in BP (assessed by OBP or ABPM) when compared to group A. In conclusion, the duration of action of amlodipine extends largely beyond the 24-h span, and when patients omit their treatment for 3 days BP does not significantly increase.",1999.0,0,0
53,10417501,"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.",1999.0,1,1
54,10418209,Comparison of clinical efficacy and adverse effects between extended-release felodipine and slow-release diltiazem in patients with isolated systolic hypertension.,M S Chern; F C Lin; D Wu,"Isolated systolic hypertension (ISH) is a risk factor for cardiovascular disease. Extended-release felodipine (felodipine ER) has been shown to be effective in the treatment of ISH in Caucasians. However, its pharmacological properties are different from another calcium blocker, diltiazem. Also, the effectiveness, tolerability, and adverse reactions of these two antihypertensive agents for ISH have not been thoroughly assessed in Chinese. Sitting blood pressures (BP), heart rate, body weight, adverse reactions, and serum biochemistry were assessed in 70 patients with isolated systolic hypertension (34 treated with felodipine ER and 36 slow-release diltiazem [diltiazem SR] for 10 weeks). Each patient was given 5 mg of felodipine ER or 90 mg of diltiazem SR once daily and was doubled to twice daily if necessary. Five patients on felodipine ER and four on diltiazem SR withdrew because of intolerable side effects. By ten weeks, 67.6% of the patients responded to a daily dose of 5-10 mg of felodipine ER and 58.3% to a daily dose of 90-180 mg of diltiazem SR. At the end of treatment, felodipine ER lowered the mean BP from 187/83 mmHg at baseline to 149/74 mmHg, whereas diltiazem SR decreased the BP from 185/84 mmHg to 158/78 mmHg (not significant between the two groups). The heart rate did not change significantly in either group. Overall, these two groups of patients had the same rate of adverse reactions (50.0% vs. 50.0%) with similar profiles of the adverse effects. Equivalent doses of felodipine ER and diltiazem SR are effective first-line monotherapeutic agents for the treatment of ISH.",1999.0,0,0
55,10420860,Systematic review of antihypertensive therapies: does the evidence assist in choosing a first-line drug?,J M Wright; C H Lee; G K Chambers,,2000.0,0,1
56,10433352,A risk-benefit assessment of therapies for premature labour.,K Higby; C R Suiter,"Prematurity is the leading cause of neonatal morbidity and mortality, yet the incidence of preterm birth has not declined despite the use of multiple pharmacological agents to treat preterm labour. After reviewing the literature we conclude the following. beta-Agonists have been shown to prolong gestation for 24 to 48 hours; however, these agents have not been shown to decrease neonatal morbidity or mortality. Adverse effects are inevitable and can be life-threatening. There are no proven benefits to mother or fetus with long term therapy. More data are needed regarding the tolerability and efficacy of calcium antagonists before routine clinical use can be recommended. Oxytocin antagonists should be considered investigational drugs and further studies are needed to evaluate their effectiveness in the treatment of preterm labour. Furthermore, the tolerability of oxytocin antagonists in both mother and fetus has not been adequately established. Indomethacin, a prostaglandin inhibitor, has been shown to delay delivery in a limited number of randomised placebo-controlled clinical trials. Sulindac appears promising but has never been evaluated in a well controlled trial. Neonatal adverse effects appear to be minimal with prostaglandin inhibitors as long as the duration of treatment is short (<48 to 72 hours) and the gestational age is <32 weeks. Magnesium sulfate appears to inhibit myometrial contractility but is ineffective at prolonging gestation or preventing preterm birth. Furthermore, magnesium has not been shown to decrease neonatal morbidity or mortality; in fact, some investigators have shown an increase in infant mortality with this agent. There are no data to support adjunctive antimicrobial therapy for the treatment of preterm labour. Oral maintenance therapy with any of these tocolytic agents has not been shown to decrease the rate of preterm birth or recurrent preterm labour.",1999.0,0,0
57,10440636,Density of CD1a-labeled Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth.,P K Nurmenniemi; H E Pernu; M L Knuuttila,"The purpose of this study was to compare the distribution of Langerhans' cells in normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth by means of an immunohistochemical study. Gingival samples were collected from 11 nifedipine-medicated cardiac patients, 22 triple-medicated (azathioprine, prednisolone, and cyclosporin A) renal transplant recipients, and 28 generally healthy individuals. Patients were grouped into the immunosuppression group, the combined immunosuppression and nifedipine group, the nifedipine group, and the generally healthy control group. Five microm-thick cryostat sections were stained with monoclonal antibody (mAb) for CD1a using an avidin-biotin-enzyme complex (ABC) method. Numbers of CD1a-labeled cells/mm2 were determined in 6 areas: oral epithelium, oral sulcular epithelium, sulcular epithelium, middle connective tissue, connective tissue beneath the oral epithelium, and connective tissue beneath the sulcular epithelium. Significances of differences between the groups were tested by means of the Kruskall-Wallis test, and significances of differences between pairs of results by the Mann-Whitney U-test and the t test. Numbers of CD1a-labeled cells were significantly lower in the medicated groups than in controls in all 3 epithelial areas (P <0.0001) and in the connective tissue beneath the sulcular epithelium (P <0.0021). There were significantly fewer CD1a-labeled cells in the sulcular epithelium in the nifedipine group than in the other medication groups. The reduced numbers of CD1a-labeled cells found in nifedipine-induced gingival overgrowth were similar to the reduced numbers of CD1a-labeled cells in gingival overgrowth associated with immunosuppressive medication.",1999.0,0,0
58,10442506,Effects of amlodipine and enalapril on platelet function in patients with mild to moderate hypertension.,R Hernández-Hernández; M C Armas-Padilla; M Velasco; A R Carvajal; M J Armas de Hernández; J Guerrero-Pajuelo; B Pacheco,"The aim of this study was to compare the effect of amlodipine and enalapril on platelet aggregation, and platelet production of malondialdehyde in patients with mild to moderate arterial hypertension. A parallel, double-blind, placebo-controlled study was carried out in 24 patients (2 groups of 12 patients each). Initially all patients received placebo for four weeks; then amlodipine, 5 mg daily or enalapril 20 mg daily taken once a day at 7 am. Dosage was doubled after 4 weeks when diastolic blood pressure was > 90 mmHg in sitting position, the treatment was continued for 12 weeks. At the end of placebo and active phases a platelet aggregation test, using adenosine diphosphate, collagen and adrenaline, and a platelet malondialdehyde production test, either in basal conditions (MDA-basal) and after the stimulation of arachidonic acid pathway by adding ethylmaleimide (MDA-activated) were carried out. Blood pressure was reduced by both agents, enalapril and amlodipine. Enalapril controlled 58.3% of hypertensive patients with an average dosage of 31.7 mg/daily. Amlodipine controlled 75% of patients with a dosage of 7.1 mg/daily. Platelet aggregation was reduced by amlodipine in 15.9% for ADP (10 microM); 17.4% for collagen (2 microg/ml) and 19.9% for adrenaline (2 microM) (p < 0.025). Meanwhile enalapril slightly increased platelet aggregation by 6.7%, 1.3% and 5.6% for the three agents, respectively (p > 0.05, ns). Malondialdehyde was reduced by amlodipine in 45.33% (p < 0.05) for MDA-basal; 3.76% (p > 0.05) for MDA-activated; and the ratio MDA-basal:MDA-activated in 36.79% (p < 0.005). Meanwhile enalapril increased MDA-basal in 2.89%; MDA-activated in 3.58% and reduced the ratio MDA-basal:MDA-activated, in 10.34% (p > 0.05). Both agents, enalapril and amlodipine, reduced blood pressure, but only amlodipine reduced platelet aggregation and platelet production of malondialdehyde, indicating its action on the arachidonic acid metabolic pathway.",1999.0,0,0
59,10443063,Comparison of antihypertensive efficacy and tolerability of losartan and extended-release felodipine in patients with mild to moderate hypertension.,M J Hung; F C Lin; W J Cherng; C H Wang; K C Hung; I C Hsieh; M S Wen; D Wu,"Appropriate control of blood pressure has been shown to reduce morbidity and mortality in patients with hypertension. Losartan potassium, a selective antagonist of the angiotensin II type 1 (AT1) receptor, has been shown to lower blood pressure in patients with hypertension. The purpose of this study was to compare the efficacy and tolerability of losartan and extended-release (ER) felodipine in Taiwanese patients with mild to moderate hypertension. Patients with mild to moderate hypertension (sitting diastolic blood pressure, 95-115 mm Hg) were enrolled in this prospective, randomized, parallel study. Sitting blood pressure, heart rate, adverse reactions, and serum biochemistry values were assessed during 2 weeks of placebo and 12 weeks of active treatment. Each patient received 50 mg of losartan or 5 mg of felodipine ER once daily, and the dosage was adjusted to double the initial level at week 6 if necessary. Of the 44 patients randomly allocated to receive losartan (n = 23) or felodipine (n = 21) therapy, 37 completed the study; three patients in the losartan group and four in the felodipine group withdrew because of adverse experiences, or were lost to follow-up. The mean reductions in sitting diastolic blood pressure at 6 and 12 weeks were significant with both losartan (-8.6 and -11.38 mm Hg, respectively) and felodipine (-9.2 and -10.69 mm Hg, respectively), and did not differ significantly between the two groups. Both losartan and ER felodipine were well tolerated by patients. However, the ER felodipine group had a significantly higher rate of drug-related flushing than the losartan group (24% vs 0%, p = 0.022). The results indicate that once-daily administration of losartan is as effective and well tolerated as once-daily ER felodipine in blood pressure reduction.",1999.0,0,0
60,10449203,Diuretic therapy for hypertension: a cancer risk?,G Y Lip; R E Ferner,,1999.0,0,0
61,10449212,Comparison between isosorbide dinitrate aerosol and nifedipine in the treatment of hypertensive emergencies.,A F Rubio-Guerra; G Vargas-Ayala; J J Lozano-Nuevo; J L Narvaez-Rivera; L Rodriguez-Lopez,"Nitric oxide donors have been used in the management of hypertensive emergencies (HE). Isosorbide dinitrate aerosol (ISA) is a nitric oxide fast-acting donor. The aim of this study is to compare the efficacy of ISA and nifedipine in the treatment of HE. Sixty adult patients with an HE were randomised to receive either ISA (2.5 mg) or nifedipine (10 mg). Patients were given an electrocardiogram (ECG) immediately prior, and 30 min after administering the medication. Blood pressure (BP) was measured every 5 min for the first 30 min, and then every 30 min for a period of 6 h. Blood pressure values for all patients in the ISA group decreased significantly (187 +/- 13/121 +/- 6 to 153 +/- 15/92.3 +/- 7.6 mmHg, P < 0.005). Two of the patients in this group had angor pectoris with evidence of subepicardial ischaemia as seen in the first ECG, both of which disappeared with the drug. Heart rate decreased by 14%. Similarly, all patients in the nifedipine group had significant decreases in BP (190 +/- 23/115 +/- 7 to 153 +/- 26/86 +/- 6 mm Hg, P < 0.005). Their first ECG was normal. Two patients suffered angor pectoris after nifedipine, with subepicardial ischaemia registering in the second ECG. Heart rate increased 11.9% in this group. During the follow-up period, no clinically significant side effects or cases of rebound hypertension were observed in the ISA group, whereas in the nifedipine group, eight patients reported having headaches and four others rebound hypertension. Our results show a favourable effect of ISA in the treatment of HE.",1999.0,0,0
62,10449213,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
63,10454779,Efficacy of amlodipine in pediatric patients with hypertension.,K B Tallian; M C Nahata; M A Turman; J D Mahan; J R Hayes; M I Mentser,"We designed a study to determine the efficacy and safety of amlodipine given once daily in the pediatric population. Twenty-one patients (mean age 13.1 years) with either essential (n=160) or renal (n=5) hypertension, and newly diagnosed (n=15) or poorly controlled or intolerant on existing antihypertensive therapy (n=6), were included. Patients received amlodipine once daily at a starting mean dose of 0.07+/-0.04 mg/kg per day. The total daily dose of amlodipine was increased 25%-50% every 5-7 days if the mean home blood pressure measurements (HBPM) were above the 95th percentile for age and gender. A baseline followed by a repeat 24-h ambulatory blood pressure monitor study (ABPM) was performed in 20 patients when the mean HBPM was below the 95th percentile goal. The mean titrated dose required to control BP was 0.29+/-0.11 mg/kg per day for those < 13 years, 0.16+/-0.11 mg/kg per day for those > or = 13 years, 0.23+/-0.14 mg/kg per day for essential, hypertension and 0.24+/-0.13 mg/kg per day for renal hypertension. The ABPM demonstrated that amlodipine provided effective BP control as primary therapy in 14 essential patients. Adverse effects included fatigue (n=6), headache (n=5), facial flushing (n=4), dizziness (n=3), edema (n=3), abdominal pain (n=3), chest pain (n=2), nausea (n=1), and vomiting (n=1). Quality of life appeared to improve during therapy. Amlodipine was an effective once daily antihypertensive agent with an acceptable safety profile. Higher doses of amlodipine were required for younger patients, and monotherapy was effective in patients with essential hypertension.",1999.0,0,0
64,10457878,"Comparison of intravenous metoprolol, verapamil and diltiazem on the attenuation of haemodynamic changes associated with tracheal extubation.",D Yörükoğlu; A Göktug; Z Alanoğlu; M Tulunay,"Changes in heart rate, systolic, diastolic and mean blood pressure were measured after extubation in 60 ASA Grade I and II patients to assess the effects of diltiazem (0.2 mg kg-1), verapamil (0.05 mg kg-1) and metoprolol (0.02 mg kg-1) given as a bolus 2 min before tracheal extubation. All the haemodynamic variables measured increased significantly after extubation in the control and diltiazem groups when compared with the base-line recordings (P < 0.05). Metoprolol effectively blocked the increases in heart rate after extubation and the increase in blood pressure in this group was less when compared with the control group (P < 0.05). Verapamil alleviated the increase in both heart rate and blood pressure. However, profound hypotension and bradycardia requiring therapy, occurred in the verapamil group. For this reason, careful observation is necessary when using verapamil and the routine use of this drug in patients with coronary artery disease requires further studies.",1999.0,0,0
65,10460781,Hypertension and diabetic retinopathy--what's the story?,J T Gillow; J M Gibson; P M Dodson,,1999.0,0,0
66,10470991,"Acute hypotensive, natriuretic, and hormonal effects of nifedipine in salt-sensitive and salt-resistant black normotensive and hypertensive subjects.",A Damasceno; A Santos; M Pestana; P Serrão; P Caupers; P Soares-da-Silva; J Polónia,"In a randomized double-blind study, we compared the short-term effects of nifedipine (10 mg 3x daily for 1 day) versus placebo on 24-h blood pressure, diuresis, natriuresis, urinary excretion of dopamine and metabolites, and on plasma renin activity (PRA) and plasma aldosterone levels in 18 black hypertensive (HT) patients [eight salt-resistant (HT-SR) and 10 salt-sensitive (HT-SS)], and in 20 black normotensive (NT) subjects (12 NT-SR and eight NT-SS) who were studied randomly with both a high- (HS) and a low-salt (LS) diet. In comparison to placebo, nifedipine significantly decreased 24-h mean BP in all groups either with HS or LS diets (all p<0.05). With HS, greater hypotensive effects were achieved in NT-SS (-10+/-2 mm Hg) versus NT-SR (-3+/-1 mm Hg; p<0.05) and in HT-SS (-18+/-2 mm Hg) versus HT-SR (-12+/-2 mm Hg; p<0.05). In NT-SS and HT-SS, nifedipine induced greater (p<0.05) BP decrease with HS (-10+/-2 and -18+/-2 mm Hg) than with LS (-4+/-1 and -9+/-1 mm Hg, respectively), whereas in NT-SR and HT-SR, the hypotensive effect did not differ between HS and LS. Nifedipine versus placebo significantly increased natriuresis and fractional excretion of sodium in all groups only with HS (p<0.05) but not with LS diets. Only in HT-SS were the hypotensive and natriuretic effects of nifedipine significantly correlated (r = -0.77; p<0.01). Nifedipine produced a similar increase of the urinary excretion of dopamine, L-DOPA, and of DOPAC in all subjects, which did not correlate with hypotensive and natriuretic effects. Nifedipine did not modify plasma levels of renin and of aldosterone except in NT-SS with HS, in whom nifedipine increased PRA levels (p <0.05). We conclude that although nifedipine reduces BP in all groups of NT and HT with LS and HS diets, the effect is greater in salt-sensitive subjects with HS. Although in HT-SS with HS, the short-term natriuretic response to nifedipine may contribute to its hypotensive effects, the diuretic-natriuretic effect of nifedipine is not necessary for the expression of its hypotensive effect. Moreover, it is unlikely that any short-term effects of nifedipine either on the renal dopaminergic system or on the secretion of aldosterone explain nifedipine short-term hypotensive and diuretic-natriuretic effects.",1999.0,0,0
67,10483964,Pretreatment with verapamil in patients with persistent or chronic atrial fibrillation who underwent electrical cardioversion.,A De Simone; G Stabile; D F Vitale; P Turco; M Di Stasio; F Petrazzuoli; M Gasparini; C De Matteis; R Rotunno; T Di Napoli,"To evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion (C). The increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload. One hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C. During the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04). Six days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone.",1999.0,0,0
68,10486668,[Effect of intensive antihypertensive treatment and of aspirin in a low dose in the hypertensive. The HOT (Hypertension Optimal Treatment) study].,J M Mallion; A Benkritly; L Hansson; A Zanchetti,"The aim of the HOT Study (Hypertension Optimal Treatment) was to determine the optimal diastolic blood pressure decrease and to assess the effect of the acetyl salicylic acid as a primary prevention on the cardiovascular morbidity and mortality in hypertensive patients. The HOT Study is an open, prospective, randomised, international trial with blinded end points. This study included 18,790 patients, 50 to 80 years old (mean 61.5 years) in 26 countries (1,574 patients in France) with a primary hypertension (100 < or = PAD < or = 115 mmHg). The patients were randomised in 3 target diastolic blood pressure: < or = 80 mmHg (n = 6,262), < or = 85 mmHg (n = 6,264), < or = 90 mmHg (n = 6,264). The felodipine LP, a long acting dihydropyridine, was selected as a first line therapy, other hypertension drugs combined if necessary. The lowest incidence of cardiovascular events was observed at a diastolic blood pressure level of 82.6 mmHg. There was no increased risk below this level even in the hypertensive patients with medical history of coronary heart disease or stroke. In the diabetic population, the diastolic blood pressure decrease from 90 to 80 reduced the incidence of the major cardiovascular events by 51%. The acetyl salicylic acid reduced the myocardial infarction risk in the blood pressure well-controlled population.",1999.0,0,0
69,10486696,Effect of amlodipine on exercise-induced platelet activation in patients affected by chronic stable angina.,V Sanguigni; M Gallù; L Sciarra; D Del Principe; A Menichelli; G Palumbo; D Cannata; A Strano,"Literature concerning exercise-induced platelet activation in chronic stable angina is somewhat confusing. The reason lies in the type of exercise as well as in methodological problems. A powerful, recently introduced procedure to detect platelet activation is flow cytometry. Platelet response to activating factors is mediated by calcium uptake; however, calcium antagonist effect on platelet activity is still unclear. The study was undertaken to investigate exercise-induced platelet activation before and after treatment with amlodipine in chronic stable angina. Twenty patients with chronic stable angina were entered into the study. Each subject underwent a symptom-limited cycloergometer stress test following a washout period of 2 weeks. Blood samples were collected before and immediately after exercise. All subjects were then randomized into two groups of 10 patients each, with Group 1 and Group 2 taking amlodipine 10 mg/day, and placebo for 4 weeks, respectively. They subsequently underwent a second exercise stress test, and blood samples were obtained before and immediately after exercise. Flow-cytometric evaluation of platelet activity was performed in order to recognize GMP-140 expression on platelet membrane. Strenuous exercise induced a significant increase in platelet activation in all subjects prior to therapy. No significant differences were observed in platelet activity at rest between Groups 1 and 2, whereas a significant decrease in exercise-induced platelet activation was demonstrated in Group 1 compared with Group 2. Our data provide evidence of the favorable effect of amlodipine on exercise-induced platelet activation in patients affected by chronic stable angina.",1999.0,0,0
70,10499144,Pharmacovigilance: characteristics of the most widely used drugs in Bulgaria.,I Getov; Z Dimitrova,"In the present study we analysed registered adverse drug reactions caused by 19 most used drugs in Bulgaria during three-year period. The cases were assembled from the spontaneous reporting system operated in our country. We described demographic characteristics of the patients, clinical diagnosis and reporting rates per 100,000 inhabitants for each drug. The data for antibiotics were compared with the results of our previous research. We analysed 188 adverse drug reactions i.e. 21% of all reports received in the Centre for Drug Safety of the National Drug Institute. Adverse drug reactions type B such as oedema, allergy, coma, etc. predominate. The number of cases with perforated ulcer and melaena caused by acetylsalicylic acid is considerable. The frequency of adverse drug reaction for the investigated drugs in ""rare"" according to WHO standards. It is necessary to assemble more information on adverse drug reactions and every serious case and inform medical doctors and pharmacists as a first step for improving the pharmacovigilance system in Bulgaria.",1999.0,0,0
71,10513787,Atenolol versus amlodipine versus isosorbide-5-mononitrate on anginal symptoms in syndrome X.,G A Lanza; G Colonna; V Pasceri; A Maseri,"The effects of a beta blocker (atenolol), a calcium antagonist (amlodipine), and a nitrate (isosorbide-5-mononitrate) on anginal symptoms in 10 patients with syndrome X were assessed in a crossover, double-blind, randomized trial. Only atenolol was found to significantly improve chest pain episodes, suggesting that it should be the preferred drug when starting pharmacologic treatment of patients with syndrome X.",1999.0,0,1
72,10522582,Combined diltiazem and lidocaine reduces cardiovascular responses to tracheal extubation and anesthesia emergence in hypertensive patients.,Y Fujii; Y Saitoh; S Takahashi; H Toyooka,"Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to compare the efficacy of combined diltiazem and lidocaine with each drug alone in suppressing the hemodynamic changes during tracheal extubation. Sixty hypertensive patients (ASA II), defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg (WHO), undergoing elective orthopedic surgery received, in a randomized, double-blind manner, 0.2 mg x kg(-1) diltiazem, 1.0 mg x kg(-1) lidocaine, or 0.2 mg x kg(-1) diltiazem plus 1.0 mg x kg(-1) lidocaine (n=20 of each) i.v. before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation. Hemodynamic changes during tracheal extubation were less in patients receiving diltiazem plus lidocaine than in those receiving diltiazem or lidocaine as a sole medicine (RPP; 10322 +/- 1674 (combined) vs 11532 +/- 1802 (diltiazem), 15388 +/- 2050 (lidocaine), mean +/- SD, P < 0.05). Combined diltiazem and lidocaine is more effective prophylaxis than diltiazem or lidocaine alone for attenuating the cardiovascular responses to tracheal extubation and emergence from anesthesia in hypertensive patients.",1999.0,0,0
73,10523477,Effectiveness of nifedipine GITS in combination with atenolol in chronic stable angina.,C B Toal; M Motro; M G Baird; P Klinke; S Sclarowski; A Zilberman; A Marmor; W J Kostuk; C Lotan; A Weiss; P Erne; A Palant; D Stolero; L Bélanger; A Turpie,"Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides stable plasma concentrations over the entire 24 h dosing interval. Two-hundred and one patients with Canadian Cardiovascular Society class II to III angina who were on 50 mg of atenolol yet still experiencing angina symptoms were randomized to receive either placebo or nifedipine GITS 30, 60 or 90 mg/day. After four weeks of treatment, the changes in time from baseline to onset of 1 mm ST segment depression in the 183 eligible patients were 26.7+/-10.2 s, 40.9+/-11.3 s, 63.2+/-12.9 s and 70.3+/-12.6 for the placebo, and 30, 60 and 90 mg/day groups, respectively. These differences were significant (P<0.05) for the 60 and 90 mg/day groups compared with placebo and for the 60 mg/day group compared with the 30 mg/day group. The times to onset of pain and termination of exercise showed similar prolongation but did not achieve statistical significance. During the one-year open label phase of the study, patients exhibited statistically significant improvements in the time to onset of ST segment depression, time to anginal pain and time to termination of exercise at a mean dose of 52.3 mg/day of nifedipine GITS. Adverse events were primarily vasodilatory in nature. This study supports the use of nifedipine GITS in patients with chronic stable angina inadequately controlled on beta-blocker alone.",1999.0,0,0
74,10529039,Amlodipine lowers blood pressure without affecting cerebral blood flow as measured by single photon emission computed tomography in elderly hypertensive subjects.,N D Pandita-Gunawardena; S E Clarke,"To evaluate the effect of amlodipine on blood pressure and cerebral blood flow in elderly subjects with mild to moderate hypertension. A double-blind, parallel group study of 26 patients. After a 4-week placebo run-in period, amlodipine (5-10 mg) or matching placebo was given once daily for 8 weeks. Amlodipine significantly reduced blood pressure compared with baseline. Diastolic blood pressure was significantly reduced by amlodipine compared with placebo (P< 0.02 to P< 0.01). Ambulatory blood pressure monitoring showed that blood pressure control was sustained over the 24-h dosing interval. Relative regional cerebral blood flow, assessed using single photon emission computed tomography, was not significantly affected by amlodipine. Three placebo patients, but no amlodipine patients, withdrew because of adverse events. Amlodipine was a well-tolerated and effective antihypertensive agent, and did not reduce regional cerebral blood flow in elderly hypertensive patients.",1999.0,0,0
75,10535341,Nifedipine versus ritodrine for suppression of preterm labor; a meta-analysis.,S G Oei; B W Mol; M J de Kleine; H A Brölmann,"Since large randomized clinical trials comparing the effectiveness of nifedipine and ritodrine in the suppression of preterm labor are lacking, we performed a meta-analysis on the subject. We searched the databases Medline and EMBASE using the keywords 'nifedipine', 'ritodrine' and 'randomized' or 'randomised'. The studies were scored for blinding, method of randomization and type of analysis ('intention-to-treat' versus 'par protocol'). Subsequently, two by two tables were constructed using 'delay of labor by 48 hours or more', 'delay of labor beyond 36 weeks gestation', perinatal mortality, respiratory distress syndrome and admission to a neonatal intensive care unit as end points. Homogeneity between the studies was tested with a Breslow-Day test. Pooled odds ratios were calculated in case homogeneity could not be rejected. We could detect ten studies that were published between 1986 and 1998, incorporating data of 681 patients. Nifedipine reduced the risk of delivery within 48 hours compared to ritodrine, but this difference was not statistically significant (odds ratio 0.85, 95% confidence interval 0.54 to 1.1). Nifedipine also reduced the risk of delivery before 36 weeks compared to ritodrine, and this difference was statistically significant (odds ratio 0.59, 95% confidence interval 0.39 to 0.90). We are not aware of studies reporting on long-term outcome. Since studies reporting on long-term outcome are lacking, the choice between nifedipine and ritodrine can only be based on obstetrical and short-term neonatal outcomes. From that perspective, nifedipine should be the drug of first choice for the suppression of preterm labor.",1999.0,0,0
76,10545432,"Initiation of atrial fibrillation by ectopic beats originating from the pulmonary veins: electrophysiological characteristics, pharmacological responses, and effects of radiofrequency ablation.",S A Chen; M H Hsieh; C T Tai; C F Tsai; V S Prakash; W C Yu; T L Hsu; Y A Ding; M S Chang,"Atrial fibrillation (AF) can be initiated by ectopic beats originating from the atrial or great venous tissues. This study investigated the anatomic characteristics and electrophysiological properties of pulmonary veins (PVs), as well as the possible mechanisms and response to drugs of ectopic foci, and assessed the effects of radiofrequency (RF) ablation on AF initiated by ectopic beats originating from PVs. Seventy-nine patients with frequent episodes of paroxysmal AF and 10 control patients were included. Distal PVs showed the shortest effective refractory periods (ERPs), and right superior PVs showed a higher incidence of intra-PV conduction block than left superior PVs. Superior and left PVs had longer myocardial sleeves than inferior and right PVs, respectively. These electrophysiological characteristics were similar between AF and control patients. Propranolol, verapamil, and procainamide suppressed ectopic beats that originated from the PVs. Of 116 ectopic foci that initiated AF, 103 (88.8%) originated from PVs. A mean of 7+/-3 RF applications completely eliminated 110 ectopic foci (94.8%). During the 6+/-2-month follow-up period, 68 patients (86. 1%) were free of AF without any antiarrhythmic drugs. Follow-up transesophageal echocardiogram showed 42.4% of ablated PVs had focal stenosis. One patient had mild exertional dyspnea after ablation, but it resolved 3 months later; 1 patient had onset of mild exertional dyspnea 5 months after ablation. Electrophysiological characteristics of PVs are different from those in the atria. Ectopic beats from PVs can initiate AF, and beta-adrenergic receptor blocker, calcium channel blockers, and sodium channel blockers can suppress these ectopic beats. Careful mapping and elimination of these ectopic foci can cure paroxysmal AF.",1999.0,0,1
77,10547174,Calcium channel blockers and mortality in elderly patients with myocardial infarction.,J G Jollis; R J Simpson; M K Chowdhury; W E Cascio; J R Crouse; M W Massing; S C Smith,"Although calcium channel blockers are a useful therapy in relieving angina, lowering blood pressure, and slowing conduction of atrial fibrillation, growing evidence has cast doubt on their safety in patients with coronary disease. To examine the association between calcium channel blocker therapy at hospital discharge and mortality in a population-based sample of elderly patients hospitalized with acute myocardial infarction. Retrospective cohort study using data from medical charts and administrative files. All acute care hospitals in 46 states. All Medicare patients with a principal diagnosis of acute myocardial infarction consecutively discharged from the hospital alive during 8-month periods between 1994 and 1995 (N = 141,041). Mortality at 30 days and 1 year. Calcium channel blockers were widely prescribed at hospital discharge to elderly patients with myocardial infarction between 1994 and 1995 (n = 51,921), the most commonly prescribed being diltiazem (n = 21,175), nifedipine (n = 12,670), amlodipine (n = 11,683), and verapamil (n = 3639). After adjusting for illness severity and concomitant medication use, patients who were prescribed calcium channel blockers at hospital discharge did not have increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Bepridil differs from other calcium channel blockers because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly patients. We did not identify a mortality risk in a large consecutive sample of elderly patients with myocardial infarction, which supports the need for additional prospective trials examining calcium channel blocker therapy for ischemic heart disease.",2001.0,1,1
78,10547639,Sex difference in response of blood pressure to calcium antagonism in the treatment of moderate-to-severe hypertension.,E D Loeb; J A Diamond; L R Krakoff; R A Phillips,"The pressor response to examination in the clinic setting is called the 'white coat effect' (WCE). This response may be a confounder when investigators use clinic blood pressure as a measure of response to antihypertensive therapy. ;To study the effect of the pressor response by evaluating the sex-specific effect of treatment with calcium antagonism on blood pressure measured in the clinic and by ambulatory blood pressure monitoring (ABPM). Untreated hypertensive subjects (n=39) with seated clinic diastolic blood pressures (DBP) > or = 100 and < or = 130mmHg were studied. Same-day clinic systolic blood pressure (SBP) and ambulatory SBP were obtained after 1 week of placebo, and after 1 month of treatment with either nifedipine or verapamil in a randomized, blinded, parallel trial. With placebo, women s average SBP was 18+/-;4mmHg lower than clinic SBP. By contrast, men s average SBP with placebo was 4+/-15mmHg lower than clinic SBP. There was a significantly greater reduction in clinic SBP for women than there was for men after 1 month of treatment (by 33+/-13 versus 18+/-18mmHg, P<0.005). However, reduction in ambulatory SBP after 1 month was the same for both sexes (20+/-11 versus 19+/-12mmHg). In this study of moderate-to-severe hypertensives, the large WCE measured for women, which markedly diminished with treatment, accounts for the observed sex difference in response of clinic SBP to calcium antagonism. By contrast, with ABPM there was an equivalent response to treatment for both sexes. Use of ABPM could be a valuable means of eliminating the WCE as a confounder in clinical research.",1999.0,0,0
79,10551431,"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
80,10560156,[The hemodynamic effects of lomir and adalat in patients with postoperative arterial hypertension].,A A Eremenko; T P Ziuliaeva; L V Bozh'eva; R Iu Borisov,"Comparison of the hypotensive effects of lomir (isradipine) and adalat (nifedipine) in 36 patients showed lomir to be more effective after aortocoronary bypass surgery. Normalization of arterial pressure started 5-10 min after lomir infusion, followed by a 24.5% increase in cardiac output and decrease in peripheral vascular resistance by 43.8%. Arterial pressure did not rise after lomir infusion was discontinued. With adalat, arterial pressure normalized 30 min later, and the therapeutic effect was achieved with a very high dose (5-7 times higher than recommended). Cardiac output did not change, and cardiac arrhythmias were observed in 11.7% patients. Therefore, lomir is a preferable Ca channel blocker for treating postoperative arterial hypertension after aortocoronary bypass surgery.",1999.0,0,0
81,10560790,Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem.,D H Smith; J M Neutel; M A Weber,"The benzothiazepine calcium channel antagonist diltiazem is a short-acting drug. To achieve effective 24-h blood pressure control with once-daily dosing, it relies on various extended drug-delivery systems that have grown in importance as a result of the recent reports relating the use of short-acting calcium channel antagonists to increased cardiovascular morbidity. This study examines the pharmacokinetics and resulting pharmacodynamics of two different delivery systems, each loaded with 240 mg of diltiazem and administered to 40 moderately hypertensive patients in a randomized, double-blind crossover trial. After a 4-week, single-blind placebo lead-in, patients with a clinical diastolic blood pressure of > or =100 mm Hg were randomized to either the single or dual microbead diltiazem delivery system for a 4-week period. At the end of this period, each subject was evaluated with 24-h ambulatory blood pressure monitoring and subjected to 24-h inpatient pharmacokinetic analysis on separate days. This was followed by a similar 4-week period in which each subject was treated with the alternative delivery system. For diltiazem, the area under the curve for plasma concentration versus time and the maximum plasma concentration attained by the single microbead system exceeded the values achieved by the dual bead system by 15% and 25%, respectively. These differences were greatest from the 3rd through the 13th h after dosing. During this period, both systolic and diastolic ambulatory blood pressure was significantly lower when the single microbead system was used. When compared with baseline blood pressure, blood pressure reductions achieved with the single microbead system exceeded reductions achieved with the dual microbead system by at least 2 mm Hg for 10 of the 24 postdose hours. Heart rates were slightly reduced but not significantly different. This improved blood pressure control at higher plasma levels of diltiazem suggests that a more efficient delivery system could provide better blood pressure control for identical doses of diltiazem.",1999.0,0,0
82,10562973,Use of calcium-channel blockers in pediatric renal transplant recipients.,D M Silverstein; J Palmer; H J Baluarte; C Brass; S B Conley; M S Polinsky,"Hypertension (HTN) is a significant problem in pediatric renal transplant (TP) recipients, predisposing the individuals to the development of cardiovascular disease and graft dysfunction. Calcium channel blockers (CCB) are considered excellent agents to treat post-TP HTN. We compared the efficacy and adverse effects of the two most commonly prescribed CCBs in our pediatric renal TP population: nifedipine (Procardia, or P) and amlodipine (Norvasc, or N). All patients (n = 24) had been started on a CCB for systolic (SBP) and/or diastolic BP (DBP) > 95%. There were no other changes in adjunctive antihypertensive medications or doses during the cross-over period. Post-TP, pretreatment (pretx) SBP was 137.6 +/- 10.9 mmHg. The post-treatment SBP were (in mmHg): 128.5 +/- 11.9 (all patients, n = 24) (p = 0.009 vs. pretx); 126.4 +/- 10.0 (P alone, n = 15) (p = 0.007 vs. pretx); 132.8 +/- 14.4 (P + other antihypertensive(s), n = 9) (p = 0.331, NS vs. pretx). The post-TP, pretreatment DBP was 88.2 +/- 11.1 mmHg. The post-treatment DBP were (in mmHg): 78.5 +/- 6.9 (all patients, n = 24) (p = 0.03 vs. pretx); 77.2 +/- 7.4 (P alone, n = 15) (p = 0.008 vs. pretx); 80.7 +/- 6.1 (P + other antihypertensive(s), n = 9) (p = 0.063, NS vs. pretx). P and N were equally effective in reducing SBP (p = 0.843, NS) and DBP (p = 0.612, NS). Cyclosporin A (CyA) dose (p = 0.81) and trough levels (p = 0.19) were similar in P- and N-treated patients. Calculated GFR was virtually identical in P- and N-treated patients (p = 0.89). Patients (or parents of) reported a higher incidence of various side-effects while receiving P, including headache, flushing, dizziness and leg cramps. Furthermore, 22/24 (91.7%) reported some degree of gingival hyperplasia during treatment with P, and all these patients reported a stabilization or reduction of hypertrophy after the switch from P to N. We conclude that CCBs (N) are efficacious drugs for the purpose of BP control and renal protection in pediatric renal TP recipients.",1999.0,0,0
83,10567194,Randomized double-blind comparison of a calcium antagonist and a diuretic in elderly hypertensives. National Intervention Cooperative Study in Elderly Hypertensives Study Group.,,"Although diuretics are recommended for the treatment of hypertension, decreased diuretic use and increased calcium antagonist use necessitate a comparison of the efficacy of these drugs in preventing cardiovascular events. Patients >/=60 years of age with systolic blood pressure of 160 to 220 mm Hg and diastolic blood pressure <115 mm Hg were enrolled. Patients were randomly assigned to 20 mg of sustained-release nicardipine hydrochloride twice daily or 2 mg of trichlormethiazide once daily by the double-dummy method and followed up for 5 years. A total of 414 patients were analyzed: 204 in the nicardipine group and 210 in the diuretic group. Blood pressure at entry was 172/94 mm Hg and 173/93 mm Hg, respectively, and decreased to 147/81 mm Hg and 147/79 mm Hg, respectively. Cardiovascular morbidity rates per 1000 persons per year were similar in the nicardipine and diuretic groups (27.8 and 26.8, respectively; P=0.923). The sex- and age-adjusted risk ratio for the nicardipine group was 0.973 (95% confidence interval, 0.514 to 1.839, P=0.932). The calcium antagonist and diuretic groups had a similarly decreased rate of cardiovascular events.",1999.0,1,1
84,10569322,Prognostic implications of ambulatory myocardial ischemia and arrhythmias and relations to ischemia on exercise in chronic stable angina pectoris (the Angina Prognosis Study in Stockholm [APSIS]).,L Forslund; P Hjemdahl; C Held; S V Eriksson; I Björkander; N Rehnqvist,"The prognostic significance of ambulatory ischemia, alone and in relation to ischemia during exercise was assessed in 686 patients (475 men) with chronic stable angina pectoris taking part in the Angina Prognosis Study In Stockholm (APSIS), who had 24-hour ambulatory electrocardiographic registrations and exercise tests at baseline (n = 678) and after 1 month (n = 607) of double-blind treatment with metoprolol or verapamil. Ambulatory electrocardiograms were analyzed for ventricular premature complexes and ST-segment depression. During a median follow-up of 40 months, 29 patients died of cardiovascular (CV) causes, 27 had a nonfatal myocardial infarction, and 89 underwent revascularization. Patients with CV death had more episodes (median 5 vs. 1; p<0.01) and longer median duration (24 vs. 3 minutes; p<0.01) of ST-segment depression than patients without events. For those who had undergone revascularization, the duration was also longer (12 vs. 3 minutes; p<0.05). In a multivariate Cox model including sex, history of previous myocardial infarction, hypertension, and diabetes, the duration of ST-segment depression independently predicted CV death. When exercise testing was included, ambulatory ischemia carried additional prognostic information only among patients with ST-segment depression > or =2 mm during exercise. When the treatment given and treatment effects on ambulatory ischemia were added to the Cox model, no significant impact on prognosis was found. Ventricular premature complexes carried no prognostic information. Thus, in patients with stable angina pectoris, ischemia during ambulatory monitoring showed independent prognostic importance regarding CV death. Ambulatory electrocardiographic monitoring and exercise testing provide complementary information, but only among patients with marked ischemia during exercise. Treatment reduced ambulatory ischemia, but the short-term treatment effects did not significantly influence prognosis.",1999.0,0,1
85,10577635,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.",2000.0,0,1
86,10605328,[24-hour blood pressure monitoring in diagnosis and therapy of arterial hypertension].,L M Bachmann; D Holm; W Vetter,"In a prospective open multicentric study two groups (A and B) of patients with essential hypertension used different methods for blood pressure measurements under treatment with the calcium channel blocker nifidipine GITS 30 and 60 mg. Fifty-one patients were followed for 6 weeks. Results of 24 hour blood pressure monitoring at visits after 2, 4 and 6 weeks were only known to physicians of group A. In this group the patients took their blood pressure twice per day. Both methods for measurement showed an overall decrease of blood pressure in the course of therapy. The mean values at the medical visits were always higher than the average measurements by 24 hour monitoring or the self assessment of blood pressure. The latter two blood pressure values tended to agree favorably. The differences between measurements during medical visits and measurements taken at home or during normal activity show that measurements in the doctor's office may lead to overestimation of hypertension. Without the results from blood pressure monitoring 4 (22%) of the patients in group B were treated without reason. Nifedipine GITS was well tolerated. Nine patients (16%) had undesired drug effects leading to a premature halt of treatment in 3 of them.",1999.0,0,0
87,10636260,"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
88,10648307,"The use of esmolol, nicardipine, or their combination to blunt hemodynamic changes after laryngoscopy and tracheal intubation.",J L Atlee; M S Dhamee; T L Olund; V George,"Laryngoscopy and tracheal intubation (LTI) often provoke an undesirable increase in blood pressure (BP) and/or heart rate (HR). We tested the premise that nicardipine (NIC) and esmolol (ESM) in combination (COMB) would oppose both. Adult surgical patients received pretreatment (randomized) with IV bolus NIC 30 microg/kg (n = 31), ESM 1.0 mg/kg (n = 34), or COMB (one-half dose each, n = 32). Peak BP and HR after LTI were compared with controls (CONT; n = 35) with no pretreatment. Anesthetic induction was standardized: IV thiopental (5-7 mg/kg), fentanyl (1-2 microg/kg), and succinylcholine (1.5 mg/kg). Systolic (S), diastolic (D), and mean (M) BP and HR awake before pretreatment (baseline) were similar in all test groups. No patient was treated for hypotension, bradycardia, or tachycardia after pretreatment or anesthetic induction. Peak HR after LTI was increased versus baseline in CONT and all test groups, but did not differ from CONT among the test groups. Peak SBP and DBP increased versus baseline in CONT, and with ESM and NIC, but not COMB. Peak SBP, DBP, and MBP were increased with ESM versus COMB, and peak DBP with ESM versus NIC. Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in BP after LTI is best blunted by the combination of nicardipine and ESM, compared with either drug alone. No single drug or combination in the doses tested opposed increased HR. Compared with no pretreatment before the IV induction of general anesthesia, the peak increase in blood pressure after laryngoscopy and tracheal intubation is best blunted by the combination of nicardipine and esmolol, compared with either drug alone. No single drug or combination in the doses tested opposed increased heart rate.",2000.0,0,0
89,10650289,Efficacy and safety of calcium channel blockers in heart failure: focus on recent trials with second-generation dihydropyridines.,R J de Vries; D J van Veldhuisen; P H Dunselman,"Chronic heart failure (CHF) has high morbidity and mortality rates despite treatment with angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Adjunctive vasodilation through calcium channel blockade has been suggested as potentially useful. However, the first-generation calcium channel blockers, including the dihydropyridine nifedipine, showed disappointing results in CHF. The second-generation dihydropyridines were expected to be of more value, and of all the calcium channel blockers, these drugs were the ones most studied in patients with CHF. The Medline databank was used to search studies in human beings (published in 1990 or later) that used dihydropyridines in patients with CHF. The references of the studies found were subsequently checked for additional data. In 17 studies and more than 2000 patients with CHF, no consistent beneficial effect was observed with regard to exercise tolerance and functional capacity, whereas plasma neurohormones were not affected. On the other hand, in general, no worsening of CHF was seen with these second-generation dihydropyridines. Two larger studies (PRAISE and V-HeFT III) have given some estimates on the long-term effects of dihydropyridines, and no overall influence on mortality rate was found. Of note, subanalysis of the PRAISE study has suggested that in patients with a nonischemic cause of CHF, amlodipine might have a beneficial effect on survival. In this review we have focused on the efficacy and safety of dihydropyridines in patients with CHF, as reported in recent trials. The data do not support the use of dihydropyridines when primarily given as treatment for CHF. The results, however, suggest that these drugs can be safely given to patients with left ventricular dysfunction or CHF who need additional treatment for angina pectoris or hypertension.",2000.0,0,0
90,10652036,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.",2000.0,1,1
91,10654213,Intravenous nicardipine for severe hypertension in pre-eclampsia--effects of an acute treatment on mother and foetus.,A G Aya; R Mangin; M Hoffet; J J Eledjam,"To assess the efficacy in lowering blood pressure, and the safety for mother and foetus of an acute nicardipine therapy in severe pre-eclampsia. Prospective clinical study. One university hospital obstetric unit. Twenty consecutive adult pre-eclamptic patients with severe hypertension. Nicardipine, 1 microgram/kg per min, was given intravenously to lower the mean arterial pressure (MAP) by at least 15%. Then, the dosage was reduced by 1/3, and the final dosage was determined to maintain MAP at 20-30% below the initial value, by increasing or decreasing the infusion rate by 0.5 mg/h. Maternal MAP and heart rate (HR) were assessed every 5 min for 1 h. Foetal HR (FHR) was recorded throughout the study period and assessed for Fischer score. Gestational age, Apgar scores, birth weight, capillary filling time and the duration of stay in the paediatric intensive care unit (ICU) were used to evaluate the short-term perinatal outcome. A 15-30% decrease in MAP occurred within 15-20 min in all patients. An increase in HR was noted, and two patients had severe tachycardia. Maternal side effects included flushing, headache, nausea and dizziness. FHR showed a transient decrease in acceleration episodes and occurrence of decelerations. No nicardipine-related foetal distress occurred. Four infants born during the study period did well at birth and had a good outcome. Acute nicardipine therapy can induce severe maternal tachycardia. No severe foetal or neonatal adverse effects occurred. This dose scheme requires comparison with alternative therapeutic options.",2000.0,0,0
92,10668836,Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the United States and Canada. Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) Investigators.,M Miller; R Byington; D Hunninghake; B Pitt; C D Furberg,"The efficacy of lipid-lowering therapy (LLT) has been well established for patients with preexisting coronary artery disease (CAD). However, limited information is available assessing the extent to which these medications are prescribed in academic medical centers. The use of LLT for patients with CAD was prospectively evaluated in 825 men and women who were recruited from 16 academic medical centers in the United States and Canada to participate in the Prospective Evaluation of the Vascular Events of Norvasc Trial (PREVENT). The assessment of LLT use during the 3-year trial was evaluated in patients receiving amlodipine therapy and placebo; levels of low-density lipoprotein cholesterol (LDL-C) were used to assess the impact of LLT. Despite a baseline prevalence of LLT in 42% of men (38% in 1994), half of the patients had high levels of LDL-C (>3.36 mmol [>130 mg/dL]). During the subsequent 3 years, the prevalence of elevated LDL-C levels dropped in men (29%) but remained stagnant in women (48%). These changes were associated with increased LLT in men (55%) but not in women (35%) (P = .04). In 1994, the LDL-C target goal (<2.59 mmol/L [<100 mg/dL]) was attained in 17% of men and 6% of women (P = .006). At study completion in 1997, the LDL-C target goal was achieved in 31% of men and only 12% of women (P = .001). This study highlights the relatively low treatment rates of hyperlipidemia among patients with CAD overall and women in particular who were participating in a clinical trial at academic medical centers in the United States and Canada. Because LLT has been proven to reduce future cardiovascular events, these results suggest that more intensive efforts should be promoted in order to maximize CAD reduction.",2000.0,1,1
93,10668837,"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.",2000.0,1,1
94,10676602,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
95,10678340,The evidence regarding the drugs used for ventricular rate control.,J B Segal; R L McNamara; M R Miller; N Kim; S N Goodman; N R Powe; K Robinson; D Yu; E B Bass,"Our goal was to determine what drugs are most efficacious for controlling the ventricular rate in patients with atrial fibrillation. We conducted a systematic review of the literature published before May 1998, beginning with searches of The Cochrane Collaboration's CENTRAL database and MEDLINE. We included English-language articles describing randomized controlled trials of drugs used for heart rate control in adults with atrial fibrillation. Abstracts of trials were reviewed independently by 2 members of the study team. We reviewed English-language abstracts of non-English-language publications to assess qualitative consistency with our results. Forty-five articles evaluating 17 drugs met our criteria for review. In the 5 trials of verapamil and 5 of diltiazem, heart rate was reduced significantly (P <.05), both at rest and with exercise, compared with placebo, with equivalent or improved exercise tolerance in 6 of 7 comparisons. In 7 of 12 comparisons of a beta-blocker with placebo, the beta-blocker was efficacious for control of resting heart rate, with evidence that the effect is drug specific, as nadolol and atenolol proved to be most efficacious. All 9 comparisons demonstrated good heart rate control with beta-blockers during exercise, although exercise tolerance was compromised in 3 of 9 comparisons. In 7 of 8 trials, digoxin administered alone slowed the resting heart rate more than placebo, but it did not significantly slow the rate during exercise in 4 studies. The trials evaluating other drugs yielded insufficient evidence to support their use, but those drugs may yet be promising. The calcium-channel blockers verapamil or diltiazem, or select beta-blockers are efficacious for heart rate control at rest and during exercise for patients with atrial fibrillation without a clinically important decrease in exercise tolerance. Digoxin is useful when rate control during exercise is less a concern.",2000.0,1,1
96,10679507,"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
97,10689266,"Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction.",J E Udelson; C A DeAbate; M Berk; G Neuberg; M Packer; N K Vijay; J Gorwitt; W B Smith; M L Kukin; T LeJemtel; T B Levine; M A Konstam,"A preliminary study suggested that the long-acting late-generation calcium-channel blocker amlodipine has favorable effects on exercise tolerance and is safe to use in heart failure, in contrast to earlier generation agents. The goal of 2 multicenter studies was to assess the effect of adjunctive therapy with amlodipine in addition to standard therapy on exercise capacity, quality of life, left ventricular function, and safety parameters in patients with heart failure and left ventricular systolic dysfunction. Two large multicenter trials examining the effects of amlodipine on these parameters over a 12-week period of therapy were undertaken in patients with mild to moderate heart failure and left ventricular systolic dysfunction. A total of 437 patients with stable heart failure were studied in a randomized, double-blind, placebo-controlled prospective design. Amlodipine at a dose of 10 mg/day in addition to standard therapy in such patients was associated with no significant difference in change in exercise tolerance on a Naughton protocol compared with placebo in each trial. Among all patients taking amlodipine, exercise time increased 53 +/- 9 (SE) seconds; exercise time for those taking placebo increased 66 +/- 9 seconds (P = not significant). There were no significant differences in changes of quality of life parameters between amlodipine- and placebo-treated patients, and there were no significant differences in symptom scores or New York Heart Association classification between groups. Left ventricular function (measured as ejection fraction) improved 3. 4% +/- 0.5% in amlodipine-treated patients and 1.5% +/- 0.5% in placebo-treated patients (P =.007). There was no statistically significant excess of important adverse events (episodes of worsening heart failure in 10% amlodipine-treated vs 6.3% of placebo-treated patients) or differences in need for changes in background medication between groups. The addition of 10 mg of amlodipine per day to standard therapy in patients with heart failure is associated with no significant improvement in exercise time compared with placebo therapy over a 12-week period, and there was no increased incidence of adverse events. These data suggest that the addition of amlodipine to standard therapy in heart failure will not result in additional efficacy per se beyond standard therapy.",2000.0,1,1
98,10694836,Bisoprolol and nifedipine retard in elderly hypertensive patients: effect on quality of life.,C J Bulpitt; M Connor; M Schulte; A E Fletcher,"Subjects over the age 60 with sustained sitting diastolic pressures of 95-115 mm Hg were randomised to a regime based on bisoprolol (n = 368) or nifedipine retard (n = 379) for 24 weeks. The goal diastolic pressure was < or =90 mm Hg and to achieve this, double-blind medication could be doubled (5/10 mg bisoprolol, 40/80 mg nifedipine retard) or hydrochlorothiazide 25 mg (unblinded) could be added to the higher dose. In an intention-to-treat analysis, 309 subjects in both the bisoprolol and nifedipine retard treated group provided at least a baseline and a second quality of life assessment (82%). An excess of symptoms was observed in the nifedipine group for oedema of the legs, nocturia, constipation, racing heart and heart thumping. Fewer patients reported wheeze in the nifedipine group. For quality of life, there were no statistically significant differences between the two groups after 8 weeks. However, when analysing the results of the last available assessment (usually at 24 weeks) there were significant (P < 0.05) improvements in tension/anxiety, anger/ hostility, vigour/activity, and confusion/bewilderment, assessed by the Profile of Mood States (POMS) in patients receiving bisoprolol in comparison to those receiving nifedipine retard. The Sickness Impact Profile and objective tests of cognitive function did not differ statistically between the two groups. Quality of life was maintained at a good level on both treatments with advantages for bisoprolol in certain areas. Journal of Human Hypertension (2000) 14, 205-212.",2000.0,1,1
99,10695096,A comparison of the effects of two modified release preparations of nifedipine-nifedipine retard 10 mg twice daily and nifedipine GITS 20 mg once daily--in the treatment of mild to moderate hypertension.,B J Kirby; N R Kitchin,"A multicentre, randomised, double-blind, cross-over comparison of nifedipine GITS 20 mg once daily and nifedipine retard 10 mg twice daily in 49 patients with mild to moderate hypertension was conducted. Both treatments resulted in clinically significant trough blood pressure reductions (nifedipine GITS -10.1/-8.9 mmHg, nifedipine retard -7.5/-8.2 mmHg). The study demonstrated that nifedipine GITS was 'at least equivalent' to nifedipine retard in the reduction of trough diastolic blood pressure (one-sided lower 95% confidence limit, -1.2 mmHg). The overall incidence of adverse events (nifedipine GITS 25.5%, nifedipine retard 34.0%), as well as the incidences of headache (nifedipine GITS 8.5%, nifedipine retard 12.8%) and peripheral oedema (nifedipine GITS 2.1%, nifedipine retard 8.5%), was higher with nifedipine retard compared to nifedipine GITS. Nifedipine GITS 20 mg once daily is 'at least equivalent' to nifedipine retard 10 mg twice daily in patients with mild to moderate hypertension, as well as being better tolerated.",2000.0,0,0
100,10703656,The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth.,J A James; J J Marley; S Jamal; B A Campbell; C D Short; R W Johnson; P S Hull; H Spratt; C R Irwin; S Boomer; A P Maxwell; G J Linden,"To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.",2000.0,0,0
101,10716459,Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).,B Jørgensen; S Simonsen; K Endresen; K Forfang; K Vatne; J Hansen; J Webb; C Buller; G Goulet; J Erikssen; E Thaulow,"Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA. In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events). Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis). Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.",2000.0,0,1
102,10719133,Blood pressure biofeedback treatment of white-coat hypertension.,M Nakao; S Nomura; T Shimosawa; T Fujita; T Kuboki,"The objective of the study was to compare blood pressure (BP) biofeedback treatment (BF) effects between white-coat hypertension and essential hypertension. Fifteen white-coat hypertensive out-patients and 23 essential hypertensive out-patients were randomly assigned to groups A or B. Subjects in group A underwent BF once a week for a total of four sessions. Those in group B visited the clinic only to measure BP and later underwent the same BF. In group A, BPs of white-coat hypertensives and essential hypertensives were significantly reduced by 22/11 and 14/8 mmHg, respectively. In group B, they were unchanged during the same period but later suppressed by BF. Under BF, pulse and respiratory rates were significantly higher, and elevation of diastolic BP due to mental stress testing was better suppressed in white-coat hypertensives than in essential hypertensives. This treatment was effective in both types of hypertension, and pressor response to stress seems to be important in the differentiated BF effect.",2000.0,0,0
103,10721156,[A critical analysis of the Hypertension Optimal Treatment (HOT) Study (appeared in Lancet 1998; 351: 1755-1762)].,F Skrabal,"In the HOT-study 18,790 patients in 26 countries (age 50-80 years, mean age 61.5 years) with hypertension (diastolic blood pressure between 100 and 115 mm Hg--mean value 105 mm Hg) were randomised into 3 groups with different target blood pressures (90 mm Hg, 85 mm Hg, 80 mm Hg). The basic treatment was with Felodipin (5 mg q. d.): if the target pressure was not achieved, further steps were initiated: either ACE-inhibitors or -blockers were added, in a third step the Felodipindose was increased to 100 mg and in a further step the doses of ACE-inhibitors or -blockers were doubled. If target pressure was still not achieved, a diuretic was added. Furthermore half of the patients in all groups received either placebo or 75 mg acetyl-salicylic acid. To prevent cardiovascular events the best benefit was shown, when a diastolic pressure of 82.6 mm Hg was reached. Acetyl-salicylic acid showed a further benefit in preventing myocardial infarction, but not in preventing strokes.",2000.0,0,0
104,10723113,Alpha-1-antitrypsin phenotypes in patients with renal arterial fibromuscular dysplasia.,A Bofinger; C Hawley; P Fisher; N Daunt; M Stowasser; R Gordon,"Fibromuscular dysplasia (FMD) is a significant cause of renal artery stenosis, especially in young females. A rare association between FMD and alpha 1-antitrypsin (alpha 1-AT) deficiency has been reported. We compared the alpha 1-AT phenotype distribution in 83 patients with renal arterial FMD with those published for Australian populations. alpha 1-AT phenotyping was performed by isoelectric focusing between pH 4.2 and pH 4.9 on polyacrylamide gels with PiM1M2, PiFM (non-deficiency alleles), PiMS and PiMZ (deficiency alleles) markers. Following phenotyping, alpha 1-AT genotyping was performed in 10 patients to confirm the presence of S and/or Z alleles. The phenotype distribution and allele frequencies were similar to those reported for normal subjects from two Australian populations (72 (86.7%) PiMM phenotype, one (1.2%) PiFM, seven (8.4%) PiMS, two (2.4%) PiMZ and one (1.2%) PiSZ), suggesting that alpha 1-AT deficiency is not a common aetiological factor in renal arterial FMD. However, despite FMD being three times less common in males than females, and carotid artery dissection being a rare occurrence, a male with PiMS deficiency phenotype presented with internal carotid artery dissection and had bilateral renal artery FMD. Further, a patient with PiSZ deficiency phenotype was one of two sisters with FMD and was more severely affected than her PiMM normal phenotype sibling. These two patients from the present series together with nine culled from the literature with alpha 1-AT deficiency phenotype and FMD suggest that the chance combination of alpha 1-AT deficiency and FMD may predispose to severe manifestations of FMD.",2000.0,0,0
105,10724194,Natural history of erythromelalgia: presentation and outcome in 168 patients.,M D Davis; W M O'Fallon; R S Rogers; T W Rooke,"To describe the demographics, presentation, and outcome in patients with erythromelalgia--a rare and poorly understood clinical syndrome defined by the triad of red, hot, painful extremities. Retrospective medical record review with follow-up by survey questionnaire. Large tertiary care medical center. Patients with erythromelalgia examined at the Mayo Clinic, Rochester, Minn, between 1970 and 1994. The medical records of 168 patients were analyzed. Follow-up data, which consisted of answers to 2 survey questionnaires or the most recent information in the medical record from patients still alive and death certificates or reports of death for those deceased patients, were obtained for all but 13 patients. Survival, morbidity, and quality of life. All patients were white; 122 (72.6%) were female, and 46 (27.4%) were male. At presentation, the patients' mean age was 55.8 years (age range, 5-91 years). Symptoms had been present since childhood in 7 patients (4.2%). Six patients (3.6%) had a first-degree relative with erythromelalgia. Symptoms were intermittent in 163 patients (97.0%) and constant in 5 (3.0%). Symptoms predominantly involved feet (148 patients [88.1%]) and hands (43 patients [25.6%]). Kaplan-Meier survival curves revealed a significant decrease in survival compared with that expected in persons of similar age and of the same sex (P<.001). After a mean follow-up of 8.7 years (range, 1.3-20 years), 30 patients (31.9%) reported worsening of, 25 (26.6%) no change in, 29 (30.9%) improvement in, and 10 (10.6%) complete resolution of the symptoms. On a standard health status questionnaire, scores for all but one of the health domains were significantly diminished in comparison with those in the US general population. Erythromelalgia is a syndrome with significantly increased mortality and morbidity compared with the US general population.",2000.0,0,0
106,10731625,"Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans.",B A Johnson; N Ait-Daoud; L T Wells,"D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.",2000.0,0,0
107,10737282,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
108,10746815,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.",2000.0,1,1
109,10755206,"Calcium channel antagonist controversy: symposium at the Congress of the International Society of Cardiovascular Pharmacotherapy on March 30, 1999, in Amsterdam.",W Rutishauser,,2000.0,0,0
110,10758419,Esophageal motility disorders: current concepts of pathogenesis and treatment.,P J Kahrilas,"Current concepts of esophageal motility disorders are summarized. Primary data sources were located via MEDLINE or cross-citation. No attempt was made to be comprehensive or inclusive of the literature because fewer than 10% of citations are discussed. Instead, emphasis was placed on new developments in diagnosis, therapeutics and practice patterns. Controlled therapeutic trials and pathophysiological observations are emphasized. Achalasia is a rare disease of failed lower sphincter relaxation and aperistalsis. Diffuse esophageal spasm (DES), an equally rare disease, is defined by nonpropagated esophageal contractions. Nonspecific motility disorders, including nutcracker esophagus and hypertensive lower esophageal sphincter, are identified only by manometry and are 10 times as prevalent. Neuromuscular pathology is evident only with achalasia (myenteric plexus neuron destruction). Pharmacological therapies have limited efficacy with achalasia, more limited efficacy with DES and no efficacy with the nonspecific motility disorders. More efficacious therapies for the nonspecific disorders are directed at associated reflux disease or psychiatric disorders. Pneumatic dilation is effective therapy for achalasia in 72% of instances but frequently requires repeat dilation and is complicated by a 3% perforation rate. Surgical myotomy is effective in 88% of patients with achalasia; morbidity from thoracotomy has been the major limitation but has been sharply reduced with a laparoscopic approach. In conclusion, although it has been suggested that esophageal motility disorders are distinct clinical entities, critical review of the literature supports this only in the case of achalasia, a disease of well defined pathophysiology, functional disturbance and therapies. This clarity diminishes progressively for DES and nonspecific esophageal motility disorders.",2000.0,0,0
111,10774785,Cardiovascular adverse drug reaction associated with combined beta-adrenergic and calcium entry-blocking agents.,Y Edoute; P Nagachandran; B Svirski; H Ben-Ami,"Numerous studies have shown a beneficial effect of combination therapy with beta-blockers and calcium antagonists in patients with anginal syndrome and/or hypertension. However, because both agents exert a negative chronotropic effect, their combined use may cause bradyarrhythmias with resultant symptoms of cerebral, coronary, and systemic hypoperfusion. We describe our clinical experience with patients who had cardiovascular adverse drug reactions (CVADRs) with combination therapy. This prospective study included 26 patients who had CVADRs among 2,574 admissions during a 2-year period. The study group included 14 men and 12 women with a median age of 73 years. Various combinations of calcium antagonists and beta-blockers were associated with the CVADRs. The most frequent pharmacologic combination was diltiazem plus propranolol. The CVADRs were the cause for hospital admission in 10 patients, an associated cause in nine patients, and developed during hospitalization in seven patients. Cardiac bradyarrhythmias were found in 22 patients. These rhythm abnormalities resolved within 24 h after discontinuation of the offending drugs. Temporary transvenous pacemaker insertion was necessary in only one patient with complete atrioventricular block. Twenty-two patients recovered, two patients died of pump failure not associated with CVADRs, and in two patients, the CVADRs contributed to the patients' death. CVADRs are not uncommon in elderly patients with ischemic heart disease and/or hypertension treated with the concomitant use of calcium antagonist and beta-adrenergic blocking drugs. Use of calcium antagonist plus beta-blocker may unpredictably cause serious hemodynamic events, marked suppression of sinus node activity, and prolongation of atrioventricular conduction in some patients. Enhanced therapeutic monitoring may be warranted when calcium antagonists are combined with beta-blockers.",2000.0,0,0
112,10778687,,,,,0,0
113,10778689,Comparison of efficacy of intravenous diltiazem and esmolol in terminating supraventricular tachycardia.,A Gupta; A Naik; A Vora; Y Lokhandwala,"Paroxysmal supraventricular tachycardia (PSVT) can be effectively terminated by the intravenous administration of adenosine or verapamil. However adenosine is expensive and injectable verapamil currently is scarcely available. While intravenous diltiazem has been shown to be useful for terminating PSVT, the efficacy of esmolol in this regard has not been evaluated previously. Hence these latter two drugs were studied for their efficacy in terminating PSVT. A prospective, randomised, crossover study was undertaken in patients presenting with hemodynamically tolerated PSVT to the ICCU. While 50 patients had been planned for the trial, the study had to be prematurely terminated after 32 patients had been enrolled due to the marked superiority of diltiazem. Two sequential doses with a 5 minute interval of either drug were administered before crossover. Diltiazem was given in a dose of 0.25 mg/kg while the esmolol dose was 0.5 mg/kg. Diltiazem terminated PSVT in all the 16 patients in whom it was given as the first drug. The 12 patients who did not respond to esmolol were also effectively treated with diltiazem. Thus totally 28/28 patients responded to diltiazem while only 4/16 patients responded to esmolol (p < 0.001). Of the 28 patients who responded to diltiazem, in 13 patients the second bolus of diltiazem worked after the first one had failed. No significant adverse effects were seen. Intravenous diltiazem is highly effective and safe for terminating PSVT. When the first bolus is ineffective, the second bolus given after 5 minutes usually succeeds. Esmolol in the dose of 0.5 mg/kg has poor efficacy for terminating PSVT, even when 2 boluses are administered.",2000.0,0,0
114,10791374,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
115,10792199,Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study.,P Lusardi; E Piazza; R Fogari,"As melatonin has been found to play a role in the mechanisms of cardiovascular regulation, we designed the present study to evaluate whether the evening ingestion of the pineal hormone might interfere with the antihypertensive therapy in hypertensive patients well-controlled by nifedipine monotherapy. Forty-seven mild to moderate essential hypertensive outpatients taking nifedipine GITS 30 or 60 mg monotherapy at 08.30 h for at least 3 months, were given placebo or melatonin 5 mg at 22.30 h for 4 weeks according to a double-blind cross-over study. At the end of each treatment period patients underwent a 24 h noninvasive ambulatory blood pressure monitoring (ABPM) during usual working days; sleeping period was scheduled to last from 23.00 to 07.00 h. The evening administration of melatonin induced an increase of blood pressure and heart rate throughout the 24 h period (DeltaSBP = + 6.5 mmHg, P < 0.001; DeltaDBP = + 4.9 mmHg, P < 0.01; DeltaHR = + 3.9 beats min-1, P < 0.01). The DBP as well as the HR increase were particularly evident during the morning and the afternoon hours. We hypothesize that competition between melatonin and nifedipine, is able to impair the antihypertensive efficacy of the calcium channel blocker. This suggests caution in uncontrolled use of melatonin in hypertensive patients. As the pineal hormone might interfere with calcium channel blocker therapy, it cannot be considered simply a dietary supplement.",2000.0,0,0
116,10803042,[Clinical study of the month. The STOP-2 study of arterial hypertension in the elderly].,A J Scheen,"After the demonstration of the efficacy of beta-blockers or diuretics versus placebo to prevent cardiovascular complications in elderly hypertensive patients in the first STOP-Hypertension study in 1991, a Swedish group published at the end of 1999 the STOP-2 Hypertension study. The latter randomised trial showed in a similar population that the cardiovascular protection of more recent antihypertensive agents such as calcium antagonists and angiotensin-converting-enzyme inhibitors is similar to that of the conventional antihypertensive drugs used in the first study. In fact, the degree of blood pressure control appears to be more important than the type of antihypertensive drugs used, and this conclusion is reinforced by the observation that numerous patients should rapidly be treated by more than one antihypertensive agent to reach blood pressure targets.",2000.0,0,0
117,10803490,Progress report on the Nordic diltiazem study (NORDIL): an outcome study in hypertensive patients.,T Hedner,"NORDIL--the Nordic Diltiazem Study (NORDIL)--is a prospective, randomized, open blinded-endpoint (PROBE), multicenter, parallel-group morbidity/mortality outcome study in hypertensive patients designed to compare an intervention strategy based on the calcium antagonist diltiazem with a strategy based on conventional antihypertensive drug treatment (diuretics or beta-adrenergic blockers). Patient recruitment was started in Norway and Sweden in September 1992, and ended on December 15, 1996, when 10.896 male and female patients, aged 50-74 years, with essential hypertension had been randomized. In this paper we describe the baseline data of the patient cohort and blood pressures achieved in the two treatment groups during the early part of the study. The patient cohort consists of 5294 males and 5602 females with a mean age of 59.6 and 60.3 years, respectively. Concomitant disorders and risk factors in the cohort are: smoking 22%, ischemic heart disease 3.0%, previous myocardial infarction (MI) 2.0%, previous stroke 1.5%, diabetes mellitus 7.0%, and renal impairment 0.3%. There were no differences between the treatment groups in these respects. The blood pressure treatment goal is a target diastolic blood pressure of < or =90 mmHg or a 10% diastolic blood pressure reduction from the inclusion pressure. In the treatment group randomized to a diltiazem-based treatment strategy, blood pressure was 174/106 mmHg at baseline and 156/90 mmHg after 12 months of follow-up on active treatment. In the group randomized to a conventional treatment strategy, baseline blood pressure at randomization was 173/106 mmHg and 153/90 mmHg after 12 months on active therapy. The NORDIL study will terminate on October 31, 1999 and the final results should be available by mid-2000.",2000.0,1,1
118,10806014,Prognostic implications of results from exercise testing in patients with chronic stable angina pectoris treated with metoprolol or verapamil. A report from the Angina Prognosis Study In Stockholm (APSIS).,L Forslund; P Hjemdahl; C Held; I Björkander; S V Eriksson; U Brodin; N Rehnqvist,"To evaluate the prognostic implications of results from exercise testing, and of antianginal treatment among patients with chronic stable angina pectoris. Out of 809 patients in the Angina Prognosis Study In Stockholm (APSIS), 731 (511 men) performed evaluable exercise tests before and after 1 month on double-blind treatment with metoprolol or verapamil. During a median follow-up of 40 months, 32 patients suffered a cardiovascular death and 29 a non-fatal myocardial infarction. Prognostic implications of results from exercise tests were assessed in a multivariate Cox model which included sex, previous myocardial infarction, hypertension and diabetes mellitus. Maximal ST-segment depression, especially if >/=2 mm and occurring after exercise, as well as exercise duration independently predicted cardiovascular death. Similar results were obtained for the combined end-point of cardiovascular death+myocardial infarction. Among patients with a positive exercise test at baseline, verapamil reduced the maximal ST-depression more markedly than metoprolol (P<0. 01). However, when the treatment given and treatment effects on ST-segment depression were added to the Cox model, no impact on prognosis could be detected for either cardiovascular death alone or combined with myocardial infarction. Anginal pain carried no prognostic information. Marked ST-segment depression during and after exercise, and a low exercise capacity independently predicted an adverse outcome in patients with stable angina pectoris, whereas anginal symptoms had no predictive value. Short-term treatment effects on ischaemia did not seem to influence prognosis. Post-exercise ischaemia should be examined carefully when evaluating patients with stable angina pectoris.",2000.0,0,1
119,10806134,"Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea.",H Kraiczi; J Hedner; Y Peker; L Grote,"We compared the effects of atenolol (50 mg), amlodipine (5 mg), enalapril (20 mg), hydrochlorothiazide (25 mg), and losartan (50 mg) given in once-daily oral doses on office and ambulatory blood pressures (BPs) in patients with hypertension and obstructive sleep apnea (OSA). Each of 40 randomized patients was treated in sequence with two of the five agents (balanced incomplete block design). Treatment periods lasted 6 wk and were separated by a 3-wk washout period. Changes in BP from baseline with the study substances were compared through analysis of variance. Office diastolic BP, our primary outcome variable, was most effectively lowered by atenolol, with all four post hoc differences between atenolol and the remaining substances being statistically significant. Reductions in office systolic and daytime ambulatory BP were not significantly different among the five compounds. However, atenolol reduced mean nighttime ambulatory diastolic and systolic BP more effectively than did amlodipine, enalapril, or losartan (but not hydrochlorothiazide). Severity of sleep-disordered breathing and well-being during the day were not significantly influenced by any of the study compounds. Our findings are in accordance with the hypothesis that an overactivity of the sympathetic nervous system is an important mechanism behind the development or maintenance of hypertension in patients with OSA.",2000.0,0,0
120,10812109,Increased incidence of infection in verapamil-treated kidney transplant recipients.,G Nanni; N Panocchia; R Tacchino; M Foco; E Piccioni; M Castagneto,,2000.0,0,0
121,10818061,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
122,10824049,"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
123,10826403,Effect of amlodipine on hemodynamic and endocrine responses to mental stress.,J D Spence; C Munoz; M W Huff; S Tokmakjian,"Little is known about the effects of antihypertensive drugs on hemodynamic responses to mental stress. We studied 24 patients with mild-to-moderate hypertension in a double-blind random-sequence crossover study comparing placebo with amlodipine titrated up from 5 to 10 mg daily. After 1 month of treatment, the subjects performed 20 min of a frustrating cognitive task. At baseline before task, amlodipine significantly reduced systolic pressure (128.9+/-8.2 mm Hg v 140.3+/-10.7 mm Hg, P < .001), diastolic pressure (81.7+/-7.7 mm Hg v 90+/-7.5 mm Hg, P < .001), and total peripheral resistance (37.5+/-15 v 45.6+/-23.7 mm Hg/L/min, P < .05), while elevating baseline norepinephrine levels (2286+/-731 pmol/L v 1788+/-546 pmol/L, P < .001). Blood pressure during the stress task was significantly less with amlodipine than with placebo (systolic 142.3+/-12.3 mm Hg v 150.9+/-14.6 mm Hg, P < .001; diastolic 87.9+/-8.4 mm Hg v 97.7+/-9.3 mm Hg, P < .001), whereas norepinephrine was significantly higher (2754+/-1007 pmol/L v 1970+/-740 pmol/L, P < .001). There were no significant differences in cardiac output, plasma lipids or lipoproteins, or markers of platelet activation. Heart rate increased significantly during stress, but there was no significant difference between amlodipine and placebo either at baseline or during stress. Our conclusion is that amlodipine reduces blood pressure at baseline and during mental stress, but raises basal and stress-related plasma catecholamines. This finding may have implications for the recent controversy over the safety of calcium channel antagonists, and suggests the potential relevance of combining amlodipine with adrenergic blockers.",2000.0,0,0
124,10826461,"Medical therapy, symptoms, and the distress the cause: relation to quality of life in patients with angina pectoris and/or hypertension.",N K Hollenberg; G H Williams; R Anderson,"Adverse events during drug therapy can be assessed through measurement of 2 features: their frequency and their severity. Their severity, in turn, can be measured by assessing the distress that they cause. Our goal was to relate the magnitude of the distress induced by treatment with calcium-channel blocking agents to the change in quality of life assessed through psychosocial instruments in patients treated with calcium-channel blocking agents, either for hypertension or for angina pectoris. Four hundred seventy-five patients with angina pectoris were randomized to double-blind treatment with PPR (physiological pattern release) verapamil hydrochloride, amlodipine besylate, amlodipineatenolol combination, or placebo. In addition, 557 hypertensive patients were randomized either to PPR verapamil or nifedipine GITS (gastrointestinal system). Both studies were double-blind. Significant differences in treatment of angina pectoris or hypertension, were not found between the regimens. Overall quality of life also failed to show a significant difference in either group. In both groups, however, remarkable concordance was found between the degree of distress associated with specific symptoms and a change in quality of life. An unchanged, stable symptom distress was associated with a significant improvement in the quality of life of about 0.1 SD. Improvement or erosion of symptom distress represented by 1 step was associated with a 0.1- to 0.2-SD change. The extreme change in symptom distress was associated with a substantially larger change in global quality of life. The magnitude of symptom distress or relief associated with symptoms in 2 patient populations correlated strongly with a shift in quality of life. The assessment of distress associated with symptoms provides valuable additional information on drug therapy.",2000.0,0,0
125,10832825,Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT),W E Boden; W H van Gilst; R G Scheldewaert; I R Starkey; M F Carlier; D G Julian; A Whitehead; M E Bertrand; J J Col; O L Pedersen; K I Lie; J P Santoni; K M Fox,"Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.",2000.0,0,0
126,10841241,Prospective randomized comparison of antiarrhythmic therapy versus first-line radiofrequency ablation in patients with atrial flutter.,A Natale; K H Newby; E Pisanó; F Leonelli; R Fanelli; D Potenza; S Beheiry; G Tomassoni,"Despite the high success rate of radiofrequency (RF) ablation, pharmacologic therapy is still considered the standard initial therapeutic approach for atrial flutter. We prospectively compared the outcome at follow-up of patients with atrial flutter randomly assigned to drug therapy or RF ablation. Patients with at least two episodes of symptomatic atrial flutter in the last four months were randomized to regimens of either antiarrhythmic drug therapy or first-line RF ablation. After institution of therapy, end points included recurrence of atrial flutter, rehospitalization and quality of life. A total of 61 patients entered the study, 30 of whom were randomized to drug therapy and 31 to RF ablation. After a mean follow-up of 21 +/- 11 months, 11 of 30 (36%) patients receiving drugs were in sinus rhythm, versus 25 of 31 (80%) patients who underwent RF ablation (p < 0.01). Of the patients receiving drugs, 63% required one or more rehospitalizations, whereas post-RF ablation, only 22% of patients were rehospitalized (p < 0.01). Following RF ablation, 29% of patients developed atrial fibrillation which was seen in 53% of patients receiving medications (p < 0.05). Sense of well being (pre-RF 2.0 +/- 0.3 vs. post-RF 3.8 +/- 0.5, p < 0.01) and function in daily life (pre-RF 2.3 +/- 0.4 vs. post-RF 3.6 +/- 0.6, p < 0.01) improved after ablation, but did not change significantly in patients treated with drugs. In a selected group of patients with atrial flutter, RF ablation could be considered a first-line therapy due to the better success rate and impact on quality of life, the lower occurrence of atrial fibrillation and the lower need for rehospitalization at follow-up.",2000.0,0,1
127,10845189,Neonatal poisonings in middle Anatolia of Turkey: an analysis of 72 cases.,S Kurtoglu; H Caksen; M H Poyrazoglu,"In this study, 72 newborn infants who were followed with the diagnosis of poisoning in Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Neonatology, between 1975 and 1997 were evaluated retrospectively. Our purpose was to emphasize the importance of newborn poisoning among general poisoning in childhood. The age of infants ranged from 10 min to 25 days (0.82 +/- 2.81 days). Forty-seven (65.2%) infants were poisoned before or during delivery. Of the 47 infants' mothers, 46 had preeclampsia or eclampsia, and 27 received only magnesium sulfate; nine magnesium sulfate + diazepam; four magnesium sulfate + nifedipine; and the others received various drug combinations. Aside from these, one mother had Addison's disease and she used long-term dexamethasone during her pregnancy. In the newborn period, five (6.9%) infants inhaled organophosphate insecticides; eight (11.1%) ingested corrosive agents (four benzalkonium chloride; three chlorhexidine gluconate + cetrimide and an infant ammonium); four (5.5%) were poisoned by overdose of digoxin; three (4.1%) ingested overdose of phenobarbital; and two (2.7%) received acepromazine maleate. In addition, each infant ingested diphenoxilate HCL + atropine sulfate, pipenzolate bromid and tizanidine HCL. Follow-up period of the infants ranged from 24 hr to 26 days (0.82 +/- 2.81 days). The mortality rate was 17% (12/72). Death was not noted in the infants who were followed with poisoning after delivery. The causes of death were as follows: sepsis in four infants, meningitis, respiratory distress syndrome and necrotizing enterocolitis in two infants each, and the effects of overdose of magnesium sulfate and diazepam in two infants, respectively. In conclusion, we would like to stress that newborn infants whose mothers received magnesium sulfate or another drug during pregnancy or delivery should be closely monitored, and calculation of drug doses should be carefully taught to hospital nurses. When baby-rooms are disinfected with organophosphate insecticides in a hospital or house, infants should be removed from the room for at least 24 hr, and use of drugs should be explained in detail to the mothers.",2000.0,0,0
128,10848725,Antihypertensive drugs and the risk of idiopathic aplastic anaemia.,M W Myers; C Vasilakis; M R Kaufman; H Jick,"A recent report has raised concern that nifedipine may be associated with an increased risk of aplastic anaemia. This large population-based study evaluated the risk of idiopathic aplastic anaemia in users of calcium channel blockers compared with that of other antihypertensive drugs. The study was based on information derived from the General Practice Research Database. We conducted a follow-up study with a nested case-control analysis of 322 448 subjects who received antihypertensive drugs. Cases were people who had a first-time diagnosis of aplastic anaemia during January 1, 1988 through September 30, 1997. The risk estimate of aplastic anaemia was calculated for all antihypertensive drugs. For the nested case-control analysis, six controls were matched to each case on age, sex and general practice attended. Odds ratios compared the risk of idiopathic aplastic anaemia for all antihypertensive drugs relative to nonusers. There were 13 cases of newly diagnosed idiopathic aplastic anaemia. The estimated risk of aplastic anaemia per 100 000 users was 0.8 (95% CI 0.1, 4.7) for calcium channel blockers, 1.4 (95% CI 0.5, 4.1) for beta-adrenoceptor blockers, 2.3 (95% CI 0.6, 8.6) for angiotension-converting enzyme (ACE) inhibitors and 5.9 (95% CI 1.6, 21.5) for users of other antihypertensive drugs. In the case-control analysis of 13 cases and 77 controls, the odds ratio was 0.3 (95% CI 0.02, 3.3) for calcium channel blockers, 0.5 (95% CI 0.1, 2.5) for beta-adrenoceptor blockers, 0.7 (95% CI 0.1, 5.6) for ACE inhibitors, 1.2 (95% CI 0.1, 11.8) for users of other antihypertensive drugs and 0.7 (95% CI 0.1, 7.2) for users of multiple drugs with a calcium channel blocker compared with nonusers. The present study suggests that the use of calcium channel blockers is not associated with an increased risk of aplastic anaemia.",2000.0,0,1
129,10852091,The use of calcium salts in the prevention and management of verapamil-induced hypotension.,L R Moser; M A Smythe; J E Tisdale,"To review the available literature on the use of intravenous calcium salts for the prevention of hypotension associated with intravenous verapamil. A MEDLINE search (1966-June 1999) identified pertinent articles; references from these articles were identified to serve as additional resources. Verapamil is effective in inhibiting atrioventricular nodal conduction, thereby controlling ventricular rate in patients with atrial fibrillation/flutter and terminating paroxysmal supraventricular tachycardia. However, hypotension may be caused by the negative inotropic and vasodilating effects of verapamil. In vitro and animal data suggest that calcium pretreatment may minimize the effects of verapamil on cardiac output and blood pressure. Case reports suggest that intravenous calcium may be useful for both prevention and reversal of the hemodynamic effects of verapamil. A number of small clinical trials have been performed, suggesting that calcium administered prior to intravenous verapamil results in a decreased incidence of hypotension. The most common adverse effect of intravenous calcium is flushing. Calcium pretreatment prior to intravenous calcium-channel blocker administration should be considered in patients in whom further reductions in blood pressure may precipitate hypoperfusion or worsen underlying cardiovascular status. A dose of calcium gluconate 1 g (ionized calcium 90 mg) administered over three minutes is recommended for preventing or lessening the hypotensive effect of verapamil without affecting the antiarrhythmic effects of verapamil.",2000.0,0,0
130,10854683,"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
131,10855738,"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
132,10856736,"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
133,10863557,Cytoprotective properties of nisoldipine and amlodipine against oxidative endothelial cell injury.,I T Mak; J Zhang; W B Weglicki,,2000.0,0,0
134,10877984,"Maternal and neonatal outcome of preeclamptic pregnancies: the potential roles of factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase.",J Rigó; B Nagy; L Fintor; J Tanyi; A Beke; I Karádi; Z Papp,"To investigate the potential perinatal effects of Factor V Leiden mutation and 5,10 methylenetetrahydrofolate reductase C677T polymorphism in preeclamptic women. One hundred twenty preeclamptic women (N = 120) and 101 healthy pregnant controls (N = 101) were recruited and evaluated for frequency of Leiden and 5,10 methylenetetrahydrofolate reductase (MTHFR) mutations using polymerase chain reaction (PCR). Perinatal outcomes were then recorded and analyzed for all study participants and their neonates. Laboratory analysis yielded 22 (18.33%) heterozygous carriers of Factor V Leiden mutation among preeclamptic women and 3 (2.97%) heterozygous carriers among the healthy controls; differences between the two groups were found to be statistically significant [p < 0.001, the relative risk (RR) = 6.17, 95% confidence interval (95% CI) = 1.90-20.02]. Homozygous MTHFR mutations were found in 8 of 120 (6.67%) preeclamptic women and in 6 of the 101 (5.94%) healthy controls evaluated. Among preeclamptic women, episodes of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome were reported in 7 of 22 (31.81%) of those with Factor V Leiden mutation and in 11 of 98 (11.22%) of those who were negative for the mutation. Group differences were determined to be statistically significant (p < 0.015, RR = 2.83, 95% CI = 1.24-6. 48). Perinatal indicators collected from the two groups included frequency of intrauterine growth retardation, birth weight, and gestational age. No statistically different perinatal outcomes were found between Factor V Leiden positive and negative preeclamptic women. In addition, MTHFR gene polymorphism did not appear to be correlated with the development of preeclampsia. Although the frequency of Factor V Leiden mutation appears to be significantly higher among preeclamptic women, the mechanism of pathogenesis and potential influence on perinatal outcomes is not yet well understood. Relatively high rates of HELLP syndrome among those with Factor V Leiden mutation suggest that this thrombogene mutation may play a significant role in hemostatic system activation. Our results suggest that the role of MTHFR polymorphism and other factors such as folic acid supplementation will require more extensive analysis in controlling worldwide morbidity and mortality associated with this important maternal condition.",2000.0,0,0
135,10878692,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
136,10893735,[A study of the tolerability and effectiveness of nicardipine retard in cognitive deterioration of vascular origin].,J A González-González; R Lozano,"Nicardipine is a calcium antagonist which in previous trials has been shown to be effective in the prevention of stroke and the treatment of its sequelae, such as cognitive deterioration of vascular origin. We consider a phase IV study at primary care level to analyze the tolerability and efficacy of a retarded action formulation of 40 mg nicardipine. In this open, prospective, multicentric trial 6,375 patients took part, of whom 5,593 were evaluated (87.7%). All were diagnosed as having vascular-type dementia (Hachinski > 6) and were given treatment with nicardipine retard (40 mg/day/6 months). The patients were assessed on the Montorio (daily activity) and SPMSQ (cognitive function) scales at the first visit and after one, three and six months, together with a record of side effects. Only 0.9% of the patients recruited abandoned the study for problems of tolerability of the drug. The average improvement seen on Montorio's test was statistically significant from the first month, and reached 9% after six months. The 65.5% of the patients who started the study in seriously deteriorated condition showed improvement after six months. For the SPMSQ test, the average improvement was also statistically significant from the first visit and over 40% after six months. There was improvement in 64.4% of the patients who were severely deteriorated at the start of the study. Nicardipine retard is a drug which is safe and effective when used for the treatment of mental deterioration of vascular origin.",2000.0,0,0
137,10894321,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.",2000.0,0,1
138,10898425,"Use of metoprolol CR/XL to maintain sinus rhythm after conversion from persistent atrial fibrillation: a randomized, double-blind, placebo-controlled study.",V Kühlkamp; A Schirdewan; K Stangl; M Homberg; M Ploch; O A Beck,"The primary objective of the present study was to assess the efficacy of metoprolol CR/XL to reduce the risk of relapse after cardioversion of persistent atrial fibrillation to sinus rhythm. Indirect data from studies with d,l sotalol provide evidence that the beta-blocking effects of the compound are important in maintaining sinus rhythm after cardioversion of atrial fibrillation. After successful conversion to sinus rhythm, 394 patients with a history of persistent atrial fibrillation were randomly assigned to treatment with metoprolol CR/XL or placebo. The two treatment groups were similar with respect to all pretreatment characteristics. Patients were seen on an outpatient basis for recording of resting electrocardiogram (ECG) after one week, one, three and six months of follow-up or whenever they felt that they had a relapse into atrial fibrillation or experienced an adverse event. In the metoprolol CR/XL group, 96 patients (48.7%) had a relapse into atrial fibrillation compared with 118 patients (59.9%) in the placebo group (p = 0.005). Heart rate in patients after a relapse into atrial fibrillation was significantly lower in the metoprolol group (98 +/- 23 beats/min) than in the placebo group (107 +/- 27 beats/min). The rate of adverse events reported was similar in both groups when the difference in follow-up time was taken into account. The results of this double-blind, placebo-controlled study in patients after cardioversion of persistent atrial fibrillation showed that metoprolol CR/XL was effective in preventing relapse into atrial fibrillation or flutter.",2000.0,0,0
139,10908083,Plasma norepinephrine and atrial natriuretic peptide in heart failure: influence of felodipine in the third Vasodilator Heart Failure Trial. V-HeFT III investigators.,R F Smith; T Germanson; D Judd; M Wong; S Ziesche; I S Anand; W R Taylor; J N Cohn,"Reflex activation of the sympathetic nervous system by short-acting dihydropyridine calcium channel antagonists has been reported to harm hypertensive patients. Different neurohormonal profiles and their response to treatment may influence the effectiveness of dihydropyridine vasodilator treatment of heart failure. Four hundred fifty men with left ventricular (LV) systolic dysfunction were administered standard heart failure treatment and felodipine extended release (ER) or placebo in the Vasodilator Heart Failure Trial III (V-HeFT III). Plasma norepinephrine (PNE) levels, atrial natriuretic peptide (ANP) levels, exercise capacity, LV ejection fraction (EF), cardiac dimensions and function, and arrhythmia frequency were measured. Hospital-free survival for baseline neurohormonal classes was assessed. Distributions of ANP and PNE levels at baseline in patients with heart failure of ischemic and nonischemic causes were virtually identical. ANP levels at baseline were inversely related to LVEF (r = -0.39; P = .0001), exercise duration (r = -0.19; P = .0001), and peak oxygen consumption (r = -0.27; P = .008) and directly related to LV (r = 0.23; P = .0006) and right ventricular dilatation (r = 0.23; P = .0008). The increase in ANP levels between baseline and 3 months (P = .02) and 1 year (P = .03) was significantly less in the felodipine-ER group than in the placebo group, but PNE levels did not differ between treatment groups. Hospital-free survival was directly related to baseline ANP (P = .0002) and PNE levels (P = .004). All-cause mortality was related to baseline PNE levels (P = .02) but not baseline ANP levels. Levels of ANP and PNE hormones are related to LV dysfunction, exercise performance, and hospital-free survival in heart failure and PNE levels are related to all-cause mortality. Treatment with felodipine ER did not adversely affect survival in any neurohormone subclass.",2001.0,1,1
140,10915232,Effects of diltiazem retard on ambulatory blood pressure and heart rate variability in patients with essential hypertension.,Y Kawano; Y Makino; N Okuda; S Takishita; T Omae,"Dihydropyridine calcium antagonists increase heart rate due to reflex activation of the sympathetic nervous system, although these effects are less obvious for long-acting agents. To study the effects of diltiazem retard, a long-acting nondihydropyridine calcium antagonist, on 24h blood pressure, heart rate and autonomic nerve activity in patients with essential hypertension. Randomized crossover design. Thirteen patients [five men and eight women, aged 64+/-2 years (mean+/-SEM)] were administered placebo or diltiazem retard (100-200mg once daily) for 4 weeks each. Ambulatory monitoring of blood pressure and heart rate, and electrocardiography were carried out at the end of each period using a multibiomedical recorder (TM-2425). Autonomic nerve activity was evaluated by power spectral analysis of variability of heart rate using the high-frequency component as an index of parasympathetic nerve activity and the ratio of the low-frequency component and the high-frequency component as an index of sympathovagal balance. Treatment with diltiazem retard significantly decreased 24h average blood pressure and heart rate by 11.6+/-3.6/5.7+/-1.8mmHg and 5.0+/-1.1 beats/min, respectively. The changes in daytime and night-time values were comparable. Diltiazem retard also significantly decreased daytime and 24h low:high-frequency-component ratio (2.0+/-0.2 versus 1.7+/-0.2 and 1. 8+/-0.2 versus 1.6+/-0.2, respectively). These results indicate that diltiazem retard is effective as a once-daily antihypertensive agent and has favorable effects on heart rate and the autonomic nervous system.",2000.0,0,0
141,10917075,Silent myocardial ischaemia in the elderly.,P C Deedwania,"Coronary artery disease (CAD) is a leading cause of death and disability in the elderly. Several recent studies have shown that silent myocardial ischaemia (SMI) is a common manifestation of CAD, especially in the elderly. As many as 40% of elderly patients with no prior history of CAD may have underlying asymptomatic disease and up to 50% of elderly patients with known CAD might have evidence of SMI. The results of studies in elderly patients with CAD have also shown that SMI might exist despite antianginal therapy that is considered adequate for symptom control. In order to diagnose such residual SMI, the clinician would need to perform 24- to 48-hour Holter monitoring in the ambulatory setting while the patient is performing routine daily activities. Although a number of anti-ischaemic drugs have been evaluated for the treatment of SMI, available data suggest that beta-blocker given alone or in combination with a nitrate compound or calcium antagonist provides the best therapeutic choice. The long term benefit of SMI suppression in elderly patients has not been established. Future studies need to evaluate the clinical benefits of therapy given for SMI in the elderly.",2001.0,0,0
142,10922432,Long-term effects of diltiazem and verapamil on mortality and cardiac events in non-Q-wave acute myocardial infarction without pulmonary congestion: post hoc subset analysis of the multicenter diltiazem postinfarction trial and the second danish verapamil infarction trial studies.,R S Gibson; J F Hansen; F Messerli; K B Schechtman; W E Boden,"The main objective of this retrospective analysis was to evaluate the long-term effect of the heart rate-lowering calcium antagonists verapamil and diltiazem on the incidence of combined cardiac events and all-cause mortality in patients who had experienced a non-Q-wave acute myocardial infarction (AMI), but who did not also have pulmonary congestion. In addition, factors having an independent association with these 2 outcomes were identified. Of 817 non-Q-wave patients, 81 (9.9%) died during 12 to 52 months of follow-up. The unadjusted mortality rate was 42% lower in patients randomized to calcium antagonist therapy than placebo (7.2% vs 12.4%, p = 0.010). Non-Q-wave patients who died during follow-up were older than patients who survived (62 vs 58 years, p = 0.001). Other factors found to have an independent association with all-cause mortality included diuretic use (RR 2.79), diabetes mellitus (RR 2.86), and New York Heart Association class >I (RR 1.73). The covariate adjusted all-cause mortality risk ratio associated with randomization to calcium antagonist therapy was 0.65 (95% confidence interval [0.40 to 1.05, p = 0.079]). Overall, 153 patients (18.7%) died or had nonfatal reinfarction. The unadjusted combined event rate was 31% lower in patients randomized to calcium antagonist therapy than to placebo (15.2% vs 21.9%, p <0.006). Factors found to have an independent association with cardiac events included age, diabetes (RR 2.82), diuretic use (RR 2.04), and previous AMI (RR 1. 71). In addition, randomization to the calcium antagonist group had a significant independent association with reduced cardiac events (p = 0.031). The covariate adjusted event rate RR associated with randomization to the calcium antagonist group was 0.69 (95% confidence interval [0.49 to 0.97]). In conclusion, the heart rate-lowering calcium antagonists diltiazem and verapamil may play an important role in reducing long-term mortality and reinfarction in non-Q-wave AMI without pulmonary congestion.",2000.0,0,0
143,10928302,Effects of antihypertensive treatment on endpoints in the diabetic patients randomized in the Systolic Hypertension in Europe (Syst-Eur) trial.,W H Birkenhäger; J A Staessen; J Gasowski; P W de Leeuw,"In this review we attempt to determine the role of calcium channel blockers in preventing cardiovascular sequela in patients with both hypertension and diabetes mellitus. The data have been collected from three sources: post hoc analyses of subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP, Syst-Eur, Syst-China); a stepped care blood pressure oriented trial (HOT); and comparative trials primarily focussing on metabolic aspects and intermediate endpoints (ABCD, FACET). On balance, the data seem to indicate that long-acting calcium channel blockers score remarkably well in preventing cardiovascular complications in diabetic hypertensive patients.",2001.0,0,1
144,10928396,Extended-release nifedipine bezoar identified one year after discontinuation.,L M Niezabitowski; B N Nguyen; J G Gums,"To report a case of tablet impaction of nifedipine extended-release tablets (Procardia XL) discovered one year after discontinuation of the drug in a patient with peptic stricture. English-language references identified via a MEDLINE search from 1966 through September 1998 and bibliographic review of pertinent articles. Extended-release nifedipine has been associated with the formation of medication bezoars in case reports. Bezoars are concretions of undigested material within the gastrointestinal (GI) tract. Although they can occur throughout the GI tract, bezoars are most frequently located in the stomach and, rarely, in the duodenum. We report an unusual case of tablet impaction with a gastric outlet obstruction in the duodenal area discovered one year after the patient stopped taking extended-release nifedipine. Extended-release nifedipine is associated with tablet impaction, even long after discontinuing administration. Although rare, clinicians should be aware of this potential problem when prescribing extended-release medications to patients at risk, and should consider this possible etiology when refractory epigastric pain and weight loss occur.",2001.0,0,1
145,10933370,Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.,P A Carson; C M O'Connor; A B Miller; S Anderson; R Belkin; G W Neuberg; J H Wertheimer; D Frid; A Cropp; M Packer,"The purpose of this study was to address the timing of sudden death in advanced heart failure patients. Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.",2000.0,0,1
146,10950401,Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension.,S Nalbantgil; I Nalbantgil; R Onder,"The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has reported that combinations of low doses of antihypertensive agents from different classes may provide additional antihypertensive efficacy and minimize the likelihood of dose-dependent adverse effects. Doxazosin and amlodipine, alone and in combination, were compared for efficacy in reducing blood pressure (BP) in 75 patients with predominantly moderate (Stage 2) hypertension. This was a double-blind, randomized, crossover study. After a 2-week washout period, patients in group A (n = 37) received amlodipine 10 mg and patients in group B (n = 38) received doxazosin 4 mg for 6 weeks. All patients then received reduced-dose combination therapy (amlodipine 5 mg and doxazosin 2 mg) for 6 weeks. Subsequently, patients received 6 weeks of monotherapy with the alternate medication (group A received doxazosin 4 mg and group B received amlodipine 10 mg). During both monotherapy periods, doxazosin and amlodipine significantly reduced systolic and diastolic BP (P < .001 v baseline). BP further decreased with combination therapy (P < .01 v monotherapy). The percentage of patients with Stage 2 hypertension who achieved a target BP of < 140/< 90 mm Hg increased from 78% with monotherapy to 94% with combination therapy. Fewer adverse effects were observed during combination therapy. It is concluded that there is an additional fall in blood pressure when reduced doses of doxazosin and amlodipine are used in combination for the treatment of hypertension, suggesting that doxazosin should be considered as an effective add-on treatment to calcium-channel blockers.",2001.0,0,0
147,10951830,[Single daily dose of verapamil (COER-24 180/24 mg) in mild and moderate hypertension evaluated by ambulatory blood pressure monitoring].,K C Ortega; J L Santello; F Nobre; O Kohlman Júnior; P C Jardim; L S da Costa; G A Rosito; J J Raposo Filho; W Oigman; D Mion Júnior,"To evaluate the anti-hypertensive effect of verapamil COER-24 180/240 mg in a single dose at bedtime as single therapy in mild to moderate hypertensives. A multicentric, open, placebo controlled study of 81 hypertensive patients older than 20 years-old followed to 8 weeks. Blood pressure was measured in doctor's office and by 24 h ambulatory monitoring (ABPM). We observed a decreased in systolic and diastolic blood pressure in doctor's office at 4th and 8th weeks. ABPM showed that both systolic, diastolic and mean blood pressure, heart rate and the mean 24-hour blood pressure load decreased after the 8-week treatment. In addition, there was a reduction of the double-product, especially in the morning and 68% of the patients didn't have any adverse events. The therapy verapamil COER-24 180/240 mg in a single dose is useful for mild and moderate hypertensive patients, with significant pressure decrease in both office blood pressure measurements and in the ABPM/24 hours, as well as showing good tolerability.",2000.0,0,0
148,10971664,The efficacy of divalproex sodium in the prophylactic treatment of children with migraine.,J M Caruso; W D Brown; G Exil; G G Gascon,"To determine the beneficial use of divalproex sodium as a prophylactic treatment for migraine in children. Previous studies for treatment of migraine in adults have shown a greater than 50% reduction in migraine attack frequencies. Few data exist, however, regarding the efficacy and safety of divalproex sodium use in children with migraine. We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects. A total of 42 patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated with divalproex sodium for headache. All had a history of migraine with or without aura. Baseline headache frequency during a minimum 6-month period was one to four headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their abortive medications. After 4 months' treatment, 50% headache reduction was seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients became headache-free. These results indicate divalproex sodium to be an effective and well-tolerated treatment for the prophylaxis of migraine in children.",2001.0,0,0
149,10972367,Randomised trial of effects of calcium antagonists compared with diuretics and beta-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study.,L Hansson; T Hedner; P Lund-Johansen; S E Kjeldsen; L H Lindholm; J O Syvertsen; J Lanke; U de Faire; B Dahlöf; B E Karlberg,"Calcium antagonists are a first-line treatment for hypertension. The effectiveness of diltiazem, a non-dihydropyridine calcium antagonist, in reducing cardiovascular morbidity or mortality is unclear. We compared the effects of diltiazem with that of diuretics, beta-blockers, or both on cardiovascular morbidity and mortality in hypertensive patients. In a prospective, randomised, open, blinded endpoint study, we enrolled 10,881 patients, aged 50-74 years, at health centres in Norway and Sweden, who had diastolic blood pressure of 100 mm Hg or more. We randomly assigned patients diltiazem, or diuretics, beta-blockers, or both. The combined primary endpoint was fatal and non-fatal stroke, myocardial infarction, and other cardiovascular death. Analysis was done by intention to treat. Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups (reduction 20.3/18.7 vs 23.3/18.7 mm Hg; difference in systolic reduction p<0.001). A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group (16.6 vs 16.2 events per 1000 patient-years; relative risk 1.00 [95% CI 0.87-1.15], p=0.97). Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group (6.4 vs 7.9 events per 1000 patient-years; 0.80 [0.65-0.99], p=0.04) and fatal and non-fatal myocardial infarction in 183 and 157 patients (7.4 vs 6.3 events per 1000 patient-years; 1.16 [0.94-1.44], p=0.17). Diltiazem was as effective as treatment based on diuretics, beta-blockers, or both in preventing the combined primary endpoint of all stroke, myocardial infarction, and other cardiovascular death.",2000.0,1,1
150,10972368,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.",2000.0,1,1
151,10973843,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.",2000.0,0,1
152,10981547,"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
153,10981801,Modulation of tear film protein secretion with phosphodiesterase inhibitors.,V Evans; M D Willcox; T J Millar,"A double-blind randomized clinical study was conducted to determine whether nicardipine hydrochloride was a useful treatment for dry eye.We examined its effect on the tear film, ocular surface and ocular comfort. Nicardipine hydrochloride, 3-isobutyl-1-methylxanthine and pilocarpine hydrochloride were dissolved in an artificial tear vehicle and applied topically to one eye of 12 subjects on separate days. Ocular physiology, ocular comfort and tear volume were assessed. The trial was repeated with nicardipine in an aqueous gel vehicle. Tears were collected and assessed for protein concentration and protein profile, using electrophoresis and mass spectrometry. Nicardipine induced conjunctival redness and symptoms of dryness and irritation. There was no change in total tear protein concentration or volume. An increase in a 68 kDa protein was observed, this was probably due to conjunctival vessel dilation and leakage of albumin. The adverse symptomatology and increased conjunctival redness experienced with nicardipine make it an undesirable treatment for dry eye.",2001.0,0,0
154,10984813,Outcomes of an amlodipine-to-felodipine therapeutic interchange program.,D R Clay; M P Bourg; D B Lawrence,,2001.0,0,1
155,10988281,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
156,10989730,[Calcium channel blocking agents and albuminuria in diabetic and hypertensive patients. A pilot study].,M Lamarre-Cliche; R Lambert; P Van Nguyen; J Cusson; R Wistaff; P Larochelle,"Diltiazem tends to decrease proteinuria in hypertensive diabetic subjects in comparison to amlodipine that does not modify it. Since estimated glomerular pressure is identical in amlodipine treated and diltiazem treated subjects, differences in albuminuria may be explained by different renal tubular reabsorption rates. To compare plasma clearances (PC) of technetium labeled albumin (albumin-Tc99m) obtained by serial plasma measurements with PC obtained by urinary excretion measurements. Indirectly evaluate tubular reabsorption of albumin-Tc99m. Test the hypothesis that amlodipine decreases renal tubular reabsorption of albumin in diabetic hypertensive subjects. Fourteen diabetic and hypertensive subjects (DH) (average plasma creatinine: 94 mmol/L) and 6 normal subjects (average plasma creatinine: 82 mmol/L) had previously been assessed for albumin-Tc99m PC. Eleven of these 14 DH subjects were then randomized to diltiazem 300 mg/daily (6 subjects) or amlodipine 10 mg/daily (5 subjects). Their glomerular filtration, glomerular pressure and albumin-Tc99m PC were then assessed on the 3rd, 6th, and 12th month of the study. Albumin-Tc99m PC obtained from serial blood draws: A decrease in PC between months 0 and 3 from 14 to 10.6 cc/min was observed in subjects treated with amlodipine but subjects on diltiazem showed PC stability (from 11.9 to 12 cm3/min). PC obtained from urinary excretion: Amlodipine and diltiazem treated subjects showed PC stability. Plasma volume in amlodipine treated subjects decreased from 156 to 127% and diltiazem treated subjects from 128 to 117%. A decrease in PC obtained with plasma measurements and stability of PC based on urinary excretion measurements tends to identify a decrease in plasma volume. A decrease in albumin-Tc99m tubular reabsorption was not observed. The estimate of albumin PC with Tc 99m labelled albumin measurements still needs to be validated.",2000.0,0,0
157,10990295,Commonly encountered prescription medications in medical-legal death investigation: a guide for death investigators and medical examiners.,M M Heninger,"The most common prescription medications encountered and recorded in the normal course of a death investigation by a medical examiner's office in a moderate-sized jurisdiction in an urban city are tallied, based on data collected from 2233 deaths reported in 1998. Medication history was available for 775 of these deaths and is reviewed in this study. The 25 most common medications are each briefly discussed, particularly adverse effects and possible toxicity of concern in the investigation of death. Medications to treat cardiovascular disease are by far the most commonly encountered. The 10 most common medications regardless of category were furosemide, digoxin, nitroglycerin, potassium, lisinopril, warfarin, albuterol, nifedipine, codeine, and amlodipine.",2001.0,0,0
158,10999500,Retrospective evaluation of the conversion of amlodipine to alternative calcium channel blockers.,D Parra; N P Beckey; L Korman,"To evaluate the effectiveness, safety, and costs associated with a formulary conversion from amlodipine to alternative calcium channel blockers. Retrospective study. Veterans Affairs Medical Center. One hundred patients with hypertension who were receiving amlodipine. Data from a random sample of 100 patients who were taking amlodipine and converted to a formulary calcium channel blocker from February 1, 1999-October 30, 1999, were entered into an Excel database for evaluation of the conversion. Patients were required to have a diagnosis of hypertension and have had two consecutive clinic visits with blood pressure measurements (and no changes in antihypertensive therapy) before conversion. End points were changes in average systolic blood pressure, diastolic blood pressure, and mean arterial pressure (MAP) from the two clinic visits before and after conversion. In addition, data were collected and analyzed with regard to adverse drug reactions, average dosage of the alternative calcium channel blocker, number of additional antihypertensives begun or discontinued, and number of dosage changes in antihypertensives within the two visits after conversion, and the overall cost impact of conversion. Average systolic blood pressure was reduced from 141.6 +/- 15.1 to 139.2 +/- 15.3 mm Hg after the conversion (NS). Average diastolic blood pressure was significantly reduced from 74 +/- 9.5 to 72.6 +/- 10.1 mm Hg after conversion (p=0.032), as was MAP (97.0 +/-q 9.3 to 94.8 +/- 10.0 mm Hg, p=0.026). Five patients had other changes in therapy made concurrently at the time of conversion, and 19 had changes after conversion. When these patients were excluded from analysis, the reduction in systolic blood pressure after conversion was significant (141.4 +/- 14.5 to 137.7 +/- 14.3 mm Hg, p=0.022), as were reductions in diastolic blood pressure (74.4 +/- 9.4 to 71.7 +/- 9.8 mm Hg, p=0.014) and MAP (96.7 +/- 9.1 to 93.7 +/- 9.3 mm Hg, p=0.007). Of patients who had postconversion changes in therapy, 8 (42%) were converted to diltiazem ER, nifedipine CC, or doses of felodipine that were 50% of the original dose of amlodipine. The overall cost impact of the conversion was a net savings of $14,858/year for each 100 patients converted. Conversion from amlodipine to other calcium channel blockers resulted in statistically significant reductions in diastolic blood pressure and MAP, and was safe as well as cost-effective. Conversion to calcium channel antagonists other than felodipine or less than equal dosages of felodipine may require dosage titration. When converting patients from amlodipine, dosages usually should be equal to those of felodipine; if converting to other calcium channel antagonists, the need for adjustments should be anticipated.",2001.0,0,0
159,10999574,Calcium channel blocker ingestions in children.,M G Belson; S E Gorman; K Sullivan; R J Geller,"Limited data exists regarding toxicity of calcium channel blockers (CCBs) in children. The purpose of this study was to determine the frequency, the range of toxicity, the appropriate observation time, and to assess effective interventions for CCB ingestions in children. A 6-year retrospective review of CCB ingestions in children younger than 7 years of age reported to one regional poison center was undertaken. Patients with coingestants with recognized cardiovascular or central nervous system (CNS) effects were excluded. Two hundred eighty-three patients met criteria for review. The mean age was 27 months with 52% of all patients being boys. Nifedipine (38%), verapamil (34%), and amlodipine (14%) were most commonly ingested. Seventy-five percent of ingestions reportedly involved < or =1 pill. Symptoms occurred in 16/283 (6%): 4 had vomiting, and 12 had CNS or cardiovascular effects. The mean time to onset of symptoms for regular-release and for sustained-release (SR) CCB preparations were 1.5 hours (range 0.5 to 3 hr) and 4.5 hours (range 1 to 14 hr) respectively. 74% of patients had no clinical effects, 4% minor effects, 2% moderate effects, and 20% other. No deaths or major effects were reported. 88% of patients evaluated in an emergency department received gastric decontamination, usually one dose of charcoal. Calcium chloride was given in three verapamil SR cases. Five of six patients had reversal of hypotension with IV fluids and decontamination alone. Most pediatric CCB ingestions involve ingestions of small amounts of drug with no effects. Asymptomatic children in this study group who were known to have ingested <12 mg/kg of verapamil SR or <2.7 mg/kg of nifedipine SR could have been monitored at home. Of the children requiring evaluation and monitoring in a health care facility, an observation period for regular-release and SR-CCBs for 3 and 14 hours respectively would have been appropriate. There were insufficient cases with symptoms to draw conclusions for optimal therapeutic interventions.",2000.0,0,0
160,11004045,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
161,11004140,Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators.,B Pitt; R P Byington; C D Furberg; D B Hunninghake; G B Mancini; M E Miller; W Riley,"The results of angiographic studies have suggested that calcium channel-blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (P:=0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0. 0126-mm decrease in the amlodipine group (P:=0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.",2001.0,1,1
162,11018607,Intensive medical management of ureteral calculi.,J T Cooper; G M Stack; T P Cooper,"To compare two treatment regimens in patients with ureteral calculi. One regimen (control arm) used routine drugs, and the second regimen (treatment arm) used the same routine drugs plus uncommonly used drugs. Between February and October 1998, 70 consecutive patients were evaluated for symptomatic ureteral calculi. Thirty-five patients were randomized to a control arm and received ketorolac, oxycodone, and acetaminophen combination tablets and prochlorperazine suppositories. Thirty-five patients were randomized to the treatment arm and received the same medications plus nifedipine XL, prednisone, and trimethoprim/sulfa combination tablets and plain acetaminophen. Stone passage rates, work days lost, emergency room visits, surgical interventions, and possible side effects of the drugs were recorded. The treatment arm (addition of nifedipine XL, prednisone, trimethoprim/sulfa, and plain acetaminophen) had higher (86% versus 56%) stone passage rates and fewer lost work days (mean 1.76 versus 4.9), emergency room visits (1 versus 4), and surgical interventions (2 versus 15). Both arms exhibited similar potential drug side effects. The addition of a calcium channel blocking agent, steroids, antibiotics, and more acetaminophen effected a higher stone passage rate and fewer lost work days, emergency room visits, and surgical interventions.",2001.0,0,0
163,11018608,Effectiveness of nifedipine and deflazacort in the management of distal ureter stones.,F Porpiglia; P Destefanis; C Fiori; D Fontana,"To evaluate the effectiveness of medical therapy during watchful waiting in patients with distal ureter stones. Ninety-six patients with radiopaque stones located in the distal tract of the ureter and with stone sizes of 1 cm or smaller were involved in the study. The patients were randomly divided into two groups. Group A (n = 48) received oral treatment with 30 mg of deflazacort daily (maximum 10 days) plus 30 mg of slow-release nifedipine daily (maximum 4 weeks). Group B (n = 48) underwent a wait-and-watch approach. Both groups of patients were allowed to use diclofenac on demand. Statistical analyses were carried out using Student's t test, the chi-square test, and Fisher's exact test. The average stone size was 5.8 +/- 1.8 mm for group A and 5. 5 +/- 1.4 mm for group B. No statistically significant difference was found in stone size. Stone expulsion was observed in 38 (79%) of 48 patients in group A and in 17 (35%) of 48 patients in group B. The average expulsion time was 7 days (range 2 to 10) for group A and 20 days (range 10 to 28) for group B. A statistically significant difference was observed in both the expulsion rate and the expulsion time (P <0.05). The mean amount of sodium diclofenac used was 15 mg per patient for group A and 105 mg per patient for group B (P <0.05). The medical treatment proved to be effective and safe, as demonstrated by the increased stone expulsion rate, decreased expulsion time, and reduced need for analgesic therapy.",2001.0,0,0
164,11021955,Patterns of amlodipine and felodipine use in an elderly Quebec population.,O Sheehy; J LeLorier,"To assess drug prescription patterns and medical resource consumption in an elderly population in Quebec receiving amlodipine or felodipine for the treatment of hypertension. Sociodemographic, clinical and drug claim data for a random sample of hypertensive patients 65 years of age and older with at least one claim for amlodipine or felodipine between August 1, 1990 and August 31, 1997 were extracted from the Régie de l'assurance maladie du Québec (RAMQ) database. Patterns of prescription renewal, drug switch and compliance rates, and health care resource use were established for both an amlodipine and a felodipine group. Long term persistence on treatment was quantified by survival curve analysis. The amlodipine (5188 patients) and felodipine (2630 patients) groups were similar in terms of sex ratio (66.7% female) and age (mean 74 years). Average compliance rates for amlodipine patients (67.9%) were significantly higher than for felodipine patients (66.2%) (P<0.01), and switch rates were 5.4-fold higher in the latter group. Patients initiating treatment with felodipine had a 27% increased rate of discontinuation (relative risk 1.27) compared with the amlodipine patients. In addition, patients with at least one year of follow-up data were more likely to maintain amlodipine as part of their antihypertensive regimens than felodipine. After adjustment, medical resource consumption patterns were similar for both groups except for an increase in the number of specialist visits for the amlodipine treatment group. Patients who received amlodipine, either as a monotherapy or as part of a multitherapy regimen, were more compliant and persistent with their treatment than patients on felodipine. The data suggest that amlodipine may provide more effective long term hypertension control than felodipine, and that the two drugs are not therapeutically equivalent.",2001.0,0,0
165,11041159,Treatment of hypertensive children with amlodipine.,J T Flynn; W E Smoyer; T E Bunchman,"Amlodipine, a long-acting dihydropyridine calcium channel blocking agent, was administered to 55 children (age: 11.5 +/- 5.4 years) with hypertension, 49 of whom (89%) had secondary hypertension. Efficacy was assessed by comparing pretreatment blood pressure (BP) to follow-up BP obtained in our outpatient Pediatric Nephrology clinic. Thirty-two (58%) patients achieved BP control with amlodipine alone, and 31 (55%) patients received amlodipine twice daily. Eleven patients received amlodipine as a suspension. Mean amlodipine dose was 0.16 +/- 0.12 mg/kg/day; there was an inverse relationship between patient age and amlodipine dose. Follow-up BP were significantly lower than pretreatment BP: systolic BP fell from 129 +/- 12 to 122 +/- 12 mm Hg (P = .004), and diastolic BP fell from 78 +/- 13 to 70 +/- 19 mm Hg (P = .003). A small, clinically insignificant increase in heart rate (from 91 +/- 19 beats/min to 99 +/- 26 beats/min; P = .02) occurred during amlodipine treatment. Adverse effects reported included dizziness (three patients), fatigue (two patients), flushing (two patients), and leg edema (one patient). All improved with dose reduction. We conclude that amlodipine provides effective BP control without significant adverse effects in children with hypertension, and can be used as monotherapy in most children. Young children appear to require significantly higher doses per kilogram of body weight than older children. Twice-daily dosing may be required in many children to achieve BP control. Detailed pharmacokinetic studies are needed to confirm these observations.",2001.0,0,0
166,11045391,A randomized prospective crossover trial of amlodipine in pediatric hypertension.,J W Rogan; D A Lyszkiewicz; D Blowey; S Khattak; G S Arbus; G Koren,"Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life, allowing for once-daily administration. The objective of this study was to compare the efficacy and compliance of amlodipine with that of standard long-acting calcium channel blockers (felodipine or nifedipine) in hypertensive children. A randomized, prospective, crossover study of 11 hypertensive children (9-17 years of age, 10 renal transplant patients) was performed with electronic monitoring of compliance. Each treatment arm was 30 days. No significant differences were observed in mean systolic (SBP) and diastolic blood pressures (DBP) between amlodipine and the other calcium channel blockers. Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP. Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods. These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine. Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation.",2001.0,0,0
167,11048472,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
168,11057441,Haemodynamic and metabolic effects of rilmenidine in hypertensive patients with metabolic syndrome X. A double-blind parallel study versus amlodipine.,N De Luca; R Izzo; D Fontana; G Iovino; L Argenziano; C Vecchione; B Trimarco,"To compare the effects of rilmenidine with those of amlodipine on blood pressure, glucose metabolism, plasma lipid concentration and fibrinolysis parameters. A four-month randomized double-blind, parallel group study. Obese hypertensive patients with hypertriglyceridaemia (> or = 2.3 mmol/l) and impaired glucose tolerance (OMS-ADA) were included (n = 52). A placebo run-in period of 2 weeks was followed by 4 months of double-blind treatment with either rilmenidine or amlodipine. Blood pressure was recorded using a mercury sphygmomanometer. Glucose metabolism was evaluated by an oral glucose tolerance test Of the 52 patients recruited, 47 (21 rilmenidine and 26 amlodipine) completed the 4-month treatment period. The intention-to-treat analysis showed a comparable reduction in systolic and diastolic blood pressure (SBP, DBP) with the two anti-hypertensive treatments (rilmenidine -13.9/-13.5 mmHg; amlodipine - 17.6/-15.0 mmHg). Insulin concentrations under basal conditions and 2 h after a standard oral glucose load did not change significantly after treatment in both groups. Plasma glucose under basal conditions and 2 h after a standard oral glucose load as well as the area under the plasma glucose concentration curve tended to decrease in the rilmenidine group and to increase in the amlodipine group so that the changes in these parameters were significantly different between the two study groups (P= 0.041, P = 0.042 and P = 0.015, respectively). Plasminogen activator inhibitor type 1 (PAI-1) antigen and PAI-1 activity were only decreased in the rilmenidine group (not statistically significant). Our results demonstrate that rilmenidine and amlodipine have a comparable anti-hypertensive effect but only rilmenidine is able to improve glucose metabolism.",2001.0,0,0
169,11061055,Monotherapy with amlodipine or atenolol versus their combination in stable angina pectoris.,S K Pehrsson; I Ringqvist; S Ekdahl; B W Karlson; G Ulvenstam; S Persson,"The basic cause of angina pectoris is imbalance between the metabolic needs of the myocardium and the capacity of the coronary circulation to deliver sufficient oxygenated blood to satisfy these needs. The study was undertaken to evaluate whether the effect of combined amlodipine and atenolol therapy on patients with stable angina pectoris and with ST-depression during exercise testing and 48-h ambulatory electrocardiographic monitoring is superior to that of either agent given alone. Patients with stable angina pectoris and ST depression during exercise and ambulatory monitoring were randomized to receive amlodipine (n = 116) or atenolol (n = 116), or both (n = 119). All patients were also treated with short- and long-acting nitrates. The design was a double-blind, randomized, triple-arm parallel group study with 10 weeks of administration of the test medication. In terms of time to onset of ST depression > 1 mm, time to onset of angina, total exercise time, maximum achieved workload, and peak intensity of angina, amlodipine and atenolol alone were as effective as their combination. During ambulatory monitoring, atenolol was more effective than amlodipine regarding total time and number of ST-depression episodes, and as effective as the combined drugs. For individual patients with stable angina pectoris, combination of a beta blocker with a calcium antagonist is not necessarily more effective than either drug given alone.",2001.0,1,1
170,11070565,Combination therapy with beta-adrenergic blockade and amlodipine as second line treatment in essential hypertension.,M Mettimano; F Pichetti; L Fazzari; A Migneco; L Specchia; V Romano Spica; L Savi,"In hypertension both beta-blockers and calcium antagonists are drugs with proved efficacy. Because only half the patients respond to a single drug, even at full dosage, a second hypotensive agent is frequently required to obtain adequate blood pressure control. The combination of a dihydropyridine calcium antagonist and a beta-blocker can be justified by their different mechanisms of action. A randomised double blind parallel group study versus placebo was performed, in order to assess the efficacy of atenolol combined with amlodipine in the treatment of stage I-II essential hypertension not controlled by atenolol alone. Twenty-four-hour arterial blood pressure monitoring showed that amlodipine added to atenolol produced a statistically significant reduction of blood pressure values compared with placebo in patients whose blood pressure was not controlled by atenolol alone. Blood pressure circadian rhythm was unchanged. The reduction of side-effects, obtained by adding a dihydropyridine derivate to a beta-blocker, confirms the effectiveness of this combination.",2001.0,0,0
171,11078175,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
172,11078178,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
173,11085972,Cardiovascular drugs. Dofetilide.,J P Mounsey; J P DiMarco,,2001.0,0,0
174,11090788,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
175,11092108,Bisoprolol alone and in combination with amlodipine or nifedipine in the treatment of chronic stable angina.,J D Ferguson; O Ormerod; A J Lenox-Smith,"Beta-blockers and calcium antagonists are both effective monotherapy for stable angina. When symptoms persist, these two agents are commonly co-prescribed in the hope that this combination has added benefit compared with monotherapy alone. We investigated the additional efficacy of the calcium antagonists amlodipine and nifedipine when added to bisoprolol in patients with stable angina. Patients were randomised in a multicentre, single-blind study, with crossover of three treatments consisting of bisoprolol 10 mg once daily, bisoprolol plus nifedipine 20 mg twice daily, and bisoprolol plus amlodipine 5 mg once daily. Exercise tests were performed at the end of each four-week study period and the exercise time to onset of angina was assessed. A total of 198 patients from 17 centres were recruited of whom 147 were evaluable for efficacy. There were no statistically significant differences in exercise duration to onset of angina between any of the groups. The combination of bisoprolol plus nifedipine was least well tolerated. In summary, this study suggests there is little benefit in adding a calcium antagonist to bisoprolol in treating patients with stable angina.",2001.0,0,0
176,11094241,Management of mild chronic hypertension during pregnancy: a review.,R L Ferrer; B M Sibai; C D Mulrow; E Chiquette; K R Stevens; J Cornell,"To conduct a systematic review of evidence relating to management of mild chronic hypertension during pregnancy, including associated risks, benefits, and harms of treatment with antihypertensive agents, nonpharmacologic measures, and aspirin and benefits of various monitoring strategies. Using four broad search strategies, we searched English and non-English-language citations in 16 electronic databases from their inception to February 1999 and consulted relevant textbooks, references, and experts. Reviewers screened 6228 abstracts and found 215 articles that met multiple prespecified patient selection, study population, and design criteria. Forty-six studies consistently showed that chronic hypertension triples the risk for perinatal mortality (odds ratio [OR] 3.4; 95% confidence interval [CI] 3.0, 3.7) and doubles the risk for placental abruption (OR 2.1; 95% CI 1.1, 3.9). Thirteen small, randomized controlled trials had inadequate power to rule in or rule out moderate-to-large (20%-50%) benefits of antihypertensive treatment. Possible adverse effects were fetal renal failure when angiotensin-converting enzyme inhibitors are used in the second or third trimester and growth restriction when atenolol is used early in pregnancy. Trials showed that aspirin neither reduces nor increases perinatal and maternal morbidity, but they did not rule out possible small-to moderate beneficial or adverse effects. No studies provide guidance on benefits or consequences of various nonpharmacologic therapies or monitoring strategies. Mild chronic hypertension is associated with increased maternal and fetal risks. Beneficial treatment and monitoring regimens are not clear, but some treatments, such as angiotensin-converting enzyme inhibitors, are best avoided.",2001.0,0,0
177,11099990,"Rate-control versus conversion strategy in postoperative atrial fibrillation: a prospective, randomized pilot study.",J K Lee; G J Klein; A D Krahn; R Yee; K Zarnke; C Simpson; A Skanes; B Spindler,"Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm. Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period. There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 +/- 3. 2 vs 11.8 +/- 3.9 hours; P =.8). With the use of Cox multivariate analysis to control for the effects of age, sex, beta-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P =.08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 +/- 0.7 vs 13.2 +/- 2.0 days; P =.05). In-hospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P =.24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P =.6). This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay.",2001.0,0,0
178,11100296,Therapeutic agents in preterm labor: tocolytic agents.,A E Hearne; D A Nagey,,2001.0,0,0
179,11105796,Blood pressure reduction associated with preservation of renal function in hypertensive patients with IgA nephropathy: a 3-year follow-up.,Y Kanno; H Okada; T Saruta; H Suzuki,"The relative importance of hypertension in the progression of renal failure is well understood. Recently, several studies have provided evidence that antihypertensive therapy enhances renal survival. However, the specific antihypertensive drug regimens that are most effective in generating such long-term effects remain controversial. Forty-nine hypertensive IgA nephropathy (IgAN) patients (39 +/- 7 years old, serum creatinine 1.1 +/- 0.2 mg/dl) with proteinuria received antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEi: 2.5-10 mg of benazapril daily) and calcium channel blockers (CCBs: 2.5-10 mg amlodipine daily) for 3 years. The patients' blood pressures in group one were controlled below 140/85 mmHg by increases in their first drug dose or by addition of the second drug in group 1. Blood pressures for patients in group 2 were controlled using the same two options, except to levels below 130/70 mmHg. Patients within the two groups were selected and controlled with regard to sex, age, and serum creatinine. The renal protective effects of each protocol were evaluated in terms of reductions in creatinine clearance. After 3 years of the above outlined blood pressure control regimens, the reductions in creatinine clearance were compared. Creatinine clearances decreased in group 1 patients (from 85.7 +/- 2.4 ml/min to 72.9 +/- 2.4 ml/min, p < 0.05). On the other hand, creatinine clearance remained essentially unchanged for patients in group 2 (from 87.2 +/-4.7 ml/min to 85.9 +/- 5.9 ml/min). Although creatinine clearance in both groups was almost the same at the start of study, there was a significant difference between them by the conclusion of the study (p < 0.05). Proteinuria and hematuria did not change significantly throughout the study and there were no significant differences in these respects between these two corresponding groups. There were no significant differences between the groups with reference to side-effects or complications. These data provide evidence that reducing blood pressure has protective renal effects in cases of mild renal insufficiency with hypertension in IgA nephropathy.",2001.0,0,0
180,11109422,[Effectiveness of felodipine in hypertensive patients with mild cerebral cognition disorders in a randomized double-blind study].,S Lehrl; E Grässel; C Eicke,"Cognitive impairment occurs more frequently in hypertensives than in normotensive individuals. Early signs of cognitive impairment are predictors of dementia in late life. Felodipine is capable of almost normalizing plasma viscosity, which is elevated in most of hypertensive patients, thus improving microcirculation. The aim of this study was to evaluate whether this hemorheologic property of felodipine in addition to its blood pressure lowering effect can improve cognitive performance in hypertensive patients. Randomized, double-blind comparison between felodipine 10 mg and hydrochlorothiazide 50 mg amiloride 5 mg (HCT/amiloride) in patients 50-70 years of age with impaired cognitive function (c.l. test 1-2 points) and with resting blood pressure values of diastolic > 95 and < or = 115 mmHg and/or systolic > 160 and < or = 210 mmHg. Blood pressure measurements and evaluation of total short term storage capacity were done at the beginning and after 12 weeks of treatment. 31 patients (14 felodipine and 17 HCT/amiloride) were included in the per protocol analysis. Blood pressure values at the beginning and after 12 weeks of treatment were (mmHg): for felodipine systolic 168 +/- 4 and 150 +/- 6 (p < 0.01), diastolic 108 +/- 3 and 88 +/- 4 (p < 0.001). For amiloride/HCT systolic 173 +/- 8 and 150 +/- 10 (p < 0.01), diastolic 105 +/- 5 and 88 +/- 5 (p < 0.001). Short term storage capacity improved by 15 +/- 6 bits during felodipine treatment (p < 0.001) and by 9 +/- 9 bits during amiloride/HCT treatment (p < 0.05). Thus cognitive improvement was superior by 67% in the felodipine group compared to amiloride/HCT (p < 0.05). In this study a pronounced improvement of mental performance occurred in patients treated with felodipine. Since the cognitive gain was significantly superior to amiloride/HCT treatment there must be an additional blood pressure-independent effect of felodipine, such as enhancing microcirculation. Whether these properties possibly counteract the development of dementia in hypertensives has to be evaluated in long term studies in more patients.",2001.0,0,0
181,11111143,Effects of a slow-release nifedipine on 24-hour ambulatory blood pressure and ischemic changes on 24-hour ambulatory electrocardiogram in patients with severe coronary artery disease.,N Matsumoto; M Ideishi; M Sasaguri; T Nii; Y Nakashima; K Arakawa,"Calcium antagonists have long been used as first-line drugs for hypertension and angina. However, deleterious effects have also been reported in patients treated with calcium antagonists. Thus, we evaluated the effect of a slow-release twice-daily formulation of nifedipine in 10 patients with severe coronary artery disease. Twenty-four-hour ambulatory electrocardiography (AECG) and blood pressure monitoring (ABPM) were performed simultaneously to detect any association between ischemic episodes on the ECG and changes in blood pressure (BP) and heart rate with and without nifedipine. Increased oxygen demand due to an increased systolic BP and heart rate was associated with ischemic episodes without nifedipine, while those with nifedipine were accompanied by a fall in diastolic BP and a rapid increase in heart rate. This slow-release twice-daily formulation of nifedipine may induce myocardial ischemia through a heart-rate increase and a decrease in coronary blood flow due to lower diastolic BP in patients with severe coronary artery disease. A once-daily formulation of nifedipine might be of great value for such patients.",2001.0,0,0
182,11116287,Vatanidipine hydrochloride: a new long-lasting antihypertensive agent.,Y Matsumura; K Hayashi,"Vatanidipine is a novel dihydropyridine (DHP)-type calcium channel blocker with slow-onset pharmacological actions, which are probably due to both its slow uptake into vascular tissues and resistance in its approach to the calcium channel binding site. Vatanidipine once incorporated into vascular tissues is not easily released, even by repeated washing, thus resulting in a long-lasting action of the agent. A slow-onset and long-lasting hypotensive action was observed in various experimental hypertensive models. Clinical trials using human subjects with essential hypertension indicated that vatanidipine exerts an antihypertensive effect with a slow onset and long duration. In spite of its potent hypotensive effect, the incidence of adverse effects by vatanidipine administration has been reported to be lower than that in cases of nitrendipine. In addition to its vasodilatory effects, vatanidipine efficiently suppressed noradrenaline release from sympathetic nerve endings, thus suggesting this agent exhibits a beneficial effect in the treatment of hypertensive patients, in which the reflex activation of peripheral sympathetic nerves is unfavourable to antihypertensive therapy. In a double-blind study, vatanidipine did not show reflex tachycardia, despite producing a potent and long-lasting hypotensive effect, in contrast to the administration of nitrendipine. In an animal study, vatanidipine exhibited a protective effect against cerebrovascular lesions, through a mechanism independent of its hypotensive effect. In addition, a renoprotective effect was also observed in experimental hypertensive models. In cholesterol-fed rabbits, vatanidipine exerted an anti-atherosclerotic action, which is probably attributable to the inhibitory action of the agent on low-density lipoprotein oxidation. In essential hypertensive patients, the plasma levels of cholesterol and triglyceride decreased after vatanidipine treatment, thus suggesting that this agent may have a therapeutic potential in preventing such vascular diseases as atherosclerosis. Taken together, vatanidipine appears to be a novel and useful antihypertensive agent, which can both prevent target-organ damage and reduce cardiovascular morbidity and mortality.",2001.0,0,0
183,11117374,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
184,11117910,Rhythm or rate control in atrial fibrillation--Pharmacological Intervention in Atrial Fibrillation (PIAF): a randomised trial.,S H Hohnloser; K H Kuck; J Lilienthal,"Atrial fibrillation is the most commonly encountered sustained cardiac arrhythmia. Restoration and maintenance of sinus rhythm is believed by many physicians to be superior to rate control only. However, there are no prospective data that compare both therapeutic strategies. The Pharmacological Intervention in Atrial Fibrillation (PIAF) trial was a randomised trial in 252 patients with atrial fibrillation of between 7 days and 360 days duration, which compared rate (group A, 125 patients) with rhythm control (group B, 127 patients). In group A, diltiazem was used as first-line therapy and amiodarone was used in group B. The primary study endpoint was improvement in symptoms related to atrial fibrillation. Over the entire observation period of 1 year, a similar proportion of patients reported improvement in symptoms in both groups (76 responders at 12 months in group A vs 70 responders in group B, p=0.317). Amiodarone administration resulted in pharmacological restoration of sinus rhythm in 23% of patients. Walking distance in a 6 min walk test was better in group B compared with group A, but assessment of quality of life showed no differences between groups. The incidence of hospital admission was higher in group B (87 [69%] out of 127 vs 30 [24%] out of 125 in group A, p=0.001). Adverse drug effects more frequently led to a change in therapy in group B (31 [25%] patients compared with 17 [14%] in group A, p=0.036). With respect to symptomatic improvement in patients with atrial fibrillation, the therapeutic strategies of rate versus rhythm control yielded similar clinical results overall. However, exercise tolerance is better with rhythm control, although hospital admission is more frequent. These data may serve as a basis to select therapy in individual patients.",2001.0,1,1
185,11130522,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.",2001.0,1,1
186,11130523,"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.",2001.0,1,1
187,11133211,Prognostic implications of intima-media thickness and plaques in the carotid and femoral arteries in patients with stable angina pectoris.,C Held; P Hjemdahl; S V Eriksson; I Björkander; L Forslund; N Rehnqvist,"Ultrasonographic assessments of intima-media thickness and plaques in the carotid artery are widely used as surrogate markers for coronary atherosclerosis, but prospective evaluations are scarce and appear to be lacking in patients with coronary artery disease. Ultrasonographic evaluations of femoral vascular changes have not been studied prospectively. In the Angina Prognosis Study in Stockholm (APSIS), 809 patients with stable angina pectoris were studied prospectively during double-blind treatment with verapamil or metoprolol. Ultrasonographic assessments of intima-media thickness, lumen diameter and plaques in the carotid and femoral arteries were evaluated in a subgroup of 558 patients (182 females) with a mean age of 60 +/-7 years, and related to the risk of cardiovascular death (n = 18) or non-fatal myocardial infarction (n = 26), or revascularization (n = 70) during follow-up (median 3.0 years). Univariate Cox regression analyses showed that carotid intima-media thickness and plaques were related to the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness was related to cardiovascular death or myocardial infarction, as well as to revascularization, whereas femoral plaques were only related to the latter. After adjustment for age, sex, smoking, previous cardiovascular disease and lipid status, carotid intima-media thickness failed to predict any cardiovascular event, whereas carotid plaques tended (P = 0.056) to predict the risk of cardiovascular death or myocardial infarction. Femoral intima-media thickness (P < 0.01) and plaques (P < 0.05) were also related to the risk of revascularization after adjustments. Carotid and femoral vascular changes were differently related to cardiovascular events. Carotid intima-media thickness was a weak predictor of events, whereas femoral intima-media thickness predicted revascularization. Plaques in the carotid artery were related to cardiovascular death or non-fatal myocardial infarction, whereas plaques in the femoral artery were related to revascularization. Evaluations of plaques provided better prediction than assessments of intima-media thickness in patients with stable angina.",2001.0,0,1
188,11142488,Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma.,D Belpomme; S Gauthier; E Pujade-Lauraine; T Facchini; M J Goudier; I Krakowski; G Netter-Pinon; M Frenay; C Gousset; F N Marié; M Benmiloud; F Sturtz,"Verapamil (VER), a potent calcium channel blocker, has been found to overcome P-gp-mediated multi-drug resistance (MDR) and to increase sensitivity to cytotoxic anticancer drugs in refractory myeloma and non-Hodgkin lymphoma. The value of VER for treating solid tumors is still a matter for debate. We performed a prospective study in 99 patients with anthracycline-resistant metastatic breast carcinoma (MBC), to assess the clinical effect of oral VER given in association with chemotherapy. Instead of retreating patients with anthracycline, we used a partially noncross-resistant regimen (VF), combining vindesine (VDS) and 5-fluorouracil given as a continuous infusion (5-FU CI). Patients were randomly assigned to two cohorts. One cohort (47 patients) was treated in 28-day cycles, each involving the administration of VDS (3 mg/m2 i.v. bolus on days 1 and 10) and 5-FU CI, (400 mg/m2/day i.v. from day 1 to day 10). The other cohort (52 patients) received the same VDS and 5-FU treatment and an additional oral VER treatment (240 mg/day divided in 2 doses), from day 1 to day 28 of each cycle. Patients were treated until progression. The treatment was well tolerated and no side effects that could be attributed to VER were detected. Patients treated with VER had longer overall survival (OS) (median OS: 323 vs. 209 days, P = 0.036) and a higher response rate (27% vs. 11%, P = 0.04) than those not given VER. Progression-free survival (PFS) was also longer but the difference was not statistically significant (median PFS: 4.6 and 2.7 months for the VER and non-VER groups respectively, P = 0.6). This clinical trial demonstrates that a chemosensitizer, such as VER, can increase the survival of MBC patients with acquired anthracycline resistance.",2001.0,0,1
189,11146977,Costs and outcomes of switching from amlodipine to felodipine.,C D Williams,,2001.0,0,1
190,11151741,The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients.,J S McLay; T M MacDonald; J Hosie; H L Elliott; Logimax Group,"The aims of this study were to study the efficacy and tolerability of felodipine extended release (ER) 5 mg and metoprolol controlled release (CR/ZOC) 50 mg given as a fixed combination (Logimax) or as a free combination in elderly (age greater than 60 years) hypertensive patients, using ambulatory blood pressure (BP) monitoring. A secondary aim was to relate the efficacy of the free and fixed combinations with pharmacokinetic profiles. This was a double-blind, placebo-controlled randomised three-way crossover multi-centre study. BP was measured for 26 h using ambulatory blood pressure monitoring (ABPM), which was performed on the last day of the three treatment phases. Mean sitting BPs, measured during the trough period with ABPM, were significantly lower with both the free and fixed combinations of metoprolol and felodipine than placebo (141/83 mmHg free, 140/83 mmHg fixed, 156/93 mmHg placebo). The mean BPs measured over 24 h using ABPM were 143/82 mmHg, 140/82 mmHg and 158/93 mmHg for the free, fixed and placebo treatment arms, respectively. The trough-to-peak ratios (T:P) were 75% and 79% for the systolic BP and 70% and 70% for the diastolic BP for the free and fixed combinations, respectively. Pharmacokinetic evaluation revealed identical plasma concentration-time curves for felodipine given as the free or fixed combination. Comparison of the plasma concentration-time curves for metoprolol revealed a delay in the release rate from the fixed combination formulation. No significant differences in BP control between the active treatments were noted during this period. Of 26 patients entered into the study, 3 withdrew during active phase for non-drug-related reasons. No patient withdrew from active treatment due to treatment-related adverse events. The frequency of adverse event reporting for the fixed combination of felodipine and metoprolol was similar to that for placebo (60% and 58%, respectively). The results suggest that once-daily dosing with either the free or fixed combination of felodipine 5 mg and metoprolol 50 mg produces a significant sustained reduction in systolic and diastolic BP with similar plasma concentration profiles over a 24-h period.",2001.0,0,0
191,11156667,Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study.,T Levy; S Walker; M Mason; P Spurrell; S Rex; S Brant; V Paul,"To determine the importance of rhythm regulation or rate control in patients with permanent atrial fibrillation (AF) and normal left ventricular function. Thirty six patients with a mixed fast and slow ventricular response rate to their AF were randomised to either His bundle ablation (HBA) and VVIR pacemaker (HBA group) or VVI pacemaker and atrioventricular modifying drugs (Med group). Outcomes assessed at one, three, six, and 12 months included exercise duration and quality of life. Exercise duration significantly improved from baseline in both groups. There was no difference in outcome between the groups (Med +40% v HBA +20%, p = NS). The heart rate profile on exercise was similarly slowed in both groups compared to baseline. Quality of life significantly improved in both treatment arms for the modified Karolinska questionnaire (KQ) (Med +50% v HBA +50%, p = NS) and the Nottingham health profile (NHP) (Med +40% v HBA +20%, p = NS). However, for the individual symptom scores of each questionnaire more were improved in the Med group (KQ-Med 6 improved v HBA 4, NHP-Med 3 v HBA 1). Left ventricular function was equally preserved by both treatments during follow up. In these patients control of ventricular response rate with either HBA + VVIR pacemaker or atrioventricular modifying drugs + VVI pacemaker will lead to a significant improvement in exercise duration and quality of life. Rhythm regulation by HBA did not confer additional benefit, suggesting rate control alone is necessary for the successful symptomatic treatment of these patients in permanent AF.",2001.0,0,0
192,11191937,Amlodipine versus slow release metoprolol in the treatment of stable exertional angina pectoris (AMSA).,K Midtbø; P Mølstad; AMSA study group (Amlodipine Metoprolol Stable Angina),"To compare the effects of amlodipine and slow release metoprolol on subjective symptoms and signs of ischaemia during bicycle ergometric exercise tests in patients with stable angina pectoris. A randomized double-blind comparison of the two drugs in patients with documented coronary disease required to have at least three attacks of angina per week and to perform a symptom-limited exercise test with significant signs of ischaemia in the ECG. Out of 127 patients, 117 completed the study. Both amlodipine and metoprolol significantly increased total exercise time, total workload, time to onset of angina and time to 1 mm ST-depression with no significant differences between the drugs. Amlodipine was significantly more efficient than metoprolol in reducing ST-depression at maximum workload. Diary data revealed no differences in patients' self-rating of drug effects. Judged by suppression of subjective symptoms and performance on exercise tolerance tests amlodipine represents a useful alternative to metoprolol as monotherapy in stable angina pectoris.",2001.0,1,1
193,11192138,Treatment of hypertension in patients > or =65 years of age: experience with amlodipine.,C Langdon,"Hypertension is a common finding in patients > or =65 years of age that contributes to cardiovascular morbidity and mortality, but many patients are untreated or their hypertension inadequately controlled. Recent randomized controlled studies have demonstrated the benefits of treating hypertension in the elderly. This study was undertaken to assess the efficacy and tolerability of amlodipine, a long-acting calcium channel blocker, in elderly (> or =65 years of age) patients with mild to moderate hypertension (diastolic blood pressure 95 to 114 mm Hg). This was an open-label, multicenter, 10-week, general-practice study involving patients >18 years of age. Patients with malignant or secondary hypertension or unstable angina were excluded, as were those who had experienced an acute myocardial infarction or stroke in the preceding 3 months or had been treated with an alpha-blocker in the preceding 6 months. Patients were assigned to 1 of 4 treatment schedules: amlodipine monotherapy or combination therapy and amlodipine given once daily in the morning or in the evening. Approximately 50% of patients would receive a morning dose, and approximately 80% would receive amlodipine as monotherapy. The paired t test was used to assess the significance of differences from baseline values, with significance set at P < 0.05. A total of 5135 patients received amlodipine and were included in the tolerability analysis. Of these, 3511 of 3628 patients (96.8%) <65 years and 1471 of 1507 patients (97.6%) > or =65 years (including 336 of 349 [96.3%] > or =75 years) were included in the efficacy analysis. Significant reductions (P < 0.05) in blood pressure were noted in all groups after 4 and 8 weeks of treatment. The equivalence of efficacy in all age groups was seen in terms of reduction in blood pressure (reduction of 21/15 mm Hg in patients <65 years of age, 25/16 mm Hg in those > or =65 years of age, and 26/17 mm Hg in those > or =75 years of age) compared with baseline. Therapy was successful in 2878 patients (82.0%) <65 years of age, in 1238 patients (84.2%) > or =65 years of age, and in 284 patients (84.5%) > or =75 years of age. The incidence of adverse events was similar in all age groups (18.0%, <65 years; 22.3%, > or =65 years; and 24.1%, > or =75 years), with no statistically significant differences between groups. Tolerability was rated as good or excellent in all patients, with no significant differences between groups. Once-daily amlodipine was effective in the treatment of mild to moderate hypertension in this patient population and demonstrated a low frequency of adverse events, a high degree of tolerability, and improved well-being. Morning rather than evening dosing appeared to confer a slight advantage.",2001.0,0,1
194,11195606,,,,,0,1
195,11195622,Which fasting triglyceride levels best reflect coronary risk? Evidence from the Turkish Adult Risk Factor Study.,A Onat; V Sansoy; B Yildirim,"Association between raised low-density lipoprotein cholesterol (LDL-C) levels and high risk for coronary heart disease (CHD) is well established and taken into account in guidelines on coronary prevention. The relationship between risk for coronary heart disease (CHD) and the levels of fasting plasma triglycerides was studied in the cohort of the Turkish Adult Risk Factor Study, a representative random sample of an adult population. In 829 men and 907 women aged > or =27 years (mean 48.5+/-11), plasma lipids and lipoproteins were measured by the enzymatic dry method in the postabsorptive state. A sample of values was validated in a reference laboratory. Apoliprotein (apo) A-I and B were measured by the turbidimetric immunoassay using commercial kits in part of the cohort. Blood pressure and anthropometric measurements were made. Criteria for the diagnosis of CHD were based on history, cardiovascular examination, and Minnesota coding of resting electrocardiograms. Coronary heart disease was diagnosed in about 7% of the subjects. Participants were divided into four categories depending on their triglyceride levels: I = < 100 mg/dl (282 men, 400 women), II = 100-139 mg/dl (204 men, 228 women), III = 140-212 mg/dl (188 men, 180 women), and IV = > or = 212 mg/dl (155 men, 99 women). After adjustment for age, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, smoking, and body mass index by logistic regression analysis, and after assigning the CHD risk of 1 to Category I, the relative risk for men and women combined rose to 1.42 in Category III (p<0.045) while it diminished to 0.94 in Category IV (p = 0.79). In women, the odds ratio (OR) rose gradually up to 1.78 (p< 0.025) in Category III, only to decline in Category IV. The OR in men was slightly, insignificantly, and equally elevated in Categories III and IV. Patients with CHD in Category III were not distinguished from those in Category IV by the studied risk parameters. It was suggested that high risk for CHD--particularly in subjects with slightly elevated or normal cholesterol levels-is often not reflected by extreme increases of fasting triglycerides but best by modest elevations (140-212 mg/dl), which serve better as a marker of triglyceride-rich lipoprotein particles. This knowledge may prove to be of value in population screening and individual risk assessment.",2001.0,0,1
196,11198728,A comparison of nisoldipine ER and amlodipine for the treatment of mild to moderate hypertension.,C Whitcomb; G Enzmann; H A Pershadsingh; R Johnson; V Ciuryla; E Reisin,"This multicentre, double-blind, double-dummy, randomised trial compared the efficacy and tolerability of nisoldipine extended release (10-40 mg) and amlodipine (2.5-10 mg) in 161 patients. The primary end point was a between-treatment comparison of change from baseline to week 8 in mean office diastolic blood pressure (DBP). The least squares mean reductions in systolic (S)BP/DBP (+/- standard error) for nisoldipine and amlodipine were -11.7/-9.3 +/- 1.4/0.8 and -14.3/-12.0 +/- 1.4/0.8 mmHg, respectively. The DBP treatment difference was 2.7 mmHg (90% confidence interval: 1.1 to 4.3 mmHg; p = 0.005). Tolerability profiles were similar between treatments. The drug acquisition cost per mmHg DBP reduction was 40% lower with nisoldipine; an acquisition cost analysis revealed that amlodipine was 80% more expensive than nisoldipine for treating hypertension. In summary, nisoldipine and amlodipine provide clinically equivalent antihypertensive efficacy; however, nisoldipine is more economical than amlodipine.",2001.0,0,0
197,11203289,18th Scientific meeting of the International Society of Hypertension.,A H Danser; M P Schuijt,,2001.0,0,0
198,11206672,A new chronotherapeutic oral drug absorption system for verapamil optimizes blood pressure control in the morning.,D H Smith; J M Neutel; M A Weber,"A novel verapamil chronotherapeutic oral drug absorption system (CODAS-Verapamil) designed for bedtime dosing and with controlled onset and extended-release properties was evaluated in 257 patients with mild-to-moderate essential hypertension in an 8-week, double-blind, placebo-controlled trial. After bedtime dosing (9 PM to 11 PM, this delivery system delays drug release for 4 to 5 h, and provides the highest concentrations of verapamil between 6 AM and noon. The study results showed that CODAS-verapamil produced its greatest antihypertensive effect during this morning period (6 AM to 12 noon) and also provided effective trough diastolic blood pressure reductions at 200, 300, and 400 mg. Significant trough systolic blood pressure reductions were achieved only with the 300- and 400-mg doses. The nighttime dosing regimen was not associated with excessive blood pressure (BP) reductions during the sleeping hours, when the antihypertensive effect was generally slightly less than that of the 24-h mean reduction. The CODAS-verapamil provides enhanced BP reduction during the morning period when compared with other time intervals of the 24-h dosing period.",2001.0,0,0
199,11206682,Effects of short- and long-acting calcium channel blockers on the relationship between blood pressure and physical activity.,S Kakinoki; A Nomura; S Takechi; A Kitabatake,"Calcium channel blockers are widely used as antihypertensive drugs. However, there is some controversy as to how they should be used. Our first aim was to clarify how the dihydropyridine calcium channel blocker, benidipine, affects the quantitative relationship between blood pressure (BP) and physical activity. The second aim was to determine whether there is a relationship between systolic blood pressure (SBP) and physical activity in patients with hypertension when treating with a short-acting (nifedipine) or long-acting (benidipine) calcium channel blocker. In Study 1, ambulatory BP and physical activity were measured simultaneously in 27 patients with hypertension before and after 6 months with benidipine. In Study 2, ambulatory BP and physical activity were measured simultaneously in 16 patients with hypertension before (placebo) and after 6 weeks of crossover treatment with nifedipine and benidipine. In Study 1, there was no difference in the SBP change caused by physical activity between the pre- and posttreatment periods. In Study 2, SBP was significantly related to physical activity in the placebo (16/16) and benidipine (16/16) groups but not in the nifedipine (12/16) group. The lowest BP during day-time and nighttime in the nifedipine group were significantly lower than those in the benidipine group. Plasma renin activity (ng/mL/h) was significantly higher in the nifedipine group (1.20+/-1.05) than in the placebo (0.57+/-0.59) and benidipine (0.75+/-0.78) groups. These findings indicate that nifedipine might interfere with the adaptation mechanism of BP changed by physical activity and that the activated renin-angiotensin system might cause cardiac events.",2001.0,0,0
200,11212971,Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension.,A M Pellizzer; P W Kamen; M D Esler; S Lim; H Krum,"L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertension, perhaps due to adverse effects on autonomic nervous system (ANS) function. Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects. This double-blind, parallel group study compared the effect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) versus mibefradil (T-type CCB) on ANS function in patients with mild-moderate essential hypertension. Sixteen patients (10 male, 6 female; age 57.2 +/- 2.3 years), diastolic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg daily or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibefradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) was assessed using norepinephrine kinetics. Parasympathetic nervous system activity (PSNA) was assessed from 24 h Holter recordings of heart rate variability (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS. Patient groups were well matched at baseline. Achieved DBP was lower in patients treated with mibefradil compared with nifedipine, (83.4 +/- 1.7 versus 95.25 +/- 3.3 mmHg). There were no significant differences in SNSA and BRS between groups, however the root mean square of successive differences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 +/- 1.6 versus -3.36 +/- 1.2 ms, P < 0.05) and (+ 0.28 +/- 0.1 versus -0.23 +/- 0.1 ms2, P < 0.01), respectively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group, (0.71 +/- 0.02 versus 0.74 +/- 0.03, P = 0.046). No differences existed between effect of L- and T-type CCBs on SNSA and BRS. However, T-type CCBs increased PSNA, independent of achieved changes in heart rate.",2001.0,0,0
201,11212974,"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
202,11212979,A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study.,J P Emeriau; H Knauf; J O Pujadas; C Calvo-Gomez; G Abate; G Leonetti; C Chastang; European Study Investigators,"To analyse the efficacy of indapamide sustained-release (SR) 1.5 mg in reducing blood pressure versus amlodipine 5 mg and hydrochlorothiazide 25 mg, in elderly hypertensive patients. Double-blind, randomized, 12 week study using three parallel groups. European teaching hospitals and general practices. Randomized patients, (n = 524) including 128 patients with isolated systolic hypertension (ISH); mean age: 72.4 years; mean systolic/diastolic blood pressures (SBP/DBP): 174.5/97.9 mmHg. Clinic systolic and diastolic blood pressure variations. Indapamide SR 1.5 mg demonstrates a similar efficacy to that of amlodipine 5 mg, as well as to that of hydrochlorothiazide 25 mg (equivalence P < 0.001); the mean decreases in SBP/DBP were -22.7/-11.8 mmHg, -22.2/-10.7 mmHg and -19.4/-10.8 mmHg, respectively. In the ISH subgroup, indapamide SR 1.5 mg tends to have greater efficacy than hydrochlorothiazide 25 mg in reducing the SBP (-24.7 versus -18.5 mmHg, respectively; equivalence P = 0.117), while similar results are obtained with amlodipine 5 mg (-23 mmHg, equivalence P < 0.001). The normalization rate was relatively high for indapamide SR 1.5 mg (75.3%), when compared with amlodipine (66.9%) and hydrochlorothiazide (67.3%), especially in the subgroup of isolated systolic hypertensive patients: 84.2 versus 80.0% for amlodipine, and versus 71.4% for hydrochlorothiazide. Indapamide SR 1.5 mg shows similar antihypertensive efficacy to amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients, while in patients with isolated systolic hypertension, indapamide SR 1.5 mg shows a similar efficacy to amlodipine 5 mg but a greater efficacy than hydrochlorothiazide 25 mg.",2001.0,0,0
203,11216977,"Efficacy and safety of out-of-hospital self-administered single-dose oral drug treatment in the management of infrequent, well-tolerated paroxysmal supraventricular tachycardia.",P Alboni; C Tomasi; C Menozzi; N Bottoni; N Paparella; G Fucà; M Brignole; R Cappato,"We tested the efficacy of two drug treatments, flecainide (F) and the combination ofdiltiazem and propranolol (D/P), administered as a single oral dose for termination of the arrhythmic episodes. Both prophylactic drug therapy and catheter ablation are questionable as first-line treatments in patients with infrequent and well-tolerated episodes of paroxysmal supraventricular tachycardia (SVT). Among 42 eligible patients (13% of all screened for SVT) with infrequent (< or =5/year), well-tolerated and long-lasting episodes, 37 were enrolled and 33 had SVT inducible during electrophysiological study. In the latter, three treatments (placebo, F, and D/P) were administered in a random order 5 min after SVT induction on three different days. Conversion to sinus rhythm occurred within 2 h in 52%, 61%, and 94% of patients on placebo, F and D/P, respectively (p < 0.001). The conversion time was shorter after D/P (32 +/- 22 min) than after placebo (77 +/- 42 min, p < 0.001) or F (74 +/- 37 min, p < 0.001). Four patients (1 placebo, 1 D/P, and 2 F) had hypotension and four (3 D/P and 1 F) a sinus rate <50 beats/min following SVT interruption. Patients were discharged on a single oral dose of the most effective drug treatment (F or D/P) at time of acute testing. Twenty-six patients were discharged on D/P and five on F. During 17 +/- 12 months follow-up, the treatment was successful in 81% of D/P patients and in 80% of F patients, as all the arrhythmic episodes were interrupted out-of-hospital within 2 h. In the remaining patients, a failure occurred during one or more episodes because of drug ineffectiveness or drug unavailability. One patient had syncope after D/P ingestion. During follow-up, the percentage of patients calling for emergency room assistance was significantly reduced as compared to the year before enrollment (9% vs. 100%, p < 0.0001). The episodic treatment with oral D/P and F, as assessed during acute testing, appears effective in the management of selected patients with SVT. This therapeutic strategy minimizes the need for emergency room admissions during tachycardia recurrences.",2001.0,0,1
204,11219319,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
205,11219325,Cardiogenic shock following a single therapeutic oral dose of verapamil.,D Stajer; M Bervar; M Horvat,"Cardiogenic shock and apnoea appeared in a 78-year-old woman with a history of biventricular heart failure, following ingestion of a single 80 mg verapamil tablet. She was resuscitated with artificial ventilation, dobutamine, norepinephrine and calcium gluconate. Toxicological analysis revealed unexpectedly high plasma verapamil concentration, which was attributed to the patient's liver failure. In patients with advanced heart failure a single oral therapeutic dose of verapamil may have a severe toxic effect.",2001.0,0,1
206,11219482,Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg.,C B Toal; Canadian Investigators,"Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.",2001.0,0,0
207,11220888,[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
208,11221291,The long-term efficacy and safety profile of barnidipine.,J G Smilde,"Two multicentre trials have investigated the efficacy and tolerability of treatment with once-daily barnidipine, in patients with mild to moderate essential hypertension. The long-term efficacy and safety of barnidipine were demonstrated in a long-term, multicentre, open-label study. In total, 106, 79 and 32 patients were followed for the first, second and third year, respectively. Patients received barnidipine at a dose titrated to achieve a sitting DBP > or = 90 mmHg or a decrease in sitting BDP > or = 10 mmHg. If necessary, another antihypertensive agent was added to achieve normalisation of blood pressure. In the first year, normalisation of blood pressure was achieved in 91% of patients. This was maintained in 91% and 81% of patients in the second and third years, respectively. At the end of treatment in both years, over 60% of patients remained on barnidipine monotherapy (10 or 20 mg/day). A low incidence of adverse events possibly or probably related to barnidipine (10 or 20 mg/day) monotherapy was reported in the first and second years with headache, peripheral oedema and palpitations the most commonly reported. In the third year of follow-up, only one adverse event, an ECG abnormality, was considered to be possibly related to the study medication. The effective 24 hour control of blood pressure with barnidipine monotherapy was confirmed in a randomised, double-blind, placebo-controlled, cross-over study of 20 patients. These patients were given 6 week regimens of both barnidipine (20 mg/day) and placebo. Office and 24 hour ambulatory blood pressures were recorded at the end of each treatment phase. Barnidipine lowered blood pressure to a significantly greater extent than placebo both at night and during the day. Adverse events were classified as mild or moderate and fewer adverse events were reported with barnidipine treatment compared with placebo. Barnidipine monotherapy (20 mg/day) is safe and effective in providing 24 hour control of blood pressure. Furthermore, the efficacy and tolerability of barnidipine monotherapy (10 or 20 mg/day) are maintained for at least 2 years.",2001.0,0,0
209,11227186,[Treatment of renal hypertension].,A Oksa; V Spustová; R Dzúrik,"In recent years in conjunction with medicamentous treatment of renoparenchymatous hypertension in particular two problems were discussed: target blood pressure values and renoprotective effects of antihypertensive drugs. Prospective studies revealed that a blood pressure reading of < 130/80 mm Hg significantly retards the progression of nephropathy whereby patients with proteinuria > 1 g/d benefit from even lower BP readings. In diabetic nephropathy the drugs of choice are inhibitors of angiotensin converting enzyme (ACEI), already in the incipient stage and also in normotensive patients. The importance of ACEI in the treatment of non-diabetic nephropathies was confirmed recently by controlled prospective studies AIPRI and REIN. A maximal renoprotective effect of ACEI probably calls for larger doses than those needed for normalization of BP. Long-term investigations of the renoprotective effect of antagonists of angiotensin AT1 receptors and comparative studies with ACEI resp. are not available. Dihydropyridine blockers of calcium channels with a short-term action (nifedipine) may have a negative influence on the progression of diabetic nephropathy, the effect of dihydropyridines of the second generation is tested in prospective studies. Non-dihydropyridine calcium channel blockers have a renoprotective action in diabetic nephropathy. In cca two thirds of the patients combined treatment with ACEI and diuretics or with calcium channel blockers is necessary. As to other antihypertensive drugs, vasodilatating beta-blockers and perspectively antagonists of endothelin receptors are useful.",2001.0,0,0
210,11230280,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
211,11233957,Proarrhythmia.,G V Naccarelli; D L Wolbrette; J C Luck,"Proarrhythmia is defined as the aggravation of an existing arrhythmia or the development of a new arrhythmia secondary to antiarrhythmic drug. Proarrhythmic events include drug-induced bradyarrhythmias, atrial and ventricular proarrhythmias. New onset sustained or incessant ventricular tachycardia and torsade de pointes can be life threatening. This article reviews the incidence, aggravating factors, and treatment of proarrhythmia.",2001.0,0,0
212,11248761,Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses.,R H Hernández; M J Armas-Hernández; J A Chourio; M C Armas-Padilla; L López; M Alvarez; B Pacheco,"To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.",2001.0,0,0
213,11249891,"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
214,11259889,Nicardipine versus nitroprusside for breakthrough hypertension following carotid endarterectomy.,T Dorman; D A Thompson; M J Breslow; P A Lipsett; B A Rosenfeld,"To evaluate the effectiveness of nicardipine and nitroprusside for breakthrough hypertension following carotid endarterectomy. Prospective, randomized, double-blind, controlled effectiveness trial. University-based surgical intensive care unit. 60 ASA physical status I, II, III, and IV patients experiencing breakthrough hypertension at the time of admission to the intensive care unit (ICU). Patients received either nicardipine (n = 29) and placebo or nitroprusside (n = 31) and placebo for up to 6 hours postoperatively. Loading doses of nicardipine were provided, but placebo was used as a load for patients randomized to nitroprusside. Rapidity and variability of blood pressure (BP) control were assessed. During the first 10 minutes, 83% of nicardipine patients compared to 23% of nitroprusside-treated patients, achieved BP control (p < 0.01). Following initial control, 12 nicardipine- and 24 nitroprusside-treated patients required additional titration of their infusions to maintain blood pressure within the targeted range (p < 0.05). No patient suffered a stroke, myocardial infarction, or was returned to the operating room (OR) for bleeding. Nicardipine administration produced more rapid BP control, most likely related to the administration of a loading dose. In addition to more rapid control, nicardipine-treated patients had less variability in BP and required significantly fewer additional interventions. Although no patient suffered a major event during this study, this study was not powered sufficiently to assess safety.",2001.0,0,0
215,11269621,The QT interval.,M M Bednar; E P Harrigan; R J Anziano; A J Camm; J N Ruskin,"The effects of disease states and therapeutic drugs on the QT interval have been extensively studied in an attempt to understand the relationship between QT and the risk of torsade de pointes and sudden cardiac death. Differences in heart rate correction methods, electrocardiogram lead placement, and other internal (eg, genetic, physiologic) and external (eg, food, time of day) factors have confounded the interpretation of this relationship. A comprehensive review of the epidemiologic literature suggests that the corrected QT interval (QTc) is an important but imprecise marker of cardiovascular disease. The association between QTc prolongation and mortality has been identified in patients with cardiac disease but is unclear in patients without cardiac disease. Drug-related prolongation of QTc can clearly increase the risk of torsade de pointes, but this arrhythmia is rarely associated with a QTc of less than 500 ms. It also appears that noncardiac drugs that are associated with QTc prolongation are not identical in their proarrhythmic capacities and that increased exposure via clinically significant drug interactions is a major contributor to the liability of noncardiac drug-induced arrhythmia. Recognition of the aforementioned variables in conjunction with careful QTc measurements assists in establishing a more precise benefit-risk ratio for a specific drug therapy or for arrhythmia risk associated with various pathophysiologic or genetic states.",2001.0,0,0
216,11272481,Nifedipine and nimodipine competitively inhibit uridine kinase and orotidine-phosphate decarboxylase: theoretical relevance to poor outcome in stroke.,T Najarian; T W Traut,"Nifedipine and nimodipine, dihydropyridine calcium channel blockers, are commonly used as antihypertensive and antianginal agents in patients at risk for stroke. At least one stroke trial suggests that patients receiving calcium channel blockers at the time of an acute stroke have worse outcomes than those receiving other or no antihypertensive medications. We hypothesize that the poor outcome may not be related to blood pressure changes but instead may be mediated by competitive inhibition of important enzymes of pyrimidine synthesis whose products are needed to repair nerve cell membranes after an acute stroke. Both drugs acted as competitive inhibitors of the only enzymes that are known to synthesize the nucleotide uridine-5'-phosphate: uridine kinase and orotidine-5'-phosphate decarboxylase. Nifedipine produced Ki values of 28 microM for uridine kinase and 105 microM for orotidine-5'-phosphate decarboxylase. Nimodipine produced Ki values of 20 microM for uridine kinase and 18 microM for orotidine-5'-phosphate decarboxylase. For uridine kinase, these inhibitors bound more tightly than the physiologic substrates uridine or cytidine. For the decarboxylase, the inhibitors bound less tightly than the normal physiologic substrate orotidine-5'-phosphate. Additional experiments are needed to determine whether the concentrations of nifedipine or nimodipine, and of cytidine, uridine, and orotidine-5'-phosphate in human brain, are such that this inhibition would affect stroke outcome.",2001.0,0,0
217,11275919,Testing the effectiveness of converting patients to long-acting antianginal medications: The Quality of Life in Angina Research Trial (QUART).,J A Spertus; T Dewhurst; C M Dougherty; P Nichol,"Our purpose was to test the hypothesis that converting patients with stable angina to long-acting antianginal medications would improve their functional status, symptom control, treatment satisfaction, and quality of life. A single-blind randomized trial of 100 patients with stable coronary artery disease was performed in the outpatient clinic of a Veterans Affairs Health System. Outpatients with chronic stable angina taking at least 2 antianginal medications were studied. Patients were randomized to one of two treatments: optimal adjustment of their usual antianginal medications or conversion to solely long-acting medications (long-acting diltiazem +/- nitroglycerin patches +/- atenolol) with subsequent optimization. The primary outcome was the 3-month change in Seattle Angina Questionnaire scores. Although no differences in physical limitation scores were noted, patients randomized to receive long-acting medications had improved symptom control (3-month improvement in anginal stability [19.1 vs 5.6, P =.02] and anginal frequency [17.8 vs 5.5, P =.006]), more treatment satisfaction (3-month improvement of 8.2 vs 3.0, P =.057), and better quality of life (3-month improvement of 11.2 vs 5.6, P =.09) compared with patients whose pretrial medications were optimized. The improvement in symptom control was statistically significant. Converting patients with chronic, stable angina to long-acting antianginal medications resulted in substantial improvements in symptom control with a trend toward better treatment satisfaction and quality of life.",2001.0,0,1
218,11279402,Postoperative atrial fibrillation: an old problem crying for new solutions.,L L Creswell; R J Damiano,,2001.0,0,0
219,11281234,"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
220,11281339,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.",2001.0,0,1
221,11288788,Macrophages and lymphocyte subpopulations in nifedipine- and cyclosporin A-associated human gingival overgrowth.,H E Pernu; M L Knuuttila,"Nifedipine and cyclosporin A (CsA) induce gingival overgrowth. Both drugs have immunomodulating effects. It has been suggested that altered immune response is associated with drug-induced gingival overgrowth. In this study, we evaluated whether there were differences in macrophages and lymphocyte subpopulations in human nifedipine- and CsA-associated gingival overgrowth as compared with those in normal gingiva. Biopsy samples of overgrown gingiva were obtained from 9 nifedipine-treated cardiac outpatients, 13 CsA-treated renal transplant recipients including 9 patients who were also receiving nifedipine, and 30 healthy control individuals undergoing dental treatment. Serial 5 microm thick cryostat sections were stained with mAbs for CD20 (B-pan), CD68 (macrophages), CD4 (T-helper/inducer), and CD8 (T-cytotoxic/suppressor) using an avidin-biotin-horseradish peroxidase complex method. Numbers of mAb-labeled and all nucleated cells were determined in 3 areas: the connective tissue beneath the sulcular epithelium, the middle connective tissue, and the connective tissue beneath the oral epithelium. Distributions of each type of cell were expressed as percentages of mAb-labeled cells in relation to total number of nucleated cells in a counting zone. Significances of differences between groups were tested by means of the Kruskal-Wallis test, and between pairs of results by means of the Mann-Whitney U-test. The proportion of CD8-labeled cells was significantly higher in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P = 0.014). In both medicated groups, the proportions of CD68-labeled cells were higher in all counting zones than in the controls, but statistically significantly only in the nifedipine group in the connective tissue beneath the oral epithelium (P = 0.008). No intergroup differences were found with respect to CD4- and CD20-labeled cells. The CD4/CD8 ratio was significantly lower in connective tissue beneath the sulcular epithelium in the nifedipine group than in the controls (P= 0.013). The results support the idea that immune response may be altered in drug-induced gingival overgrowth.",2001.0,0,0
222,11288789,Mitotic activity of keratinocytes in nifedipine- and immunosuppressive medication-induced gingival overgrowth.,P K Nurmenniemi; H E Pernu; M L Knuuttila,"The purpose of the study was to compare mitotic activity in the basal cell layer of normal human gingiva and in nifedipine- and immunosuppressive medication-induced gingival overgrowth. Gingival samples were collected from 19 generally healthy individuals, 12 nifedipine-medicated cardiac patients, and 22 immunosuppression-medicated (azathioprine, prednisolone, and cyclosporin A) organ transplant recipients. The transplant recipients were divided into those not taking nifedipine and those taking nifedipine. Cryostat sections were stained with monoclonal antibody for Ki-67, using an avidin-biotin-enzyme complex method. The mitotic activities of epithelial cells were determined as percentages of Ki-67 labeled cells in relation to total numbers of epithelial cells in the basal layer of oral, oral sulcular, and sulcular epithelium. Mitotic activities were significantly higher in all 3 medication groups in the oral epithelium (P < or =0.003), and in the immunosuppression group in the sulcular epithelium (P= 0.032) than in the controls. In the oral sulcular epithelium, mitotic activity was fairly similar in all medication groups. In the nifedipine group a significant negative correlation was found between duration of nifedipine medication and the percentage of Ki-67 labeled cells in the oral epithelium (P= 0.025). The results suggest that the increased epithelial thickness observed in nifedipine- and cyclosporin A-induced gingival overgrowth is associated with increased mitotic activity, especially in the oral epithelium.",2001.0,0,0
223,11288822,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.",2001.0,0,1
224,11295959,"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.",2001.0,0,0
225,11296693,Clinical features and natural history of nonalcoholic steatosis syndromes.,Y Falck-Ytter; Z M Younossi; G Marchesini; A J McCullough,"Nonalcoholic steatohepatitis, along with other forms of nonalcoholic fatty liver disease, is a chronic liver disease that is attracting increasing significance. It is a clinicopathologic syndrome that was originally described in obese, diabetic females who denied alcohol use but in whom the hepatic histology was consistent with alcoholic hepatitis. This typical patient profile has been expanded and is now recognized to occur even in normal weight males without overt abnormalities in carbohydrate metabolism. Although originally believed to be a benign clinical entity, nonalcoholic steatohepatitis is now recognized as a cause of progressive fibrotic liver disease with adverse clinical sequelae. It is important to emphasize that nonalcoholic steatohepatitis is best considered one type of a larger spectrum of nonalcoholic fatty liver disease that is a consequence of insulin resistance and ranges from fat alone to fat plus inflammation, fat plus ballooning degeneration, and nonalcoholic steatohepatitis, the latter being the most serious form. As with any disease, the clinical importance of nonalcoholic steatohepatitis is related to its prevalence and natural history. Recent studies using different methodologies indicate that in the general population the prevalence of fatty liver and nonalcoholic steatohepatitis is approximately 20% and 3%, respectively. These prevalence rates are increased in certain subpopulations such as obesity and type II diabetes. Of greater concern is the recognition that cirrhosis and liver-related deaths occur in approximately 20% and 8% of these patients, respectively, over a 10-year period. Risk factors for these adverse clinical symptoms include patients older than the age of 45, the presence of diabetes or obesity, an aspartate aminotransferase/alanine aminotransferase ratio > 1 and hepatic histology. However, a number of important unresolved issues must be clarified before the true natural history of this disease can be fully understood.",2001.0,0,0
226,11298624,Topical diltiazem ointment in the treatment of chronic anal fissure.,J S Knight; M Birks; R Farouk,"Chronic anal fissure has traditionally been treated surgically. Initial enthusiasm for chemical sphincterotomy has waned because of poor outcomes with glyceryl trinitrate ointment. In this study the use of topical 2 per cent diltiazem ointment has been investigated as an alternative method of chemical sphincterotomy. A prospective assessment of 71 consecutive patients with a chronic anal fissure treated with 2 per cent topical diltiazem ointment for a median duration of 9 (range 2--16) weeks was performed. Fifty-one patients (75 per cent) experienced healing of the fissure after 2--3 months of treatment with topical diltiazem. Seventeen patients who did not heal were treated for a further 8 weeks with topical diltiazem. Eight of these patients subsequently healed with diltiazem. Fifty-nine of 67 patients who completed follow-up therefore healed on diltiazem ointment. Four patients experienced perianal dermatitis and one patient experienced headaches. No other side-effects were recorded. After a median of 32 (range 14--67) weeks' follow-up following completion of treatment, 27 of 41 patients available remain symptom free. Six of seven patients with recurrent fissure were treated successfully by repeat chemical sphincterotomy. Topical 2 per cent diltiazem ointment used as an agent for chemical sphincterotomy for chronic anal fissure offers significant healing rates but does not have a significant side-effect profile, which may aid compliance to treatment. Early recurrences are common but usually amenable to further chemical sphincterotomy.",2001.0,0,0
227,11300453,Increased dispersion and shortened refractoriness caused by verapamil in chronic atrial fibrillation.,H Ramanna; A Elvan; F H Wittkampf; J M de Bakker; R N Hauer; E O Robles de Medina,"The objective was to assess the effect ofverapamil on atrial fibrillation (AF) cycle length and spatial dispersion of refractoriness in patients with chronic AF. Previous studies have suggested that verapamil prevents acute remodeling by AF. The effects of verapamil in chronic AF are unknown. During electrophysiologic study in 15 patients with chronic AF (duration >1 year), 12 unipolar electrograms were recorded from right atrial free wall, right atrial appendage and coronary sinus, along with monophasic action potential recordings from the right atrial appendage. The mean fibrillatory interval at each atrial recording site was used as an index for local refractoriness. Dispersion of refractoriness was calculated as the standard deviation of all local mean fibrillatory intervals expressed as a percentage of the overall mean fibrillatory interval. After baseline measurements, verapamil (0.075 mg/kg intravenous in 10 min) was infused and the measurements were repeated. After administration ofverapamil, mean fibrillatory intervals shortened by a mean of 16.6 +/- 3.3 ms (p < 0.001) at the right free wall, 15.0 +/- 3.5 ms (p < 0.001) at the appendage and 17.1 +/- 3.2 ms (p < 0.01) in the coronary sinus. Monophasic action potential duration decreased by 15.9 +/- 4.0 ms (p < 0.01). Dispersion of refractoriness increased in all patients from 3.8 +/- 0.8 to 5.1 +/- 1.8 (p < 0.001). A strong correlation between mean fibrillatory intervals and action potential duration was found, both before and after verapamil. Verapamil caused shortening of refractoriness and increase in spatial dispersion of refractoriness in patients with chronic AF. This implies that verapamil is not useful in reversing the remodeling process in these patients.",2001.0,0,1
228,11301961,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
229,11303016,Effects of pretreatment with verapamil on early recurrences after electrical cardioversion of persistent atrial fibrillation: a randomised study.,E Bertaglia; D D'Este; A Zanocco; F Zerbo; P Pascotto,,2001.0,1,1
230,11311906,Clinical outcomes of aneurysmal subarachnoid hemorrhage patients treated with oral diltiazem and limited intensive care management.,A K Papavasiliou; K S Harbaugh; N J Birkmeyer; J M Feeney; P B Martin; C Faccio; R E Harbaugh,"Aneurysmal subarachnoid hemorrhage (SAH) patients are frequently treated with prophylactic nimodipine and undergo invasive monitoring of blood pressure and volume status in an intensive care unit (ICU) setting to decrease the incidence of delayed ischemic neurological deficit (DIND) and improve functional outcomes. The goal of this study was to examine the incidence of DIND and poor functional outcomes in a consecutive series of SAH patients treated with a different regimen of prophylactic oral diltiazem and limited use of intensive care monitoring. The study involved a consecutive series of 123 aneurysmal SAH patients treated by the senior author who were admitted within 72 hours of hemorrhage and who never received nimodipine or nicardipine. Functional outcomes were graded using the Glasgow Outcome Scale (GOS). Of the 123 patients identified, favorable outcomes (GOS 4 and 5) were achieved in 74.8%. The incidence of DIND was 19.5%. Hypertensive, hypervolemic, hemodilutional (HHH) therapy was used in 10 patients (8.1%) and no patients were treated for DIND by endovascular means. Seven patients (5.7%) had a poor functional outcome or death because of DIND and two of these were related to complications of HHH therapy. These results were compared to contemporary series of SAH patients managed with other treatment protocols. Functional outcomes of patients treated with a regimen of oral diltiazem, limited use of ICU monitoring and HHH therapy for DIND compare favorably with other contemporary series of SAH patients.",2001.0,0,0
231,11316514,Pharmacologic therapy of persistent pulmonary hypertension of the newborn.,B Weinberger; K Weiss; D E Heck; D L Laskin; J D Laskin,"Persistent pulmonary hypertension of the newborn (PPHN) is a potentially life-threatening condition characterized by a failure of pulmonary vascular resistance to decrease adequately during the transition to extrauterine life. Inhaled nitric oxide, a vasodilator that acts selectively on the pulmonary circulation, has revolutionized the treatment of this condition. However, inhaled nitric oxide has not proven effective in all patients, particularly those with congenital diaphragmatic hernias or meconium aspiration syndrome. Furthermore, large clinical trials of inhaled nitric oxide have failed to demonstrate significant differences in mortality between nitric oxide-treated and control infants with PPHN. Other therapeutic approaches to PPHN have been limited by a relative lack of specificity for the pulmonary circulation, and have received much less attention. Pharmacologic approaches, including pulmonary surfactants, prostacyclin, endothelin antagonists, Ca(2+)-channel blockers, magnesium sulfate, and tolazoline, have exhibited varying degrees of efficacy in lowering pulmonary vascular pressures in humans and/or animals. A number of these agents are also effective when used in combination. For example, phosphodiesterase inhibitors have been reported to act synergistically with inhaled nitric oxide. Surfactants also appear to be useful in PPHN, particularly in patients with congenital diaphragmatic hernia, when used in combination with other therapies. Surfactant lavage and other novel therapies may also be effective in combination therapy of meconium aspiration syndrome. Further studies should be directed at defining the optimal therapies in specific clinical settings. Validation of multiple therapeutic modalities for PPHN, including inhaled nitric oxide, will allow for rational, combined vasodilator strategies that are specific for the underlying pathophysiology in each patient.",2002.0,0,0
232,11317194,Chronotherapeutic delivery of verapamil in obese versus non-obese patients with essential hypertension.,W B White; W J Elliott; M F Johnson; H R Black,"The effect of controlled-onset, extended-release (COER) verapamil on haemodynamic parameters in obese and non-obese patients is evaluated in this analysis. Data were pooled from three clinical trials evaluating efficacy and tolerability of COER-verapamil. Hypertensive men and women (stage I to III) were randomised to COER-verapamil (180-540 mg at bedtime) or placebo for 4-8 weeks and stratified according to body mass index (BMI-obese > 28 kg/m2). Efficacy was assessed as change from baseline in blood pressure (BP), heart rate, and rate-pressure product during four time periods throughout the dosing interval. Safety and tolerability were assessed by monitoring all adverse events and changes in metabolic laboratory parameters. Reductions in all haemodynamic parameters were significantly greater following COER-verapamil compared with placebo for all time periods. The haemodynamic effects of COER-verapamil in obese (n = 166, BMI = 32.8 kg/m2) and non-obese patients (n = 115, BMI = 25.0 kg/m2) were similar. COER-verapamil was well tolerated in both subgroups, but the incidence of constipation was significantly less in obese patients (P < 0.001). COER-verapamil is effective in reducing BP, heart rate, and rate-pressure product independently of BMI.",2001.0,0,0
233,11319567,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
234,11319569,Improved efficacy and safety of controlled-release diltiazem compared to nifedipine may be related to its negative chronotropic effect.,S K Basu; C D Kinsey; A J Miller; A Lahiri,"The objective of this study was to assess the safety and efficacy of long-acting preparations of two commonly used calcium antagonists with particular reference to their effects on heart rate. Twenty patients with chronic stable angina were recruited to a double-blind, double-dummy crossover study of controlled-release diltiazem (diltiazem CR) versus sustained-release nifedipine (nifedipine SR) and underwent clinical assessment, symptom and adverse event reporting, and repeated treadmill exercise tests over a 10- to 11-week period. The main outcome measures were heart rate at rest and exercise, incidence of angina and nitroglycerin use, treadmill exercise performance (duration, time to angina, time to 1-mm ST-segment depression, heart rate at equivalent maximal exercise, and maximal ST-segment depression), and adverse events. Diltiazem CR significantly reduced heart rate at rest and equivalent exercise and incidence of angina and nitroglycerin use compared with nifedipine SR. Exercise duration time to angina and time to 1-mm ST-segment depression (but not maximal ST-segment depression) were all significantly improved by diltiazem CR. Diltiazem CR also caused significantly fewer adverse events than nifedipine SR. Calcium antagonists with negative chronotropic effects (eg, diltiazem CR) are safer and more efficacious as monotherapy in chronic stable angina than dihydropyridines (eg, nifedipine SR) even when a long-acting formulation of the latter is used.",2001.0,0,1
235,11323730,Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease.,J B Serro-Azul; R S de Paula; C Gruppi; L Pinto; H Pierri; A Nussbacher; O Gebara; P Moffa; A C Pereira-Barreto; M Wajngarten,"Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6+/-4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. Both treatments lowered systolic and diastolic blood pressures. The number of ischemic episodes on ambulatory electrocardiogram recordings was reduced with the use of chlorthalidone (2.5+/-3.8) and diltiazem (3.2+/-4.2) when compared with placebo (7.9+/-8.8; p<0.05). The total duration of ischemic episodes was reduced in both treatments when compared with placebo (chlorthalidone: 19.2+/-31.9min; diltiazem: 19.3+/-29.6min; placebo: 46.1+/-55.3min; p<0.05). In elderly hypertensive patients with coronary artery disease, chlorthalidone reduced myocardial ischemia similarly to diltiazem. This result is consistent with epidemiological studies and suggests that reduction of arterial blood pressure with thiazide therapy plays an important role in decreasing myocardial ischemia.",2001.0,0,1
236,11327628,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
237,11328214,The risk of limb deficiencies and other congenital abnormalities in children exposed in utero to calcium channel blockers.,H T Sørensen; A E Czeizel; M Rockenbauer; F H Steffensen; J Olsen,"Calcium channel blockers given to pregnant rats have shown an increased prevalence of digital and limb defects and their safety in pregnant women has thus been questioned. We examined the risk of malformations following exposure in utero to calcium channel blockers. We conducted a nationwide case-control study based on the Hungarian Case-Control Surveillance of Congenital Abnormalities and identified 22,865 cases with congenital abnormalities and 31,151 population controls during the period 1980-1996. Data on drug exposure were obtained from official questionnaires and obligatory prenatal care logbooks. Among the cases, 586 mothers (2.6%) had been exposed to calcium channel blockers during pregnancy compared with 907 controls (2.4%). The overall prevalence ratios for 17 congenital abnormalities varied between 1.1 and 1.4, and there was no significant increased risk of limb deficiencies or other congenital abnormalities. Our data did not indicate an increased prevalence of congenital abnormalities in offspring exposed to calcium channel blockers in utero.",2001.0,1,1
238,11336577,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
239,11336618,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
240,11346125,Contemporary management of chronic stable angina.,A D Staniforth,"Chronic stable angina is a common condition with a prognosis that is less benign than is generally appreciated. The optimal treatment strategy of this disorder is unclear, and few anti-ischaemic agents have been rigorously tested in prospectively randomised mortality studies. The evidence base for the anti-ischaemic therapy of chronic angina draws upon data 'borrowed' from studies in acute coronary syndromes, and from studies in chronic angina using surrogate endpoints such as ambulatory silent ischaemia. Such evidence leads us to believe that anti-ischaemic therapy with beta-blockers offers a mortality benefit in chronic angina. In contrast, the mortality benefit of lipid lowering therapy and antiplatelet agents is well proven. Angioplasty offers no mortality benefit in the treatment of chronic angina, although it is more effective than medical therapy alone for the relief of symptoms. In a few patients with high order proximal coronary disease, coronary bypass surgery offers a distinct mortality advantage compared with medical treatment alone. Most patients, however, do not warrant such an approach, and only require surgery for when they remain symptomatic despite adequate medical therapy. Alternative strategies such as cardiac transplantation, transmyocardial laser revascularisation and spinal cord stimulation are now accepted in a subgroup of patients for the treatment of chronic angina refractory to standard therapy.",2001.0,0,0
241,11348956,Diltiazem treatment does not alter renal function after thoracic surgery.,D Amar; M Fleisher,"There are conflicting reports on the effects of diltiazem treatment on renal function in surgical patients. We sought to determine whether diltiazem treatment alters renal function in patients undergoing major thoracic surgery. In a prospective study, 330 patients scheduled for elective thoracic surgery received either IV diltiazem (n = 167) or placebo (n = 163) immediately after the operation and orally thereafter for 14 days in an effort to prevent postoperative atrial arrhythmias. Serum creatinine and BUN levels were compared before and during the first postoperative week. Patients treated with diltiazem were similar to control subjects in terms of age (mean +/-SD, 66 +/- 10 years vs 67 +/- 10 years, respectively), baseline serum creatinine or BUN levels, prevalence of comorbid conditions, and surgical characteristics. During the first 5 postoperative days, the two groups did not differ in terms of serum creatinine or BUN levels. The incidence of renal failure was 0.6% in the diltiazem group and 1.2% in the placebo group (difference was not significant). There was no difference in the length of hospitalization or mortality rate. In patients without renal disease who are undergoing elective thoracic surgery, prophylactic diltiazem treatment did not alter postoperative renal function.",2001.0,0,0
242,11349617,[Amlodipine versus nifedipine retard. A randomized double-blind comparative study on long-term efficacy and safety of amlodipine and nifedipine retard in the monotherapy of chronic stable angina pectoris].,N Sauerbrey-Wullkopf; W Kupper,"This double-blind study compared the efficacy and safety of once daily amlodipine (5-10 mg/day) vs twice daily nifedipine (40-80 mg/day) in 244 patients with chronic stable angina pectoris. Efficacy was assessed after 4 and 24 weeks by bicycle exercise test. No statistically significant differences were found between the two treatment groups at the end of treatment with regard to the ergometry parameters determined (maximum ST segment deviation, maximum workload in watts, maximum exercise duration and time to 0.1 mV ST segment depression). Furthermore, the two treatment groups were comparable with regard to the effected reduction in anginal attacks and short acting nitrate consumption. The incidence of adverse events was lower in the amlodipine relative to the nifedipine group (11.5% vs 19.1%). The results of this study show that once daily amlodipine offers comparable antianginal and antiischemic efficacy as twice daily sustained release nifedipine in the monotreatment of chronic stable angina pectoris. Given the lower incidence of adverse events with amlodipine and its convenient once daily dosing regimen, however, amlodipine may help to enhance patient compliance.",2001.0,0,1
243,11368462,Effects of amlodipine on baroreflex and sympathetic nervous system activity in mild-to-moderate hypertension.,J P Siché; J P Baguet; D Fagret; F Trémel; R de Gaudemaris; J M Mallion,"To investigate the effect of amlodipine on baroreflex sensitivity and sympathetic system activity, 36 patients with essential hypertension were randomized to once-daily, double-blind treatment with amlodipine 5 mg or placebo 5 mg for 60 days. Measurements with a Finapres device allowed calculation of baroreflex sensitivity and blood pressure (BP) variability. Adrenergic activity was assessed via measurements of lymphocyte beta2-adrenoceptors and plasma catecholamine concentrations. Compared with placebo, amlodipine significantly decreased BP, but did not significantly alter baroreflex sensitivity. Spectral analysis of Finapres data showed that, compared with placebo, amlodipine decreased the variability of systolic blood pressure, diastolic blood pressure, and RR interval in the low frequency band. There were no simultaneous changes in adrenergic function, however, suggesting that these effects of amlodipine were not mediated via sympathetic nervous system activation.",2001.0,0,0
244,11386927,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.",2001.0,1,1
245,11393383,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.",2001.0,1,1
246,11393673,Isradipine improves endothelium-dependent vasodilation in normotensive coronary artery disease patients with hypercholesterolemia.,C Bracht; X W Yan; H P Brunner-LaRocca; G Sütsch; F W Amann; W Kiowski,"The dihydropyridine calcium antagonist isradipine has anti-atherosclerotic effects in animals and improves endothelium-mediated nitric oxide (NO)-dependent vasodilation in vitro. As improved endothelial function may be beneficial we investigated its effects in patients with a high likelihood of endothelial dysfunction. Thirty patients (two female, age 55.4 +/- 10.5 years) with known coronary artery disease and elevated (> 6 mmol/l) total cholesterol (cholesterol: mean 6.7 +/- 0.78 mmol/l) or a cholesterol/high density lipoproteins (HDL) ratio of > 5 not on lipid lowering therapy, participated in the study. Endothelial vasodilator function was assessed before and after double-blind, randomized administration of isradipine 5 mg/day or placebo for 3 months. Endothelial function was assessed as forearm blood flow (FBF, venous occlusion plethysmography) responses to graded brachial artery infusions of acetylcholine (Ach), to the NO-synthase blocker NG-monomethyl-L-arginine (L-NMMA) and to the endothelium-independent vasodilator sodium nitroprusside (SNP). Blood pressure was measured either directly from the brachial arterial or by sphygmomanometer during clinic visits. Blood pressure was unchanged in both groups after 3 months (isradipine: 88.8 versus 92.1 mmHg; placebo: 81.0 versus 82.5 mmHg; NS) but cholesterol levels decreased similarly in both groups (isradipine: 6.7 versus 6.1 mmol/l, NS; placebo: 6.6 versus 5.9 mmol/l, P< 0.05). The vasodilator response to SNP and the decrease in FBF in response to blockade of NO synthesis by L-NMMA were unchanged in both groups. However, isradipine, but not placebo, enhanced the NO-dependent vasodilator response to Ach (P < 0.05). Isradipine improves acetylcholine-mediated vasodilation in hypercholesterolemic patients independent of changes in lipids or blood pressure.",2001.0,0,0
247,11393682,Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients.,F H Messerli; J F Hansen; R S Gibson; K B Schechtman; W E Boden,"To analyse effects of a heart rate-lowering calcium antagonist in hypertensive post-myocardial infarction patients. From three large, randomized, placebo-controlled, secondary prevention trials investigating verapamil or diltiazem (the first and second Danish Verapamil Infarction Trials and the Multicentre Diltiazem Post-Infarction Trial) data from a total of 1,325 hypertensive post-myocardial infarction patients (drugs = 667, placebo = 658) were pooled to assess effect of blinded therapy on mortality and event rates. Treatment with heart rate-lowering calcium antagonists was associated with significant reduction in event rates [21.4 versus 27.4%; risk ratio (RR) = 0.76, confidence interval (CI) = 0.61 -0.95, P= 0.013]. Mortality rates in the treatment group were 15.1 versus 17.5% in the control group (RR = 0.87, CI = 0.66-1.13, P= 0.296). Among the subset of 964 hypertensive patients without pulmonary congestion, there was some reduction in mortality rate (11.3 versus 15.3% in the control group; RR = 0.72, P= 0.066) and significant reduction in event rates (18 versus 24.4% for control group; RR = 0.70, P= 0.011). In patients with pulmonary congestion and hypertension, however, calcium antagonists were associated with a 25% increase in mortality (RR = 1.25, P= 0.339), while event rate RR was 1.00. After an adjustment for significant covariates, RR for mortality in treatment versus control groups was 0.76 (P= 0.159). For event rates, RR was 0.74 (P= 0.057). Heart rate-lowering calcium antagonists decrease event rates in hypertensive post-myocardial infarction patients, but only in those without pulmonary congestion.",2001.0,0,1
248,11394395,Prevalence and risk of gingival enlargement in patients treated with nifedipine.,J Miranda; L Brunet; P Roset; L Berini; M Farré; C Mendieta,"Gingival enlargement is a known side effect of nifedipine use. This study was conducted to determine the prevalence and risk factors for gingival enlargement in nifedipine-treated patients. A cross-sectional study was conducted in a primary care center. Data from 65 patients taking nifedipine were compared with 147 controls who had never received the drug. All patients were examined for the presence of gingival enlargement using 2 different indices: vertical gingival overgrowth index (GO) in 6 points around each tooth, and horizontal MB index in the interdental area. Gingival index, plaque index, and probing depth were also evaluated. The prevalence of gingival enlargement was significantly higher in nifedipine-treated cases than in controls (GO index, 33.8% versus 4.1%; MB index, 50.8% versus 7.5%, respectively). Higher gingival and plaque indices were observed in patients taking nifedipine. Among the possible risk factors, only the gingival index showed a significant association with gingival enlargement. The risk (odds ratio [OR]) of gingival enlargement associated with nifedipine therapy was 10.6 (3.8-29.1) for the GO index and 14.4 (6-34.6) for the MB index. Gingival index-adjusted ORs were 9.6 (3.3-28.1) and 9.7 (3.9-23.3), respectively. In the subset of high nifedipine exposure patients, the odds ratio for gingival enlargement increased to 17.4 (5.3-56.3) for the GO index and 23.6 (7.7-72.3) for the MB index. The concordance between GO and MB indices showed a kappa value of 0.689 in controls and 0.642 in patients treated with nifedipine. Patients taking nifedipine are at high risk for gingival enlargement, and gingivitis acts as a predisposing factor.",2001.0,0,0
249,11395591,Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias.,G Delle Karth; A Geppert; T Neunteufl; U Priglinger; M Haumer; M Gschwandtner; P Siostrzonek; G Heinz,"To compare the rate-lowering effect of diltiazem and two amiodarone regimens in critically ill patients with recent-onset atrial tachyarrhythmias. Prospective, randomized, controlled study. Medical cardiologic intensive care unit in a university hospital. Sixty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] III score 70 +/- 30, age 67 +/- 10 yrs). Patients with atrial fibrillation (n = 57), atrial flutter (n = 2), or atrial tachycardia (n = 1, and a heart rate consistently >120 beats/min over 30 mins were randomly assigned to one of three intravenous treatment regimens. Group 1 received diltiazem in a 25-mg bolus followed by a continuous infusion of 20 mg/hr for 24 hrs, group 2 received amiodarone in a 300-mg bolus, and group 3 received amiodarone in a 300-mg bolus followed by 45 mg/hr for 24 hrs. The primary study end point was a >30% rate reduction within 4 hrs. The secondary study end point was a heart rate <120 beats/min (a patient was considered to have uncontrolled tachycardia if heart rate was >120 beats/min 4 hrs after study drug). The primary study end point was achieved in 14/20 (70%), 11/20 (55%), and 15/20 (75%) of patients in groups 1, 2, and 3, respectively (chi2 = 1.95, p =.38). Uncontrolled tachycardia was more frequently observed in group 2 (0/20, 9/29 [55%], and 1/20 [5%] of patients in groups 1, 2, and 3, respectively; chi2 = 17, p =.00016). In patients achieving tachycardia control, diltiazem showed a significantly better rate reduction (p =.0001 group 1 vs. group 3, p =.0001 over time; p =.0001 group 1 vs. group 2, p =.001 over time) when compared with the amiodarone groups. Premature drug discontinuation due to hypotension was required significantly more often in group 1 (6/20 [30%], 0/20, and 1/20 [5%] for groups 1, 2, and 3, respectively; chi2 = 10, p =.01). Sufficient rate control can be achieved in critically ill patients with atrial tachyarrhythmias using either diltiazem or amiodarone. Although diltiazem allowed for significantly better 24-hr heart rate control, this effect was offset by a significantly higher incidence of hypotension requiring discontinuation of the drug. Amiodarone may be an alternative in patients with severe hemodynamic compromise.",2001.0,0,0
250,11397358,Heart failure in 2001: a prophecy revisited.,A M Katz,,2001.0,0,0
251,11398000,[Tocolysis with calcium-channel-blockers].,V Tsatsaris; B Carbonne,"To evaluate the use of calcium-channel-blockers (CCBs) for tocolysis. We reviewed the literature retrieved from the Medline database from 1967 to 200 dealing with fetal toxicity and efficacy of CCBs compared with beta-adrenergic agonists. Data on fetal toxicity in animals were inconsistent. A teratologic effect has been observed during early pregnancy at supratherapeutic dosage. At usual therapeutic dosage, no fetal abnormalities have been observed. The efficacy of CBs for tocolysis is superior to that of beta-adrenergic drugs and allows a reduction of neonatal morbidity. Calcium channel blockers are better tolerated than beta-adrenergic agonists. Published data suggest that CCBs could be used a first line tocolytic agents. Although use of CCBs is extremely simple, they should not be prescribed in low-risk outpatients.",2001.0,0,0
252,11402591,Female sexual dysfunction.,J R Berman; I Goldstein,"The ideal approach to female sexual dysfunction would be a collaborative effort between therapists and physicians and would include a complete medical and psychosocial evaluation, and inclusion of the partner spouse in the evaluation and treatment process. Despite significant anatomic and embryologic parallels between men and women, the multifaceted nature of female sexual dysfunction clearly is distinct from that of the man. The clinician cannot approach female patients or their sexual function problems in the same fashion as in male patients. The context in which a woman experiences her sexuality is equally if not more important than the physiologic outcome she experiences, and these issues should be determined before beginning medical therapy or determining treatment efficacies.",2001.0,0,0
253,11403364,"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.",2002.0,1,1
254,11408386,Calcium channel blocker nifedipine slows down progression of coronary calcification in hypertensive patients compared with diuretics.,M Motro; J Shemesh,"Calcium controls numerous events within the vessel wall. Permeability of the endothelium is calcium dependent, as are platelet activation and adhesion, vascular smooth muscle proliferation and migration, and synthesis of fibrous connective tissue. Double-helix computerized tomography is a noninvasive technique that can detect, measure, and compare coronary calcification in the coronary arteries. Using this method, our objective was to determine whether administration of nifedipine once daily in lieu of diuretics in high-risk hypertensive patients will arrest or slow down the progression of coronary artery calcification. The study was designed as a side arm of INSIGHT (International Nifedipine Study: Intervention as Goal for Hypertension Therapy), aimed to show the efficacy of nifedipine once daily versus co-amilozide (hydrochlorothiazide 25 mg, amiloride 2.5 mg) in high-risk hypertensive patients. A total of 201 patients with a total calcium score of >/=10 at the onset of study who underwent an annual double-helix computerized tomography for 3 years were analyzed for efficacy. Inhibition of coronary calcium progression was significant in the nifedipine versus the co-amilozide group during the first year (3.18% versus 27%, respectively, P=0.02), not significant during the second year (28.5% versus 47%, respectively, P=0.14), and significant during the third year (40% versus 78%, respectively, P=0.02). The results point to a slower progression of coronary calcification in hypertensive patients on nifedipine once daily versus co-amilozide.",2001.0,0,0
255,11416701,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
256,11430394,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,,2001.0,0,0
257,11439313,Antihypertensive efficacy of amlodipine in children with chronic kidney diseases.,R O von Vigier; L M Franscini; N D Bianda; R Pfister; C Casaulta Aebischer; M G Bianchetti,"In adults the calcium antagonist amlodipine given once a day has proved to be an attractive addition to the antihypertensive armamentarium. The present report describes our experience in 43 paediatric outpatients (26 boys and 17 girls, aged between 1.1 and 19, median 9.8 years) with chronic kidney diseases. The patients were given amlodipine for 16 weeks as part of their antihypertensive treatment. Before amlodipine arterial pressure was 150 (142-163)/90 (84-95) mm Hg (median and interquartile range). Six patients withdrew from amlodipine because of oedema, flushing or headache. In the remaining patients amlodipine 7.7 (6.9-9.4) mg/m(2) body surface area once a day significantly decreased arterial pressure by 17 (13-22)/10 (7-13) mm Hg. The efficacy of amlodipine was more pronounced in girls than in boys. No changes in heart rate, body weight and circulating haemoglobin, sodium, potassium and creatinine were noted. In none of the patients circulating potassium, sodium or creatinine changed by more than 0.5 mmol/l, 5 mmol/l respectively 20%. In 11 patients concomitantly treated with cyclosporine the dosage and the trough-level of this agent were stable throughout the trial. In conclusion the present experience in paediatric outpatients with chronic kidney diseases supports the view that amlodipine is an effective and rather well tolerated antihypertensive drug when given once a day.",2001.0,0,0
258,11447499,Current concepts in the treatment of hypertension.,Y K Seedat,"In spite of the effective drug therapy available for hypertensive patients in general, economic and social considerations continue to influence the low rate of detection, treatment and control of hypertension in the population of the developing world. The Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure stated that in 1993 age-adjusted stroke rates rose slightly and that the age-adjusted rate of decline for coronary heart disease appeared to be levelling. Furthermore, rates for the incidence of end-stage renal disease increased, with hypertension the second most common cause. The Report also stated that hypertension control rates did not improve (National Health and Nutrition Examination Survey, NHANES III, Phase 1) from 1991 to 1994, and there were only 27% on control. These disturbing trends support the need to enhance public and professional education and to translate the results of research into improved health.",2001.0,0,0
259,11450659,High-altitude illness.,P H Hackett; R C Roach,,2001.0,0,0
260,11450689,,,,,1,1
261,11461753,Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation.,J A Chiladakis; C Stathopoulos; P Davlouros; A S Manolis,"Drugs currently available for the acute treatment of paroxysmal atrial fibrillation have significant limitations. We assessed the safety and effectiveness of intravenous magnesium sulfate versus diltiazem therapy in patients with prolonged episodes of paroxysmal atrial fibrillation. In a prospective randomized trial, 46 symptomatic patients presenting with paroxysmal atrial fibrillation were given intravenous magnesium sulfate (n=23) or diltiazem (n=23) therapy. Primary outcome measures were effects on ventricular rate control and proportion of patients restored to sinus rhythm at 6 h after initiation of treatment. There were no differences in baseline characteristics between the two groups. Both forms of treatment were well tolerated, with no adverse clinical events. Both drugs had similar efficacy in reducing the ventricular rate at the first hour of treatment (P<0.05) with a tendency toward a further decrease during infusion times of 2 (P<0.01), 3, 4, 5 and 6 h, respectively (P<0.001). However, at the end of the 6-h treatment period, restoration of sinus rhythm was observed in a significantly higher proportion of patients in the magnesium group compared with the diltiazem group [13 of 23 patients, (57%), versus five of 23 patients, (22%), P=0.03]. Magnesium sulfate favorably affects rate control and seems to promote the conversion of long lasting episodes of paroxysmal atrial fibrillation to sinus rhythm, representing a safe, reliable and cost-effective alternative treatment strategy to diltiazem.",2001.0,0,0
262,11464260,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.",2001.0,0,0
263,11467760,Less adrenergic response to mental task during verapamil compared to amlodipine treatment in hypertensive subjects.,K Sevre; J D Lefrandt; I Eide; A J Smit; M Rostrup,"We compared the effects of amlodipine and verapamil slow release on autonomic responses to a 5-min mental arithmetic test (MST) in patients with mild to moderate hypertension. Twenty subjects received 8 weeks of verapamil slow release 240 mg or amlodipine 10 mg in a double-blind crossover design, both after 4 weeks' placebo. Heart rate (HR) and blood pressure (BP) were continuously monitored. Venous plasma catecholamines were analysed by a radioenzymatic assay. Baroreflex sensitivity (BRS) was estimated with the transfer function technique. Calculations of the area under the curve (AUC) were used to estimate average HR, BP and catecholamine concentrations. The reactivity to MST was estimated as percent change from the basal AUC. A paired t-test was performed. Data are means +/-SEM. Compared to verapamil, amlodipine increased average noradrenaline (NA) concentrations (245 +/- 23 vs 191 +/- 17 pg/l, respectively, p = 0.005), NA reactivity (14.0 +/- 5.5% vs -2.9 +/- 3.3, p = 0.004), average HR (65 +/- 2 vs 61 +/- 2 beats/min, p < 0.001) and HR reactivity (2.5 +/- 1.0 vs 0.1 +/- 0.9%, p = 0.056). BP did not differ significantly. BRS correlated with average and baseline HR on both medications (r = -0.53 and -0.63, p < or = 0.03). We conclude that adrenergic responses to MST are blunted on treatment with verapamil compared to amlodipine in hypertensive patients.",2002.0,0,0
264,11467764,"Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation.",S E Kjeldsen; S Julius; H Brunner; L Hansson; M Henis; S Ekman; J Laragh; G McInnes; B Smith; M Weber; A Zanchetti,"Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.",2002.0,1,1
265,11468543,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
266,11469424,VERDICT: the Verapamil versus Digoxin Cardioversion Trial: A randomized study on the role of calcium lowering for maintenance of sinus rhythm after cardioversion of persistent atrial fibrillation.,T Van Noord; I C Van Gelder; R G Tieleman; H A Bosker; A E Tuinenburg; C Volkers; N J Veeger; H J Crijns,"Many relapses of atrial fibrillation (AF) occur, especially during the first week(s) after electrical cardioversion (ECV). The aim of the present study was to compare in a randomized design the efficacy of verapamil (intracellular calcium lowering) versus digoxin (calcium increasing) for maintenance of sinus rhythm after ECV. Ninety-seven patients with persistent AF were randomized to verapamil (n = 49) or digoxin (n = 48) for 1 month before and 1 month after ECV. The first month after ECV, patients recorded heart rhythm using daily transtelephonic monitoring. No additional antiarrhythmic drugs were given. Of the 97 patients, 43 patients (20 verapamil) underwent ECV per protocol. Median previous AF duration was 18 and 26 days for verapamil and digoxin, respectively. There were no differences in atrial dimensions and underlying heart disease between the two groups. The success rate of ECV was 75% versus 83% (P = NS). After 1 month, 47% versus 53% (P = NS) had recurrence of AF. Median time to recurrence was 5 days (range 0 to 26) versus 8 days (range 2 to 28) (P = NS), respectively. Stand-alone intracellular calcium lowering by verapamil around ECV does not enhance cardioversion outcome.",2002.0,1,1
267,11471852,"A randomized, double-blind, parallel-group study to compare the anti-hypertensive effects of imidapril and nifedipine in the treatment of mild-to-moderate essential hypertension.",R van der Does; R Euler,"This 12-week, multicentre, double-blind, placebo-controlled, parallel-group study compared efficacy of the angiotensin-converting enzyme (ACE) inhibitor imidapril 5 - 10 mg/day and the calcium channel blocker nifedipine slow-release (SR) formulation 20 - 40 mg twice daily. In total 320 patients aged 18 - 75 years, with mean sitting diastolic blood pressures of 95 - 115 mmHg, were randomized to treatment with imidapril (n = 157) or nifedipine SR (n = 163). Efficacy evaluations were based on the intent-to-treat principle. On study completion, there was no difference between the groups with respect to the primary efficacy variable of response to treatment (imidapril 63.1%; nifedipine SR 61.3%). After 2 weeks' treatment, clinically relevant decreases in blood pressure were observed in both groups, with a trend towards further reductions until study end. Fewer patients in the imidapril-treated group than the nifedipine group withdrew due to adverse events that occurred on treatment with study medication (3.2% versus 16.0%) or experienced adverse events (40.1% versus 49.7%). In addition, fewer adverse events were causally related to imidapril (24.2%) compared with nifedipine SR (41.7%). These results show that imidapril is effective in the treatment of essential hypertension and is better tolerated than nifedipine SR.",2002.0,0,0
268,11486240,"A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina.",S K Chugh; K Digpal; T Hutchinson; C J McDonald; A J Miller; A Lahiri,"A randomized, double-blind, parallel-group study comparing the efficacy and tolerability of once-daily diltiazem capsules with amlodipine tablets in patients with stable angina. After a run-in period of 1 to 3 weeks, 34 patients received once-daily diltiazem and 33 patients received amlodipine. Patients received either diltiazem, 240 mg/day, or amlodipine, 5 mg/day, for 2 weeks followed by diltiazem, 360 mg/day, or amlodipine, 10 mg/day, for 2 weeks. Standard treadmill exercise testing was the primary efficacy assessment. Patients also recorded incidence of angina attacks and use of glyceryl trinitrate spray. Both treatments gave significant improvement in time to onset of angina and time to maximal exercise. With the exception of amlodipine, 5 mg/day, both treatments gave significant increases in time to 1-mm ST segment depression. Diltiazem, 360 mg/day, gave a significant decrease in rate pressure product. There were no significant treatment differences in any of the exercise test parameters. Both treatments reduced incidence of angina attacks and use of glyceryl trinitrate spray. The incidence of edema was significantly less in patients receiving diltiazem. In conclusion, both treatments were effective in controlling patients' angina, but diltiazem was better tolerated, with a lower incidence of edema.",2002.0,0,1
269,11487379,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
270,11494095,Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.,D E Hilleman; A P Reyes; R L Wurdeman; M Faulkner,"Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination of amlodipine/ benazepril can be successfully accomplished in the majority of patients.",2001.0,0,0
271,11495141,Connective tissue growth factor in drug-induced gingival overgrowth.,M I Uzel; A Kantarci; H H Hong; C Uygur; M C Sheff; E Firatli; P C Trackman,"Drug-induced gingival overgrowth is a known side effect of certain chemotherapeutic agents used for the treatment of systemic disorders. The pathogenesis and mechanisms responsible for this condition are not fully understood. This study assesses for the presence and localization of connective tissue growth factor (CTGF) in drug-induced gingival overgrowth tissues. CTGF immunostaining was compared with sections stained with transforming growth factor (TGF)-beta1 and CD31 antibodies in order to investigate possible pathogenic mechanisms. Gingival overgrowth samples were obtained from patients undergoing therapy with phenytoin (n = 9), nifedipine (n = 4), cyclosporin A (n = 5), and control tissues from systemically healthy donors (n = 9). Tissue sections were subjected to peroxidase immunohistochemistry and were stained with CTGF and TGF-beta1 polyclonal primary antibodies. Possible relationships between CTGF staining and angiogenesis were also studied using an anti-CD31 antibody as a marker for endothelial cells. Staining was analyzed by computer-assisted quantitative and semiquantitative methodology at 5 defined sites in all samples based on the location of specific landmarks including epithelium and underlying connective tissues. Cellular and extracellular CTGF content in phenytoin gingival overgrowth tissues was significantly (P<0.05) higher compared to the other gingival overgrowth tissues and the controls. Higher CTGF staining in phenytoin gingival overgrowth tissues was accompanied by an increased abundance of fibroblasts and connective tissue fibers. No strong association of CTGF staining with TGF-beta1 or CD31 staining was found. The data from the present study show significantly higher CTGF staining in phenytoin-induced gingival overgrowth tissues compared to controls, cyclosporin A-, or nifedipine-induced gingival overgrowth. Moreover, semiquantitative analyses of histologic samples support the concept that the phenytoin overgrowth tissues are fibrotic. These associations suggest a possible role for CTGF in promoting development of fibrotic lesions in phenytoin-induced gingival overgrowth.",2001.0,0,0
272,11501335,Antihypertensive drug prescription trends at the primary health care centres in Bahrain.,K A Jassim al Khaja; R P Sequeira; A W Wahab; V S Mathur,"To determine the antihypertensive drug prescribing pattern by primary care physicians in patients with uncomplicated essential hypertension; to identify whether such pattern of prescription is appropriate and in accordance with international guidelines for pharmacotherapy of hypertension; and to estimate the impact of such prescriptions on cost of treatment. A prescription-based survey among patients with uncomplicated essential hypertension was conducted in seven out of a total of 18 health centres in Bahrain. The relevant data for our study was collected using cards, designed for chronically-ill patients. A total of 1019 male and 1395 female (62.9%) out of 3838 of the study population were on monotherapy, whereas 596 male and 828 female (37.1%) were on antihypertensive combination therapy. Among the monotherapy category, the various antihypertensive drugs used were as follows: beta-blockers (58.8%), angiotensin converting enzyme (ACE) inhibitors (14.2%), calcium channel blockers (11.1%), diuretics (8.1%) and alpha-methyldopa (7.0%). With respect to overall utilization pattern, beta-blockers were the most frequently prescribed (65.5%), diuretics ranked second (27.4%), followed by ACE inhibitors (20.6%), calcium channel blockers (19.9%) and alpha-methyldopa (8.5%). Within each class of antihypertensives used, the most frequently used individual agents were as follows: (a) among beta-blockers 97.7% used atenolol; (b) among the diuretics, indapamide (35.4%), hydrochlorothiazide (HCTZ) (32.7%), HCTZ in combination with triamterene (25.7%), and chlorthalidone (4.6%); (c) among the ACE inhibitors, captopril (44.9%), enalapril (29.7%), and lisinopril (19.0%); (d) among the calcium channel blockers, nifedipine (98.2%). Significant age- and gender-related differences in prescribing patterns were seen. Short-acting nifedipine monotherapy was inappropriately prescribed in a significant number of patients above the age of 50 years. ACE inhibitors accounted for approximately two-thirds of the total antihypertensive drug expenditure, although these drugs represent only one-fifth of overall antihypertensives used. There is a trend towards excessive use of expensive thiazide-like diuretics such as indapamide which seems to be unjustifiable practice, particularly in a study population free from diabetic hypertensive patients. The general pattern of antihypertensive utilization appears to be in accordance with the guidelines of WHO and the Joint National Committee issued in the 1990s. The trends of prescribing of antihypertensives were in favour of conventional ones such as the beta blockers and diuretics, and the introduction of newer classes of antihypertensives had a generally minimal impact on the prescribing profile. Almost two-thirds of the patients were treated with monotherapy. A disproportionately large percentage of antihypertensive drug cost was due to overt use of ACE inhibitors, and indapamide, instead of thiazide diuretics. The use of short-acting calcium channel blockers especially in the elderly is unjustifiable.",2001.0,0,0
273,11505744,[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
274,11512496,Chronic hypertension in pregnancy.,J C Livingston; B M Sibai,"Pregnant women with chronic hypertension are at risk for maternal and perinatal morbidity. Careful assessment and management of these patients during pregnancy are the keys to reducing maternal and fetal complications. Antihypertensive treatment should be used in women with high-risk chronic hypertension, whereas drug therapy does not improve pregnancy outcome in women at low risk. Prophylactic low-dose aspirin started early in pregnancy in women with chronic hypertension is not effective in reducing the frequency of superimposed preeclampsia and should be avoided.",2002.0,0,0
275,11515708,Adverse drug reaction monitoring--digitoxin overdosage in the elderly.,M Hippius; B Humaid; T Sicker; A Hoffmann; M Göttler; J Hasford,"Drug-related illness is an everlasting universal problem and also an important cause of admissions to hospitals. Adverse reactions are still grossly underreported by medical professions. Little information is available regarding the frequency or type of ADRs managed in hospitals. Since January 1997, we have taken part in a study, supported by the German Federal Institute for Drugs and Medical Device to improve the spontaneous drug information reporting system in Germany. Three German regionalized Departments of Clinical Pharmacology--Jena, Dresden, Rostock--serve as Pharmacovigilance Centers in collaboration with the Pharmacoepidemiology Research Group of the University of Munich. Since January 1997, the regional group in Jena has been monitoring the University Clinic of Internal Medicine for admissions caused by adverse drug reactions. All emergency cases and patients on intensive care units were checked for adverse drug reactions. We present our results, including clinical and demographic data, concerning intoxications and especially those involving digitoxin in 210 patients with ADR. Forty patients with digitoxin toxicity had an average age of 81 years (81.1+/-6.3), a low body weight (59.7+/-12.7 kg) and 3 out of 4 were women. 75% of all patients with digitoxin side effects had elevated serum digitoxin levels with concentrations higher than 25 microg/ml. The relatively high frequency of digitoxin intoxications in our hospital may reflect the advanced age and low body weight of patients. Patients received digitoxin regardless of age, weight and, sometimes, clinical indication. Physicians should be aware of drugs having a high risk when used in elderly patients. The use of digitoxin assays and keeping serum levels within or near the therapeutic range will diminish the incidence of overdoses.",2002.0,0,0
276,11520524,"Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial.",L H Lindholm; H Anderson; T Ekbom; L Hansson; J Lanke; B Dahlöf; U de Faire; K Forsén; T Hedner; E Linjer; B Scherstén; P Wester; T Möller,"Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.",2001.0,0,0
277,11521694,Incidental retinal phototoxicity associated with ingestion of photosensitizing drugs.,M Mauget-Faÿsse; M Quaranta; N Francoz; D BenEzra; M Mauget-Fa,"to report on the possible correlation between incident retinal phototoxicity and the use of photosensitizing drugs. four patients were examined because of scotomas and visual loss after an incidental exposure to a strong light source. One patient (two eyes) was exposed to standard camera flash; one patient (one eye) had a brief exposure to welding light; one patient (two eyes) underwent uncomplicated phacoemulsifications with intraocular lens implantation. The fourth patient had a severe retinal phototoxicity following a secondary intraocular lens implantation. All four patients underwent a thorough assessment including history of systemic drug use. These patients had ophthalmologic evaluation including: best corrected visual acuity (ETDRS charts), fundus examination, fluorescein and indocyanine green angiographies and were followed for 1 year. on presentation, the mean visual acuity was 7.5/20 (range: 20/400-20/20). Fundus examination disclosed yellow-gray sub-retinal lesions in all affected eyes. Early phase fluorescein angiography showed one or multiple hypofluorescent spots surrounded by a halo of hyperfluorescent window defect. In the late phase, some of these spots leaked the fluorescein dye. Indocyanine green angiography demonstrated hypofluorescent spots throughout with ill-defined borders of hyperfluorescence observed during the late stages. The common finding in these four patients was the fact that they were all taking one or more photosensitizing drugs (hydrochlorothiazide, furosemide, allopurinol, and benzodiazepines). Three of the patients had a full visual recovery a few months after the phototoxicity. The fourth patient remained with a visual acuity of 20/60 12 months after the light exposure. Despite the visual recovery, non-homogeneous retinal pigment epithelial disturbances persisted in all affected eyes. phototoxicity following incidental light exposure may occur in patients taking drugs of photosensitizing potential. Therefore, the thorough history of systemic drug ingestion should be obtained if patients have exposure to strong light sources.",2002.0,0,0
278,11524073,Effect of diltiazem on the recurrence rate of paroxysmal atrial fibrillation.,H F Tse; C P Lau; Q Wang; F Pelosi; H Oral; B P Knight; S A Strickberger; F Morady,,2001.0,1,1
279,11550107,Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial.,H Celis; L Thijs; J A Staessen; W H Birkenhäger; C J Bulpitt; P W de Leeuw; G Leonetti; C Nachev; J Tuomilehto; R H Fagard; Syst-Eur Investigators,"To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives. Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n = 861), defined as reporting NSAID intake on at least 50% of the patient forms. There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56-1.06)) and higher incidence of bleeding (1.13 (0.63-2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07). The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.",2001.0,0,1
280,11550111,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
281,11551370,Clinical trials report. The effect of Ramipril versus Amlodipine on renal outcomes in hypertension nephrosclerosis.,D G Vidt,,2001.0,0,0
282,11551875,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
283,11561910,A systematic approach to the management of preterm labor.,E R Norwitz; J N Robinson,"Preterm birth occurs in 7% to 12% of all deliveries, but accounts for over 85% of all perinatal morbidity and mortality. Although the ability of obstetric care providers to identify women at risk for preterm delivery has improved, the overall incidence of preterm birth has remained unchanged for the past 30 years. Preterm birth remains the single greatest challenge for physician-researchers in the field of maternal-fetal medicine in the 21st century. This article reviews in detail the current state of the literature as regards the etiology, pathophysiology, prevention, and treatment of premature labor and preterm birth. A better understanding of the molecular mechanisms responsible for the process of labor, both at term and preterm, will improve our ability to identify and manage women at risk of premature delivery.",2002.0,0,0
284,11562301,A prevention strategy for circumventing drug resistance in cancer chemotherapy.,G D Frenkel; P B Caffrey,"The development of drug resistance is considered to be a major cause for the failure of chemotherapy in a number of types of cancer, including ovarian, breast and lung. Most previous research has focused on approaches to reverse drug resistance once it has arisen, that is, on the use of agents which can make drug-resistant tumors more sensitive to chemotherapy. Unfortunately, this approach has thus far met with only limited clinical success. Because of the prevalence of drug resistance in cases of advanced cancer, there exists an urgent need to develop new approaches to dealing with this problem. We have hypothesized the feasibility of an alternative approach: the use of specific agents to prevent the development of resistance before it arises. Our initial studies to examine this hypothesis have focused on ovarian cancer. We have designed both in vitro and in vivo systems in which resistance develops rapidly after exposure of tumor cells or xenografts to melphalan or cisplatin. Using these systems we have shown that two selenium compounds, selenite and selenomethionine are able to prevent the induction of resistance. Furthermore, inclusion of selenite in a chemotherapeutic protocol can result in a significant enhancement of the efficacy of cisplatin in suppressing the growth of human ovarian tumor xenografts. These results have supported the idea that prevention may be a useful new approach to the problem of drug resistance in cancer chemotherapy.",2002.0,0,0
285,11564991,"A multicenter, randomized double-blind study of valsartan/hydrochlorothiazide combination versus amlodipine in patients with mild to moderate hypertension.",P Palatini; E Malacco; R Fogari; R Carretta; D Bonaduce; F Bertocchi; J Mann; M Condorelli; Italian Collaborative Study Group,"To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension. In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348). The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006). The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.",2002.0,0,0
286,11565492,,,,,0,0
287,11565517,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
288,11565518,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
289,11569658,Pharmacological management of detrusor instability.,D Robinson; V Khullar; L Cardozo,"Urinary incontinence and lower urinary tract dysfunction remain an important cause of morbidity, affecting at least 14% of women over the age of 30 years. Whilst the etiology and pathophysiology of detrusor instability remains to be elucidated drug therapy remains important in the management of women with the irritative symptoms of urgency, frequency and urge incontinence. The number of drugs which have been developed illustrates the point that none are ideal, often having systemic adverse effects limiting their therapeutic usage and affecting compliance. This review aims to assess the current pharmacological management of detrusor instability as well as examining recent progress in the development of new agents, some of which may prove to be efficacious.",2002.0,0,0
290,11571824,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
291,11574740,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
292,11576319,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
293,11579708,"Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study.",R Scorza; M Caronni; B Mascagni; V Berruti; S Bazzi; E Micallef; G Arpaia; M Sardina; L Origgi; M Vanoli,"Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.",2002.0,0,0
294,11583866,Use of risk stratification to identify patients with unstable angina likeliest to benefit from an invasive versus conservative management strategy.,D H Solomon; P H Stone; R J Glynn; D A Ganz; C M Gibson; R Tracy; J Avorn,"This study was designed to determine whether patient characteristics collected at presentation can identify which patients benefit from immediate coronary angiography and revascularization. Risk stratification may offer a method for identifying which patients with unstable angina or non-Q-wave myocardial infarction (NQMI) are likeliest to benefit from invasive management strategies. The analysis was based on data from a randomized controlled trial that enrolled 1,473 patients presenting with unstable angina or NQMI who were randomly assigned to an early invasive or early conservative (medical) management strategy. We constructed a risk-stratification score for each patient based on adjusted odds ratios for clinical variables likely to predict adverse outcomes. We stratified all trial subjects by their risk scores and studied the rates of death or myocardial infarction (MI) of the early invasive management strategy in each stratum. The final multivariate model included older age, ST segment depression on presentation, history of complicated angina before presentation, and elevation in baseline creatine kinase-MB fraction. Although patients with a higher risk score had an increased rate of death or MI within 42 days and 365 days (p < 0.001) in both management strategies, early invasive management for patients in the high and very high risk categories was associated with a lower rate of death or MI within 42 days compared with conservative management. No such benefit was seen in patients in the larger group of patients in the very low, low or moderate risk categories (p = 0.03 for the interaction between risk category and management assignment). Risk stratification may be an effective method for identifying those patients with unstable angina or NQMI most likely to benefit from early invasive management. Selective use of early invasive management can have a substantial impact in reducing morbidity and mortality in higher risk patients, but may not be warranted in lower risk patients.",2001.0,0,1
295,11588535,"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.",2002.0,1,1
296,11591190,T cell involvement in cutaneous drug eruptions.,Y Hari; K Frutig-Schnyder; M Hurni; N Yawalkar; M P Zanni; B Schnyder; A Kappeler; S von Greyerz; L R Braathen; W J Pichler,"The most frequent side-effects of drug therapy are skin eruptions. Their pathomechanism is rather unclear. In this prospective study we investigated the T cell activation and drug specificity in different forms of drug-induced exanthemas from 22 patients. During acute drug allergy, liver parameters and T cell subset activation in the circulation (up-regulation of CD25 and HLA-DR) were evaluated and skin biopsies of the acute lesion performed. After recovery, the causative drug was identified by lymphocyte transformation (LTT) and scratch-patch tests. Seventeen of 22 (17/22) patients had maculo-papular exanthema, 4/22 bullous exanthema and 1/22 urticaria. The causative drugs were mainly antibiotics, anti-epileptics and anti-hypertensives. Up-regulation of HLA-DR on circulating CD4(+) and/or CD8(+) T cells was detected in 17 patients, being most marked in patients with bullous reactions or hepatic involvement. The LTT was positive in 14/21 analysed and the patch test in 7/15. All patients showed lymphocytic infiltration in the skin biopsy of the acute lesion. Generally CD4(+) T cells dominated; a higher percentage of circulating CD8(+) T cells was found in patients with bullous skin reactions or hepatic involvement. Our data demonstrate activation and drug specificity of T cells in drug-induced skin eruptions. A predominant CD8(+) T cell activation leads to more severe (bullous) skin symptoms or liver involvement, while predominant activation of CD4(+) cells elicits mainly maculo-papular reactions.",2002.0,0,0
297,11593094,Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study.,G Mancia; S Omboni; G Parati; D L Clement; W E Haley; S N Rahman; R P Hoogma,"The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure <or= 90 mmHg, 117 to <or= 85 mmHg and 118 to <or= 80 mmHg. Additional analyses included computation of: (1) trough-to-peak ratio and (2) the smoothness index (the ratio between the average of the 24 hourly blood pressure reductions after treatment and its standard deviation). Taking the subgroup as a whole, baseline 24 h average blood pressures (146 +/- 18/90 +/- 10 mmHg) were significantly and markedly lower than office blood pressures (170 +/- 14/105 +/- 3 mmHg, P < 0.01). Office, 24 h, day and night blood pressures were all significantly reduced by treatment, but there was a smaller fall in ambulatory, than in office pressures. The between group differences in office blood pressure were smaller than those observed in the overall HOT sample. Between-group differences in 24 h blood pressure were even smaller. Trough-to-peak ratios and smoothness indices were lowest in the highest blood pressure target group and highest in the lowest blood pressure target group. Office and ambulatory blood pressures were similar in the groups randomized to placebo (n = 170) or acetylsalicylic acid (n = 177). In conclusion, in the HOT study, treatment reduced not only office but also ambulatory blood pressure throughout the 24 h. The reduction was less marked for ambulatory than for office blood pressure.",2002.0,0,1
298,11593109,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.",2002.0,1,1
299,11601835,ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology.,V Fuster; L E Rydén; R W Asinger; D S Cannom; H J Crijns; R L Frye; J L Halperin; G N Kay; W W Klein; S Lévy; R L McNamara; E N Prystowsky; L S Wann; D G Wyse; American College of Cardiology; American Heart Association; European Society of Cardiology; North American Society of Pacing and Electrophysiology,,2002.0,0,0
300,11601935,Guidelines for the management of patients with chronic stable angina: treatment.,S D Fihn; S V Williams; J Daley; R J Gibbons; American College of Cardiology; American Heart Association; American College of Physicians-American Society of Internal Medicine,"The dual aims of treating patients with chronic stable angina are 1) to reduce morbidity and mortality and 2) to eliminate angina with minimal adverse effects and allow the patient to return to normal activities. In the absence of contraindications, beta-blockers are recommended as initial therapy. All beta-blockers seem to be equally effective. If the patient has serious contraindications to beta-blockers, unacceptable side effects, or persistent angina, calcium antagonists should be administered. Long-acting dihydropyridine and nondihydropyridine agents are generally as effective as beta-blockers in relieving angina. Long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid developing tolerance. All long-acting nitrates seem to be equally effective. Patients with angina should take 75 to 325 mg of aspirin daily unless they have contraindications. Such risk factors as smoking, elevated low-density lipoprotein cholesterol level, diabetes, and hypertension should be treated appropriately. Coronary revascularization has not been shown to improve survival for most patients with chronic angina but may be required to control symptoms. However, coronary artery bypass grafting (CABG) is often indicated for symptomatic patients with left-main disease, three-vessel disease, or two-vessel disease including proximal stenosis of the left anterior descending coronary artery; it improves their survival. Percutaneous transluminal coronary angioplasty is an alternative to CABG for patients with normal left ventricular function and favorable angiographic features. Coronary artery bypass grafting is initially more effective in relieving angina than medical therapy, but the two procedures yield similar results after 5 to 10 years. Eighty percent of patients who undergo CABG remain angina-free 5 years after surgery. In low-risk patients, percutaneous transluminal coronary angioplasty seems to control angina better than medical therapy, but recurrent angina and repeated procedures are more likely than with CABG. Patient education is an important component of management. Long-term follow-up should be individualized to ascertain clinical stability at regular intervals and to reassess prognosis when warranted.",2001.0,0,0
301,11603612,Left ventricular outflow tract obstruction unmasked by nifedipine: a therapeutic pitfall in the management of chronic aortic regurgitation.,G M Novaro; L L Rodriguez,"This case report illustrates the aggravation of a clinically silent left ventricular outflow tract obstruction by maintenance use of nifedipine in a patient with chronic severe aortic regurgitation, and demonstrates a potential limitation of vasodilator therapy in the management of this patient population. Recognition of this clinical scenario is imperative, as decision making in patients with chronic severe aortic regurgitation rests on the development of symptoms and/or left ventricular dysfunction in relation to the regurgitant volume. The importance of echocardiography in the detection of this valvular finding and in the follow up of these patients is emphasized.",2002.0,0,0
302,11642080,[Effects of long-acting calcium antagonists--amlodipine and diltiazem in patients with stable angina of effort: comparative randomized controlled trial].,S Iu Martsevich; D P Sementsov; N P Kutishenko; E V Alimova,"To compare effectiveness of two long-acting calcium antagonists--amlodipin and diltiazem--in patients with ischemic heart disease (IHD) and stable angina of effort (SAE). 31 IHD patients with SAE entered the double blind randomized trial. The patients received either amlodipin (5-10 mg once a day) or diltiazem (120-180 mg twice a day) for 4 weeks. Selection of the effective single dose and control over the drug effectiveness in regular intake was carried out using treadmill tests made at the height of the drug activity (peak effect) and before taking the next dose (end effect). 1 patient quitted the trial because of frequent anginal attacks while amlodipin administration. Both drugs showed positive effect in relation to exercise tolerance, peak effect of diltiazem was significantly higher than that of amlodipin, the end effect was the same. Amlodipin increased the heart rate at rest while diltiazem insignificantly decreased it. Amlodipin induced side effects more often, all of them were typical for dihydropiridin calcium antagonists. Amlodipin and diltiazem of prolonged action have pronounced antianginal effect, diltiazem being more effective and less toxic.",2002.0,0,0
303,11673357,ACC/AHA/ESC Guidelines for the Management of Patients With Atrial Fibrillation: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology.,V Fuster; L E Rydén; R W Asinger; D S Cannom; H J Crijns; R L Frye; J L Halperin; G N Kay; W W Klein; S Lévy; R L McNamara; E N Prystowsky; L S Wann; D G Wyse; R J Gibbons; E M Antman; J S Alpert; D P Faxon; V Fuster; G Gregoratos; L F Hiratzka; A K Jacobs; R O Russell; S C Smith; W W Klein; A Alonso-Garcia; C Blomström-Lundqvist; G de Backer; M Flather; J Hradec; A Oto; A Parkhomenko; S Silber; A Torbicki; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation); North American Society of Pacing and Electrophysiology,,2002.0,0,0
304,11674903,What is the best treatment for slowing the progression to end-stage renal disease (ESRD) in African Americans with hypertensive nephropathy?,J R McConaghy,,2002.0,0,0
305,11676305,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
306,11684921,Treating hypertension in the elderly.,R W Schrier,"Hypertension is highly prevalent in elderly individuals, the most rapidly growing segment of the US population. Epidemiologic studies have established that increased risk of cardiovascular disease is associated with elevated blood pressure. Treatment of hypertension in elderly patients significantly reduces their cardiovascular morbidity and mortality. However, antihypertensive therapy is often challenging in this patient population because of potential metabolic and physiologic alterations, multiple comorbidities, polypharmacy, and biologic variability. Drugs with a convenient dosing schedule, minimal side effects, and the ability to impact comorbid conditions are important considerations in the treatment of hypertension in the elderly.",2002.0,0,0
307,11686806,The gingival inflammatory infiltrate in cardiac patients treated with calcium antagonists.,P Bullón; G Machuca; J R Armas; J L Rojas; G Jiménez,"To analyse the periodontal inflammatory infiltrates in patients with cardiac disease, some of these patients were treated with calcium antagonists (nifedipine and diltiazem) and some were not, to compare them with a healthy control group, and to evaluate the changes in the inflammatory infiltrate after periodontal treatment. A ""healthy group"" (HG, n=12), a ""cardiac group"" (CG, n=12) without treatment with calcium antagonists, a ""nifedipine group"" (NG, n=18) and a ""diltiazem group"" (DG, n=13) were analysed. Biopsies were taken from a zone 2-3 mm below the upper part of the interproximal papillae 12-13 and 33-32 before causal periodontal treatment and after 1 year. Using haematoxylin-eosin staining, the plasma cells (P), lymphocytes (L), histiocytes (H) and polymorphonuclear cells (PMN) were counted. T and B lymphocytes were evaluated using the monoclonal antibodies anti-CD20 and anti-CD45RO. Statistical tests used: chi2 for study of the sample composition; ANOVA for comparison between groups; Student t-test and Wilcoxon test for comparison between visits; post-hoc test Bonferroni. When the cells were compared statistically, differences were established for L at the first visit (p<0.00001) and at the last visit (p<0.02), for the B lymphocytes (first visit p<0.0021, last visit p<0.022) and for the T lymphocytes (first visit p<0.0042, last visit p<0.0021). Between the 2 visits, HG showed significant reductions for P (p<0.01), L (p<0.045) and H (p<0.033); and the NG for L (p<0.0001). Lymphocytes showed differences in the NG with respect to the B lymphocytes (p<0.008). Nifedipine affects the inflammatory infiltrate with a greater number of lymphocytes (especially B) and these cells fell significantly in number after periodontal treatment.",2002.0,0,0
308,11688766,"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.",2002.0,1,1
309,11697754,Comparative pharmacokinetics and pharmacodynamics of amlodipine in hypertensive patients with and without type II diabetes mellitus.,R A Preston; M Chung; M Gaffney; A Alonso; N M Baltodano; M Epstein,"Recent clinical trials aimed at attenuating complications in diabetes mellitus have generated interest in the impact of drug formulation and altered pharmacokinetics and pharmacodynamics in diabetes. Specifically, it has been proposed that the diabetic state may alter the pharmacokinetics of several cardiovascular drugs, including some calcium antagonists. The present study investigates the effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of amlodipine in hypertensive subjects with and without diabetes mellitus to determine whether the diabetic state alters these parameters. This trial consisted of a 2-week placebo washout phase, a 2-week titration phase, and a 2-week maintenance phase. Study patients included 18 hypertensive patients with type II diabetes mellitus and 10 nondiabetic hypertensive patients. Blood samples were collected after administration of amlodipine and AUC, Cmax, and tmax were determined. The acute 24-hour pharmacodynamic response to amlodipine was assessed by blood pressure and telemetric heart rate measurements. There were no significant differences for either amlodipine 5 or 10 mg in AUC (p = 0.40 for 5 mg; p = 0.59 for 10 mg), Cmax (p = 0.41 for 5 mg; p = 0.45 for 10 mg), and tmax (p = 0.79 for 5 mg; p = 0.67 for 10 mg) between diabetic and nondiabetic hypertensive subjects. Similarly, the 24-hour pharmacodynamic effects of amlodipine on systolic blood pressure, diastolic blood pressure, and heart rate did not differ between diabetic and nondiabetic subjects as assessed by repeated-measures analysis of variance. Because of the theoretical basis for anticipating that diabetes mellitus may provoke important pharmacokinetic and pharmacodynamic alterations, our study provides an important database in clearly demonstrating that the diabetic milieu did not alter the pharmacokinetics or pharmacodynamics of amlodipine.",2002.0,0,0
310,11705254,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
311,11707019,Adverse and beneficial effects of tocolytic therapy.,P G Pryde; R E Besinger; J G Gianopoulos; R Mittendorf,"In addition to questions raised about the efficacy of many tocolytics, appropriate concern has been voiced about the safety of these potent drugs. Although some degree of risk for adverse effects with drugs promising a strong therapeutic effect can be accepted, caution needs to be exercised when benefits are marginal or unproven. Unfortunately, some of the tocolytics, most notably the betamimetics and magnesium sulfate, have been found to have considerable potential for adverse maternal cardiovascular and respiratory effects. Although less clearly established, the use of indomethacin appears to be associated with increased fetal and neonatal risks. Concerning magnesium sulfate, in addition to the well-known maternal effects, the accumulating evidence showing an increased frequency of adverse outcomes in the fetus and neonate has led to the recommendations to abandon its use entirely as a tocolytic. Given the limitations of our current state of knowledge, nifedipine would appear to be among the more efficacious and safer tocolytics available to use when properly indicated.",2002.0,0,0
312,11711020,"Does a change to long-acting antianginals provide better symptom control, treatment satisfaction, and quality of life?",M M Maniscalco; W Newton,,2002.0,0,0
313,11711508,One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.,H R Black; W J Elliott; M A Weber; W H Frishman; J A Strom; P R Liebson; C T Hwang; D A Ruff; R Montoro; V DeQuattro; D Zhang; M M Schleman; M I Klibaner,"Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.",2002.0,1,1
314,11717605,Safety of controlled-onset extended-release verapamil in middle-aged and older patients with hypertension and coronary artery disease.,W B White; M F Johnson; R J Anders; W J Elliott; H R Black,"Our purpose was to study the safety of controlled-onset, extended-release (COER) verapamil in patients with hypertension or coronary artery disease, with a focus on elderly patients. Adverse event data were pooled from 7 double-blind, multicenter, randomized trials including 1999 patients with hypertension or chronic stable angina pectoris. There were 1042 patients who received COER verapamil 180 to 540 mg once daily in the evening for up to 10 weeks, 373 patients who received placebo, and 584 who received an active comparator agent. Data were analyzed according to the following groups: all patients, patients with hypertension, patients with angina, older patients (>/=65 years old), and younger patients (<65 years old). Adverse event rates were compared across the treatment groups by the Fisher exact test. In all patients combined, the incidence of constipation (13% vs 2%), dizziness (6% vs 2%), and back pain (3% vs 1%) was higher in patients treated with COER verapamil than with placebo. Patients with hypertension had more back pain (4% vs 1%) and constipation (12% vs 1%) with COER verapamil than with placebo, whereas patients with angina had more bradycardia (2.6% vs 0%), dizziness (8% vs 2%), and constipation (15% vs 3%). Older patients treated with COER verapamil had more bradycardia, constipation, dizziness, and fatigue and had fewer headaches compared with younger patients treated with COER verapamil. Second- or third-degree atrioventricular block was not observed after administration of COER verapamil in any subgroup. These data demonstrate that COER verapamil has an acceptable safety profile that is largely unrelated to age in patients with hypertension or coronary artery disease.",2002.0,0,1
315,11718496,Comparison of 24-hour blood pressure profiles in patients with hypertension who were switched from amlodipine to nisoldipine.,T L Lenz; R L Wurdeman; D E Hilleman,"To compare 24-hour blood pressure control and adverse effects in patients with essential hypertension who were switched from amlodipine to nisoldipine. Open-label, one-way crossover study. Cardiac clinic and patients' homes. Twenty-five patients with stage I or II essential hypertension stabilized with amlodipine for at least 3 months, of whom 21 patients completed the study. All patients underwent 24-hour ambulatory blood pressure monitoring while receiving amlodipine 5 or 10 mg/day. Patients then were switched to nisoldipine 10 mg/day (> or = 65 yrs old) or 20 mg/day (< 65 yrs old) and returned to the clinic at 2-week intervals to assess cuff blood pressure, heart rate, adverse effects, and compliance. No adverse effects were experienced in 15 of the 25 patients. Lower extremity edema was the most commonly reported adverse effect (four patients). Two patients discontinued treatment because of pulmonary edema in one and chest pain in the other. Two patients were lost to follow-up. After a mean of 10.6 weeks, repeat 24-hour ambulatory monitoring was performed to evaluate blood pressure control with nisoldipine. Systolic and diastolic ambulatory results for daytime, nighttime, and total 24 hours were calculated. For amlodipine versus nisoldipine, no significant differences existed in any of the blood pressure parameters (p>0.05) in the 21 patients who completed the study, except for 24-hour diastolic pressure (p<0.05); however, this latter difference was only 2 mm Hg (nisoldipine 77 mm Hg, amlodipine 75 mm Hg). Both amlodipine and nisoldipine have similar 24-hour ambulatory blood pressure profiles. The frequency of lower extremity edema was no different after the switch to nisoldipine than when the patients were taking amlodipine.",2002.0,0,0
316,11721720,Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction.,G Pizzetti; A Mailhac; L Li Volsi; F Di Marco; C Lu; A Margonato; S L Chierchia,"Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function. We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%. Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up). Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.",2002.0,0,0
317,11724204,The effects of dihydropyridine and phenylalkylamine calcium antagonist classes on autonomic function in hypertension: the VAMPHYRE study.,J D Lefrandt; J Heitmann; K Sevre; M Castellano; M Hausberg; M Fallon; L Fluckiger; A Urbigkeit; M Rostrup; E Agabiti-Rosei; K H Rahn; M Murphy; F Zannad; P J de Kam; A M van Roon; A J Smit,"The aim of the present study was to compare the effects of a long-acting dihydropyridine (amlodipine) and a nondihydropyridine (verapamil) on autonomic function in patients with mild to moderate hypertension. A total of 145 patients with a diastolic blood pressure (BP) between 95 and 110 mm Hg received 8 weeks of verapamil sustained release (240 mg) and amlodipine (5 mg) in a prospective randomized, double blind, cross-over study, both after 4 weeks of placebo. The 24-h autonomic balance was measured by analysis of 24-h heart rate variability and short-term autonomic control of BP by baroreflex sensitivity measurements. Plasma norepinephrine was sampled at rest. Blood pressure was equally reduced from 153/100 mm Hg to 139/91 mm Hg with verapamil and 138/91 mm Hg with amlodipine, P = .50/.59. The low- to high-frequency ratio (LF/HF), reflecting sympathovagal balance, was higher with amlodipine than with verapamil (4.66 v 4.10; P = .001). Baroreflex function was improved by both treatments; however, baroreflex sensitivity (BRS) was significantly higher with verapamil than with amlodipine (8.47 v 8.06 msec/mm Hg; P = .01). Plasma norepinephrine (NE) level was higher with amlodipine than with verapamil (1.59 v 1.32 nmol/L; P < .0001). Amlodipine induces a shift in sympathovagal balance, as measured by heart rate variability indices and plasma NE, toward sympathetic predominance compared with vagal predominance with verapamil. Short-term autonomic control of BP, as assessed by BRS, is more effectively improved by verapamil than by amlodipine. These contrasting effects on autonomic function suggest that the nondihydropyridine calcium antagonist verapamil may have additional beneficial effects beyond lowering BP compared with the dihydropyridine amlodipine.",2002.0,0,0
318,11736880,Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension.,J D Lefrandt; J Heitmann; K Sevre; M Castellano; M Hausberg; M Fallon; A Urbigkeit; M Rostrup; E Agabiti-Rosei; K H Rahn; M Murphy; F Zannad; P J de Kam; A J Smit,"To compare the effects of two long-acting calcium antagonists of different types on cardiovascular stress responses in hypertension. One-hundred and forty-five patients with mild to moderate hypertension and a mean (+/- s.e.mean) age of 51 +/- 0.9 years received for 8 weeks the phenylalkylamine verapamil sustained release (240 mg) and the dihydropyridine amlodipine (5 mg) in a double-blind cross-over design, both after 4 weeks of placebo. Blood pressure, heart rate and plasma noradrenaline were monitored during 3 min of sustained isometric handgrip and 2 min of cold pressor. Blood pressure was equally reduced by both drugs. After 3 min handgrip, systolic blood pressure, heart rate and rate-pressure product were lower with verapamil compared with amlodipine. Verapamil attenuated the increases in systolic blood pressure (25 +/- 2 vs 30 +/- 2 mmHg, difference 4.6, 95% CI (1.0, 8.1), P < 0.01) and rate-pressure product (3.1 +/- 0.2 vs 3.6 +/- 0.3 x 10(3) mmHg x beats min(-1), difference 0.5, 95% CI (0.1, 0.9), P < 0.01) during handgrip compared with amlodipine. Similar results were observed during cold pressor. Plasma noradrenaline levels were lower with verapamil compared with amlodipine at rest and after both tests, but the increases in plasma noradrenaline were not significantly different. Verapamil is more effective in reducing blood pressure and rate-pressure product responses to stress compared with amlodipine. Although plasma noradrenaline is lower with verapamil at rest and after stress, the increase during stress is not different.",2002.0,0,0
319,11737121,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
320,11740135,"A double-blind, parallel-group study of amlodipine versus long-acting nitrate in the management of elderly patients with stable angina.",R Hall; C Chong,"Ninety-seven elderly patients with stable angina were included in a 28-week, randomized, double-blind, parallel-group comparison of amlodipine 5-10 mg and isosorbide mononitrate 25-50 mg once daily. The total exercise time, as limited by angina, was recorded together with the median incidence per week of angina attacks and glyceryl trinitrate consumption. Safety was assessed by adverse event frequency, measurement of vital signs and laboratory parameters, and quality of life. At the final visit, the total exercise time was significantly greater relative to baseline with amlodipine than isosorbide mononitrate (final/baseline difference: 112.2 vs. 32.2, p = 0.016). There were no statistically significant differences between the groups in relation to the incidence of adverse events. Once daily amlodipine provides significantly better control of stable angina than isosorbide mononitrate in this elderly population.",2002.0,1,1
321,11740389,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.",2002.0,0,1
322,11747385,Atrial fibrillation after cardiac surgery.,W H Maisel; J D Rawn; W G Stevenson,"To review the epidemiology, mechanisms, complications, predictors, prevention, and treatment of atrial fibrillation following cardiac surgery. MEDLINE search of English-language reports published between 1966 and 2000 and a search of references of relevant papers. Clinical and basic research studies on atrial fibrillation after cardiac surgery. Relevant clinical information was extracted from selected articles. Atrial fibrillation occurs in 10% to 65% of patients after cardiac surgery, usually on the second or third postoperative day. Postoperative atrial fibrillation is associated with increased morbidity and mortality and longer, more expensive hospital stays. Prophylactic use of beta-adrenergic blockers reduces the incidence of postoperative atrial fibrillation and should be administered before and after cardiac surgery to all patients without contraindication. Prophylactic amiodarone and atrial overdrive pacing should be considered in patients at high risk for postoperative atrial fibrillation (for example, patients with previous atrial fibrillation or mitral valve surgery). For patients who develop atrial fibrillation after cardiac surgery, a strategy of rhythm management or rate management should be selected. For patients who are hemodynamically unstable or highly symptomatic or who have a contraindication to anticoagulation, rhythm management with electrical cardioversion, amiodarone, or both is preferred. Treatment of the remaining patients should focus on rate control because most will spontaneously revert to sinus rhythm within 6 weeks after discharge. All patients with atrial fibrillation persisting for more than 24 to 48 hours and without contraindication should receive anticoagulation. Atrial fibrillation frequently complicates cardiac surgery. Many cases can be prevented with appropriate prophylactic therapy. A strategy of rhythm management for symptomatic patients and rate management for all other patients usually results in reversion to sinus rhythm within 6 weeks of discharge.",2002.0,0,1
323,11758079,Statin-associated myopathy.,I Hamilton-Craig,"Myopathy occurs in 0.1%-0.2% of patients receiving statins in clinical trials. This adverse effect is shared by all statins, but is more common with cerivastatin, especially in combination with gemfibrozil. The risk of myopathy is increased by: the use of high doses of statins, concurrent use of fibrates, concurrent use of hepatic cytochrome P450 inhibitors, acute viral infections, major trauma, surgery, hypothyroidism and other conditions. Statin-associated myopathy should be suspected when a statin-treated patient complains of unexplained muscle pain, tenderness or weakness. Statin therapy should be stopped in cases of suspected myopathy, and serum creatine kinase levels should be checked and monitored. No specific therapies other than statin withdrawal and supportive measures for rhabdomyolysis are currently available.",2002.0,0,0
324,11765303,A review of class III antiarrhythmic agents for atrial fibrillation: maintenance of normal sinus rhythm.,J P Tsikouris; C D Cox,"A noteworthy shift from class I to class III antiarrhythmic agents for suppression of atrial fibrillation has occurred. Sotalol, amiodarone, and dofetilide have been evaluated for their ability to maintain sinus rhythm in patients with chronic atrial fibrillation. All of these agents are moderately effective; however, amiodarone appears to be most efficacious. Aside from their common class III actions, these agents have profoundly different pharmacologic, pharmacokinetic, safety, and drug interaction profiles that help guide drug selection. Amiodarone and dofetilide are safe in patients who have had a myocardial infarction and those with heart failure. The safety of commercially available d,l-sotalol in these patients is poorly understood. Torsades de pointes is the most serious adverse effect of sotalol and dofetilide, and risk increases with renal dysfunction. Amiodarone has minimal proarrhythmic risk but has numerous noncardiac toxicities that require frequent monitoring. Overall, an ideal antiarrhythmic agent does not exist, and drug selection should be highly individualized.",2002.0,0,0
325,11773987,"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
326,11775133,Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy.,W B White; M F Johnson; H R Black; W J Elliott; D A Sica,"The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended-release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER-verapamil in patients with mid-stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil (N = 273) or placebo (N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. Treatment with COER-verapamil caused significant reductions in 24-h and early-morning systolic and diastolic BP in all of the subpopulations as compared with placebo (P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (-15.1 v -10.0 mm Hg; P < .001) and diastolic (-10.4 v -8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (-10.2 v -8.2 mm Hg; P < .05) and heart rate (-5.7 v -4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients.",2002.0,0,0
327,11786162,Post-exercise ST segment elevation preceding myocardial infarction in a patient with nearly normal coronary arteries. A rare form of variant angina.,Eleftheria P Tsagalou; John N Nanas,,2002.0,0,0
328,11788225,Evidence-based evaluation of calcium channel blockers for hypertension: equality of mortality and cardiovascular risk relative to conventional therapy.,Lionel H Opie; Robert Schall,"OBJECTIVES; We present a meta-analysis based on three recent, substantial, randomized outcome trials and several smaller trials that compared calcium channel blockers (CCBs) with conventional therapy (diuretics or beta-blockers) or with angiotensin-converting enzyme (ACE) inhibitors. There is continuing uncertainty about the safety and efficacy of CCBs in the treatment of hypertension. Previous meta-analyses conflict and suggest that CCBs increase myocardial infarction (MI) or protect from stroke. Standard procedures for meta-analysis were used to analyze three major trials on 21,611 patients and another three lesser studies to a total of 24,322 patients. Calcium channel blockers have a strikingly similar risk of total and cardiovascular mortality and of major cardiovascular events to conventional therapy. Calcium channel blockers give a lower risk of nonfatal stroke (-25%, p = 0.001) and a higher risk of total MI (18%, p = 0.013), chiefly nonfatal (18%). After performing the Bonferroni correction for multiplicity, these p values become 0.004 and 0.052, respectively. When compared with ACE inhibitors in 1,318 diabetic patients, CCBs had a substantially higher risk of nonfatal (relative risk [RR] = 2.259) and total MI (RR = 2.204, confidence interval 1.501 to 3.238; p = 0.001 or 0.004 with Bonferroni correction). Total and cardiovascular mortality rates are similar. To confirm the hypothesis that ACE inhibitors are superior to CCBs in diabetic patients requires more trial data, especially with renal end points. Mortality (total and cardiovascular) and major cardiovascular events with CCBs were apparently similar to those events seen with conventional first-line therapy (diuretics or beta-blockers). Stroke reduction more than balanced increased MI. In diabetics, CCBs may be less safe than ACE inhibitors.",2002.0,1,1
329,11791019,Sympathetic overactivity as a cause of hypertension in chronic renal failure.,Robert A Augustyniak; Meryem Tuncel; Weiguo Zhang; Robert D Toto; Ronald G Victor,"To review the current literature on sympathetic mediation of hypertension in chronic renal failure. Hypertension is present in the vast majority of patients with chronic renal failure and constitutes a major risk factor for the excessive cardiovascular morbidity and mortality in this patient population. Although, traditionally, this hypertension is thought to be largely volume-dependent, an increasing body of literature suggests that there is an important sympathetic neural component. Microneurographic studies have demonstrated sympathetic overactivity without baroreflex impairment in both hypertensive chronic hemodialysis patients as well as in those with less advanced renal insufficiency. Sympathetic nerve activity was found to be normal in hemodialysis patients with bilateral nephrectomy, leading to the hypothesis that sympathetic overactivity in uremia is caused by a neurogenic signal (carried by renal afferents) arising in the failing kidney. This hypothesis is supported by rat studies showing that renal deafferentation abrogates hypertension in the 5/6 nephrectomy model of chronic renal insufficiency. In addition, in patients with chronic renal insufficiency and renin-dependent hypertension, sympathetic overactivity was normalized by chronic angiotensin converting enzyme inhibition but not by calcium channel blockade, implicating a major central neural action of angiotensin II. Sympathetic overactivity in chronic renal failure is caused by neurohormonal mechanisms arising in the failing kidney. Future clinical studies are needed to determine whether normalization of sympathetic activity should constitute an important therapeutic goal in this high-risk patient population.",2002.0,0,0
330,11791032,,,,,0,0
331,11793132,Evaluation of the safety of short-acting nifedipine in children with hypertension.,David W Egger; Douglas D Deming; Norman Hamada; Ronald M Perkin; Shobha Sahney,"Concerns regarding the safety of nifedipine emerged in 1995 with the report of an increased risk of myocardial infarction associated with adult patients receiving short-acting calcium channel blockers. There have been few case reports of adverse events in children. The purpose of this study is to investigate the effect on blood pressure (BP) and the incidence of adverse events associated with nifedipine in our pediatric population. We conducted a retrospective chart review of pediatric patients who received nifedipine. We recorded the dose administered, all BP measurements and all adverse events reported within six hours of a nifedipine dose regardless of the likelihood that those events were related to the nifedipine dose. 1,746 doses of nifedipine in 166 pediatric patients were reviewed. Systolic BP decreased by a mean of 17% and a maximum of 63%. Diastolic BP decreased by a mean of 28% and a maximum of 89%. Adverse events included: a) change in neurologic status, six cases; b) hypotension, two cases; c) oxygen desaturation, 16 cases. Neurologic events occurred in 33% of patients with acute CNS injury and 3.6% of all patients. Short-acting nifedipine is an important and effective oral antihypertensive agent which can be safely used for the treatment of hypertensive emergencies in children. It should be used with caution in children with acute CNS injury.",2002.0,0,0
332,11794458,Autonomic tone as a cardiovascular risk factor: the dangers of chronic fight or flight.,Brian M Curtis; James H O'Keefe,"Chronic imbalance of the autonomic nervous system is a prevalent and potent risk factor for adverse cardiovascular events, including mortality. Although not widely recognized by clinicians, this risk factor is easily assessed by measures such as resting and peak exercise heart rate, heart rate recovery after exercise, and heart rate variability. Any factor that leads to inappropriate activation of the sympathetic nervous system can be expected to have an adverse effect on these measures and thus on patient outcomes, while any factor that augments vagal tone tends to improve outcomes. Insulin resistance, sympathomimetic medications, and negative psychosocial factors all have the potential to affect autonomic function adversely and thus cardiovascular prognosis. Congestive heart failure and hypertension also provide important lessons about the adverse effects of sympathetic predominance, as well as illustrate the benefits of beta-blockers and angiotensin-converting enzyme inhibitors, 2 classes of drugs that reduce adrenergic tone. Other interventions, such as exercise, improve cardiovascular outcomes partially by increasing vagal activity and attenuating sympathetic hyperactivity.",2002.0,0,0
333,11799973,Effectiveness of nifedipine and deflazacort in the management of distal ureter stones.,Ralph V Clayman,,2002.0,0,0
334,11800156,Possible role of diltiazem in a recalcitrant case of Darier's disease.,H Lorentzen; E Svejgaard,,2002.0,0,0
335,11817970,Cutaneous drug reaction case reports: from the world literature.,,,2002.0,0,0
336,11817974,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
337,11818701,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
338,11821720,Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system.,Henry L Elliott; Mamoun Elawad; Robert Wilkinson; Shyam P Singh,"In this randomized, double-blind, crossover study, the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) was compared following missed doses. Design and methods In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30-60 mg) once daily for 12 weeks, then vice versa. During weeks 8, 10 and 12 of each treatment period, compliance failures were simulated by patients missing 0, 1 or 2 doses of their medication, and ambulatory systolic (SBP) and diastolic (DBP) blood pressure measurements were obtained. Following steady-state treatment (i.e. 'perfect compliance'), there was no difference between amlodipine and nifedipine GITS in SBP (140.1 versus 134.2 mmHg) or DBP (84.0 versus 85.8 mmHg) at 0-24 h post-dose. When compliance was not perfect, i.e. when one or two doses were missed, DBP was maintained at a significantly lower level with amlodipine compared with nifedipine GITS at 24-48 h post-dose (83.1 versus 86.4 mmHg, P = 0.005) and at 48-72 h post-dose (84.2 versus 89.7 mmHg, P < 0.001). Plasma concentrations of amlodipine were better maintained than those of nifedipine GITS. At 72 h post-dose, the plasma concentration of amlodipine was 61% (17.0 +/- 11.2 ng/ml) compared with < 25% (28.3 +/- 49.9 ng/ml) for nifedipine GITS. During short periods of non-compliance, antihypertensive efficacy remains more predictable with amlodipine than with nifedipine GITS.",2002.0,0,0
339,11821721,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.",2002.0,0,1
340,11824857,Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension.,Richard H Grimm; Henry Black; Randall Rowen; Andrew Lewin; Harry Shi; Mathieu Ghadanfar; Amlodipine Study Group,"The study was to compare the effects of amlodipine (calcium channel antagonist), chlorthalidone (diuretic), and placebo in adults more than 50 years of age with stage 1 isolated systolic hypertension (ISH). After a 4-week placebo run-in phase, 150 patients were randomly assigned in a double-blind fashion to treatment with 5 mg of amlodipine (n = 48), 15 mg of chlorthalidone (n = 50), or placebo (n = 52). Patients who failed to meet the systolic blood pressure (BP) reduction goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of chlorthalidone, and maintained at this increased dose for 12 weeks. Results showed a mean reduction (mean +/- SD) in sitting systolic BP from baseline to the last treatment visit of -14.6+/-12.2 mm Hg (95% confidence interval [CI] -18.2, -11.0), -14.0+/-13.46 mm Hg (95% CI -17.8, -10.2), and -3.4+/-11.83 mm Hg (95% CI -6.7, -0.1) for the amlodipine, chlorthalidone, and the placebo treatment groups, respectively. Both active treatments showed significantly greater reductions than the placebo group (P < or = .001), but were not significantly different from each other. Sixty-seven percent of the amlodipine, 69% of the chlorthalidone, and 25% of the placebo-treated patients reached the protocol defined systolic BP goal (P = .001). Both active treatment groups showed a trend of better systolic BP response in older patients (> or =65 years). Secondary efficacy measures including pulse pressure, standing systolic, diastolic, and the 24-h ambulatory BP were also statistically significantly improved for both active treatments at the end of treatment, except for chlorthalidone in standing diastolic BP. Adverse events that occurred during the study were as expected and were well tolerated. The results of this study support the efficacy and safety of amlodipine and chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment.",2002.0,0,0
341,11824861,"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
342,11831838,Effect of verapamil in elderly patients with left ventricular diastolic dysfunction as a cause of congestive heart failure.,M J Hung; W J Cherng; L T Kuo; C H Wang,"Fifteen elderly patients with normal left ventricular (LV) systolic function and New York Heart Association functional class II-III were studied. The effect of verapamil on LV diastolic function was assessed by congestive heart failure (CHF) score, treadmill exercise test, and Doppler echocardiography at baseline, and after each three-month treatment period (placebo or verapamil 120 mg once daily), separated by a one-week washout period before crossover. Blood pressure, heart rate, LV ejection fraction, LV mass, and cardiac output were unaltered by placebo or verapamil. Verapamil treatment significantly improved CHF score at 3 months (3.5 +/- 0.5, p<0.05) compared with baseline (5.6 +/- 0.5) or placebo (5.5 +/- 0.5). The exercise time was similar at baseline (7.4 +/- 1.2 min) and after placebo (7.4 +/- 1.3 min) treatment but significantly (p<0.05) increased after verapamil (8.3 +/- 1.2 min) treatment. The ratio of mitral A wave duration/pulmonary venous atrial systolic reversal duration increased after verapamil (1.11 +/- 0.08) treatment compared with placebo (0.91 +/- 0.07, p<0.05) and baseline (0.89 +/- 0.08) which had similar durations. The isovolumic relaxation time was significantly (p<0.05) decreased from 84 +/- 12 ms at baseline and 86 +/- 13 ms with placebo to 73 +/- 9 ms with verapamil. The results of this study suggest that in elderly patients with Doppler evidence of diastolic dysfunction as the cause of CHF, three months treatment with verapamil can improve CHF, increase exercise tolerance and improve LV diastolic function.",2002.0,1,1
343,11835928,Resolution of ST-segment elevation following intravenous administration of nitroglycerin and verapamil.,John F Beltrame; Simon Stewart; Susan Leslie; Susan Poropat; John D Horowitz,,2002.0,0,0
344,11841884,Slow-infusion of calcium channel blockers in the emergency management of supraventricular tachycardia.,S H Lim; V Anantharaman; W S Teo,"To compare the efficacy of verapamil and diltiazem as slow infusions in terminating spontaneous supraventricular tachycardia (SVT) in the emergency department (ED). Patients of at least 10 years of age who presented to our ED with regular narrow complex tachycardia not converted with a vagal manoeuvre with an ECG diagnosis of SVT were included. Those who were haemodynamically unstable were excluded. Patients were randomized to undergo either verapamil infusion at a rate of 1 mg/min to a maximum of 20 mg or diltiazem infusion at a rate of 2.5 mg/min to a maximum of 50 mg. Eighty-one patients were randomized to receive verapamil infusion and 80 were randomized to receive the diltiazem infusion. There is no difference in success rate between verapamil (98.8%) and diltiazem (96.3%) infusion. The dose of medication required to convert 25,50 and 75% of SVTs were 4.0,5.0 and 8.0 mg for the verapamil infusion and 10.0,12.5 and 17.5 mg for the diltiazem infusion. There was one complication in each group. Calcium channel blockers infusions were safe and efficacious in terminating spontaneous SVT. There was no difference between the success rates of verapamil and diltiazem infusions.",2002.0,0,0
345,11848193,"Comparative study of calcium-channel blockers on cell proliferation, DNA and collagen syntheses, and EGF receptors of cultured gingival fibroblasts derived from human nifedipine, nicardipine and nisoldipine responders.",H Matsumoto; I Noji; Y Akimoto; A Fujii,"Our previous study indicated that fibroblasts derived from patients reactive to nifedipine might be susceptible to the other calcium-channel blockers (nicardipine, verapamil and diltiazem) in terms of cell proliferation, DNA synthesis, and collagen synthesis. Thus, the present investigation was designed to clarify the cross-reactivity among dihydropyridine calcium-channel blockers (nifedipine, nicardipine, and nisoldipine). Human gingival fibroblasts derived from seven, two, and one patients who developed gingival overgrowth as a result of nifedipine, nicardipine, and nisoldipine medications, respectively, were examined in terms of the effect of calcium-channel blockers (nifedipine, diltiazem, verapamil, and nicardipine) on cell proliferation, DNA synthesis, collagen synthesis, and the number of epidermal growth factor (EGF) receptors. Phenytoin was used as a positive control. With most of the calcium-channel blockers and phenytoin, fibroblasts from patients reactive to nifedipine and nicardipine medications gave a better cell proliferation rate, DNA synthesis, and an increased number of EGF receptors, compared to non-drug-treated control. However, this was not the case for calcium-channel blockers tested in fibroblasts from patients reactive to nisoldipine medication.",2002.0,0,0
346,11852965,Delirium in the intensive care unit: are we helping the patient?,J M Webb; E F Carlton; D M Geehan,"The intensive care unit (ICU) represents a dynamic interaction between patient factors and interventional factors. The complexity of this situation can generate an impaired consciousness in the patients. The critical care provider is faced with deducing the etiology and treatment of delirium in the ICU. Many of the therapeutic agents that are used in the ICU may precipitate delirium. Patients may also experience delirium as part of their underlying medical conditions. Withdrawal syndromes, delirium tremens in particular, are known to cause delirium. By a combination of appropriate selection of medications and an awareness of delirium as a side effect, the patient in the ICU may be treated in a manner to minimize the clouding of consciousness. An understanding of the proposed pathophysiology of various types of delirium will allow appropriate clinical measures to be taken.",2002.0,0,0
347,11854123,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
348,11863244,Effect of amlodipine compared to atenolol on small arteries of previously untreated essential hypertensive patients.,Ernesto L Schiffrin; Qian Pu; Jeong Bae Park,"In a previous retrospective study, long-term treatment of essential hypertensive patients with a slow-release calcium channel blocker resulted in normal resistance artery structure and endothelial function, which did not occur with a beta-blocker. In the present prospective study, 19 previously untreated essential hypertensive patients (aged 47 +/- 2 years, 75% male) were treated for 1 year in a double-blind randomized study with the long-acting calcium channel blocker amlodipine or the beta-blocker atenolol. Resistance arteries (lumen diameter, 150 to 350 microm) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph. Blood pressure (BP) control (129 +/- 2/85 +/- 2 mm Hg) was identical in both groups for the last 6 months of the study. After 1 year of treatment with amlodipine, the media-to-lumen ratio (M/L) of resistance arteries decreased from 7.89% +/- 0.40% to 6.81% +/- 0.41% (P < .05). Acetylcholine-induced endothelium-dependent relaxation tended to improve from 84.3% +/- 5.5% to 90.5% +/- 4.8% (P = .06), whereas sodium nitroprusside-induced relaxation was unchanged in the patients treated with amlodipine. In the beta-blocker-treated group there was no significant change in M/L or acetylcholine-induced relaxation. In conclusion, treatment with the calcium channel blocker amlodipine corrected altered resistance artery structure and tended to improve endothelial function in essential hypertensive patients, whereas similar good control of BP with the beta-blocker atenolol did not. Whether the vascular protective effect of amlodipine will result in improved outcomes in hypertension remains to be demonstrated.",2002.0,0,0
349,11864542,,,,,0,0
350,11867945,"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
351,11868797,Trough:peak ratio and smoothness index in the evaluation of 24-h blood pressure control in hypertension: a comparative study between valsartan/hydrochlorothiazide combination and amlodipine.,Paolo Palatini; Ettore Malacco; Somma Salvatore Di; Renzo Carretta; Francesca Dorigatti; Federico Bertocchi; Jessica Mann,"The aim of this study was to measure the time-effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure (BP) monitoring. Of the 310 randomized outpatients with uncomplicated mild-to-moderate primary hypertension, 259 (133 on valsartan/hydrochlorothiazide, 126 on amlodipine) were eligible for analysis. After a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either valsartan 80 mg once daily (o.d.) or amlodipine 5 mg o.d. for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. The trough:peak ratio (global and individualized approaches) and smoothness index (i.e., the ratio between the average of the 24-hourly BP changes after treatment and the corresponding standard deviation) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment. Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks (all P<0.001) but, among the responders, the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks (P=0.03/0.02). In the responders, the placebo-adjusted, mean trough:peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group (n = 111) and 0.66/0.62 in the amlodipine group (n = 101). The corresponding global trough:peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine. However, the between-group differences in individual or global trough:peak ratios were not significant. The smoothness index was slightly, but insignificantly, greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole. Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP, but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval. Trough:peak ratio and smoothness index did not reflect this finding accurately.",2002.0,0,0
352,11869204,A granuloma annulare-like eruption associated with the use of amlodipine.,Adrian C Lim; Kim Hart; Dédée Murrell,"A granuloma annulare-like drug reaction is a rarely encountered clinical entity. A 64-year-old Caucasian female developed a granuloma annulare-like reaction 13 days after starting amlodipine and cleared within 3 months after drug cessation. The eruption consisted of multiple erythematous pruritic papules, distributed symmetrically over the lateral aspects of the legs and thighs, as well as on both palms. Histology showed focal collagen degeneration and significant interstitial histiocytic dermal infiltrate suggestive of granuloma annulare. We review previously reported cases of granuloma annulare-like drug reactions, in the context of a recently proposed classification for drug-induced interstitial granulomatous reactions.",2002.0,0,0
353,11875324,,,,,0,1
354,11877570,Cross-sectional study of health-related quality of life in African Americans with chronic renal insufficiency: the African American Study of Kidney Disease and Hypertension Trial.,John W Kusek; Paul Greene; Shin-Ru Wang; Gerald Beck; Delia West; Kenneth Jamerson; Lawrence Y Agodoa; Marquetta Faulkner; Betty Level,"We measured health-related quality of life (HRQL) by using the Medical Outcomes Study 36-Item Short-Form (SF-36) in a cross-sectional study of 1,094 African American men and women with mild to moderate chronic renal insufficiency (mean glomerular filtration rate, 45.7 mL/min/1.73 m2) caused by hypertension before randomization onto the African American Study of Kidney Disease and Hypertension (AASK) Trial. Scales contributing to physical health and a summary measure, the Physical Component Summary (PCS) score (mean, 43.4 +/- 10.9 [SD]), were significantly lower than scales relating to mental health and the Mental Component Summary (MCS) score (51.3 +/- 10.3). All scales (except Role-Physical) and the PCS and MCS were significantly higher in men (44.3 +/- 10.9 and 51.8 +/- 10.0, respectively) than women (41.9 +/- 10.8 and 50.5 +/- 10.6, respectively). In multivariate analysis, employment status, education level, household income, body mass index, comorbid medical conditions, years of hypertension, number of antihypertensive drugs prescribed, exercise status, and male sex were significant independent predictors of PCS. Fewer factors predicted MCS and included employment status, marital status, current smoking, age, comorbid medical conditions, and male sex. In the entire AASK cohort, mean scores for individual scales, except Mental Health, and the PCS were lower, but the mean MCS score was slightly higher than values for the US general population. Values for individual scales of the SF-36 and the PCS were substantially higher among AASK participants compared with African-American hemodialysis patients. Six of the eight scales were lower in the AASK cohort compared with groups of racially mixed and exclusively African-American hypertensive subjects. We conclude that physical aspects of quality of life are substantially reduced compared with mental components among AASK participants, and a number of demographic and clinical characteristics significantly impact on HRQL.",2002.0,0,1
355,11880137,Nifedipine versus terbutaline in management of preterm labor.,W Weerakul; A Chittacharoen; S Suthutvoravut,,2002.0,0,0
356,11885871,A randomised trial to compare the efficacy and safety of Felodipine (Plendil) and Nifedipine (Adalat) retard in patients with mild-to-moderate hypertension.,B J Onwubere; J O Obodo; D A Oke; B N Okeahialam; S S Danbauchi; A C Mbakwem,"The efficacy and tolerability of Felodipine extended-release was compared with Nifedipine retard in the management of patients with mild-to-moderate hypertension. A total of one hundred and thirty three patients were screened out of which one hundred and twenty-one patients were enrolled in a 9-week multicentre open, randomised rising-dose trial to receive either Felodipine 5-10 mg once daily or Nifedipine 10-20 mg twice daily. Blood pressure was measured at the end of the dosing interval that is 24 hours and 12 hours after Felodipine and Nifedipine respectively. Both drugs, Felodipine and Nifedipine were found to lower blood pressure significantly compared with baseline. After three weeks of treatment, seated blood pressure was reduced by 20/14 mmHg (systolic/diastolic) and by 24/16 mmHg after 6 weeks in the felodipine group. Corresponding values in the Nifedipine group were 16/09 mmHg and 24/13mmHg. Pulse rate was not significantly affected by either drugs. The percentage of patients who had satisfactory control after 3 weeks treatment was 57.6% for Felodipine and 33.3% for Nifedipine (significant). After dose titration (where necessary), at the end of the study the response rates were 76.3% (n=45) and 79.6% (n=43) for Felodipine and Nifedipine respectively (non significant). Both drugs were metabolically inert and did not derange the haematologic and biochemical profile of patients. They produced no significant weight changes. The pattern of side effects were similar in both groups but tended to be more severe with Nifedipine necessitating withdrawal of two patients in this group. In conclusion, Felodipine ER 5mg - 10mg once daily, and Nifedipine Retard, 20mg twice daily were equally effective medications for mild-to-moderate hypertension but Felodipine was better tolerated.",2002.0,0,0
357,11896502,Is there an epidemic of primary aldosteronism?,J M C Connell,,2002.0,0,0
358,11897766,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
359,11903250,Hair darkening in porphyria cutanea tarda.,F C G Shaffrali; A J G McDonagh; A G Messenger,"Repigmentation of grey hair is rare, but has been described in several clinical settings. It has most often been reported as a postinflammatory effect, but several drugs, chronic arsenic exposure and coeliac disease have also been cited in addition to darkening as a spontaneous phenomenon. We report two patients with sustained repigmentation of the hair in association with porphyria cutanea tarda. The mechanism for this repigmentation remains elusive, but presumably involves recruitment of outer root sheath melanocytes, which are then activated to form functional hair bulb melanocytes.",2002.0,0,0
360,11910315,"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
361,11916357,Prior calcium channel blockade and short-term survival following acute myocardial infarction.,R W Parsons; J Hung; I Hanemaaijer; R Jbroadhurst; K Jamrozik; M S Hobbs,"There is concern over the safety of calcium channel blockers (CCBs) in acute coronary disease. We sought to determine if patients taking calcium channel blockers (CCBs) at the time of admission with acute myocardial infarction (AMI) had a higher case-fatality compared with those taking beta-blockers or neither medication. Clinical and drug treatment variables at the time of hospital admission predictive of survival at 28 days were examined in a community-based registry of patients aged under 65 years admitted to hospital for suspected AMI in Perth, Australia, between 1984 and 1993. Among 7766 patients, 1291 (16.6%) were taking a CCB and 1259 (16.2%) a betablocker alone at hospital admission. Patients taking CCBs had a worse clinical profile than those taking a beta-blocker alone or neither drug (control group), and a higher unadjusted 28-day mortality (17.6% versus 9.3% and 11.1% respectively, both P < 0.001). There was no significant heterogeneity with respect to mortality between nifedipine, diltiazem, or verapamil when used alone, or with a beta-blocker. After adjustment for factors predictive of death at 28 days, patients taking a CCB were found not to have an excess chance of death compared with the control group (odds ratio [OR] 1.06, 95% confidence interval [CI]; 0.87, 1.30), whereas those taking a beta-blocker alone had a lower odds of death (OR 0.75, 95% CI; 0.59, 0.94). These results indicate that established calcium channel blockade is not associated with an excess risk of death following AMI once other differences between patients are taken into account, but neither does it have the survival advantage seen with prior beta-blocker therapy.",2002.0,0,1
362,11923801,Antiarrhythmic effects of azimilide in paroxysmal supraventricular tachycardia: efficacy and dose-response.,Richard L Page; Stuart J Connolly; William E Wilkinson; Stephen R Marcello; Daniel J Schnell; Edward L C Pritchett; Azimilide Supraventricular Arrhythmia Program (ASAP) Investigators,"Azimilide is a novel classification III antiarrhythmic agent that blocks both I(Kr)and I(Ks)and shows evidence of efficacy in patients with atrial fibrillation or flutter. Its effect on paroxysmal supraventricular tachycardia (PSVT) has not been reported. One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter. Patients received oral azimilide (100 mg in SVA-1 and SVA-3, 35 or 75 mg in SVA-2, and 125 mg in SVA-4) or matching placebo twice daily for 3 days (loading period), followed by once-daily dosing (maintenance period). The primary outcome variable was the first recording of a symptomatic supraventricular arrhythmia (either PSVT, atrial fibrillation, or atrial flutter) recorded on a transtelephonic electrocardiographic event recorder. The duration of study was 270 days in SVA-1 and SVA-2 and 180 days in SVA-3 and SVA-4. Combined analysis results of the PSVT stratum from the 4 studies showed a dose-response relationship in prolongation of time to recurrence (P =.02). In the combined 100-mg daily dose, the hazard ratio (placebo:azimilide) was 2.35 (P =.023). The hazard ratio for the 125-mg daily dose measured 1.28 (P = not significant). However, the time to recurrence was prolonged when the patients receiving 100 and 125 mg daily were combined and compared with placebo (P =.02). There were no deaths and 1 case of torsades de pointes. These trial results suggest a significant dose-related suppression of PSVT with azimilide, with a low risk of serious adverse events.",2002.0,0,0
363,11926699,Dipyridamole may be used safely in patients with ischaemic heart disease.,D M Humphreys; J Street; H Schumacher; J M Bertrand-Hardy; R Palluk,"It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease. The published literature, periodic safety update reports, the randomised controlled trials of antiplatelet agents in stroke prevention and those including dipyridamole in cardiovascular indications, have been reviewed and analysed. The early reports of serious adverse cardiac effect attributable to dipyridamole occurred in patients with severe coronary artery disease using dipyridamole as a stress test adjunct to cardiac imaging. The randomised controlled trials databases show no evidence of mortality and only isolated cases of significant cardiac morbidity attributable to dipyridamole at recommended oral doses in patients with ischaemic heart disease. We conclude that patients with cerebrovascular and mild to moderate concomitant ischaemic heart disease may be treated safely with dipyridamole for the secondary prevention of stroke.",2002.0,0,0
364,11936280,Faecal incontinence: common and treatable.,Michael A Kamm,,2002.0,0,0
365,11942883,Nifedipine or hydralazine as a first-line agent to control hypertension in severe preeclampsia.,Bibi Shahnaz Aali; Samira Shahabi Nejad,"Pre-eclampsia is one of the most serious and common complications of pregnancy. Nifedipine, a calcium channel blocker, and the vasodilator hydralazine have both been used as antihypertensive agents in this condition. The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre-eclampsia. One hundred and twenty-six pre-eclamptic patients with a gestational age of more than 20 weeks were randomized to receive either 8 mg nifedipine sublingually or 5-10 mg intravenous hydralazine. Women with a history of heart failure and women receiving antihypertensive treatment during the course of the current pregnancy were excluded. For each patient the following data were recorded; the number of drug administrations, the time needed to control blood pressure, mean urinary output, the time interval between effective control and a new hypertensive crisis after each drug administration and relevant adverse effects in mother or fetus. Effective control of blood pressure was achieved in both treatment arms. Data analysis indicated significantly fewer drug administrations in the nifedipine arm of the study. The time interval before a new hypertensive crisis following initial effective control of blood pressure was significantly longer in the nifedipine group when compared with hydralazine. Effective control of blood pressure was achieved more rapidly in multiparous patients receiving nifedipine (p=0.026). Mean urinary output before and after delivery was greater in the nifedipine arm of the study. There were no significant differences between the two groups in other variables. In addition, in neither group were there any serious adverse effects in mother or fetus. Nifedipine is safe and more effective than hydralazine in controlling blood pressure in severe pre-eclampsia. It has the added advantage of being cheaper and more widely available than the latter and is easily administered.",2002.0,0,0
366,11952579,Randomized clinical trial assessing the side-effects of glyceryl trinitrate and diltiazem hydrochloride in the treatment of chronic anal fissure.,H M Kocher; M Steward; A J M Leather; P T Cullen,"Glyceryl trinitrate (GTN) ointment (0 small middle dot2 per cent) has an efficacy of up to 68 per cent in healing chronic anal fissure, but with headache as a major side-effect. Diltiazem hydrochloride (DTZ) cream (2 per cent) is expected to have fewer side-effects. A prospective double-blind randomized two-centre trial requiring at least 26 patients in each group (alpha = 0.05, beta = 0.9) was instituted after approval of the local ethics committee, to compare the incidence of side-effects (primary endpoint) with 0.2 per cent GTN ointment and 2 per cent DTZ cream in the treatment of chronic anal fissure. Treatments were applied perianally, twice daily for 6-8 weeks. All patients gave written informed consent. Both groups were comparable in patient demographics and clinical characteristics. Twelve patients violated the protocol, withdrew or did not attend follow-up. There were more side-effects with GTN (21 of 29 patients) than with DTZ (13 of 31) (relative risk (RR) 1.84 (95 per cent confidence interval (c.i.) 1.11 to 3.04), P = 0.01). In particular, more headaches occurred with GTN (17 of 29 patients) than with DTZ (eight of 31) (RR 2.06 (95 per cent c.i. 1.18 to 3.59), P = 0.01). There were no significant differences in healing and symptomatic improvement rates between patients receiving GTN (25 of 29) and DTZ (24 of 31). DTZ cream caused substantially fewer headaches than GTN ointment. There was no significant difference in the healing or improvement of chronic anal fissure between the treatments. DTZ may be the preferred first-line treatment for chronic anal fissure.",2002.0,0,0
367,11959131,Effect of calcium channel antagonist diltiazem and calcium ionophore A23187 on cyclosporine A-induced apoptosis of renal tubular cells.,Chi-Hung Cheng; Chin-Ling Hsieh; Kuo-Hsiung Shu; Yen-Ling Chen; Hong-Chen Chen,"Calcium channel antagonists have been reported to have a favorable impact on cyclosporin A (CsA)-treated kidney transplant recipients. However, it is not clear whether this is because of their direct effect on antagonizing the toxicity of CsA to renal tubular cells. In this study, we have used Madin-Darby canine kidney tubular cells as a model to examine the effect of diltiazem, a calcium channel antagonist, on CsA-induced apoptosis. Moreover, to investigate the possible regulation of CsA cytotoxicity by intracellular calcium level, the effect of the calcium ionophore A23187 on CsA-induced apoptosis was also examined. We found that treatment of CsA (20 microM) alone caused 20-30% cell death, which was apparently (30-40%) enhanced by diltiazem at 100 microg/ml, accompanied by more severe DNA fragmentation, activation of caspases, and a decreased level of Bcl-2. The caspase inhibitor ZVAD-fmk or Bcl-2 overexpression was capable of suppressing apoptosis induced by the synergistic effect of diltiazem and CsA. Moreover, the survival rate of cells treated with CsA (30 microM) alone remained only 30%, however, it was markedly (approximately 40%) elevated by co-treatment with A23187 (75 ng/ml). The rescue of cells from CsA-induced apoptosis by A23187 was correlated with AKT activation, BAD phosphorylation, and caspase-3 inactivation. Taken together, our results suggest that the reported favorable impact of diltiazem on kidney grafts is likely not because of its direct protection on renal tubular cells. Instead, it enhances the toxicity of CsA to renal tubular cells. In addition, our findings raise a possibility that the intracellular calcium level and the AKT pathway may participate in the regulation of CsA cytotoxicity.",2002.0,0,0
368,11963384,[Comparison of nicardipine and isradipine in hypertension following coronary artery bypass graft].,S Madi-Jebara; D Khater-Rassi; A Yazigi; F Haddad; G Hayek; R Achkouty; M C Antakly,"Compare the efficacy of isradipine to that of nicardipine for the control of arterial hypertension following coronary artery bypass graft (CABG). Clinical prospective, randomised study. 40 patients ASA II or III, mean age 66 +/- 8 years, scheduled for elective CABG were included. If the mean arterial pressure (MAP) was > or = 100 mmHg within the first six post operative hours, the patients were included and randomly attributed to either one of the 2 groups: Gr I (n = 20) received nicardipine, Gr II (n = 20) received isradipine in bolus then in continuous perfusion. HR, MAP, MPAP, CVP, PCWP, CI, SVRI, PVRI and SVI were recorded at: T0 before administration of drugs, T1 = 2 min after the first bolus. T2 when MAP reached 85 +/- 5 mmHg. T3, T4, T5, T6, T7 and T8 at 5, 10, 30, 60, 90 and 120 min after the continuous perfusion. T9 before stopping the perfusion. No significant changes in HR, CVP, PCWP, MPAP or PVRI at any time in both groups. Significant increase in CI at T2 in both groups. Reduction of MAP at T2 was more important (-27%) in Gr I compared to that in Gr II (-22%). This was mainly due to a significant decrease in SVRI. Isradipine is effective in the treatment of arterial hypertension following CABG. However there is not any significant beneficial effect of isradipine over nicardipine.",2002.0,0,0
369,11967245,Effects of chronic calcium channel blockade on sympathetic nerve activity in hypertension.,Christian Binggeli; Roberto Corti; Isabella Sudano; Thomas F Luscher; Georg Noll,"The sympathetic nervous system (SNS) is an important regulator of the circulation. Its activity is increased in hypertension and heart failure and adversely affects prognosis. Although certain drugs inhibit SNS, dihydropyridine calcium antagonists may stimulate the system. Phenylalkylamine calcium antagonists such as verapamil have a different pharmacological profile. We therefore tested the hypothesis of whether amlodipine, nifedipine, or verapamil differs in the effects on muscle sympathetic nerve activity (MSA). Forty-three patients (31 men, 12 women) with mild to moderate hypertension were randomly assigned to 1 drug for 8 weeks. Blood pressure, heart rate, and MSA (by microneurography) were measured at baseline and after 8 weeks of treatment. All calcium antagonists led to a similar decrease in blood pressure of 5.0+/-1.5 to 6.4+/-1.4 mm Hg at 8 weeks (P<0.001 versus baseline). There were no significant differences in MSA between groups. With amlodipine, MSA averaged 49+/-3 bursts/min (3 versus baseline); with nifedipine, 48+/-3 bursts/min (2 versus baseline); and with verapamil, 49+/-2 bursts/min (all, P=NS). With verapamil, norepinephrine decreased by 4% but tended to increase by about one third with amlodipine or nifedipine (P=NS). Thus, in hypertension slow release forms of verapamil, nifedipine, and amlodipine exert comparable antihypertensive effects and do not change MSA, although there was a trend toward decreased MSA and plasma norepinephrine with verapamil.",2002.0,0,0
370,11973410,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
371,11975840,Atrial fibrillation.,Wilbert S Aronow,"The prevalence and incidence of atrial fibrillation increase with age. Atrial fibrillation is associated with a higher incidence of coronary events, stroke, and mortality than sinus rhythm. A fast ventricular rate associated with atrial fibrillation may cause tachycardia-related cardiomyopathy. Management of atrial fibrillation includes treatment of underlying causes and precipitating factors. Immediate direct-current cardioversion should be performed in persons with atrial fibrillation associated with acute myocardial infarction, chest pain due to myocardial ischemia, hypotension, severe heart failure, or syncope. Intravenous beta-blockers, verapamil, or diltiazem may be used to immediately slow a fast ventricular rate associated with atrial fibrillation. An oral beta-blocker, verapamil, or diltiazem should be given to persons with atrial fibrillation if a rapid ventricular rate occurs a rest or during exercise despite digoxin. Amiodarone may be used in selected persons with symptomatic life-threatening atrial fibrillation refractory to other drug therapy. Nondrug therapies should be performed in persons with symptomatic atrial fibrillation in whom a rapid ventricular rate cannot be slowed by drug therapy. Paroxysmal atrial fibrillation associated with the tachycardia-bradycardia syndrome should be managed with a permanent pacemaker in combination with drugs. A permanent pacemaker should be implanted in persons with atrial fibrillation in whom symptoms such as dizziness or syncope associated with non-drug-induced ventricular pauses longer than 3 seconds develop. Elective direct-current cardioversion has a higher success rate and a lower incidence of cardiac adverse effects than medical cardioversion in converting atrial fibrillation to sinus rhythm. Unless transesophageal echocardiography shows no thrombus in the left atrial appendage before cardioversion, oral warfarin should be given for 3 weeks before elective direct-current or drug cardioversion of atrial fibrillation and continued for at least 4 weeks after maintenance of sinus rhythm. Many cardiologists prefer the treatment strategy of ventricular rate control plus warfarin rather than to maintain sinus rhythm with antiarrhythmic drugs, especially in older patients. Digoxin should not be used in persons with paroxysmal atrial fibrillation. Patients with chronic or paroxysmal atrial fibrillation who are at high risk for stroke should be treated with long-term warfarin to achieve an International Normalized Ratio (INR) of 2.0 to 3.0. Persons with atrial fibrillation who are at low risk for stroke or who have contraindications to warfarin should receive 325 mg aspirin daily.",2002.0,0,0
372,11984011,Arrhythmias and sudden death in hypertrophic cardiomyopathy.,William J McKenna; Sami Firoozi; Sanjay Sharma,,2002.0,0,0
373,11996640,Class benefits of AT(1) antagonists in Type 2 diabetes with nephropathy.,Sheila A Doggrell,"Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT(1)) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was approximately 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT(1) antagonists. These clinical trials suggest that there may be a class renoprotective action with AT(1) antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT(1) antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.",2002.0,0,0
374,11998554,Adverse drug reactions as a cause for admissions to a department of internal medicine.,Tom Mjörndal; Marit Danell Boman; Staffan Hägg; Martin Bäckström; Bengt-Erik Wiholm; Anders Wahlin; Rune Dahlqvist,"To assess the occurrence and pattern of adverse drug reactions as a cause for acute hospital admission. In 681 randomly selected patients, acutely admitted to a clinic of internal medicine at a Swedish university hospital, information was collected from their medical records about current symptoms and use of drugs, previous diseases and the results of medical investigations and tests. In addition, a standardized interview according to a questionnaire was carried out. A group of experts in clinical pharmacology assessed the data obtained from the patients' case records and the results of the interviews, and then, according to WHO criteria, judged the probability that an adverse drug reaction could have caused or contributed to the actual admission to hospital. Out of the 681 cases included, 94 (13.8%) had symptoms and signs that were judged as drug-related and that had caused or contributed to the admission. Eighty-two patients (12.0%) had altogether 99 symptoms that were classified as adverse drug reactions. Of these, 91% were type A reactions. The relationship between the medication and the reaction was judged certain in eight, probable in 17, and possible in 74 cases. The most common adverse drug reactions were cardiovascular (36.3%). Twelve patients (1.8%) had symptoms indicating intoxications. The prevalence of drug-related problems causing or contributing to admission to a clinic of internal medicine is high and is dominated by type A reactions, i.e. reactions in principle predictable and preventable. This implies a possibility to increase drug safety by preventive measures.",2002.0,0,0
375,12003698,Effect of ramipril versus amlodipine on renal outcomes in hypertensive nephrosclerosis.,John M Flack,,2002.0,0,0
376,12010934,Meta-analysis of randomised controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation.,G Nichol; F McAlister; B Pham; A Laupacis; B Shea; M Green; A Tang; G Wells,"To conduct a meta-analysis of randomised controlled trials to estimate the effectiveness of antiarrhythmic drugs at promoting sinus rhythm in patients with atrial fibrillation. Articles were identified by using a comprehensive search of English language papers indexed in Medline from 1966 to August 2001. For the outcomes of sinus rhythm and death, a random effects model was used to model repeated assessments within a study at different time points. Emergency departments and ambulatory clinics. Patients with atrial fibrillation. Antiarrhythmic agents grouped according to their Vaughan-Williams class. Sinus rhythm and mortality. 91 articles met a priori criteria for inclusion in the analysis. Median duration of follow up was one day (range 0.04-1096, mean (SD) 46 (136) days). The median proportion of patients in sinus rhythm at follow up was 55% (range 0-100%) and 32% (range 0-90%) receiving active treatment and placebo, respectively. Median survival was 99% (range 55-100%) and 99% (range 55-100%). Compared with placebo, the following drug classes were associated with increased sinus rhythm at follow up: IA (treatment difference 21.5%, 95% confidence interval (CI) 16.3% to 26.8%); IC (treatment difference 33.1%, 95% CI 23.3% to 42.9%); and III (treatment difference 17.4%, 95% CI 11.5% to 23.3%). Class IC drugs were associated with increased sinus rhythm at follow up compared with class IV drugs (treatment difference 43.2%, 95% CI 11.5% to 75.0%). There was no significant difference in mortality between any drug classes. Class IA, IC, and III drugs are associated with increased sinus rhythm at follow up compared with placebo. It is unclear whether any antiarrhythmic drug class is associated with increased or decreased mortality.",2002.0,0,1
377,12013485,How safe are calcium antagonists in hypertension and coronary heart disease?,G Mancia; P A van Zwieten,,2002.0,0,0
378,12014417,"Topical lidocaine does not limit autonomic dysreflexia during anorectal procedures in spinal cord injury: a prospective, double-blind study.",Bard C Cosman; Tri T Vu; Brian K Plowman,"Autonomic dysreflexia is a common and potentially dangerous response in patients with spinal cord injury at T6 or above. Acute blood pressure elevation may be precipitated by rectosigmoid distention and anal manipulation. Topical anesthetics are widely recommended to minimize the incidence and severity of autonomic dysreflexia, although no scientific evidence supports or refutes this practice. This study tested whether topical lidocaine would prevent or limit anorectal procedure-associated autonomic dysreflexia. We enrolled patients with chronic, complete spinal cord injury scheduled for anoscopy and/or flexible sigmoidoscopy. In a double-blind fashion they were randomized to receive either 2% lidocaine jelly (n = 18) or nonmedicated lubricant (control; n = 32) just prior to the procedure. We measured blood pressure before, during, and after procedures. Mean maximal systolic blood pressure increased 35 +/- 25 mmHg in the lidocaine group vs. 45 +/- 30 mmHg in the control group (NS). However, there was a significant difference between anoscopic procedures and flexible sigmoidoscopies without anoscopy (49 +/- 29 vs. 25 +/- 20 mmHg). Topical lidocaine did not significantly limit or prevent autonomic dysreflexia in susceptible patients. Both anoscopy and flexible sigmoidoscopy caused significant blood pressure elevation. Anoscopy, which involves stretching of the anal sphincters, was a more potent stimulus for autonomic dysreflexia than flexible sigmoidoscopy, which involves gaseous distention of the rectosigmoid. Anal sphincter stretch and rectosigmoid distention, rather than a mucosal stimulus, are likely nociceptive triggers for procedure-associated autonomic dysreflexia.",2002.0,0,0
379,12021583,Effects of intravenous amlodipine on coronary hemodynamics in subjects with angiographically normal coronary arteries.,Danilo Neglia; Michela Gallopin; Paolo Marraccini; Ignazio Simonetti; Mauro Micalizzi; Alberto Macerata; Mario Marzilli; Antonio L'Abbate,"The aim of the current study was to assess the ability of amlodipine to dilate the coronary vessels in subjects with angiographically normal coronary arteries and normal left ventricular function. Ten patients, six women and four men (mean age 48 +/- 14 years, range 25-67 years) were enrolled. Coronary flow velocity and coronary perfusion pressure were invasively measured at baseline, during intracoronary adenosine (1-mg bolus) and at 5, 15, and 30 min following IV amlodipine (10 or 20 mg). Quantitative coronary angiography was performed at baseline and at 5, 15, and 30 min after amlodipine. Coronary cross-sectional area and mean coronary flow velocity progressively increased after amlodipine administration, resulting in an average increase in coronary flow at 30 min of 76%. On an individual basis, all patients but one showed a consistent trend toward a progressive coronary vasodilator effect of amlodipine over time. The peak effect of amlodipine on baseline mean coronary flow velocity was 43 +/- 12% that of adenosine. This is the first clinical study demonstrating that the IV administration of amlodipine produces a powerful coronary vasodilatation in subjects with angiographically normal coronary arteries and normal ventricular function, besides its known systemic vasodilating effects. The coronary vasodilating properties of amlodipine are particularly expressed at the microcirculatory level.",2002.0,0,0
380,12023676,Subgroup analysis of the NORDIL trial.,Lutgarde Thijs; Jan A Staessen; Jiguang Wang; Robert Fagard,,2002.0,0,1
381,12023696,"Influence of age, sex and blood pressure on the principal endpoints of the Nordic Diltiazem (NORDIL) Study.",Sverre E Kjeldsen; Thomas Hedner; Jan Otto Syvertsen; Per Lund-Johansen; Lennart Hansson; Jan Lanke; Lars H Lindholm; Ulf De Faire; Björn Dahlöf; Bengt E Karlberg; NORDIL Study Group,"The aim of the Nordic Diltiazem (NORDIL) Study was to compare patients with essential hypertension receiving calcium-antagonist-based treatment with diltiazem and similar patients receiving conventional diuretic/beta-blocker-based treatment, with respect to cardiovascular morbidity and mortality. To assess the influence of age, sex, severity of hypertension and heart rate on treatment effects, in a sub-analysis. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled, at health centres in Norway and Sweden, 10 881 patients aged 50-74 years who had diastolic blood pressure (DBP) of 100 mmHg or more. Systolic blood pressure (SBP) and DBP were decreased by 20.3/18.7 mmHg in the diltiazem group and by 23.3/18.7 mmHg in the diuretic/beta-blocker group - a significant difference in SBP (P < 0.001). The incidence of the primary endpoint - a composite of cardiovascular death, cerebral stroke and myocardial infarction - was similar for the two treatments. Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 patients in the conventional treatment group [relative risk (RR) 0.80, 95% confidence interval (CI) 0.65 to 0.99; P = 0.040], whereas there was a non-significant inverse tendency with respect to all myocardial infarction. There were significantly fewer cerebral strokes in patients receiving diltiazem in the subgroups with baseline SBP > 170 mmHg (n = 5420, RR 0.75, 95% CI 0.58 to 0.98; P = 0.032), DBP >/= 105 mmHg (n = 5881, RR 0.74, 95% CI 0.57 to 0.97; P = 0.030) and pulse pressure >/= 66 mmHg (n = 5461, RR 0.76, 95% CI 0.58 to 0.99, P = 0.041), and more myocardial infarctions in those with heart rate less than 74 beats/min (n = 5303, RR 1.13, 95% CI 1.01 to 1.87; P = 0.040). However, the tendencies for fewer strokes and greater incidence of myocardial infarction were present across subgroups when results were analysed for age, sex, severity of hypertension and heart rate, and treatment-subgroup interaction analyses were not statistically significant. Compared with a conventional diuretic/beta-blocker-based antihypertensive regimen, there were additional 25% reductions in stroke in the diltiazem-treated patients with blood pressure or pulse pressure greater than the medians, and an increase in myocardial infarction in those with heart rate less than the median. Such findings may be attributable to chance, but the consistency of, in particular, the stroke findings may also suggest an ability of diltiazem, beyond conventional treatment, to prevent cerebral stroke in hypertensive patients with the greatest cardiovascular risk.",2002.0,1,1
382,12035874,The effects of calcium channel blockers on cardiovascular outcomes: a review of randomised controlled trials.,Peter W De Leeuw; Willem H Birkenhäger,"The choice of antihypertensive treatment should be guided by evidence of a reduction in the risk of cardiovascular (CV) events and therefore improved long-term outcome. Using pre-determined criteria, ten randomised, controlled trials that assessed the effects of calcium channel blockers (CCBs) on CV events in patients with hypertension were identified. Six of them enrolled a relatively small number (< 1500) of hypertensive patients, whereas four of the studies were much larger (> 4500 patients). The smaller studies produced mixed findings, especially those trials where CCBs were compared with diuretics; this may reflect methodological limitations and the impact of random error. The results from the four larger studies produced a consistent message: long-acting CCBs such as nifedipine, administered in a gastro-intestinal-transport-system (GITS) formulation, nitrendipine and diltiazem, reduce CV morbidity and mortality in hypertensive patients. In the one study that specifically enrolled high-risk hypertensive patients, nifedipine GITS was as effective as diuretic therapy in reducing CV events, and in all four larger studies sub-group analyses showed that the benefits of these CCBs extend to hypertensive patients with diabetes. The available evidence supports the use of these long-acting CCBs as a first-line treatment option in hypertensive patients.",2002.0,1,0
383,12051123,Adverse drug events in hospitalized patients treated with cardiovascular drugs and anticoagulants.,R Zaidenstein; S Eyal; S Efrati; L Akivison; M Koren Michowitz; V Nagornov; A Golik,"To evaluate the incidence of serious adverse drug events (ADEs) caused by cardiovascular drugs during hospitalization in a department of internal medicine, and to identify patients at highest risk. All the patients treated with cardiovascular drugs and/or anticoagulants in the department between November 1999 and January 2000 were recruited into the study. During hospitalization the patients' charts were reviewed by a pharmacist and a clinician, and the occurrence of serious ADEs was assessed using the Naranjo algorithm. 'Possible' and 'doubtful' ADEs were not counted. Of 496 patients who were enrolled in the study, 20 (4%) had serious ADEs. Compared to patients without ADEs, patients in the ADE group were older (72 +/- 12.6 years (mean +/- SD) vs. 65 +/- 13 years, p = 0.048), their average stay in hospital was longer (7.3 +/- 5.5 days vs. 5.2 +/- 3.7 days, p = 0.018) and their mean urea levels were higher (10.8 +/- 9.3 mmol/l vs. 7.8 +/- 5.3 mmol/l, p = 0.027). The most frequent background pathologies of the 20 patients with ADEs were hypertension (in 18 (90%)) and atrial fibrillation (in nine (45%)). In 50% of the the ADE group there was a history of drug allergies. The ADEs recorded were bleeding in four (20%), arrhythmias in six (30%), orthostatic hypotension in six (30%) and skin necrosis, paranoid reaction, acute hepatitis and acute renal failure in four (20%). The causative drugs were warfarin (which accounted for 25% of the ADEs), beta-blockers (15%), propafenone (5%), amiodarone (5%), and Ca(2+)-channel blockers, nitrates and diuretics (together accounting for 50% of ADEs). Drug combinations were implicated in 50% of ADE. Serious ADEs were developed by 4% of hospitalized patients taking cardiovascular drugs. Those at highest risk were older, were receiving multiple drug therapy and had higher urea levels. Warfarin and beta-blockers were the drugs causing the largest number of adverse effects. ADEs are an important cause of preventable morbidity, often with serious economic implications and special attention should be given to their prevention.",2002.0,0,0
384,12062738,Post hoc analysis of coronary findings from the prospective randomized evaluation of the vascular effects of the Norvasc trial (PREVENT).,G B John Mancini; Michael E Miller; Gregory W Evans; Robert Byington; Curt D Furberg; Bertram Pitt; PREVENT Study Group. Prospective randomized evaluation of the vascular effects of norvasc,,2002.0,1,1
385,12070557,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
386,12071084,[Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care].,J Faller; B Hess,"Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.",2002.0,0,0
387,12074357,"A comparison of candesartan, felodipine, and their combination in the treatment of elderly patients with systolic hypertension.",Trefor Morgan; Adrianne Anderson,"Monotherapy frequently does not cause adequate blood pressure (BP) reduction and goal BP is not achieved. This double-blind, randomized, crossover, placebo-controlled study investigated, using a factorial design, the interaction between a dihydropyridine calcium channel blocking drug (felodipine 5 mg) and an angiotensin type I receptor blocking drug (candesartan 16 mg) on the control of BP as assessed by 24-h ambulatory monitoring. A total of 31 elderly patients with systolic hypertension completed all four arms of the study. Candesartan and felodipine lowered mean 24-h BP to a similar extent (candesartan 12.2 +/- 2.6/7.5 +/- 1.8; felodipine 11.9 +/- 2.2/5.7 +/- 1.4 mm Hg). The combination lowered it by 21.0 +/- 2.1/11.2 +/- 1.2 mm Hg, and this fall was significantly greater than with either of the monotherapies (P < .005) and was fully additive with no interactive term. The responder rate with the combination (90%) was greater than with candesartan (61%) or felodipine (55%). Microalbuminuria or proteinuria was present in 12 of 31 patients at randomization despite previous BP control. Candesartan and the combination both reduced urinary albumin excretion. Albumin excretion was not reduced by felodipine despite BP control similar to that achieved with candesartan. Side effects were infrequent and were fewer on the combination than on placebo or on the monotherapies. The combination of felodipine 5 mg and candesartan 16 mg has additive effects on BP in elderly patients with systolic hypertension. The combination was well tolerated and is suitable for use in patients who do not have an adequate response to monotherapy.",2003.0,0,0
388,12074363,A comparative crossover evaluation of amlodipine and nifedipine GITS before and after a missed dose: 48-h blood pressure profiles.,Naomi Nussinovitch; Gilad Rosenberg; Edna Peleg; Talma Rosenthal,,2003.0,0,0
389,12082488,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
390,12085418,"[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
391,12087923,Prospective controlled trial of two nifedipine extended release formulations in the treatment of essential hypertension.,Nediljko Pivac; Mario Naranca; Dunja Vujic-Podlipec; Jugoslav Bagatin; Zvonko Rumboldt,"The aim of this study was to assess the pharmacodynamic equivalence of two different slow-release formulations of nifedipine (CAS-21829-25-4). In a prospective, controlled, double-blind clinical trial, 42 patients with essential hypertension (sitting diastolic blood pressure (DBP) 95-114 mmHg) underwent an initial washout, drug free period of 2 weeks, after which they were randomized to receive either 30 mg of nifedipine in the test preparation ""XL"" (Nifecard) or 30 mg of nifedipine in a reference formulation, ""LA"", during six weeks. The response to treatment was assessed by measuring the blood pressure (BP) every two weeks (standard office mercury sphygmomanometry) and by 24-h ambulatory blood pressure monitoring (ABPM). Of the 42 included patients 36 (85.5%) completed the trial: 19 on ""XL"" and 17 on ""LA"". After 2 weeks of therapy the DBP decreased by about 11% (-13.4 mmHg) and 10% (-9.5%), respectively, after 4 weeks the mean decrease versus the end of the placebo period reached about 14% (-15.5 mmHg) and 11% (-13 mmHg), and at the end of the trial the DBPs were lower by about 13% (-14.5 mmHg) in both groups. In all these measurements the within group differences were significant (p < 0.001), while the between groups differences were not (p > 0.05). Quite comparable results were obtained with ABPM, e.g. in the ""XL"" group the systolic blood pressure at the end of the study was lower by 12.3% (-4.6 mm Hg) and in the ""LA"" group, by 10.6% (-9.0 mm Hg); p = 0.358. The adverse effects were similar in both groups and they required neither particular interventions nor withdrawal from the study. The drugs under study were comparably effective and well tolerated antihypertensives.",2002.0,0,0
392,12089368,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.",2002.0,0,1
393,12094189,Randomized comparison of T-type versus L-type calcium-channel blockade on exercise duration in stable angina: results of the Posicor Reduction of Ischemia During Exercise (PRIDE) trial.,Douglas S Lee; Shaun Goodman; Deanne M Dean; Jacques Lenis; Patrick Ma; Pierre B Gervais; Anatoly Langer; PRIDE Investigators,"Mibefradil is a T-type calcium-channel antagonist and arterial vasodilator with negative chronotropic effects. It is not known if T-type calcium-channel blockade is superior to L-type calcium-channel blockade in patients with stable angina pectoris. A multicenter, randomized, double-blind trial was conducted in patients with documented coronary disease and stable angina to compare a 360 mg dose of diltiazem CD with 100 mg dose of mibefradil. The primary end point was change in time to symptom-limited exercise termination from baseline to 8 weeks. Secondary efficacy parameters included time to onset of persistent ST-segment depression, time to awareness of angina, and change in exercise duration from baseline to 2 and 4 weeks of treatment. A total of 121 patients were randomized to mibefradil and 113 to diltiazem CD. At 8 weeks, the increase in exercise duration was 24.5 seconds greater in the mibefradil group (P =.017; 95% CI 4.4-44.7 seconds). At 8 weeks, time to development of > or =1 mm ST-segment depression was greater by 45.3 seconds (P =.0025; 95% CI 16.2-74.5) with mibefradil, but time to development of angina was not significantly different. T-type calcium-channel antagonism with mibefradil improved treadmill exercise parameters compared with diltiazem in patients with chronic stable angina. Further investigation and development of antagonists of T-type calcium channels with fewer adverse drug interactions is warranted and may be promising in the management of ischemic heart disease.",2002.0,1,1
394,12105139,"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
395,12106857,Effect of verapamil on secondary cardioversion in patients with early atrial fibrillation recurrence after electrical cardioversion.,Antonio De Simone; Pietro Turco; Carmine De Matteis; Vincenzo La Rocca; Pasquale Nocerino; Luciano Greco; Costantino Astarita; Vincenzo Messina; Raffaele Rotunno; Gianfranco Iaconelli; Eugenio Stabile; Giuseppe Stabile,,2002.0,0,0
396,12108529,Preventing drug-related morbidity--determining valid indicators.,C J Morris; J A Cantrill; C D Hepler; P R Noyce,"To describe the process that is being undertaken to validate a series of indicators for preventable drug-related morbidity - originally developed in the US - for application in the UK health care system. A two-round Delphi questionnaire survey after a preliminary validation of the indicators within the University of Manchester School of Pharmacy. A primary care study set in the UK. A purposively selected sample of general practitioners with a specific responsibility for prescribing-related issues (n = 6) and pharmacists actively involved in medication review in primary care (n = 10). The establishment of consensus among the participants that an indicator reflected preventable drug-related morbidity in primary care. After preliminary validation, 37 of the original 57 US indicators were retained. The Delphi panel generated 16 additional new indicators in the first round. At the end of the second round, the pre-defined level of consensus was reached for 29 indicators (19 of the US generated indicators; 10 generated by the panel in the first round). The Delphi results highlighted differences in both the clinical perspective and, possibly, philosophical viewpoints of health professionals practising in the UK and US health care systems. Further work, located in both primary and secondary care, is now in progress to operationalize the indicators. This process will form a key part of the refining, and hence further validation, of the indicators. The future development of prospective medical-record-based indicators should facilitate a reduction in the human, clinical, and economic burden of drug-related morbidity.",2002.0,0,0
397,12122965,The effects of amlodipine on cerebral circulatory values in patients with essential hypertension.,I G Alizade; N T Karayeva,This study assessed the effects of calcium channel blocker Amlodipine on the cerebral circulation in patients with essential hypertension. Cerebral circulation in 37 patients with essential hypertension and 10 healthy subjects was assessed using rheoplethysmography. In patients with essential hypertension cerebral circulation values were also re-estimated after treatment with Amlodipine (5-10 mg daily). The cerebral circulatory parameters in hypertensive patients before treatment with Amlodipine were different from those in healthy persons. Amlodipine along with the reduction in systemic blood pressure caused attenuation of cerebrovascular abnormalities: decrease in spastic signs and increase in cerebral blood supply in patients with essential hypertension. Amlodipine causes reduction of cerebral vascular resistance and promotes improvement in arterial blood filling in patients with essential hypertension. These changes in cerebral circulation may be secondary to the increase of cardiac output--known effect of Amlodipine.,2002.0,0,0
398,12123409,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
399,12126259,Systolic hypertension as a cardiovascular risk factor.,G T McInnes,,2003.0,0,0
400,12126265,Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly.,A Mazza; B Gil-Extremera; A Maldonato; T Toutouzas; A C Pessina,"The antihypertensive efficacy of nebivolol and amlodipine and their tolerability were compared in a multicentre, randomized, active-controlled, double-blind parallel-group trial in elderly patients with mild to moderate essential arterial hypertension. One hundred and eighty-four subjects aged > or = 65 years were screened. After a run-in phase of 4 weeks, only 168 of these were randomized with either nebivolol 2.5-5 mg daily (n = 81) or amlodipine 5-10 mg daily (n = 87) over a period of 12 weeks. The response rate to treatment and the changes of sitting diastolic blood pressure (BP) at week 12 were similar between the two groups. A lower sitting systolic BP (SBP) was detected with amlodipine at week 4 (p < 0.05) and at week 8 (p < 0.05). Standing BP showed no changes between the two groups; only SBP was lower with amlodipine at week 8 (p < 0.05). Heart rate was lower at all treatment visits with nebivolol (p < 0.001). The incidence of adverse events was no different between the two groups; however the incidence of headache and ankle oedema was significantly higher with amlodipine (p < 0.05). In elderly subjects with essential hypertension, the antihypertensive efficacy of nebivolol and amlodipine was similar. Both drugs were well tolerated, although amlodipine was accompanied by higher incidence of drug-related adverse events.",2003.0,0,0
401,12131321,Experience with intraplaque injection of verapamil for Peyronie's disease.,Laurence A Levine; Karen E Goldman; Jason M Greenfield,"We examined the use of intraplaque injection of verapamil for the treatment of Peyronie's disease through its effects on pain, curvature, indentation, sexual function and erectile capacity. A total of 156 men underwent treatment with intraplaque verapamil injection. Patients were assessed objectively, during dynamic penile duplex ultrasound, as well as subjectively using a questionnaire before and after initiation of the treatment protocol. Patients were also stratified by duration of disease before therapy and into 1 of 3 Kelami classification groups based on pretreatment plaque size and severity of curvature. Differences before and after treatment and among the Kelami classification groups were assessed. Of the 140 patients who completed treatment 73 (60%) had an objectively measured decrease in curvature while 79 (62%) reported a subjective decrease in curvature during the followup interview. After treatment 111 (83%) men reported an increase in girth, 107 (80%) an increase in rigidity distal to the plaque and 92 (71%) an improvement in sexual function. Among each Kelami class curvature was objectively measured to decrease in 41%, 68% and 62% of patients in classes I, II and III, respectively. There was no significant difference in response based on duration of disease (60% improvement versus 61% improvement for disease duration of less or greater than 1 year in duration, respectively). Mean followup was 30.4 months (range 10 to 81) and there was no reported recurrence of penile deformity in those men with an initial posttreatment positive response. Verapamil injection of Peyronie's plaques appears to be a clinically effective treatment option for pain and curvature and can contribute to subjective improvement in sexual function and erectile capacity. The low incidence of complications indicates that this therapy is also clinically safe.",2002.0,0,0
402,12135176,Two cases of polymorphic ventricular tachycardia induced by the administration of verapamil against paroxysmal supraventricular tachycardia.,Hirokazu Shiraishi; Kazuya Ishibashi; Norifumi Urao; Masayuki Hyogo; Masaki Tsukamoto; Natsuya Keira; Satoshi Hirasaki; Yasumasa Seo; Takeshi Shirayama; Masao Nakagawa,"Verapamil is widely used for the termination of paroxysmal supraventricular tachycardia (PSVT) with little proarrhythmic effect. We describe two cases of PSVT that changed to non-sustained polymorphic ventricular tachycardia after administration of verapamil. Electrophysiological study revealed atrioventricular nodal reentrant tachycardia in the first case, and atrioventricular reentrant tachycardia due to a concealed left lateral accessory pathway in the second case. Catecholamine-induced automaticity was one of the possible mechanisms of VT in the first case, but the mechanism is unknown in the second case.",2003.0,0,1
403,12135309,Differential effects of a long-acting angiotensin converting enzyme inhibitor (temocapril) and a long-acting calcium antagonist (amlodipine) on ventricular ectopic beats in older hypertensive patients.,Kazuo Eguchi; Kazuomi Kario; Kazuyuki Shimada,"We studied differences in the effects of a long-acting angiotensin-converting enzyme (ACE) inhibitor (temocapril) and a long-acting calcium channel blocker (amlodipine) on ventricular ectopic beats (VEB) in relation to sympathetic nerve activity in 46 patients with essential hypertension. We performed 24-h Holter electrocardiography and ambulatory blood pressure (BP) monitoring simultaneously, and examined blood samples during the baseline, temocapril and amlodipine treatment periods. The ambulatory BP was lower in the amlodipine period than in the temocapril period. However, the number of VEB was significantly increased in the amlodipine period compared to that in the baseline period (11.9 vs. 7.4/day, p<0.05). In the temocapril period, the number of VEB was not significantly increased compared to that in the baseline period (8.6 vs. 7.4/day, p=0.30). Ambulatory heart rate (HR) was significantly increased in the amlodipine period compared to that in the baseline period (24-h HR: 70 vs. 66 bpm, p<0.001; daytime HR: 75 vs. 71 bpm, p<0.001; nocturnal HR: 60 vs. 58 bpm, p<0.05). Plasma norepinephrine (NE) also was significantly increased in the amlodipine period compared to that in the baseline period (457 vs. 369 pg/ml, p<0.001). However, when patients receiving amlodipine were divided into a high dose group (8.6 +/- 1.2 mg/day) and a low dose group (4.6 +/- 1.2 mg/day), increases in HR and plasma NE levels were found only in the high dose group. These results indicate that amlodipine is effective at lowering BP in older hypertensives, although it may increase VEB, especially when given at a high dose.",2003.0,0,0
404,12136375,Admissions caused by adverse drug events to internal medicine and emergency departments in hospitals: a longitudinal population-based study.,Sebastian Schneeweiss; Joerg Hasford; Martin Göttler; Annemarie Hoffmann; Ann-Kathrin Riethling; Jerry Avorn,"To estimate incidence rates of drug-related hospitalizations (DRHs) in a longitudinal population-based study with prospective event assessment. Cohort study and time-trend analysis. All departments of internal medicine and emergency departments in the urban regions of Jena and Rostock, Germany, serving about 520,000 residents. All patients admitted between October 1997 and March 2000. Patients with severe cutaneous reactions were excluded. Incidence of DRH was defined by symptoms or diagnoses at admission that were very likely, likely, or possibly caused by prescription medications, according to a standardized assessment. The incidence of DRH was 9.4 admissions per 10,000 treated patients [95% confidence interval (CI) 9.0-9.9]. Rates were highest for antithrombotics with 26.9 admissions per 10,000 treated patients (95% CI 23.6, 30.1). Most frequent events were gastroduodenal lesions and bleeding (45%). Digitalis preparations showed a linearly increasing trend from 2/10,000 to 14/10,000 during ten quarters ( P<0.0001), which was exclusively attributable to digitoxin, the major source of digitalis in the study area (93%). The incidence of DRH increased with age (4/10,000 to 20/10,000). The mean length of stays in patients with DRH was 13+/-10.6 days. Cumulative direct costs for hospitalization were Euro 4 million in the two urban study areas. The annual direct costs for Germany were estimated to be Euro 400 million. DRHs are a considerable public health and economic burden. A longitudinal design can observe changes in population-based incidence over time. This approach can be used for public-health planning or to evaluate outcomes of quality management programs designed to reduce drug-induced illness.",2003.0,0,0
405,12147932,Should beta blockers be used in the treatment of hypertension in the elderly?,L Michael Prisant,"The lack of benefit and the potential negative side effects of beta blockers are overstated, especially in the elderly. This emphasis has led to recommendations by some investigators that these agents not be used in the management of hypertension in this age group. There are numerous reasons why these recommendations should not be followed. The use of beta blockers in the elderly hypertensive has resulted in a reduction in strokes and congestive heart failure. In addition, it should be emphasized that elderly patients are more likely to have silent coronary artery disease or sustain myocardial infarctions. There is abundant evidence that beta blockers are effective therapy in reducing mortality once a myocardial infarction has occurred. In fact, there is a clear reduction in sudden cardiac death. Furthermore, national statistics document that elderly patients have a prevalence of congestive heart failure that varies from 6%-10%. Multiple studies have now documented that beta blockers are additive to angiotensin-converting enzyme inhibitors in reducing mortality for congestive heart failure. Thus, elderly hypertensive patients may benefit from the use of beta blockers, especially if there is evidence of ischemic heart disease, cardiac arrhythmias, or congestive heart failure.",2002.0,0,0
406,12147940,Calcium channel blocker induced gingival overgrowth.,L Michael Prisant; Wayne Herman,"Gingival overgrowth occurs with phenytoin, cyclosporin, and calcium antagonists. It can be disfiguring and painful. The prevalence of gingival overgrowth with the use of calcium antagonists may be as high as 38%. The prevalence with nifedipine may be greater than with other calcium blockers. Overgrowth occurs 3.3-times more commonly in men than in women. Plaque control is necessary. Some patients may require gingival surgery.",2002.0,0,0
407,12163426,Microalbuminuria reduction with valsartan in patients with type 2 diabetes mellitus: a blood pressure-independent effect.,Giancarlo Viberti; Nigel M Wheeldon; MicroAlbuminuria Reduction With VALsartan (MARVAL) Study Investigators,"Elevated urine albumin excretion (UAER) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes. Blockade of the renin-angiotensin system lowers UAER, but whether this effect is independent of blood pressure (BP) reduction remains controversial. The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria. Three hundred thirty-two patients with type 2 diabetes and microalbuminuria, with or without hypertension, were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks. A target BP of 135/85 mm Hg was aimed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed. The primary end point was the percent change in UAER from baseline to 24 weeks. The UAER at 24 weeks was 56% (95% CI, 49.6 to 63.0) of baseline with valsartan and 92% (95% CI, 81.7 to 103.7) of baseline with amlodipine, a highly significant between-group effect (P<0.001). Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups. More patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%; P=0.001). Over the study period, BP reductions were similar between the two treatments (systolic/diastolic 11.2/6.6 mm Hg for valsartan, 11.6/6.5 mm Hg for amlodipine) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup. For the same level of attained BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria, including the subgroup with baseline normotension. This indicates a BP-independent antiproteinuric effect of valsartan.",2002.0,0,1
408,12164090,Improvement of endothelial function by amlodipine and vitamin C in essential hypertension.,Young Keun On; Cheol Ho Kim; Dae Won Sohn; Byung Hee Oh; Myoung Mook Lee; Young Bae Park; Yun Shik Choi,"The effects of antihypertensive agents on endothelial function have not been fully evaluated in human hypertension and data on the forearm circulation of humans are controversial. The aim of this study was (1) to evaluate the endothelial function in hypertensive patients (2) to investigate whether vitamin C administration has any benefit on the endothelial function and (3) to determine whether treatment with calcium antagonist improves endothelial dysfunction in hypertensive patients. The endothelial function was estimated using venous occlusion plethysmography (VOP) in 8 hypertensive patients and 8 healthy volunteers. The patients in the hypertension group were treated with amlodipine, then examined again. The change of forearm blood flow (FBF) was measured with acetylcholine infusion through brachial artery and also with intra-arterial vitamin C. Forearm blood flow response to acetylcholine was significantly enhanced with intra-arterial infusion of vitamin C in hypertensive group before antihypertensive treatment. Co-infusion of L-NMMA, an inhibitor of nitric oxide synthase, blunted forearm blood flow response to acetylcholine. After treatment with amlodipine for 2 months in hypertensive group, endothelium-dependent vasorelaxation to acetylcholine was significantly improved compared to pretreatment, and vitamin C did not affect the improved endothelial function by amlodipine treatment. Vitamin C (acutely) and amlodipine (chronically) improved endothelial function in hypertensive patients. These results suggest that increased oxidative stress, at least in part, may be involved in the decreased endothelial function in hypertension.",2002.0,0,0
409,12166353,Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients.,C S Liau; K L Chien; C L Chao; T M Lee,"The efficacy and safety profiles of barnidipine in the treatment of hypertension were evaluated in an open parallel-group study. Fifty-nine Chinese patients with mild-to-moderate essential hypertension were randomized to receive either barnidipine or felodipine (5 mg once daily, titrated to 10 mg or 15 mg once daily, as indicated) for 12 weeks. Both drugs reduced blood pressures significantly with > or = 68% of cases obtaining marked or moderate blood pressure reduction. Mean reductions in systolic and diastolic blood pressure for barnidipine treatment were 23.7 +/- 13.5 mmHg and 12.7 +/- 7.9 mmHg, and for felodipine, 24.3 +/- 18.4 mmHg and 14.5 +/- 10.0 mmHg, respectively. There was no significant difference between these two drugs in anti-hypertensive effect, heart rate, laboratory measurements or incidence of adverse events. The only difference was that more patients taking felodipine experienced palpitations. We conclude that barnidipine has similar efficacy and a similar safety profile to felodipine in the treatment of mild-to-moderate essential hypertension in Chinese patients.",2003.0,0,0
410,12166354,,,,,0,0
411,12172327,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
412,12182690,Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring.,Roberto Antonicelli; Stefano Omboni; Di Ciò Giovanni; Roberto Ansuini; Alfredo Mori; Rosaria Gesuita; Gianfranco Parati; Enrico Paciaroni,"To assess, by smoothness index (SI), distribution of the antihypertensive effect of extended-release (ER) felodipine over 24 hours in elderly patients with hypertension. After a 4-week washout phase, 35 elderly patients (mean age 69 +/- 4 years) with mild-to-moderate hypertension received 2 weeks' treatment with ER felodipine 5mg once daily. The dosage of ER felodipine was doubled to 10 mg/day and given for a further 2 weeks in non-responders (sitting clinic blood pressure > 140/90mm Hg). The study had an open-label design with no placebo control. After each period, clinic and ambulatory blood pressures were measured. Trough-to-peak (T/P) ratio was computed by dividing the blood pressure (BP) change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal BP reduction between the second and eighth hour after drug intake). SI was calculated as the ratio between the average of the 24, hourly, treatment-induced BP changes and its standard deviation. After the initial 2-week treatment period, clinic and 24-hour ambulatory BP values were higher in non-responders (145 +/- 11/87 +/- 8 and 135 +/- 17/80 +/- 6mm Hg, respectively) than in responders (133 +/- 6/81 +/- 3 and 130 +/- 9/77 +/- 7mm Hg). In non-responders, clinic and 24-hour BP values were lowered after a further 2 weeks of treatment with ER felodipine 10 mg/day (128 +/- 11/78 +/- 6 and 128 +/- 12/75 +/- 5mm Hg). SI was high in responders (0.8 +/- 0.8/0.7 +/- 0.7 for systolic/diastolic BP) and low in non-responders (0.5 +/- 0.6/0.3 +/- 0.6) during the first 2-week treatment period. It increased in non-responders after an additional 2 weeks of treatment with ER felodipine 10 mg/day (1.0 +/- 0.8/0.7 +/- 0.6). Median T/P ratios were 0.73 and 0.61 (systolic BP and diastolic BP) in responders and 0.41 and 0.61 in non-responders after 2 weeks of treatment. At variance with SI, T/P ratios did not increase in non-responders after doubling the dosage of ER felodipine (0.34 and 0.18). ER felodipine did not increase 24-hour heart rate. A total of nine adverse events were recorded in six patients (17%), but no patients withdrew from the study. ER felodipine 5 to 10 mg/day smoothly and safely reduces 24-hour ambulatory BP in elderly patients with hypertension.",2002.0,0,0
413,12191965,Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial.,Peter W De Leeuw; Lutgarde Thijs; Willem H Birkenhäger; Sophia M Voyaki; Aris D Efstratopoulos; Robert H Fagard; Gastone Leonetti; Choudomir Nachev; James C Petrie; José L Rodicio; Joseph J Rosenfeld; Cinzia Sarti; Jan A Staessen; Systolic Hypertension in Europe (Syst-Eur) Trial Investigators,"Several reports suggest that markers of renal function such as serum creatinine, serum uric acid, and urinary excretion of protein may be related to cardiovascular complications and mortality. This study analyzed the data from the Syst-Eur trial, which was a randomized, placebo-controlled, double-blind intervention trial in elderly patients with isolated systolic hypertension. The purpose was to evaluate whether serum levels of creatinine and uric acid and urinary protein excretion at entry are related to subsequent morbidity and mortality. Incidence rates of total mortality, cardiovascular mortality, stroke (fatal as well as nonfatal), coronary events, and all cardiovascular endpoints were calculated for each quintile of serum creatinine or serum uric acid or for each category of protein excretion (none, trace, and overt). Crude and adjusted relative hazard rates were also determined for each 20 micro M increase in serum creatinine, each 50 micro M increase in serum uric acid, and for each protein excretion category. Even when adjusted for age, gender, and various other covariates, serum creatinine was significantly associated with a worse prognosis. There was an U-shaped relationship between serum uric acid and total mortality, but otherwise no obvious relationships were detected between serum uric acid levels and complications when appropriate adjustments were made for confounding variables. Proteinuria at entry was a significant predictor of total mortality and all cardiovascular endpoints. It is concluded that higher levels of serum creatinine and trace or overt proteinuria are associated with an increased number of cardiovascular events and with a higher mortality in patients with isolated systolic hypertension.",2003.0,0,1
414,12192195,Chronic radiation enteritis: a ten-year follow-up.,Gaurav Jain; James Scolapio; Evan Wasserman; Martin H Floch,,2002.0,0,0
415,12195195,Diltiazem heals glyceryl trinitrate-resistant chronic anal fissures: a prospective study.,Marion Jonas; William Speake; John H Scholefield,"Both topical diltiazem, a calcium channel blocker, and glyceryl trinitrate, a nitric oxide donor, lower anal pressure and heal two-thirds of chronic anal fissures. This study evaluated the efficacy of diltiazem for fissures that failed to heal with glyceryl trinitrate. Consecutive patients with persistent chronic fissures despite treatment with 0.2 percent glyceryl trinitrate ointment underwent anal manometry before and for 1 hour after application of 700 mg of 2 percent diltiazem gel to the distal anal canal. Patients applied diltiazem twice daily for eight weeks or until the fissure had healed. At fortnightly review, fissure healing was assessed, and side effects were noted. Patients scored symptoms of pain, bleeding, and irritation using linear visual analog scales at the initial and follow-up visits. In 39 patients (13 males; median age, 42 (range, 20- 80) years), topical 2 percent diltiazem gel lowered anal resting pressure by 20 percent from a median of 93 to 74 cm H2O (P < 0.0001, Wilcoxon), and fissures healed in 19 (49 percent) within 8 weeks. Before diltiazem, 27 patients (69 percent) had used a complete course of glyceryl trinitrate (0.5 g twice daily for 8 weeks), and 12 (44 percent) of these healed with diltiazem. The remaining 12 patients had discontinued glyceryl trinitrate prematurely or used less because of headaches; 7 (58 percent) of these healed with diltiazem, and 5 (42 percent) did not. Side effects occurred in four patients (10 percent): three reported perianal itching but continued with treatment, and one developed headaches, drowsiness, and mood swings six weeks into treatment and stopped diltiazem at that time. Topical 2 percent diltiazem is effective treatment for glyceryl trinitrate-resistant chronic anal fissures. Side effects, mainly perianal itching, may occur in 10 percent of patients but are generally tolerated.",2002.0,0,0
416,12204014,,,,,1,1
417,12209278,Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol.,S Elatrous; S Nouira; L Ouanes Besbes; S Marghli; M Boussarssar; M Sakkouhi; F Abroug,"To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy. DESIGN. Randomized prospective study. The obstetric ward of the teaching hospital of Monastir Tunisia. Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension. Patients were randomly assigned to receive intravenously for 1 h either labetalol ( n=30) or nicardipine ( n=30). Treatment was titrated to achieve a 20% lowering of blood pressure (BP). Maternal BP and heart rate were measured at inclusion and repeatedly during the first hour following the drugs administration. Fetal heart rate was recorded throughout the study period. The main outcome endpoints were the success rate and the length of time needed to achieve the therapeutic goal. The rate of maternal and fetal adverse events and dose adjustments were also analyzed. Labetalol and nicardipine achieved the 20% lowering in BP in the same proportion (63% and 70% success rates, respectively). Overall nicardipine caused a significantly greater decrease in systolic and diastolic BP. No patient had any episode of hypotension. The length of time to achieve the BP goal was also similar (12 vs. 11 min, respectively). Both drugs were well tolerated except for a moderate tachycardia observed with the use of nicardipine. Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy.",2002.0,0,0
418,12215190,Primary pulmonary hypertension and cor pulmonale.,Stuart Lehrman; Patricia Romano; William Frishman; Amber Rashid; Jay Dobkin; Joseph Reichel,"Primary pulmonary hypertension and cor pulmonale represent forms of precapillary pulmonary hypertension due to intrinsic lung disease. In the case of primary pulmonary hypertension, this is due to disease of the pulmonary vasculature while cor pulmonale is related to diseases of the pulmonary vasculature, airways, or interstitium. Patients present with signs and symptoms of right ventricular dysfunction and low cardiac output including dyspnea, chest pain and peripheral edema. Therapy is directed at the underlying disease and may include supplemental oxygen for diseases causing chronic hypoxemia and anticoagulation for thrombotic disease. Vasodilator therapy has variable efficacy for pulmonary vascular disorders. Postacyclin by continuous infusion has been a major advance in the therapy of primary pulmonary hypertension and has prolonged survival and delayed the need for lung transplantation. Bosentan, an endothelin receptor blocking agent is the first oral medication approved for the therapy of pulmonary hypertension.",2002.0,0,0
419,12215828,Utility of computed tomographic renal angiogram in the management of childhood hypertension.,Aruna Vade; Rekha Agrawal; Jennifer Lim-Dunham; Denise Hartoin,"The purpose of this study was to evaluate the utility of computed tomography (CT) renal angiogram (CTRA) in the management of childhood hypertension. This is a retrospective study of 24 children with clinical suspicion of renovascular disease who underwent CTRA examinations. CTRA demonstrated surgically correctable etiology of hypertension in 38% of the patients [5 with renal artery stenosis (RAS) and 4 with renal pathology]. In 5 patients, CTRA findings of RAS were confirmed by catheter angiogram. CTRA missed RAS in 1 patient in whom catheter angiogram showed beaded narrowing of the renal artery. All 6 patients with RAS had resolution of hypertension immediately after angioplasty or surgery. One patient with diffuse renal artery stenosis had an ipsilateral multicystic dysplastic kidney. In this patient hypertension resolved spontaneously as the dysplastic kidney shrunk in size. Seven patients had a renal etiology for hypertension. In 3 of these patients hypertension resolved after nephrectomy. Malignant hypertension in the 4th patient with reflux nephropathy was controlled medically after she underwent bilateral ureteral reimplantation. The remaining 3 patients with renal etiology were managed medically. We found that the etiology was central for hypertension in 4 patients with brain abnormalities, obesity in 1 overweight patient, essential hypertension in 4 patients, and thoracic aorta coarctation in 1 patient. Our study showed that in all except 1 instance CTRA could diagnose a surgically correctable cause for hypertension. CTRA provided useful information for the management of pediatric hypertension in all our patients.",2003.0,0,0
420,12215829,,,,,0,0
421,12225716,Medical treatment of myocardial ischemia in coronary artery disease: effect of drug regime and irregular dosing in the CAPE II trial.,John E Deanfield; Jean-Marie Detry; Philippe Sellier; Paul R Lichtlen; Eric Thaulow; Jan Bultas; Claudia Brennan; Sarah T Young; Bruce Beckerman; CAPE II Trial Investigators,"The Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication. The optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease. Patients with > or = 4 ischemic episodes or > or = 20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study. In the second phase, atenolol 100 mg was added to amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL). Ambulatory monitoring (72 h) and exercise testing were repeated after both phases, on treatment and after a 24-h drug-free interval. Both monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction. Amlodipine, with its intrinsically long half-life alone or together with beta-blocker, is likely to produce superior ischemia reduction in clinical practice when patients frequently forget to take medication or dose irregularly.",2002.0,0,1
422,12227681,Oxidative stress and TGFbeta in kidney-transplanted patients with cyclosporin-induced hypertension. Effect of carvedilol and nifedipine.,L Calò; B Giacon; P A Davis; E Pagnin; A Piccin; P Riegler; W Huber; A Antonello; A Semplicini,"Cyclosporin is a powerful stimulator of oxidative stress signaling, leading to TGFbeta production, NO degradation, endothelial dysfunction, hypertension and post-transplant nephropathy. Carvedilol, alpha1-beta-blocker with strong antioxidant activity, may interfere with this chain of events. Therefore, we measured monocyte ecNOS, TGFbeta and heme oxygenase-1 (HO-1) mRNA level and plasma nitrite/nitrate, 3-nitrotyrosine, an estimate of peroxynitrite, and total plasma antioxidant power in kidney-transplanted patients with post-transplant hypertension, before and after treatment with carvedilol, 25 - 50 mg o.d. orally for 4 months (n = 15). The dihydropyridine calcium channel blocker nifedipine (n = 10) was used as comparator antihypertensive drug. Blood pressure fell to a similar extent with both drugs. Carvedilol increased plasma antioxidant power and HO-1 mRNA and reduced 3-nitrotyrosine and TGFbeta mRNA levels, while the same was not observed with nifedipine. Monocyte ec NOS mRNA levels and plasma nitrite/nitrate were higher in the patients than in a normotensive healthy control group and were unaffected by either treatment. In conclusion, carvedilol reduces the oxidative stress and corrects the altered cellular signaling mediated by oxidative stress in CsA-induced post-transplant hypertension. Therefore, it may prevent long-term complications, such as endothelial dysfunction, fibrogenesis and post-transplant nephropathy by decreasing NO degradation and production of TGFbeta, a key fibrogenic cytokine, and by activating HO-1 production.",2003.0,0,0
423,12230591,Migraine: preventive treatment.,S D Silberstein; P J Goadsby,"Migraine is a common episodic headache disorder. A comprehensive headache treatment plan includes acute attack treatment to relieve pain and impairment and long-term preventive therapy to reduce attack frequency, severity, and duration. Circumstances that might warrant preventive treatment include: (i) migraine that significantly interferes with the patient's daily routine despite acute treatment; (ii) failure, contraindication to, or troublesome side-effects from acute medications; (iii) overuse of acute medications; (iv) special circumstances, such as hemiplegic migraine; (v) very frequent headaches (more than two a week); or (vi) patient preference. Start the drug at a low dose. Give each treatment an adequate trial. Avoid interfering, overused, and contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing potential is aware of any potential risks. Involve patients in their care to maximize compliance. Consider co-morbidity. Choose a drug based on its proven efficacy, the patient's preferences and headache profile, the drug's side-effects, and the presence or absence of coexisting or co-morbid disease. Drugs that have documented high efficacy and mild to moderate adverse events (AEs) include beta-blockers, amitriptyline, and divalproex. Drugs that have lower documented efficacy and mild to moderate AEs include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate, riboflavin, and non-steroidal anti-inflammatory drugs.",2003.0,0,0
424,12230635,Acute atrial fibrillation.,Bethan Freestone; Sridhar Kamath; Gregory Lip,,2002.0,0,0
425,12231591,Management and outcome of patients with atrial fibrillation during acute myocardial infarction: the GUSTO-III experience. Global use of strategies to open occluded coronary arteries.,C-K Wong; H D White; R G Wilcox; D A Criger; R M Califf; E J Topol; E M Ohman; GUSTO-III Investigators,"To investigate the use of antiarrhythmic agents and electrical cardioversion in the management of patients with atrial fibrillation complicating acute myocardial infarction, and their relation to 30 day and one year mortality. Prospective study of 1138 patients with atrial fibrillation from the GUSTO-III trial. Of the 1138 study patients, 317 (28%) received antiarrhythmic treatment, including class I antiarrhythmic agents (12%), sotalol (5%), and amiodarone (15%); electrical cardioversion was attempted in 116 (10%). Sinus rhythm was restored in 72% of patients receiving class I antiarrhythmic agents, 67% of those receiving sotalol, 79% of those receiving amiodarone, and 64% of those having electrical cardioversion. After adjusting for baseline characteristics and complications occurring before the onset of atrial fibrillation, there was no difference among the treatment groups in the incidence of sinus rhythm at the time of discharge or before deterioration to hospital death. However, the use of class I antiarrhythmic drugs or sotalol was associated with a lower unadjusted 30 day and one year mortality. After adjustment for baseline factors and pre-atrial fibrillation complications, the odds ratios for 30 day and one year mortality were 0.42 (95% confidence interval (CI) 0.19 to 0.89) and 0.58 (95% CI 0.33 to 1.04) with class I agents, and 0.31 (95% CI 0.07 to 1.32) and 0.31 (95% CI 0.09 to 1.02) with sotalol. In contrast, there was no association between the use of amiodarone or electrical cardioversion and 30 day or one year mortality. There was a strong trend towards lower mortality associated with the use of class I antiarrhythmic agents or sotalol in managing patients with atrial fibrillation after acute myocardial infarction. Randomised trials are indicated.",2002.0,0,1
426,12297124,Antiplatelet activity of semotiadil fumarate.,Roswitha M Wolfram; Harald Kritz; Anthony Oguogho; Helmut Sinzinger,"Calcium antagonists are known to exert antiplatelet activity. Semotiadil fumarate (SD-3211), a new benzothiazine, was therefore examined for its antiplatelet activity. The inhibitory activity on adenosine diphosphate (ADP)-, collagen-, arachidonic acid (AA)-, and platelet activating factor (PAF)-induced platelet aggregation after the 1-, 30-, 60- and 120-min incubation at concentrations ranging from 1 x 10(-3), 1 x 10(-4), 1 x 10(-5), 1 x 10(-6) and 1 x 10(-7) was examined. The data were compared with those using diltiazem, nifedipine and amlodipine under identical conditions in blood from eight healthy volunteers (four males, four females; aged 23-36 years) and eight hypertensive patients (four males, four females; aged 31-46 years). Semotiadil showed a dose-dependent inhibition of platelet aggregation in vitro with all the agents examined. Using the various aggregation-inducing agents, the dose-dependent inhibitory action was comparable for all the compounds tested. The antiaggregatory potency was in the order diltiazem, semotiadil, amlodipine and nifedipine. The incubation period did not significantly affect the antiaggregatory effect. No difference between platelets derived from healthy volunteers and hypertensive patients was noted. These findings indicate potent antiplatelet activity of the new calcium antagonist semotiadil.",2003.0,0,0
427,12356398,Coronary angiographic changes in patients with cardiac events in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT).,G B John Mancini; Bertram Pitt,,2002.0,1,1
428,12374512,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.",2002.0,0,1
429,12381540,New therapeutic and surgical approaches for sporadic and hereditary pheochromocytoma.,McClellan M Walther,"Pheochromocytoma is a rare, surgically correctable cause of hypertension. Modern medical blockade has significantly improved patient survival and morbidity. The last decade has seen the identification of the genes responsible for several hereditary causes of pheochromocytoma. Evaluation of these patients has demonstrated different catecholamine profiles associated with the different syndromes. Genetic testing and new, more sensitive catecholamine tests are allowing better, earlier diagnosis of affected patients. Some patients with small tumors deemed nonfunctional by traditional methods may be safely observed until function is demonstrated. Laparoscopic surgery has supplanted the use of open surgery in the management of these tumors. Adrenocortical-sparing surgery may be performed using laparoscopy in patients with hereditary forms of pheochromocytoma.",2002.0,0,0
430,12390820,[Coagulative and fibrinolytic changes in patients with essential hypertension and the effect of sustained-release nifedipine].,Dong-Sheng Chi; Feng-Xia Jin; Yu-Wen Su; Shu-Guang Yang; Bin Ge; Bai-Ming Wu; Xiao-Su Hong; Rong-Shui Yu,"To investigate the changes of coagulation and fibrinolysis status in patients with essential hypertension (EH) and observe the therapeutic effect of sustained-release nifedipine. Ninety-nine EH patients were divided according to their diastolic blood pressure (DBP) into mild group (48 cases), moderate group (29 cases) and severe group (22 cases), and 25 patients among the groups were chosen at random to receive sustained-release nifedipine for 2 weeks. Twenty healthy subjects served as control group. Plasma D-dimer (DD), fibrin monomer (FM) and tissue-type plasminogen activator (tPA) levels were determined in all the subjects by enzyme-linked immunosorbent assay (ELISA). The plasma DD and FM levels were much higher, while tPA level was much lower in hypertensives than those of normal controls, exacerbating with the severity of the disease. DBP was positively correlated with plasma FM level (r=0.374,P<0.001). In patients with left ventricular hypertrophy, left ventricular enlargement and left atrial enlargement, higher levels of DD, FM and tPA were detected. Nifedipine treatment produced significant reduction in plasma DD and FM levels along with the increase in tPA level [DD: (40.7+/-23.5) mg/dl vs (23.8+/-16.5) mg/dl; FM: (7.0+/-1.6) ng/microliter vs (4.8+/-1.5) ng/microliter tPA: (0.31+/-0.14) ng/ml vs(0.41+/-0.05) ng/ml, P<0.001]. Enhanced coagulative activity and lowered fibrinolytic activity characterize EH patients and nifedipine may correct this disorder.",2002.0,0,0
431,12396893,"Biologic and molecular mechanisms for sex differences in pharmacokinetics, pharmacodynamics, and pharmacogenetics: Part I.",Marietta Anthony; Mary J Berg,"There are pharmacological differences between women and men that have important clinical consequences. For several drugs, there is a higher incidence in women of drug-induced QT prolongation and a potentially fatal arrhythmia, torsades de pointes. This may be a reflection of the longer baseline QT interval in women. A difference in cardiovascular disease between women and men is that women have a higher mortality rate after myocardial infarction (MI). Women also have a higher rate of hemorrhagic stroke after receiving thrombolytic therapy for an MI. Differences in effectiveness of analgesics have been demonstrated, with kappa opioids providing pain relief for women but not men. Drugs may have different pharmacokinetics in women and men because of differences in phase I and phase II enzymes that metabolize drugs. Conflicting results about biological sex differences have been reported for the major drug metabolizing enzyme, cytochrome P450 3A4 (3A4) and may be related to a role for P-glycoprotein, a cell membrane transporter, reported as two times higher in male livers than those of females. It has been reported that boys need a higher dose of 6-mercaptopurine, which is metabolized by thiopurine methyltransferase (TPMT). TPMT is reported to be 14% higher in male human liver biopsies than those from females. Verapamil, a drug for angina and hypertension, has different clearance and side effects in men and women. Ethnic/racial variations have also been demonstrated with the drug metabolizing enzymes, CYP2C9, 2C19, and 2D6.",2002.0,0,0
432,12398558,Drug-drug interactions in the elderly.,Ingeborg K Björkman; Johan Fastbom; Ingrid K Schmidt; Cecilia B Bernsten; Pharmaceutical Care of the Elderly in Europe Research (PEER) Group,"To detect the frequency of potential drug-drug interactions (DDIs) in an outpatient group of elderly people in 6 European countries, as well as to describe differences among countries. Drug use data were collected from 1601 elderly persons living in 6 European countries. The study population participated in a controlled intervention study over 18 months investigating the impact of pharmaceutical care. Potential DDIs were studied using a computerized detection program. The elderly population used on average 7.0 drugs per person; 46% had at least 1 drug combination possibly leading to a DDI. On average, there were 0.83 potential DDIs per person. Almost 10% of the potential DDIs were classified to be avoided according to the Swedish interaction classification system, but nearly one-third of them were to be avoided only for predisposed patients. The risk of subtherapeutic effect as a result of a potential DDI was as common as the risk of adverse reactions. Furthermore, we found differences in the frequency and type of potential DDIs among the countries. Potential DDIs are common in elderly people using many drugs and are part of a normal drug regimen. Some combinations are likely to have negative effects; more attention must be focused on detecting and monitoring patients using such combinations. As differences in potential DDIs among countries were found, the reasons for this variability need to be explored in further studies.",2003.0,0,0
433,12398574,Amlodipine versus Angiotensin-receptor blockers for nonhypertension indications.,James S Kalus; C Michael White,"To review the efficacy and safety data of amlodipine and the angiotensin-receptor blockers (ARBs), focusing on heart failure, angina, percutaneous coronary intervention (PCI), and renal protection. A MEDLINE search (1966-December 2001) was completed using amlodipine, angiotensin-receptor antagonist, losartan, valsartan, candesartan, and telmisartan as key words. English-language articles were identified and included. All identified articles were evaluated. Articles representative of the subject matter of our review were included. Amlodipine and the ARBs lower blood pressure to a similar extent. Amlodipine is an effective antianginal agent, whereas ARBs are not. However, amlodipine is not effective in the treatment of heart failure; ARBs may be useful in this setting. ARBs are also effective in preserving renal function and may provide some protection from restenosis in patients who have had a PCI. The ARBs may also be useful in preventing both diabetic and nondiabetic nephropathy. Concomitant disease states should be considered when choosing between an ARB and amlodipine for the management of hypertension.",2003.0,0,1
434,12400150,Optimal treatment of hypertension in African Americans. Reaching and maintaining target blood pressure goals.,George L Bakris; Keith C Ferdinand; Janice G Douglas; James R Sowers,"Treatment of hypertension in African Americans has special challenges, including a lack of objective trial data on which to base decisions and differing benefits and responses than with other patients. However, adequate control is possible and should be the goal of treating physicians. This article describes current ""best practice"" guidance on appropriate treatment of high blood pressure in African Americans. Two patient scenarios offer insight into clinical strategies.",2002.0,0,0
435,12408291,Efficacy and safety of losartan-amplodipine combination--an Indian postmarketing surveillance experience.,Nitin Gokhale; Savita Shahani; Dilip Pawar,"The present study was conducted among 719 patients enrolled by 109 doctors to evaluate the efficacy and tolerability of the combination of losartan potassium and amlodipine besylate in Indian patients with mild to moderate hypertension. Out of them 11 patients were dropped out. Of these 708 patients 643 patients received once daily dosage of the combination whereas 10 patients received 1/2 daily, 13 patients received 1 1/2 daily and 42 patients received 1 twice daily dosage of the combination. The mean SBP in the study was 172.89 +/- 19.18 mm Hg baseline. After the 10-day treatment, the mean SBP had significant reduction ie, 13.1% from basal and at the end of day 20 of the treatment, the reduction was 19.13% from the baseline which was significant. Similarly mean DBP was 105.42 +/- 10.85 mm Hg at baseline. After treatment, the mean DBP had significant reduction. After 10- day treatment, there was 12.7% reduction from the baseline and at the end of the treatment ie, after day 20, the reduction was 17.70% from basal, which was significant. Global evaluation of efficacy was done by the physicians; 93.8% of the cases had excellent to good response and 4.9% patients had fair response. Details of any adverse event reported or noted during the treatment with the combination were recorded in the appropriate section of the case record form, whether considered treatment related or not, as reported by the patients. The severity of an adverse event was graded on a 3-point scale as mild, moderate and severe. The most common side-effects reported were oedema of feet (5.08%), ankle oedema (1.98%). Remaining adverse events included some cardiovascular events such as palpitations, gastro-intestinal events such as constipation, miscellaneous events, muscular pain, weakness, generalised swelling, etc. CNS events included giddiness, headache, insomnia, etc.",2002.0,0,1
436,12408733,"Gastrointestinal safety of an extended-release, nondeformable, oral dosage form (OROS: a retrospective study.",Dorsey M Bass; Mary Prevo; Deborah S Waxman,"The OROS osmotic (OSM) dosage form optimises extended-release oral administration by controlling the rate of drug release for a predetermined time, providing constant, patterned, or pulsed delivery profiles. OSM products include prescription medications for urology, CNS, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications. This retrospective study examines US gastrointestinal (GI) safety data for the OROS dosage form following nearly two decades of use. Although GI injury and obstruction are known effects of oral medications, some reports have suggested that extended-release products pose a greater risk of GI injury and obstruction than other oral dosage forms. Products incorporating OROS technology are being prescribed to an expanding range of patients; a review of the GI safety data for this dosage form thus seemed timely and appropriate. US safety information was obtained from three sources: English language literature published from 1982 until June 1, 2000 from five major biomedical databases;postmarketing safety reports from January 1, 1983 until June 1, 2000 available through the Freedom of Information Act; andcommercial safety information obtained directly from ALZA Corporation's in-house safety database for those OSM products for which ALZA has reporting responsibility. US distribution data from IMS National Prescription Audit trade mark Plus data were used to estimate cumulative product distribution totals. These totals were combined with numbers of unique GI events to determine the estimated frequency of events. Nearly 13 billion OSM tablets are estimated to have been distributed in the US. The incidence of all clinically significant GI adverse events for OSM products (including intestinal, gastric, and oesophageal irritation, injury, and obstruction) reported in the US was approximately one case in >76 million tablets distributed. The majority (78%; estimated incidence: one case in 29 million tablets) of cases were reported in patients taking Procardia XL (nifedipine). Oesophageal and lower GI obstruction were reported primarily in patients with pre-existing abnormalities or disease of the GI tract. Among paediatric patients, one obstruction was reported in an estimated 37.7 million tablets distributed. Reports of GI irritation associated with OSM products were consistent with known effects of the same drug substances in other dosage forms. A review of long-term safety experience with products using OSM controlled-release technology yields a low incidence of clinically significant GI events. Properly prescribed, extended-release products provide substantial therapeutic and convenience benefits without additional risk.",2003.0,0,1
437,12411551,"Myocardial sympathetic denervation, fatty acid metabolism, and left ventricular wall motion in vasospastic angina.",Kenichi Watanabe; Toshihiro Takahashi; Seiichi Miyajima; Yoichi Hirokawa; Naohito Tanabe; Kiminori Kato; Makoto Kodama; Yoshifusa Aizawa; Shusaku Tazawa; Minoru Inoue,"Although various noninvasive methods have been used to detect vasospasm, none of them are sensitive enough for patients with sporadic attacks. Because abnormal fatty acid metabolism and cardiac adrenergic neuronal damage are observed in ischemic myocardium, (123)I-15-(p-iodophenyl)-3-R,S-methyl pentadecanoic acid (BMIPP) and (123)I-metaiodobenzylguanidine (MIBG) have recently been proposed as useful tracers for detection of myocardial damage. This study investigated the relationships among the coronary vasospastic regions, abnormal left ventricular regional wall motion, fatty acid metabolism, and sympathetic nerve functions and their changes during treatment in patients with vasospastic angina. We evaluated 50 patients with vasospastic angina (25 with clinically documented vasospasm [group A] and 25 with vasospasm induced by ergonovine provocation [group B]) and 25 control subjects who had chest pain but had normal coronary arteries without ergonovine provocation of spasm. Sixteen patients in group A were reevaluated 6 mo after medical treatment. The territorial regions of the vasospasm-induced coronary artery, wall motion determined by left ventriculography, and BMIPP and MIBG uptake were compared. Regions exhibiting a positive reaction to the ergonovine provocation were observed in the right coronary artery in 41 patients, the left anterior descending artery in 33, and the left circumflex artery in 21. Provocation occurred in multiple vessels in 29 patients (58%). Reduction of wall motion was observed in 19 patients (38%). Sensitivity and specificity for the identification of vasospastic angina were 86% (43/50 patients) and 88% (22/25 control subjects), respectively, for BMIPP scintigraphy and 100% (50/50 patients) and 56% (14/25 control subjects), respectively, for MIBG scintigraphy. In the region exhibiting a reduction in left ventricular wall motion, BMIPP or MIBG uptake was decreased. The sensitivity and specificity of determination of vasospasm-induced coronary arteries were 71% (67/95 arteries) and 95% (71/75 arteries), respectively, for BMIPP scintigraphy and 96% (91/95 arteries) and 55% (41/75 arteries), respectively, for MIBG scintigraphy. After 6 mo, during treatment, vasospasm was reinduced by ergonovine provocation in 6 patients (group I) and was not reinduced in 10 patients (group II). Improvements of decreased BMIPP and MIBG uptake were lower in group I (25% +/- 4% and 16% +/- 4%, respectively) than in group II (69% +/- 4% and 50% +/- 3%, respectively; both P < 0.01). The regions in which vasospasm was reinduced exhibited decreased BMIPP and MIBG uptake. Abnormal fatty acid metabolism and cardiac sympathetic denervation were observed more frequently than were wall motion abnormalities in the vasospastic region in patients with vasospastic angina. BMIPP and MIBG scintigraphy are highly accurate and noninvasive techniques for determining the presence and location of vasospasm.",2002.0,0,0
438,12411973,Primary pulmonary hypertension: Current therapy.,Olivier Sitbon; Marc Humbert; Gérald Simonneau,"Because the causes of primary pulmonary hypertension (PPH) remains unknown, the therapeutic approach of the disease can be only empirical, based on the pathology and pathobiology of pulmonary circulation. Despite the inability to cure the disease, therapeutic advances over the past 20 years have contributed to an improvement of quality of life and prolonged survival in PPH patients. Current therapeutic approach of PPH mostly includes limitation of physical activity, long-term anticoagulation, and vasodilator therapy. Among all tested oral vasodilators, calcium-channel blockers are the most efficient long-term therapies by improving symptoms and hemodynamics in a subset of PPH patients (10% to 15%) who acutely respond to such drugs. Acute pulmonary vasodilator response to inhalation of nitric oxide can predict acute and chronic responses to oral calcium-channel blockers. A better understanding of the pathogenesis of PPH has changed the focus of medical treatments from purely chronic vasodilator therapy to the evaluation of agents, such as prostaglandins, that may reverse the proliferation of pulmonary vascular cells and result in regression of the pulmonary vascular hypertrophy and remodeling. Long-term treatment with intravenous epoprostenol (prostaglandin I(2) or prostacyclin) improves exercise capacity, hemodynamics and survival in most patients with PPH in functional class NYHA III or IV, and may be currently considered as the ""gold standard"" therapy for severe patients. However, response to long-term epoprostenol therapy may be incomplete, adverse effects are common, and survival remains unsatisfactory (55% at 5 years). In such patients with severe pulmonary hypertension refractory to medical therapy, atrioseptostomy and lung transplantation can be indicated.",2002.0,0,0
439,12417374,Protective effect of anti-hypertensive treatment on cognitive function in essential hypertension: analysis of published clinical data.,Francesco Amenta; Fiorenzo Mignini; Franco Rabbia; Daniele Tomassoni; Franco Veglio,"Hypertension is a risk factor for stroke and may also contribute to the development of vascular cognitive impairment (VCI) and vascular dementia (VaD). Cognitive complications of hypertension and the influence of anti-hypertensive treatment were underestimated until recently. In this paper, trials investigating the effect of anti-hypertensive treatment on cognitive function were evaluated. Analysis of these studies revealed that until approximately 1990-1995 investigations have assessed primarily if anti-hypertensive treatment impaired cognitive function. Only more recent studies have investigated positive effects on cognition of anti-hypertensive medication. Drugs more extensively evaluated were diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, sartanes and Ca(2+) channel blockers. Available studies have confirmed that elevated diastolic blood pressure or pulse pressure and isolated systolic hypertension play an important role in the development of cognitive impairment. Randomized placebo-controlled trials have provided evidence that reduction of hypertension safely and effectively decreases morbidity and mortality rates and cognitive complications of hypertension. Ca(2+) channel blockers and ACE inhibitors have been shown to be effective and probably better than diuretics and beta-blockers on cognitive domains of hypertension. More extensive investigations could contribute to establishing optimal choice and drug dosage for the treatment of cognitive complications of hypertension.",2003.0,0,0
440,12420078,,,,,0,0
441,12428993,Atrial fibrillation in the elderly: facts and management.,Guy Chatap; Karine Giraud; Jean-Pierre Vincent,"Although atrial fibrillation is not widely known by the general public, in developed countries it is the most common arrhythmia. The incidence increases markedly with advancing age. Thus, with the growing proportion of elderly individuals, atrial fibrillation will come to represent a significant medical and socioeconomic problem. The consequences of atrial fibrillation have the greatest impact. The risk of thromboembolism is well known; other outcomes of atrial fibrillation are less well recognised, such as its relationship with dementia, depression and death. Such consequences are responsible for diminished quality of life and considerable economic cost. Atrial fibrillation is characterised by rapid and disorganised atrial activity, with a frequency between 300 and 600 beats/minute. The ventricles react irregularly, and may contract rapidly or slowly depending on the health of the conduction system. Clinical symptoms are varied, including palpitations, syncope, dizziness or embolic events. Atrial fibrillation may be paroxysmal, persistent or chronic, and a number of attacks are asymptomatic. Suspicion or confirmation of atrial fibrillation necessitates investigation and, as far as possible, appropriate treatment of underlying causes such as hypertension, diabetes mellitus, hypoxia, hyperthyroidism and congestive heart failure. In the evaluation of atrial fibrillation, cardiac exploration is invaluable, including electrocardiogram (ECG) and echocardiography, with the aim of detecting cardiac abnormalities and directing management. In elderly patients (arbitrarily defined as aged >75 years), the management of atrial fibrillation varies; it requires an individual approach, which largely depends on comorbid conditions, underlying cardiac disease, and patient and physician preferences. This management is essentially based on pharmacological treatment, but there are also nonpharmacological options. Two alternatives are possible: restoration and maintenance of sinus rhythm, or control of ventricular rate, leaving the atria in arrhythmia. Pharmacological options include antiarrhythmic drugs, such as class III agents, beta-blockers and class IC agents. These drugs have some adverse effects, and careful monitoring is necessary. The nonpharmacological approach to atrial fibrillation includes external or internal direct-current cardioversion and new methods, such as catheter ablation of specific foci, an evolving science that has been shown to be successful in a very select group of atrial fibrillation patients. Another serious challenge in the management of chronic atrial fibrillation in older individuals is the prevention of stroke, its primary outcome, by choosing an appropriate antithrombotic treatment (aspirin or warfarin). Several risk-stratification schemes have been validated and may be helpful to determine the best antithrombotic choice in individual patients.",2003.0,0,0
442,12432188,Extent of use of immediate-release formulations of calcium channel blockers as antihypertensive monotherapy by primary care physicians: multicentric study from Bahrain.,R P Sequeira; K A Jassim Al Khaja; V S Mathur,"The issue of cardiovascular safety of calcium channel blockers (CCBs) has been widely debated in view of reflex increase in sympathetic activity induced by immediate release (IR) / short acting formulations. It is generally agreed that such CCBs should not be used alone in the management of hypertension. We have determined the extent to which primary care physicians prescribe CCBs as monotherapy, especially the immediate release formulations, in the management of uncomplicated hypertension and diabetic hypertension - with an emphasis upon the age of the patients. SETTING, DESIGN AND METHODS: A retrospective prescription-based study was carried out in seven out of 18 Health Centres in Bahrain. The study involved a registered population of 229,300 representing 46% of registered individuals, and 35 physicians representing 43% of all primary care physicians. The data was collected between November 1998 and January 1999 using chronic dispensing cards. In all categories CCBs were the third commonly prescribed antihypertensive as monotherapy, with a prescription rate of 11.1% in uncomplicated hypertension, 18% in diabetic hypertension and 20.1% in elderly patients above 65 years of age. Nifedipine formulations were the most extensively prescribed CCBs. Almost half of the CCB-treated patients were on IR-nifedipine, whereas IR-diltiazem and IR-verapamil, and amlodipine were infrequently prescribed. Prescription of IR-formulations of CCBs as monotherapy by primary care physicians does not conform with recommended guidelines. In view of concerns about the safety of such practice, measures to change the prescribing pattern are required.",2003.0,0,0
443,12432193,A 34-year-old renal transplant recipient with high-grade fever and progressive shortness of breath.,R Soman; P Vaideeswar; H Shah; A F Almeida,,2003.0,0,0
444,12435255,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.",2002.0,1,1
445,12437491,Clinical treatment regimens for chronic heart failure: a review.,Paul A Gould; David M Kaye,"Chronic heart failure (CHF) is increasing in prevalence worldwide, particularly in the elderly. Accordingly, this epidemic is likely to translate into a major increase in healthcare costs. Systolic heart failure is the most common cause of CHF presentations. Although the causes vary, the most common single aetiological factor is ischaemic heart disease, which accounts for approximately 50% of heart failure presentations. Research into CHF pharmacotherapy has been copious, with the focus principally centred on systolic heart failure. The evidence base for pharmacotherapy in CHF is amongst the largest currently in clinical medicine. There have been multiple trials establishing the mortality and morbidity benefits of pharmacotherapy. Amongst these, large scale trials of angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone have provided a sound basis for evidence-based treatment approaches to the CHF patient. Recently research interest has increased in biomedical engineering with studies being performed in biventricular pacing and mechanical hearts. Early data with biventricular pacing or cardiac resynchronisation therapy is encouraging. Diastolic heart failure alone accounts for at least 20 - 40% of CHF presentations and whilst it may occur in isolation, is most commonly seen in association with systolic heart failure. In this study, we present a broad overview of the current therapeutic modalities for the management of CHF, with particular emphasis on pharmacotherapy.",2003.0,0,0
446,12438974,Rhabdomyolysis due to red yeast rice (Monascus purpureus) in a renal transplant recipient.,G V Ramesh Prasad; Timothy Wong; Galo Meliton; Salma Bhaloo,"Rhabdomyolysis is a known complication of hepatic 3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitor (statin) therapy for posttransplant hyperlipidemia, and thus monitoring for this effect is indicated. We report a case of an herbal preparation-induced rhabdomyolysis in a stable renal-transplant recipient, attributed to the presence of red yeast rice (Monascus purpureus) within the mixture. The condition resolved when consumption of the product ceased. Rice fermented with red yeast contains several types of mevinic acids, including monacolin K, which is identical to lovastatin. We postulate that the interaction of cyclosporine and these compounds through the cytochrome P450 system resulted in the adverse effect seen in this patient. Transplant recipients must be cautioned against using herbal preparations to lower their lipid levels to prevent such complications from occurring.",2002.0,0,0
447,12441210,Improvement of insulin sensitivity by a long-acting nifedipine preparation (nifedipine-CR) in patients with essential hypertension.,Yuko Koyama; Kenichi Kodama; Masaaki Suzuki; Yutaka Harano,"Nifedipine has been reported to cause impairment of insulin sensitivity. But recently a controlled-released formulation of nifedipine (nifedipine-GITS) has been reported that it could improve insulin sensitivity. We evaluated insulin sensitivity in two groups of essential hypertensive subjects before and after treatment with either long-acting nifedipine (nifedipine-CR, Adalat CR tablets; Bayer Yakuhin, Osaka, Japan) (n = 10) or metoprolol (n = 9). Insulin sensitivity was evaluated from the steady-state plasma glucose (SSPG) level measured at the steady-state insulin level (20 to 30 microU/mL) using a modification of the SSPG method previously reported. The SSPG was initially high, but was significantly reduced by nifedipine-CR treatment (from 133 +/- 14 mg/dL to 95 +/- 8 mg/dL). However, SSPG was not significantly altered by treatment in the metoprolol group (from 103 +/- 15 mg/dL to 119 +/- 12 mg/dL). Our results indicate that the long-acting nifedipine (nifedipine-CR) is associated with improved insulin sensitivity.",2003.0,0,0
448,12441211,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
449,12441226,Pedal edema--not all dihydropyridine calcium antagonists are created equal.,Franz H Messerli; Ehud Grossman,,2003.0,0,0
450,12442928,Myocardial ischaemia in patients with impaired left ventricular function undergoing coronary artery bypass grafting--milrinone versus nifedipin.,T Möllhoff; C Schmidt; H Van Aken; E Berendes; H Buerkle; P Marmann; T Reinbold; R Prenger-Berninghoff; T D T Tjan; H H Scheld; M C Deng,"Myocardial ischaemia and infarction are major complications immediately after coronary artery bypass grafting. They may be due to incomplete surgical revascularization, perioperative anaesthetic management or vasospasm of arterial grafts, e.g. the internal mammary artery. Infusions of nifedipine or milrinone have been advocated to prevent spasm of the mammary artery. The study compared the incidence of myocardial ischaemia after continuous infusion of either nifedipine (0.2 microg kg(-1) min(-1)) or milrinone (0.375 microg kg(-1) min(-1)) in patients with compromised left ventricular function scheduled for elective coronary artery bypass graft. After Institutional Review Board approval, this double-blinded randomized clinical study enrolled 30 adult patients with compromised left ventricular function (ejection fraction < 0.4) scheduled for elective coronary artery bypass grafting after written informed consent had been obtained. Ischaemia was detected by Holter electrocardiographic monitoring. The incidence of myocardial cell death was monitored by serial determinations of the creatine kinase-MB (CK-MB) and troponin-I. New ST elevation > or = 0.2 mV or new ST depression < or = 0.1 mV occurred in five of 15 patients in the milrinone group (33.3%) and in 13 of 15 patients (86.6%) in the nifedipine group (P < 0.05). There were increases in CK-MB and troponin-I in both groups. Twenty-four hours postoperatively, CK-MB (P = 0.003) and troponin-I (P = 0.001) were significantly higher in the nifedipine group. Perioperative continuous infusion of milrinone, compared with nifedipine, results in a significantly lower incidence of myocardial ischaemia and myocardial cell damage after elective coronary artery bypass grafting.",2003.0,0,0
451,12444542,"Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised, double-blind comparative trial in Asian patients.",I Ongtengco; D Morales; J Sanderson; Z-R Lu; L J Beilin; V Burke; I B Puddey; S Tanomsup; H Dayi; P Rahardjo; Dato R Zambahari; C-Y Chen; A A Soenarta; P Buranakitjaroen; C Tan; T K Soon; D-J Wu,"Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P<or=0.0001) and 2.4+/-6.3 vs 6.0+/-6.0 mmHg for diastolic BP (P<or=0.0002). Significant differences between the two drugs in mean 24-h ambulatory BP levels were already evident on day 1 after withdrawal, even though there were no significant differences on the final day of treatment. No differences in safety parameters were observed, and neither drug caused any serious or severe treatment-related adverse events. In conclusion, amlodipine provides greater protection than nifedipine GITS against loss of BP control following missed doses.",2003.0,0,0
452,12451325,,,,,0,0
453,12452980,Investigation of the effect of FK506 (tacrolimus) and cyclosporin on gingival overgrowth following paediatric liver transplantation.,S J McKaig; D Kelly; L Shaw,"Gingival overgrowth associated with immunosuppression following liver transplantation is a commonly recognized clinical problem. The aims of this study were to determine the incidence of gingival overgrowth in a group of children post liver transplantation and to compare gingival overgrowth in children receiving FK506 with those receiving cyclosporin. Seventy-nine children (aged 15-196 months) undergoing liver transplantation at Birmingham Children's Hospital between October 1998 and October 2000 were studied. Gingival overgrowth was assessed in a blinded fashion and scored in a previously validated manner. Gingival overgrowth scores of the patients on each immunosuppressant drug were then compared. Fifty-two patients were treated with cyclosporin and 27 treated with tacrolimus. Eighteen children were also receiving nifedipine (also known to cause gingival overgrowth) and were considered separately. Of the 41 children receiving cyclosporin alone, 26 exhibited gingival overgrowth compared to zero of 20 patients receiving tacrolimus alone. Those children treated with immunosuppression plus nifedipine developed gingival overgrowth, however, this was much less marked in the tacrolimus group. Tacrolimus, unlike cyclosporin, is not associated with gingival overgrowth when used for immunosuppression following liver transplantation in children, and may be the drug of choice for children.",2003.0,0,0
454,12460699,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
455,12466506,A comparison of rate control and rhythm control in patients with atrial fibrillation.,D G Wyse; A L Waldo; J P DiMarco; M J Domanski; Y Rosenberg; E B Schron; J C Kellen; H L Greene; M C Mickel; J E Dalquist; S D Corley; Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) Investigators,"There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.",2002.0,0,0
456,12466507,A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation.,Isabelle C Van Gelder; Vincent E Hagens; Hans A Bosker; J Herre Kingma; Otto Kamp; Tsjerk Kingma; Salah A Said; Julius I Darmanata; Alphons J M Timmermans; Jan G P Tijssen; Harry J G M Crijns; Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation Study Group,"Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation. We randomly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs. After a mean (+/-SD) of 2.3+/-0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group. The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups. Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion.",2002.0,0,1
457,12468576,Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.,Paolo Mulatero; Franco Rabbia; Alberto Milan; Cristina Paglieri; Fulvio Morello; Livio Chiandussi; Franco Veglio,"Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.",2003.0,0,0
458,12472930,Management of patients with hypertensive urgencies and emergencies: a systematic review of the literature.,David Cherney; Sharon Straus,"Hypertensive urgencies and emergencies are common clinical occurrences in hypertensive patients. Treatment practices vary considerably to because of the lack of evidence supporting the use of one therapeutic agent over another. This paper was designed to review the evidence for various pharmacotherapeutic regimens in the management of hypertensive urgencies and emergencies, in terms of the agents' abilities to reach predetermined ""safe"" goal blood pressures (BPs), and to prevent adverse events. medline was searched from 1966 to 2001, and the reference lists of all the articles were retrieved and searched for relevant references, and experts in the field were contacted to identify other relevant studies. The Cochrane Library was also searched. Studies that were eligible for inclusion in this review were systematic reviews of randomized control trials (RCTs) and individual RCTs, all-or-none studies, systematic reviews of cohort studies and individual cohort studies, and outcomes research. No language restrictions were used. None of the trials included in this review identified an optimal rate of BP lowering in hypertensive emergencies and urgencies. The definitions of hypertensive emergencies and urgencies were not consistent, but emergencies always involved target end-organ damage, and urgencies were without such damage. Measures of outcome were not uniform between studies. The 4 hypertensive emergency and 15 hypertensive urgency studies represented 236 and 1,074 patients, respectively. The evidence indicated a nonsignificant trend toward increased efficacy with urapidil compared to nitroprusside for hypertensive emergencies (number needed to treat [NNT] for urapidil to achieve target BP, 12; 95% confidence interval [95% CI], number of patients needed to harm [NNH], 5 to NNT, 40 compared to nitroprusside). Several medications were efficacious in treating hypertensive urgencies, including: nicardipine (NNT for nicardipine compared to plabebo, 2 in one study [95% CI, 1 to 5] and 1 in another [95% CI, 1 to 1]); lacidipine (NNT, 2; 95% CI, 1 to 8 for lacidipine vs nifedipine) or urapidil (NNT for urapidil compared to enalaprilat and nifedipine, 4; 95% CI, 3 to 6); and nitroprusside and fenoldopam (all patients reached target BP in 2 studies). The studies reported 2 cases of cerebral ischemia secondary to nifedipine. Many effective agents exist for the treatment of hypertensive crises. Because of the lack of large randomized controlled trials, many questions remain unanswered, such as follow-up times and whether any of the studied agents have mortality benefit.",2003.0,0,1
459,12476475,Effects of four antihypertensive monotherapies on cardiac mass and function in hypertensive patients with left ventricular hypertrophy: randomized prospective study.,Drago Rakić; Zvonko Rumboldt; Jugoslav Bagatin; Stojan Polić,"To compare the effects of four antihypertensive drugs, which have reportedly different effectiveness in reducing myocardial mass. A randomized, double-blind, prospective study included 80 hypertensive patients with left ventricular (LV) hypertrophy confirmed both electrocardiographically and echocardiographically. We investigated the effects of indapamide, nicardipine, propranolol, and chlorthalidone on arterial blood pressure and LV mass and function. Sixty-four patients (34 men and 30 women) completed the 6-month study. No significant differences in antihypertensive effects of the four medications were found. The average decrease in systolic and diastolic blood pressure was 12.8% and 10.4%, respectively. All four antihypertensive medications caused pronounced reduction in LV mass, between 7.9% in the propranolol group and 10.1% in the nicardipine group, with no significant difference between the groups. In patients receiving diuretics, predominant decrease was observed in LV mass and LV mass index. In patients treated with propranolol, the thickness of both the LV wall and interventricular septum was reduced, whereas the reduction in LV mass, LV wall and interventricular septum thickness was found in patients treated with nicardipine. There was no significant correlation between the changes in LV mass and other variables (blood pressure, and systolic and diastolic function). Systolic function did not improve with the reversion of LV hypertrophy in any group of patients, but improvement was observed in some indices of diastolic function. The early and late LV filling velocity and their ratio did not improve significantly, either. Clinically relevant side effects were not observed. All four antihypertensive monotherapies achieved a comparable control of hypertension and reduction in LV hypertrophy.",2003.0,0,0
460,12478497,Treatment of hypertension from volume to vasoconstriction: The ACE up your sleeve.,James C Stanley; Russell H Samson,"Control of hypertension in the vascular patient is clearly a priority. However, these patients often will have significant co-morbidities that may influence the choice of medication, a decision that also may be affected by cost or Health Plan directives. Wherever possible, monotherapy should be attempted first, although in select circumstances combination therapy may be more appropriate. The 5 main categories of drugs used in the initial treatment of hypertensive vascular diseases are (1). diuretics, (2). beta-adrenergic blockers, (3). calcium channel blockers, (4). angiotensin-converting enzyme (ACE) inhibitors, and (5). angiotensin receptor blockers (ARBs). There are also other less commonly used drugs. Each of the antihypertensive agents is roughly equally effective, producing a good antihypertensive response in 40% to 60% of cases. Some antihypertensives, especially ACE and ARBs, also may have beneficial effects on the vascular and metabolic systems separate from their blood pressure lowering effects, which suggests they may be beneficial even if blood pressure is well maintained with other agents. This report covers the basic information required for the vascular surgeon to become familiar with the various medications and their indications, dosage, and side effects. It also provides some guidelines in selecting relevant antihypertensive treatment regimens for the elderly patient with arterial vascular disease.",2003.0,0,0
461,12479637,Macrophage subpopulations in gingival overgrowth induced by nifedipine and immunosuppressive medication.,Petri K Nurmenniemi; Hilkka E Pernu; Päivi Laukkanen; Matti L E Knuuttila,"The immunomodulating effects of both immunosuppressive and nifedipine medication have been associated with drug-induced gingival overgrowth. The aim of the study reported here was to evaluate the presence of macrophage subpopulations in normal human gingiva and in gingival overgrowth induced by nifedipine and immunosuppressive medication. Gingival samples were taken from 11 nifedipine-medicated cardiac outpatients (nifedipine group), 11 triple-medicated organ-transplant recipients also taking nifedipine (immunosuppression plus nifedipine group), 12 triple-medicated organ-transplant recipients (immunosuppression group), and 20 generally healthy individuals (control group). Cryostat sections were stained with mAbs for inflammatory 27E10, reparative RM3/1, and resident 25F9 macrophages using an avidin-biotin enzyme complex method. Total numbers of mAb-labeled cells were determined in connective tissue beneath sulcular epithelium, connective tissue beneath oral epithelium, and middle connective tissue. Expression of 27E10 was determined in keratinocytes in the oral epithelium. Statistics analyses were undertaken using the chi-square test, the Mann-Whitney U test, the independent samples t test, analysis of variance, and analysis of covariance. Greater numbers of inflammatory 27E10-positive macrophages were found in all 3 medicated groups and counting zones than in the control group except in connective tissue beneath sulcular epithelium in the immunosuppression group. The incidence of specimens expressing 27E10 antigen throughout the oral epithelium was significantly higher in the immunosuppression group (8 of 12) than in the control group (4 of 20) and the nifedipine group (2 of 11). Numbers of reparative RM3/1-positive macrophages were significantly greater in the immunosuppression group in connective tissue beneath oral epithelium than in the control group. The effect was markedly associated with degree of inflammation. Numbers of resident 25F9-positive macrophages were lower in connective tissue beneath sulcular epithelium in the immunosuppression group, and higher in middle connective tissue in the nifedipine group than in the control group. Our results show that the nature of drug-induced gingival overgrowth differs somewhat between immunosuppressive and nifedipine medications.",2003.0,0,1
462,12479763,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.",2002.0,1,1
463,12483453,Dynamic and kinetic disposition of nisoldipine enantiomers in hypertensive patients presenting with type-2 diabetes mellitus.,Maria Paula Marques; Eduardo Barbosa Coelho; Neife Aparecida Guinaim Dos Santos; Tufik José Magalhães Geleilete; Vera Lucia Lanchote,"Nisoldipine (N) is a dihydropyridine calcium antagonist marketed as a racemic mixture and used for the treatment of hypertension. In the present study, we investigated the influence of type-2 diabetes mellitus (DM) on the enantioselective pharmacokinetic and dynamic parameters of N. Seventeen hypertensive patients, nine of them with DM, were investigated in a cross-over study with administration of rac-N as coat-core tablets (20 mg day(-1)) or placebo for 15 days each. Serial blood samples (0-24 h) were collected on the 15th day, and 24-h ambulatory blood pressure (BP) monitoring was simultaneously evaluated. N enantiomers in plasma samples were analysed using chiral high-performance liquid chromatography combined with gas chromatography/mass spectrometry. The enantiomeric ratios differing from one were evaluated using the Wilcoxon test, and the results are reported as means with the 95% confidence intervals. A lidocaine (L) test was carried out as an in vivo marker of CYP3A4 (and CYP1A2) activities. The following differences were observed between the (+)-N and (-)-N enantiomers, respectively, in the patients presenting with DM (means and ranges): C(max) 3.9 (1.7-6.1) ng ml(-1) versus 0.7 (0.4-1.0) ng ml(-1), AUC(0-24) 51.5 (29.0-74.0) ng ml(-1) h versus 9.4 (5.9-12.8) ng ml(-1) h, and Cl/f 3.6 (1.9-5.4) l h(-1) kg(-1) versus 18.7 (11.7-25.7) l h(-1) kg(-1). The Cl/f value of (+)-N was lower (Mann-Whitney test) in patients with DM: 6.0 (4.3-7.5) l h(-1) kg(-1) versus 3.6 (1.9-5.4) l h(-1) kg(-1). The same observation was made for the (-)-N, with Cl/f reaching 38.8 (26.8-51.0) l h(-1) kg(-1) and 18.7 (11.7-25.7) l h(-1) kg(-1) for the non-diabetic and DM groups, respectively. The L test resulted in higher ratios (P < 0.05) of plasma L/MEGX concentrations (30 min after i.v. L) for DM (11.1 vs 18.6). N significantly reduced systolic and diastolic BP (P < 0.05, Wilcoxon test) in all patients investigated relative to placebo. No differences in BP reduction were observed between diabetic and non-diabetic patients. N significantly increased noradrenaline concentrations in plasma of both patient groups. The data also demonstrated that the plasma concentrations of noradrenaline 30 min after N administration were lower (P < 0.05) in diabetic (mean 2.86 pmol ml(-1)) than in non-diabetic patients (4.80 pmol ml(-1)). The present data permit us to infer that type-2 diabetes mellitus alters the kinetic disposition of the (+)-N eutomer and (-)-N distomer, presumably due to a lower activity of CYP3A4, although it does not modify the clinical effect brought about by the reduction in BP.",2003.0,0,0
464,12487393,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
465,12492389,Jellyfish envenoming syndromes: unknown toxic mechanisms and unproven therapies.,Paul M Bailey; Mark Little; George A Jelinek; Jacqueline A Wilce,"Interest in envenoming syndromes caused by Australian jellyfish has been intense since the deaths in early 2002 of two tourists in Queensland, attributed to the Irukandji syndrome. We review current knowledge of these envenoming syndromes, mechanisms of venom action and therapy, focusing on the deadly box jellyfish, Chironex fleckeri, and the array of jellyfish thought to cause the Irukandji syndrome. Current understanding of jellyfish venom activity is very limited, and many treatments are unproven and based on anecdote.",2003.0,0,0
466,12499617,Effect of intracoronary nicorandil administration on preventing no-reflow/slow flow phenomenon during rotational atherectomy.,Akiyoshi Tsubokawa; Kinzo Ueda; Hiroki Sakamoto; Tomoyuki Iwase; Shun-ichi Tamaki,"A major limitation of the rotational atherectomy (RA) procedure is the occurrence of the no-reflow/slow flow phenomenon and the optimal strategy is still evolving. Recent clinical studies have demonstrated the beneficial effects of nicorandil, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on no-reflow in patients with acute myocardial infarction. The purpose of this study was to evaluate the effect of nicorandil on no-reflow/slow flow phenomenon during RA procedures. Sixty-one patients who underwent RA of complex coronary lesions were randomly divided into 2 groups: (i) nicorandil cocktail (n=24 patients, 37 lesions) and (ii) verapamil cocktail (n=37 patients, 63 lesions). In each group, the drug cocktail mixed with pressurized saline was infused through the 4Fr Teflon sheath of the rotablator system during the RA procedure. In the nicorandil group, the drug cocktail consisted of 24 mg of nicorandil, 5 mg of nitroglycerin, and 10,000 U of heparin. In the verapamil group, the drug cocktail consisted of 10 mg of verapamil, 5 mg of nitroglycerin, and 10,000 U of heparin. Baseline and procedure characteristics did not differ between the 2 groups. RA was performed successfully, and death, Q-wave myocardial infarction, or emergency coronary artery bypass surgery did not occur in any patients. The no-reflow/slow flow phenomenon was observed in 11/63 (17.4%) lesions of the verapamil group, but in only 1/37 (2.7%) lesions of the nicorandil group (p=0.03). No untoward complications were observed during nicorandil infusion. These data indicate that the intracoronary continuous infusion of nicorandil during RA procedures is easy and safe, and prevents no-reflow/slow flow phenomenon more effectively than infusion of verapamil.",2003.0,0,0
467,12501904,Blood pressure response to antihypertensive agents related to baseline blood pressure.,Anawat Sermswan; Yingnoi Uboldejpracharak; Tavorn Suthichaiyakul; Apichart Sukontasarn; Peera Buranakitcharoen,"Prevalence of white-coat hypertension varies approximately 20 per cent among mild hypertensives. When white-coat hypertensives are prescribed antihypertensive medication, there is usually a decrease in clinic blood pressure (BP), but little or no change in 24 hours blood pressure (ABPM). The objective of the study was to test the hypothesis that efficacy of medication therapy for hypertension is identical in any grading of severity of baseline blood pressure. The authors retrospectively analysed ABPM data from mild to moderate hypertensive patients. Efficacy in decreasing blood pressure by antihypertensives has linear relation to baseline blood pressure. Response to antihypertensive agents in white-coat hypertension is minimal but a significant effect still persists and the possibility of hypotensive adverse events from medication in the case cannot be overlooked.",2003.0,0,0
468,12503252,Citalopram-induced severe hyponatraemia with coma and seizure. Case report with literature and spontaneous reports review.,Alexander Fisher; Michael Davis; James Croft-Baker; Patrick Purcell; Allan McLean,"Numerous case reports of hyponatraemia followed increasing use of selective serotonin re-uptake inhibitors (SSRIs) but this adverse effect was only rarely observed in relation to citalopram. We report a case of severe hyponatraemia associated with deep coma, seizure, atrial fibrillation and muscle damage in a 92-year-old woman after only two doses of citalopram, and review 14 cases previously published in the literature and 28 cases spontaneously reported to Australian Drug Reaction Advisory Committee (ADRAC). The data presented suggest that citalopram, as well as SSRIs may cause hyponatraemia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The majority of symptomatic cases occurred in elderly patients (79% were older than 70 years) and in women (74%). Polymedication and concomitant use of another psychotropic drug or thiazide diuretic may precipitate and/or augment the development of hyponatraemia/SIADH. In 84% of cases, the hyponatraemia associated with citalopram was detected during the first month of treatment. High level of suspicion, close and careful monitoring of serum sodium concentration particularly in elderly patients and especially in the first month of therapy with citalopram may reduce the incidence of this serious and likely not rare adverse effect.",2003.0,0,0
469,12503925,Adverse drug events associated with hospital admission.,Hélène Peyriere; Stéphanie Cassan; Edith Floutard; Sophie Riviere; Jean-Pierre Blayac; Dominique Hillaire-Buys; Alain Le Quellec; Sylvie Hansel,"To increase the knowledge base on the frequency, causality, and avoidability of adverse drug events (ADEs) as a cause for admission in internal medicine or when occurring during hospitalization. A prospective study was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age, gender, medical history), drug utilization, and adverse drug reactions on patients hospitalized during these periods were collected by a pharmacy student. A total of 156 patients (70 men and 86 women) were included in the study. The patients' mean age +/- SD was 66.5 +/- 18.1 years and mean length of stay was 13.2 +/- 9 days. Renal and hepatic insufficiency and previous history of drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases, ADEs were identified as the reason for admission, 10 cases occurred during hospitalization, and 13 cases were present at admission, but were not the cause of admission. The most frequent ADEs involved the neurologic (23.6%), renal (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered avoidable (57.9%); 20 of these were associated with therapeutic errors (inappropriate administration, drug-drug interactions, dosage error, drug not stopped despite the onset of ADEs). Patients with ADEs stayed longer in the hospital and took more drugs both before and during their hospital stay (p < 0.05). Most of the ADEs observed in this study were avoidable. The risk/benefit ratio of administered drugs could be improved with better knowledge of the patients' medical history and the risk factors of ADEs.",2003.0,0,0
470,12504652,"Calcium channel blockers, verapamil and cancer risk.",C La Vecchia; C Bosetti,,2003.0,0,0
471,12504665,Verapamil is associated with an increased risk of cancer in the elderly: the Rotterdam study.,A B Beiderbeck-Noll; M C J M Sturkenboom; P D van der Linden; R M C Herings; A Hofman; J W W Coebergh; H G M Leufkens; B H Ch Stricker,"The association between the use of calcium channel blockers (CCB) and cancer has received ample attention, but is still controversial. In this study, we have tested the hypothesis that the observed association between CCB and cancer in earlier studies could be explained by residual confounding or by misclassification of exposure because of the use of cross-sectional data on drug use. Data from the Rotterdam Study, a prospective population-based cohort study in the municipal area Ommoord, were used. The study population consisted of a cohort of 3204 participants aged 71 years or older who were followed from a baseline interview in the period 1991-1993 for the occurrence of incident cancer. Data on drug use were gathered at baseline and through the seven community pharmacies which served the Ommoord region during the study period between 1 January 1991 and 1 January 1999. Incident cancer events were gathered from a nationwide registry of hospitalisation data and from a specialised cancer centre in the Rotterdam region. We performed three analyses. First, we followed the method, and adjusted for the same risk factors, as in the earlier studies. In the second analysis, we included all risk factors that were univariately associated with cancer in the Rotterdam Study. In the third analysis, we included exposure to CCBs as time-varying co-variates, while adjusting for potential confounders. The relative risk (RR) of cancer associated with CCB was 1.4 (95% Confidence Interval (CI): 0.9-2.0) in the first analysis and lowered to 1.2 (95% CI: 0.8-1.8) upon adjustment for the different co-variates in the second. In both analyses, however, verapamil was significantly associated with cancer with RRs of 2.1 (95% CI: 1.1-4.0) and 2.0 (1.01-3.9), respectively, whereas no associations were found with the other CCB in this study, i.e. diltiazem and nifedipine. A significantly increased risk of cancer was found for intermediate daily doses of verapamil and diltiazem. Intake of other antihypertensives such as beta-blocking agents, diuretics and ACE-inhibitors was not associated with cancer. In the third analysis with exposure to CCB as time-varying co-variates, the risk increase was non-significant for use of 2 years or less, 1.0 (95% CI: 0.7-1.5), and for use for a cumulative period of more than 2 years, 1.3 (95% CI: 0.8-2.0). However, in all models the hazard ratio was statistically significantly increased for verapamil, but not for diltiazem and nifedipine. On the basis of these analyses, we found no increase in cancer in users of diltiazem and nifedipine, nor in users of other antihypertensives. In line with earlier studies, however, we found an increased risk of cancer in users of verapamil. At variance with the conclusions from several other studies, we think that it is too early to conclude that CCB are not associated with cancer.",2003.0,1,1
472,12507022,"The use of sildenafil in patients with erectile dysfunction in relation to diabetes mellitus--a study of 1,511 patients.",K K Ng; H C P Lim; F C Ng; M K Li; D Consigliere; S J Chia; Perianan Moorthy; Malathy Munisamy,"Erectile dysfunction (ED) seriously impairs the quality of life. Patients with diabetes mellitus (DM) are prone to ED due to various factors, including vasculopathy, neuropathy and sex hormone abnormalities. This is a retrospective study involving 1,511 patients taking sildenafil. Patients with DM have significantly more comorbidities like hypertension and ischaemic heart disease. They are also more likely to be on medications which may affect erectile function, including various antihypertensive drugs. 77.9% of patients with DM reported success with sildenafil, as compared to 86.5% of patients without DM. A significant number of patients with DM require a higher dose of sildenafil as compared to those without DM.",2003.0,0,0
473,12508961,"Doxazosin, but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective, randomized-controlled study.",A Yildiz; M Hursit; A V Celik; S M Kayacan; H Yazici; V Akkaya; A O Gürol; K Karsidag,"Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this randomized-controlled study, we aimed to compare the effect of doxazosin and amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female: 5/10, mean age: 46 +/- 13 years) and 9 controls (male/female: 3/6, mean age: 35 +/- 8 years) were included. Patients and controls had no family history of diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker of IR. Patients were grouped randomly to doxazosin (n = 8; 2-4 mg/day) and amlodipine (n = 7; 5-10 mg/day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C peptide, HOMA) were similar between amlodipine and doxazosin groups. There was no difference in age, gender and body mass index among study groups. The follow-up time was 12 weeks. Patients with CRF had higher HOMA (1.83 +/- 0.55 vs 1.00 +/- 0.36, p = 0.001), fasting insulin (8.06 +/- 1.98 vs 4.46 +/- 1.31 IU/l, p < 0.001) and serum triglyceride levels (197 +/- 136 vs 112 +/- 67 mg/dl, p = 0.04) as compared to controls. Serum HDL cholesterol levels were significantly lower in patients with CRF than controls (40 +/- 10 vs 57 +/- 14 mg/dl, p = 0.02). HOMA significantly decreased after doxazosin (1.91 +/- 0.45 vs 1.41 +/- 0.21, p = 0.02), however, no difference was found after amlodipine. Also, fasting insulin levels were decreased after a 12-week doxazosin therapy from 8.17 +/- 1.22 vs 6.58 +/- 0.84 IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did not significantly change during the study period in 2 groups. No adverse effect requiring drug discontinuation was observed during the 12-week period in the study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas amlodipine has no effect. This may be of advantage in the treatment of hypertension in this group of patients for preventing some long-term complication of IR.",2003.0,0,0
474,12508971,Effects of candesartan and amlodipine on renal function and electrolytes in renal allograft recipients.,K Kisters; F Tokmak; M Kosch; M Barenbrock; M Hausberg,,2003.0,0,0
475,12517683,Efficacy and safety of a once daily graded-release diltiazem formulation in essential hypertension.,Stephen P Glasser; Joel M Neutel; Theophilus J Gana; Kenneth S Albert,"The efficacy and safety of a chronotherapeutic, graded-release diltiazem HCl extended-release (GRD) 120-, 240-, 360- and 540-mg dose administered once-daily at bedtime (10 PM) were evaluated in a 7-week randomized, double-blind comparison to placebo and to GRD 360 mg administered once-daily at 8 AM in 478 patients with moderate-to-severe essential hypertension. We assessed the change from baseline to end point in trough diastolic blood pressure (DBP) at 6 PM to 10 PM and in mean DBP from 6 AM to 12 noon between GRD 360 mg PM and GRD 360 mg AM, measured by ambulatory BP monitoring (ABPM). Bedtime doses of GRD showed dose-related mean reductions in trough DBP that were significant for GRD doses of 240 mg and higher. Bedtime GRD 360 mg was associated with a significantly greater reduction in mean DBP between 6 AM and 12 noon compared to morning GRD 360 mg with a least squares mean for treatment difference of -3.3 mm Hg (P =.0004). Similar dose-related and significant reductions in systolic BP (SBP) and heart rate (HR) were obtained. Incidence of adverse events (AEs) for all GRD groups (44.5%) was less than that obtained for the placebo group (49.3%). The 540-mg group showed an incidence of AEs (43.5%) similar to that observed for the 240-mg group (42.6%). The GRD dose-dependently significantly reduces BP and HR over the 24-h interval after once-daily bedtime dosing. Further greater reductions were obtained between 6 AM and 12 noon, when circadian BP is highest, compared to morning administration of the same dose. The 540-mg GRD was safe, well tolerated, and offers further therapeutic option for patients with severe hypertension who required additional BP control.",2003.0,0,0
476,12518180,"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
477,12521949,Drug treatment of hypertension.,Bryan Williams,,2003.0,0,0
478,12523675,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
479,12523681,Comparison of home and office blood pressure in treated hypertensives in the Nordic Diltiazem (NORDIL) Study.,Sverre E Kjeldsen; Thomas Hedner; Jan Otto Syvertsen; Per Lund-Johansen; Lennart Hansson; NORDIL Group. Nordic Diltiazem,"The aim of the Nordic Diltiazem (NORDIL) Study was to compare cardiovascular morbidity and mortality in calcium-antagonist-based treatment with diltiazem and conventional diuretic/beta-blocker-based treatment in essential hypertension. The objective of the present sub-study was to compare self-measured home blood pressure with office blood pressure at a time-point in the study when the patients' blood pressures had been treated to the level that the investigators conceived to be the blood pressure target. The NORDIL study was prospective, randomized, open and endpoint-blinded. It enrolled 10881 patients aged 50-74 years at health centers in Norway and Sweden who had diastolic blood pressure (BP) of 100 mmHg or more. The present sub-study group (n = 87) was small but fairly representative for the entire study population regarding baseline characteristics. Both systolic (4.0 mmHg, p = 0.01) and diastolic blood pressures (3.1 mmHg, p < 0.001) were significantly lower at home than in the office. Pearson correlation coefficients between the respective office and home readings were statistically highly significant (p < 0.001), but of moderate strength ranging from r = 0.41 for heart rate to r = 0.46 and r = 0.58 for diastolic and systolic blood pressures, respectively. Altman plots also gave statistical support to some inconsistency between the two methods of measurements. Pearson correlation coefficients between afternoon and morning measurements showed strong relationships with r-values >0.9 for both blood pressures and heart rate. The Altman plots also suggested excellent consistency between afternoon and morning measurements. Thus, motivated and trained hypertensive patients can perform home recordings of blood pressure and heart rate with precision; however, there are differences between recordings at home and in the investigators' offices that suggest some degree of ""white coat effect"" in these treated hypertensives.",2003.0,0,0
480,12525732,Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.,Wengui Yu; Steven H Horowitz,"Gene mutations within the P/Q type neuronal calcium channel in familial hemiplegic migraine (FHM) suggest a therapeutic role for calcium-channel blockade. The authors have previously reported abortive therapy of FHM with IV verapamil. Here the authors describe four cases of sporadic hemiplegic migraine (SHM) responsive to verapamil, administered either orally or IV. The findings indicate that verapamil is effective therapy for both SHM and FHM.",2003.0,0,0
481,12534433,Antipsychotics and QT prolongation.,D M Taylor,"To evaluate literature relating to cardiac QT prolongation and the use of antipsychotic drugs. Literature searches of EMBASE, Medline, PsychLIT were performed in December 2001 and reference sections of retrieved papers scrutinized for further relevant reports. The Cardiac QTc interval is difficult to measure precisely or accurately but appears to be a useful predictor of risk of dysrhythmia (specifically torsade de pointes) and sudden death. It is less clear that drug-induced QTc prolongation gives rise to similar risks but data are emerging, linking antipsychotic use to increased cardiac mortality. Many antipsychotics have been clearly associated with QTc prolongation. Methodological considerations arguably preclude assuming that any antipsychotic is free of the risk of QTc prolongation and dysrhythmia. Available data do not allow assessment of relative or absolute risk of dysrhythmia or sudden death engendered by antipsychotics but caution is advised. Risk of dysrhythmia can very probably be reduced by careful prescribing of antipsychotics in low doses in simple drug regimens which avoid metabolic interactions. Electrocardiographic monitoring may also help to reduce risk but review by specialist cardiologist may be necessary.",2003.0,0,0
482,12549721,Relieving migraine pain: sorting through the options.,Lisa K Mannix,"Although triptans are a major advance in the treatment of migraine, the optimal approach for acute treatment involves a combination of lifestyle modifications, nonpharmacologic symptom relief, and drug therapy.",2003.0,0,0
483,12551866,Effect of nifedipine and cerivastatin on coronary endothelial function in patients with coronary artery disease: the ENCORE I Study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function).,ENCORE Investigators,"Endothelial dysfunction is an important feature of atherosclerosis. Inhibition of the HMG-CoA pathway and of calcium channels improves endothelial function experimentally and in the forearm circulation. Thus, we investigated the effects of a statin and/or a calcium antagonist on coronary endothelial function in patients with coronary artery disease (CAD). In 343 patients undergoing percutaneous coronary intervention in 29 centers, acetylcholine (10(-6) to 10(-4) mol/L) was infused in a coronary segment without angiographically significant CAD. Changes in coronary diameter were measured by quantitative angiography. Endothelium-independent responses were assessed by intracoronary adenosine (1.2 mg/mL) and nitroglycerin (250 microg). Thereafter, patients were randomized in a double-blind manner to placebo, cerivastatin 0.4 mg/d, nifedipine 30 to 60 mg/d, or their combination. Studies were repeated at 6 months. In the most constricted segment, nifedipine but not cerivastatin reduced vasoconstriction to acetylcholine (18.8% versus placebo 10.0%; P<0.05). Patients not taking ACE inhibitors showed a smaller improvement in the placebo group (6.0%), but nifedipine still had an effect (17.0%; P<0.05 versus placebo). Analysis of all evaluable coronary segments revealed an 11% reduction of acetylcholine-induced vasoconstriction in patients receiving nifedipine and cerivastatin (P<0.05 versus placebo). Cerivastatin lowered LDL cholesterol by 35% (P<0.001). The ENCORE I trial demonstrates that multicenter studies on coronary endothelial function are feasible. After 6 months' treatment, nifedipine improved coronary endothelial function in the most constricted segment. The combination of nifedipine and cerivastatin tended to improve endothelial function; however, this only reached significance in an analysis of all coronary segments.",2003.0,0,0
484,12556647,The ALLHAT report: a case of information and misinformation.,Michael A Weber,,2003.0,0,0
485,12562110,Amlodipine reduces blood pressure and headache frequency in cocaine-dependent outpatients.,Robert Malcolm; Jason Liao; Melissa Michel; Kristina Cochran; Wesley Pye; Derik Yeager; Perry V Halushka,"Blood pressure and headache frequency were evaluated in normotensive male and female cocaine-dependent patients (N=43) participating in a placebo-controlled, double-blind trial of amlodipine for the treatment of cocaine dependence. Amlodipine produced a significant reduction in both systolic (p=0.04) and diastolic (p=0.01) blood pressures without producing dizziness or faintness. Placebo subjects had about three times the frequency of headaches compared to the amlodipine-treated subjects (p=0.004). The high frequency of headaches reported by cocaine-dependent individuals was significantly reduced by amlodipine and may reflect improved cerebrovascular tone.",2003.0,0,0
486,12565082,Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris.,Carl J Pepine; Rhonda M Cooper-DeHoff; Robert J Weiss; Michael Koren; Neville Bittar; Udho Thadani; Margaret C Minkwitz; Eric L Michelson; Howard G Hutchinson; Comparative Efficacy and Safety of Nisoldipine and Amlodipine (CESNA-II) Study Investigators,"The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n = 120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to 10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p = NS/p = NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldipine-ER and 78% of patients on amlodipine, p = NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p = NS], and increasing exercise time >60 seconds in 32% and 29% of patients, respectively [p = NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p = NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including headache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisoldipine-ER and amlodipine provided comparable antihypertensive and anti-ischemic efficacy, and both were generally well tolerated.",2003.0,0,0
487,12568207,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.",2003.0,0,0
488,12569290,"Effects of interferon-alpha, verapamil and dacarbazine in the treatment of advanced malignant melanoma.",Ronny Andersson; Per Ake Hofer; Katrine Riklund-Ahlström; Roger Henriksson,"Treatment of patients with metastatic melanoma with either dacarbazine (DTIC) or interferon-alpha (IFNalpha) as single drugs, or in combination, results in a response rate of approximately 15-20%. This study evaluated the activity and toxicity following treatment with a combination of DTIC, IFNalpha2b and verapamil (VPL). Thirty patients with disseminated metastatic melanoma received DTIC 250 mg/m(2) on days 1-5 of a 4 week schedule, IFNalpha2b 3 MIU on days 1-5 each week, and VPL 80 mg three times a day throughout the cycle, until either disease progression or serious toxicity was observed. Among the 28 evaluable patients, there were four complete responses (CRs), five partial responses (PRs) and eight patients with stable disease (SD). The overall response rate (CR + PR) was 32%. Two patients with a CR were long-term survivors (45 and 34 months) and a third is still in complete remission after 49 months. The fourth CR patient relapsed and died with progressive brain metastases after 8 months. Among the eight patients with SD, one survived for 22 months and another for 34 months. Despite one toxic death, these results suggest that this treatment regimen is well tolerated and seems to be more effective than DTIC alone in a subset of patients. A controlled randomized study would be required to determine the value of adding VPL and IFNalpha2b to DTIC.",2003.0,0,0
489,12574098,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
490,12574790,Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment.,A Zervoudaki; E Economou; C Stefanadis; C Pitsavos; K Tsioufis; C Aggeli; K Vasiliadou; M Toutouza; P Toutouzas,"This study was designed to test the hypothesis that plasma concentrations of matrix metallo-proteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P=0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances <1440 dyn s/cm(5) exhibited higher values of MMP-2 (P=0.005) and MMP-9 (P=0.001) than hypertensive patients with systemic vascular resistances >1440 dyn s/cm(5). Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P=0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.",2003.0,0,0
491,12578880,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.",2003.0,0,0
492,12580832,An update on the controversies of tocolytic therapy for the prevention of preterm birth.,Ingemar Ingemarsson; Ronald F Lamont,"Preterm birth is the major cause of perinatal mortality and morbidity in the developed world. Where there are no contraindications to their use, tocolytics can improve neonatal survival rates by approximately 3% per day between 23 and 27 weeks gestation with a concomitant reduction in morbidity. The ultimate aim of tocolytic therapy is to prolong pregnancy until growth and maturation is complete, but even short-term delay may enable the administration of antepartum glucocorticoids to reduce hyaline membrane disease or to arrange transfer to a center with neonatal intensive care facilities. Both of these have been shown to reduce neonatal mortality and morbidity. Until recently, none of the currently used tocolytics, whether licensed or unlicensed, were developed specifically for the inhibition of preterm labor and consequently, they exhibit various potentially serious side-effects. As a result of the recent licensing of the oxytocin antagonist, atosiban, developed for the treatment of preterm labor and due to its high utero-specificity, obstetricians have experienced an advance in their options for the management of spontaneous preterm labor.",2003.0,0,0
493,12584577,A basic conceptual and practical overview of interactions with highly prescribed drugs.,George K Dresser; David G Bailey,"Drug interactions are frequently the result of altered activity of the mechanism(s) responsible for drug elimination. These include drug metabolism mediated by a select group of cytochrome P450 enzymes (CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2) and drug transporters (P-glycoprotein). Adverse drug interactions can result from induction (loss of therapeutic benefit) or inhibition (increased toxicity from excessive effect) of drug elimination. CYPs and P-glycoprotein are discussed individually with regards to their characteristics, frequently prescribed drug substrates, inducers and inhibitors, and important adverse drug events. The potential for important drug interactions can be predicted based on the properties of the causative agent (oral bioavailability, mechanism of elimination, seriousness of adverse event) and the interacting agent. Consequently, drug interactions can be prevented by avoiding concomitant administration of interacting substances or possibly implementing alternative therapeutic strategies. Furthermore, susceptibility to adverse events depends not only on the interacting substances, but also on the patient and the method of drug administration. Commonly prescribed drugs that are unlikely to cause a drug interaction involving CYPs or P-glycoprotein are also discussed.",2003.0,0,0
494,12602564,Antihypertensive treatment in the elderly.,Giulio Masotti,,2003.0,0,0
495,12615382,Treatment of the scorpion envenoming syndrome: 12-years experience with serotherapy.,M Ismail,"The pathophysiology of the scorpion envenoming syndrome is described with emphasis on the body systems commonly affected. Concepts of the mechanisms underlying venom action, as can be explained by the recently discovered effects on ionic channels, are discussed. A protocol for the treatment of scorpion stings based mainly on antivenom therapy was applied nationwide in Saudi Arabia. A list of drugs with alternatives was specified to be used in adjunctive therapy, when required. Analysis of the outcome from 1,033 cases at Al-Baha region, 791 cases at Al-Qassim region and more than 2,000 cases from 12 central and specialist hospitals in the Central Province, Saudi Arabia gave impressive results. The incidence of severe venom toxicity following antivenom administration was almost negligible. The period of stay in the hospital was reduced. The early reaction to antivenom administration was lower than expected the severity of the reaction consisting mainly of skin rashes, urticaria, wheezing and bronchial hypersensitivity, but no anaphylaxis. About 13.8% of the victims had been previously treated with antivenom but only 1.7% of the patients showed positive skin tests. This might be due to the low protein content of the antivenom and the action of the venom in releasing massive amounts of catecholamines.",2003.0,0,0
496,12615758,Long-term management of atrial fibrillation: rhythm or rate control?,Katherine A Kovacs,,2003.0,0,0
497,12620169,Is topical nifedipine effective for chronic anal fissures?,Dan Merenstein; Dan Rosenbaum,"Patients in this study showed remarkable improvement when 1.5% lidocaine and 0.3% nifedipine were applied twice daily for 6 weeks. This extremely safe, well tolerated, and effective treatment should provide family physicians with a reliable nonsurgical method for treating chronic anal fissures.",2003.0,0,0
498,12623939,Outcomes with nifedipine GITS or Co-amilozide in hypertensive diabetics and nondiabetics in Intervention as a Goal in Hypertension (INSIGHT).,Giuseppe Mancia; Morris Brown; Alain Castaigne; Peter de Leeuw; Christopher R Palmer; Talma Rosenthal; Gilbert Wagener; Luis M Ruilope; INSIGHT,"To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.5 mg amiloride) daily. Doses were doubled if target blood pressures (<140/90 mm Hg) were not achieved. Primary (composite of cardiovascular death, myocardial infarction, heart failure, and stroke) and secondary outcomes (composite of primary outcomes, including all-cause mortality and death from vascular and nonvascular causes) were assessed by means of intent-to-treat analyses. There was no significant difference in the incidence of primary outcomes between nifedipine-treated and co-amilozide-treated patients with diabetes at baseline (n=1302) (8.3% versus 8.4%; relative risk, 0.99, 95% CI, 0.69 to 1.42; P=1.00). A significant benefit for nifedipine-treated patients was seen for the composite secondary outcome (14.2% versus 18.7%; relative risk, 0.76, 95% CI, 0.59 to 0.97; P=0.03). Among patients without diabetes at baseline (n=5019), there was a significant difference in the incidence of new diabetes (nifedipine 4.3% versus co-amilozide 5.6%, P=0.023). Nifedipine GITS once daily is as effective as diuretic therapy in reducing cardiovascular complications in hypertensive diabetics. Nifedipine-treated patients were also less likely to have diabetes or have secondary events (a composite of all-cause mortality, death from a vascular cause, and death from a nonvascular cause) than co-amilozide recipients. Our results suggest that nifedipine could be considered as first-line therapy for hypertensive diabetics.",2003.0,1,1
499,12623959,Short-versus long-term effects of different dihydropyridines on sympathetic and baroreflex function in hypertension.,Guido Grassi; Gino Seravalle; Carlo Turri; GianBattista Bolla; Giuseppe Mancia,"Antihypertensive treatment with dihydropyridines may be accompanied by sympathetic activation. Data on whether this is common to all compounds and similar in the various phases of treatment are not univocal, however. In 28 untreated essential hypertensives (age, 56.4+/-1.8 years; mean+/-SEM) finger blood pressure (BP, Finapres), heart rate (HR, ECG), plasma norepinephrine (NE, high-performance liquid chromatography), and muscle sympathetic nerve traffic (MSNA, microneurography) were measured at rest and during baroreceptor manipulation (vasoactive drugs) in the placebo run-in period and after randomization to double-blind acute and chronic (8 weeks) felodipine (10 mg/d, n=14) or lercanidipine (10 mg/d, n=14). Acute administration of both drugs induced pronounced BP reductions and marked increases in HR, NE, and MSNA. After 8 weeks of treatment, BP reductions were similar to those observed after acute administration, whereas HR, NE, and MSNA responses were markedly attenuated (-7%, -32%, and -14%, respectively; P<0.05). There was a small residual increase in sympathetic activity in the felodipine group, whereas in the lercanidipine group, all adrenergic markers returned to baseline values. Baroreflex control of HR and MSNA was markedly impaired (-42% and -48%, respectively) after acute drug administration, with a recovery and complete resetting during chronic treatment. Thus, the sympathoexcitation induced by 2 different dihydropyridines is largely limited to the acute administration. The 2 drugs have, nevertheless, a different chronic sympathetic effect, indicating that dihydropyridines do not homogeneously affect this function. The acute sympathoexcitation, but not the small between-drugs differential chronic adrenergic effect, is accounted for by baroreflex impairment.",2003.0,0,0
500,12624612,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
501,12624613,Stenting of a renal artery compressed by the diaphragm.,J P Baguet; F Thony; C Sessa; J M Mallion,"A 74-year-old man had a resistant hypertension with an increase in plasma aldosterone and active plasma renin levels, and an irregular appearance of the left kidney outline by ultrasound. The CT scan showed a stenosis of the left renal artery, which was pushed against the aorta by the left crus of the diaphragm. An angioplasty with placement of an autoexpansible stent was carried out with a good result on the arterial pressure level. After 3 years, the patient was re-hospitalised with severe hypertension. The CT scan demonstrated a compression of the stent by the left crus of the diaphragm, with good permeability of the artery downstream from the stent, and radiographic examination showed a fracture of the left renal artery stent. Thus, a reimplantation of the left renal artery in the aorta was carried out. Stenosis of the renal artery by fibres from a crus of the diaphragm is a rare cause of renovascular hypertension. Helicoidal angioscanner imaging is particularly useful to do the diagnosis. In the present case, renal angioplasty with stenting was complicated by a fracture of the stent that led to the surgery. Thus, when renal artery stenosis by a crus of the diaphragm is diagnosed, surgical treatment needs to be considered on a case-by-case basis in relation to the anatomy and the biological and functional data.",2003.0,0,0
502,12628083,Treatment of arrhythmias during pregnancy.,Deborah Wolbrette,"During pregnancy, significant changes occur in the hormonal and hemodynamic state of women that make arrhythmias more likely to occur. Palpitations are frequently reported, but are usually found to be associated with sinus tachycardia. The incidence of paroxysmal supraventricular tachycardia is increased during pregnancy, whereas atrial fibrillation and ventricular tachycardia are rarely seen. Women with long QT syndrome experience significantly more cardiac events in the postpartum period, making beta-blocker therapy most important during this time. Acute treatment of arrhythmias for pregnant women is much the same as that for nonpregnant patients. However, chronic drug therapy during pregnancy should be reserved for only the frequent, hemodynamically significant arrhythmia episodes.",2003.0,0,0
503,12629334,Peyronie's disease: a review.,Shahram S Gholami; Nestor F Gonzalez-Cadavid; Ching-Shwu Lin; Jacob Rajfer; Tom F Lue,"We provide a current review of Peyronie's disease. We reviewed the world peer reviewed literature on the pathology, pathogenesis, diagnosis and treatment of Peyronie's disease. The incidence of Peyronie's disease has continuously increased during the last 30 years. However, fewer patients need prosthesis surgery as the sole treatment option because of earlier diagnosis, improved medical therapy, refinement in surgical technique and better understanding of the basic sciences of the disease. Currently patients with Peyronie's disease have had improvements in prognosis and experienced an expansion of the available therapeutic options.",2003.0,0,0
504,12629592,Delayed presentation of calcium channel antagonist overdose.,Gopikrishna Punukollu; Ramesh M Gowda; Ijaz A Khan; Ozgen M Dogan,"The calcium channel antagonists are generally safe in therapeutic dosage, but severe side effects with elevated intake are increasingly described. Typical features include confusion, lethargy, hypotension, sinus node depression, and cardiac conduction defects. Even if patients are stable on presentation, this does not preclude the possible late development of adverse events from the long-acting formulations of calcium channel blockers. A case of toxic overdose with 1440 mg of slow-release diltiazem is presented; this patient was stable on presentation, but rapidly became hemodynamically unstable, requiring treatment with intravenous calcium, temporary pacemaker, inotropic support and mechanical ventilation with a successful outcome. A concise review of the therapeutic considerations is provided.",2003.0,0,0
505,12649609,Stroke units - the Norwegian experience.,Bent Indredavik,"The main aims of acute stroke care should be to reduce death and disability. Treatment in stroke units is the only treatment option proven to reduce death in acute stroke patients. Stroke unit care is also the only treatment which has shown a marked reduction in disability for general stroke patients, and also the only treatment with beneficial long-term effects on survival, disability and quality of life. Most acute hospitals in Norway have established stroke units. The recommended stroke unit model is a non-intensive combined unit able to focus simultaneously both on acute care and rehabilitation. This model has been very well evaluated in randomised trials and has achieved some of the best results regarding acute stroke care. Hence one can probably conclude that stroke unit care in Norway is evidence based.",2003.0,0,0
506,12651674,Esmolol blunts the cerebral blood flow velocity increase during emergence from anesthesia in neurosurgical patients.,Philippe Grillo; Nicolas Bruder; Pascal Auquier; Daniel Pellissier; François Gouin,"Cerebral hyperemia has been demonstrated during emergence from anesthesia in neurosurgical patients, but its mechanism is speculative. We performed this study to test the hypothesis that this could be attributed to sympathetic overactivity. Thirty neurosurgical patients were included in a prospective, randomized, double-blinded study comparing esmolol, a short-acting beta-blocker, and a placebo. Esmolol (0.3 mg. kg(-1). min(-1)) was infused from the end of anesthesia to 15 min after extubation. Cerebral blood flow velocity (CBFV), mean arterial blood pressure, and heart rate were recorded before anesthesia, during anesthesia after surgery, at extubation, and 5-60 min after extubation. Cardiac output (COe) was estimated by using an esophageal Doppler from anesthesia to 60 min after extubation. CBFV, COe, and heart rate were significantly lower in the esmolol group. Mean arterial blood pressure was comparable between the groups. There was no correlation between CBFV and COe at any time point during the study. In conclusion, esmolol blunted the CBFV increase during emergence, confirming that sympathetic overactivity contributes to cerebral hyperemia during neurosurgical recovery. Esmolol blunted the postoperative increase in cerebral blood flow velocity in neurosurgical patients. The origin of sympathetic hyperactivity and its potential deleterious consequences require further study.",2003.0,0,0
507,12652105,Antihypertensive medication and quality of life--silent treatment of a silent killer?,A Douglas Bremner,"Hypertension is one of the major killers in the modern world and one of the great ironies of the disease is that it has little or no immediate effect on affected individuals' quality of life (QOL). This makes treatment very difficult, as most medications will affect QOL negatively, either through side effects or through the change in life-style associated with chronic drug regimens. This review describes some of the conceptual background for QOL measurements and looks at the effects on QOL of different antihypertensive treatments available today. The latest addition to the range of antihypertensive drugs, angiotensin II-receptor blockers, may be a significant step forward in treatment, as their ease of dosing and excellent tolerability minimise negative effects on patients while their possible benefits on factors such as sexual function may even improve QOL in hypertensive patients.",2003.0,0,0
508,12653877,Health economics in the Hypertension Optimal Treatment (HOT) study: costs and cost-effectiveness of intensive blood pressure lowering and low-dose aspirin in patients with hypertension.,B Jönsson; L Hansson; N-O Stålhammar,"To investigate the marginal cost-effectiveness of different targets for the reduction of blood pressure and the cost-effectiveness of adding acetylsalicylic acid (ASA) to the treatment of hypertension. Patients with hypertension were randomized to three target groups for blood pressure; < or =90, < or =85 and < or =80 mmHg. Patients were also randomly assigned ASA and placebo. The average follow-up time was 3.8 years. The direct costs for drugs, visits, hospitalizations, and side-effects were calculated and related to clinical outcome. Resource utilization data from all the 26 countries in the study were pooled, and Swedish unit costs were applied to the aggregated resource utilization. A total of 18 790 patients, 50-80 years of age (mean 61.5 years), with a diastolic blood pressure between 100 and 115 mmHg (mean 105 mmHg). Antihypertensive treatment with the long-acting calcium antagonist felodipine was given to all patients. Additional therapy and dose increments in four further steps were prescribed to reach the randomized target blood pressure. Fifty per cent of the patients were randomized to a low dose, 75 mg daily, of acetylsalicylic acid. Direct health care costs, major cardiovascular (CV) events (myocardial infarction and stroke) and CV death. The average cost of drugs and visits increased with more intensive treatment. The increase in treatment costs was partly but not fully offset by a nonsignificant reduction in the cost of CV hospitalizations. For patients with diabetes there were no significant differences in total cost between the target groups. The cost of avoiding a major CV event was negative in the base case analysis, SEK -10 360 (CI: -78 195, 75 630), and SEK 18 450 (CI: -88 789, 192 980) in a sensitivity analysis. For patients on ASA, costs were slightly but significantly higher than for patients on placebo. The estimates of the cost of avoiding a major CV event varied between SEK 41 600 and SEK 477 400, with very wide confidence intervals. The treatment cost increases as the target for hypertension treatment is lowered. In patients with diabetes, intensive treatment to a lower target is cost-effective. Because of the nonsignificant difference in events, no conclusion can be made for all patients in the study. Furthermore, no conclusive evidence was found regarding the cost-effectiveness of adding ASA to the treatment of hypertension.",2003.0,0,0
509,12658059,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
510,12659989,Treatment of stable angina with low dose diltiazem in combination with the metabolic agent trimetazidine.,S C Manchanda,"The risk/benefit of moderate to high doses of calcium antagonists in stable angina is uncertain. This study investigates the efficacy and acceptability of low dose diltiazem in combination with trimetazidine for the treatment of stable angina. In a 28-day, randomized, double blind study, treatment with 90 mg diltiazem in combination with 60 mg trimetazidine or placebo per day was compared in 50 patients with stable angina. The primary outcomes were time to 1-mm ST segment depression and the Duke treadmill score. Of the 25 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was, in time to 1-mm ST segment depression, 13 (52) versus 5 (20), P<0.05; in the Duke treadmill score, 18 (72) versus 8 (32), P<0.01; and in angina 17 (68) versus 3 (12), P<0.01. Compared to placebo there was an improvement with trimetazidine in mean exercise time to 1-mm ST segment depression of 128 s (95% confidence interval 45.0-208.5; P<0.01); in the mean Duke treadmill score of 57.4% (95% confidence interval 9.9-100; P<0.02); and in mean anginal attacks of 5.1 per week (95% confidence interval, 3.1-7.3, P<0.01). The combination of low dose diltiazem with trimetazidine is effective with few side-effects in the symptomatic control of patients with stable angina.",2003.0,0,0
511,12667024,Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy.,Tomas Berl; Lawrence G Hunsicker; Julia B Lewis; Marc A Pfeffer; Jerome G Porush; Jean-Lucien Rouleau; Paul L Drury; Enric Esmatjes; Donald Hricik; Chirag R Parikh; Itamar Raz; Philippe Vanhille; Thomas B Wiegmann; Bernard M Wolfe; Francesco Locatelli; Samuel Z Goldhaber; Edmund J Lewis; Irbesartan Diabetic Nephropathy Trial. Collaborative Study Group,"Patients with diabetes have increased risk for adverse cardiovascular events. Angiotensin-converting enzyme inhibitors are protective in type 1 diabetes. However, no definitive studies have examined the use of angiotensin-receptor blockers in patients with type 2 diabetes and overt nephropathy. The primary outcomes of the Irbesartan Diabetic Nephropathy Trial were doubling of serum creatinine levels, end-stage renal disease, and death from any cause. To compare rates of cardiovascular events among patients with type 2 diabetic nephropathy who received conventional antihypertensive therapy with an angiotensin-receptor blocker (irbesartan) or a calcium-channel blocker (amlodipine), or placebo. Randomized double-blind, placebo-controlled trial with a median follow-up of 2.6 years. A time event analysis was used. 209 centers in the Americas, Europe, Israel, and Australasia. 1715 adults with type 2 diabetic nephropathy and hypertension; serum creatinine levels of 89 micromol/L (1.0 mg/dL) to 266 micromol/L (3.0 mg/dL) in women and 106 micromol/L (1.2 mg/dL) to 266 micromol/L (3.0 mg/dL) in men; and urinary protein excretion rates of at least 900 mg/d. Treatment with irbesartan, amlodipine, or placebo. Time to cardiovascular death, myocardial infarction, congestive heart failure, strokes, and coronary revascularization. The three groups were not statistically different in the composite of cardiovascular events. Among the components of the composite, there was a trend toward a decrease in strokes in patients receiving amlodipine versus those receiving placebo (hazard ratio, 0.65 [95% CI, 0.35 to 1.22]; P = 0.18). Likewise, patients receiving amlodipine had a significantly lower rate of myocardial infarction when compared with placebo recipients (hazard ratio, 0.58 [CI, 0.37 to 0.92]; P = 0.02). In contrast, patients receiving irbesartan had a significantly lower incidence of congestive heart failure when compared with placebo recipients (hazard ratio, 0.72 [CI, 0.52 to 1.00]; P = 0.048) or amlodipine recipients (hazard ratio, 0.65 [CI, 0.48 to 0.87]; P = 0.004). The composite cardiovascular event rate did not differ in patients with type 2 diabetes and overt nephropathy treated with irbesartan, amlodipine, or placebo in addition to conventional antihypertensive therapy.",2003.0,0,0
512,12678218,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
513,12682082,Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.,William B White; Daniel Duprez; Richard St Hillaire; Scott Krause; Barbara Roniker; Janice Kuse-Hamilton; Michael A Weber,"Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.",2003.0,0,0
514,12682621,The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis.,A R Odabas; R Cetinkaya; Y Selcuk; S Keles; H Bilen,"In some of the patients undergoing haemodialysis, (HD) resistance might develop against recombinant human erythropoietin (rHuEPO) used for treatment of anaemia. Recently, angiotensin-converting enzyme (ACE) inhibitors that are used to treat hypertension and congestive heart failure in HD patients have been suggested to contribute to anaemia as well by inhibiting erythropoiesis. Our purpose in this study is to investigate whether or not losartan, an angiotensin II (ATII) receptor antagonist, is causing rHuEPO resistance. In this prospective study of 12 months, we compared the effects of high dose losartan (100 mg/day) and amlodipine (10 mg/day) on rHuEPO requirement in 40 hypertensive patients receiving rHuEPO for more than 12 months on maintenance HD. Twenty normotensive rHuEPO dependent patients served as control group. Iron deficiency, hyperparathyroidism, aluminium intoxication, infections and inflammations were excluded in all patients. The mean haemoglobin level was found >8 g/dl in all groups. The mean weekly rHuEPO dose increased in the losartan group (p<0.0001 vs before) and remained constant in the other groups. No significant differences were found with PTH, iron status, aetiologies of renal failure in all groups. High-dose losartan increases rHuEPO requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications.",2003.0,0,0
515,12685512,Effects of nicardipine and clonidine on cognitive functions and electroencephalography in hypertensive patients.,T Denolle; P Sassano; H Allain; D Bentué-Ferrer; S Breton; I Cimarosti; B Ouatara; M Merienne; J M Gandon,"The aim of this study was to investigate the cognitive and electroencephalography (EEG) short-term effects of a calcium antagonist, nicardipine, compared to placebo and clonidine (which, having known sedative effects, acted as a negative control) for 15 days in elderly hypertensive patients with memory complaints. Nicardipine and clonidine were compared with placebo in a double-blind, randomized, three-way cross-over controlled study after a 2-week placebo run-in period. This was a phase II clinical study carried out on out-patients in a single research centre. Fifteen elderly (63 +/- 10 years) hypertensive patients, without dementia but with memory complaints, were included. Psychomotor performance and cognition were assessed using both an extensive battery of validated psychometric tests (which evaluated attention and vigilance, body sway and memory) and an EEG profile. Cardiovascular parameters measured were blood pressure and heart rate. No detrimental effects of nicardipine were found on attention, vigilance, body sway or memory. Nicardipine produced a significant increase in alpha EEG energies, which may indicate possible alerting effects. In contrast, clonidine induced well-known deleterious sedative effects in psychometric tests and in EEG analysis (decrease in alpha and increase in delta and theta waves). The two drugs produced equivalent decreases in blood pressure at steady state. In conclusion, clonidine induced well-known sedative effects, while nicardipine did not impair central nervous system activity and may have had some short-term alerting effects in elderly hypertensive patients with memory complaints. This study supports the hypothesis of a dissociation between blood pressure and direct drug effects on the central nervous system.",2003.0,0,0
516,12685513,"Randomized, comparative, double-blind study of amlodipine vs. nicardipine as a treatment of isolated systolic hypertension in the elderly.",Claire Mounier-Véhier; Olivier Jaboureck; Jean-Paul Emeriau; Corine Bernaud; Pierre Clerson; Alain Carre,"A 90-day, multicenter, randomized, double-blind, parallel-group study was conducted to compare the efficacy of amlodipine (once a day) with nicardipine (two to three times a day), in the treatment of isolated systolic hypertension (ISH) in the elderly. Patients (n = 133) aged > or = 60 years, with ISH were randomized to receive either amlodipine 5 mg/day, or nicardipine 60 mg/day (titrated if necessary to 10 mg/day and 100 mg/day, respectively) for 90 days. Efficacy was assessed by measuring office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM). The two treatments substantially and comparably reduced office systolic blood pressure (SBP) and pulse pressure (PP), and also produced a slight decrease in diastolic blood pressure (DBP). Amlodipine reduced SBP, as assessed by ABPM, to a significantly greater extent than nicardipine. Both treatments were well-tolerated. The sustained effect of amlodipine, compared with nicardipine, was reflected in its significantly greater antihypertensive activity, particularly during the nocturnal period, as assessed by ABPM. The study demonstrates that once a day dose of amlodipine is an effective antihypertensive treatment for elderly ISH patients.",2003.0,0,0
517,12694073,Relative perioperative bradycardia does not lead to adverse outcomes after cardiac transplantation.,Daniel R Goldstein; Christopher S Coffey; Raymond L Benza; Navin C Nanda; Robert C Bourge,"Since the effects of bradycardia after cardiac transplantation are not known, we tested the hypothesis that perioperative bradycardia would lead to an increase in adverse outcomes after cardiac transplantation. We conducted a retrospective case control study with inclusion criterion of a heart rate (HR) less than 80 bpm during the 1st week after transplantation. Control patients were matched for gender, age and time since transplantation. We identified 34 patients as having perioperative bradycardia out of the 174 who underwent cardiac transplantation between 1994 and 1997. The results demonstrated no significant differences in donor ischemic times (180 vs. 183, p = 0.88), operative surgeon (p = 0.62) or pretransplant cardiac disease (p = 0.81) between groups. Bradycardic patients were more likely to be on pretransplant amiodarone (RR = 20.4, p < 0.001). Perioperative bradycardia did not lead to increases in cellular rejection (p = 0.72) or vasculopathy (p = 0.79). The patients prescribed pretransplant amiodarone (n = 14) had a trend toward delayed time to first rejection episode (31.0 vs. 15.5 days, median, p = 0.07). In conclusion, perioperative bradycardia does not increase adverse outcomes after cardiac transplantation and is associated with pretransplant use of amiodarone. Amiodarone may modify the recipients' immune response by delaying the occurrence of rejection.",2003.0,0,0
518,12694079,Review article: Non-alcoholic fatty liver disease.,L M Alba; K Lindor,"Non-alcoholic fatty liver disease is a clinicopathological condition that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. Non-alcoholic steatohepatitis represents only a stage within the spectrum of non-alcoholic fatty liver disease and is defined pathologically by the presence of steatosis together with necro-inflammatory activity. The true prevalence of non-alcoholic fatty liver disease is unknown, but it is estimated that it affects 10-24% of the general population in different countries. The diagnosis of non-alcoholic fatty liver disease is based upon convincing evidence of absent or minimal alcohol consumption, compatible histological changes in liver biopsy and the exclusion of other liver diseases. The natural history of non-alcoholic fatty liver disease remains to be defined. Patients with pure steatosis on liver biopsy follow a relatively benign course, whereas patients with histological necro-inflammatory changes and/or fibrosis may progress to end-stage liver disease. An initial step in the treatment of non-alcoholic fatty liver disease is the management of associated conditions, such as obesity, diabetes mellitus and hyperlipidaemia. Non-alcoholic fatty liver disease patients with steatohepatitis and/or fibrosis on liver biopsy may benefit from investigational pharmacological therapy. Patients with decompensated cirrhosis from non-alcoholic fatty liver disease may be candidates for liver transplantation.",2003.0,0,0
519,12699135,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
520,12704598,Long QT syndrome caused by noncardiac drugs.,Sami Viskin; Dan Justo; Amir Halkin; David Zeltser,"Numerous medications not intended for cardiac use (including antibiotics, histamine blockers, and antipsychotic medications) incidentally block potassium channels in myocardial cells, prolong the QT interval, and may trigger malignant arrhythmias. Although the odds for a given patient for developing arrhythmias are small, the number of patients receiving such drugs is enormous. Most patients developing proarrhythmia have additional risk factors that could be easily identified from their medical history. The list of risk factors includes female gender, organic heart disease, hypokalemia, and a history of long QT or drug-induced arrhythmias. Patients without risk factors are at very low risk. For these patients, it is neither practical nor necessary to record an electrocardiogram before therapy is initiated and the most important preventive measure is to avoid concurrent administration of 2 or more drugs that prolong the QT interval or administration of a medication that impairs the metabolism of a QT-prolonging drug. We performed a computerized literature search using the key words ""long QT,"" ""torsade,"" ""drug-adverse effects,"" and ""drug-ventricular arrhythmias,"" searching for published reports of drug-induced torsade de pointes. The references in each of these reports also were reviewed to identify additional publications. In addition, we reviewed the published reviews and the Internet sites dealing with drug-induced arrhythmias. All the original articles quoted in these reviews and Web sites were examined critically.",2003.0,0,0
521,12709465,Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.,Henry R Black; William J Elliott; Gregory Grandits; Patricia Grambsch; Tracy Lucente; William B White; James D Neaton; Richard H Grimm; Lennart Hansson; Yves Lacourciere; James Muller; Peter Sleight; Michael A Weber; Gordon Williams; Janet Wittes; Alberto Zanchetti; Robert J Anders; CONVINCE Research Group,"Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.",2003.0,1,1
522,12710864,Cardiovascular drug therapy in the elderly: theoretical and practical considerations.,Bradley R Williams; Jiwon Kim,"The elderly population is expanding rapidly throughout the world. Hypertension, heart disease and other cardiovascular disorders are prevalent conditions among this age group. Consequently, clinicians will spend a large proportion of their practices managing older adults with cardiovascular disorders. A large proportion of this time will be devoted to using pharmacotherapeutic strategies for the long-term management of chronic conditions. The physiological changes that accompany aging affect cardiovascular function, and the pharmacokinetics and pharmacodynamics of many cardiovascular medications are altered by these physiological changes. The interactions of these changes can have a profound effect on the agents used to treat cardiovascular disorders and may alter their therapeutic outcomes. Several classes of medications are used to treat chronic cardiovascular disorders in older adults. These include the ACE inhibitors and angiotensin II receptor antagonists, calcium channel antagonists, beta-adrenoceptor antagonists (beta-blockers), oral antiarrhythmic agents and warfarin. Drugs such as beta-blockers may aggravate decreased cardiac output and increase peripheral resistance, but are valuable adjuncts in many patients with congestive heart failure. Agents that reduce angiotensin II activity may have several benefits for treating heart failure and hypertension. Successful treatment of cardiovascular disorders in older adults requires the choice of the most appropriate agent, taking into consideration the complex interactions of pharmacokinetics, pharmacodynamics and disease effects.",2003.0,0,0
523,12714127,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
524,12714973,"Shifting trends in the pharmacologic treatment of hypertension in a Nigerian tertiary hospital: a real-world evaluation of the efficacy, safety, rationality and pharmaco-economics of old and newer antihypertensive drugs.",A Q Adigun; D A Ishola; A O Akintomide; A A L Ajayi,"The current prescription patterns for essential hypertension and the efficacy, safety, tolerability and cost-effectiveness of the newer antihypertensive drugs were evaluated in Nigerian patients. The findings were compared with that of a previous study conducted in the same tertiary hospital 10 years earlier. A cross-sectional evaluation of blood pressure (BP) control in a hypertension clinic was undertaken among 150 Nigerian patients aged 61 +/- 12 years (55% females), with a duration of treatment on a particular drug class or combination of 9 +/- 3 months. The initial blood pressure was 176 +/- 20/108 +/- 11 mmHg and 22% of the patient had concurrent diabetes mellitus. Thiazide diuretics (D) alone or in combination remained the most commonly prescribed drugs in 56% of all patients. There were significant increases in the prescriptions of calcium channel blockers (CCBs) (51%), P < 0.0001, and ACE-inhibitors (ACEIs) (24%), P < 0.0001, but a slight reduction in the use of methyldopa, and fixed drug combinations (P < 0.01) compared to the previous study. The fall in systolic blood pressure on D (r = 0.65, P < 0.001) or CCB (r = 0.48, P < 0.02) was significantly correlated with the initial systolic blood pressure, but not age. More patients achieved normotension BP < 140/90 mmHg on CCB monotherapy (71%), than D monotherapy (56%). Combination therapy with ACEIs + D or methyldopa+thiazides normalized BP in 63 and 68%, respectively. Pulse pressure, a surrogate marker for cardiovascular complications and mortality in essential hypertension, was significantly reduced (P < 0.01) equally by all treatments, with 95% confidence intervals ranging from -28 to -1 mmHg. However, hypertensive-diabetic (HT-DM) patients (n = 33) exhibited no significant change in pulse pressure in response to treatment. Adverse drug reactions that occurred in 11% were impotence or postural dizziness with D, headache and pitting oedema with CCB, and dry cough with ACEI. Pharmaco-economic comparison of the drug classes revealed that for every US dollar (dollar) spent per month, the percentage of treated patients attaining normotension was 18.6 for D, 4.73 for CCB, 3.5 for ACEI + D and 13.6 for methyldopa + thiazides. A combination of ACEI + CCB or D was the preferred treatment for hypertensive-diabetic Nigerians, but only 24% attained a BP < 130/85 mmHg. These results demonstrate a shift in trend to a more rational and efficacious treatment of hypertension over a 10 year period. This may be associated, at least in part, with the intensive and continuous education of the prescribers in rational drug use and the introduction of a hospital formulary. Methyldopa is still a highly efficacious and cost-effective drug in this population. Black HT-DM Africans still constitute a subgroup who not only require more and costlier antihypertensive drugs, but whose BP control is suboptimal, and exhibit a poor therapeutic response to other risk factors (pulse pressure) that constitute a continuing risk for cardiovascular mortality.",2003.0,0,0
525,12719441,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
526,12740004,ACE inhibitors versus diuretics: ALLHAT versus ANBP2.,Sheila A Doggrell,"The ALLHAT (The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial) trial enrolled hypertensive patients with at least one additional risk factor for coronary heart disease (CHD) to a comparison of the diuretic chlorthalidone, the calcium channel blocker, amlodipine, and the angiotensin-converting enzyme (ACE) inhibitor, lisinopril. Throughout the study, chlorthalidone decreased the systolic blood pressure to a slightly, but significantly greater extent (0.8-3.1 mmHg) than amlodipine or lisinopril. No significance differences were reported for amlodipine versus chlorthalidone or lisinopril versus chlorthalidone on the primary outcome of combined incidence of fatal CHD and nonfatal myocardial infarction. The findings of ALLHAT support the use of thiazide-type diuretics as first choice pharmacological therapy in at risk patients with hypertension. ANBP2 (The Second Australian National Blood Pressure Study) was also a comparison between diuretics (hydrochlorothiazide) and ACE inhibitors (enalapril) but was performed in older hypertensives that had few previous cardiovascular events. Diastolic blood pressure reduction was similar in both groups at all times. The risk of the primary outcome of all cardiovascular events or death from any cause was 11% lower in the ACE group than the diuretic group and the benefit was predominantly in men. Thus, ANBP2 suggests that in relatively healthy elderly hypertensive patients, ACE inhibitors should be preferred to diuretics.",2003.0,0,0
527,12742290,Anti-ischemic properties of calcium-channel blockers: lessons from cardiac surgery.,LionelH Opie,,2003.0,0,0
528,12744223,Eplerenone. Pharmacia.,Danny Liew; Jennifer Martin; Henry Krum,"Pharmacia Corp (formerly GD Searle & Co) is developing eplerenone, an aldosterone receptor antagonist, as a potential treatment for congestive heart failure and systemic hypertension. The compound has been registered for hypertension and Pharmacia plans to submit a supplemental NDA for congestive heart failure in the first half of 2003 based on positive results from a phase III clinical trial.",2003.0,0,0
529,12745200,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
530,12745205,A specialist in clinical hypertension critiques ALLHAT.,Jay I Meltzer,,2003.0,0,0
531,12764405,"Diarrhoea, vomiting and ACE inhibitors:--an important cause of acute renal failure.",C Stirling; J Houston; S Robertson; J Boyle; A Allan; J Norrie; C Isles,"The occurrence of severe acute renal failure in 3 patients who developed diarrhoea while taking angiotensin converting enzyme (ACE) inhibitors led us to undertake a retrospective cohort survey to determine the frequency with which diarrhoea and vomiting are associated with acute renal failure in patients taking this class of drug. Serum creatinine was measured as part of the diagnostic workup of 2398 consecutive admissions to an acute medical receiving unit in a district general hospital. Outcome measures were the presence of diarrhoea and/or vomiting, and whether taking an ACE inhibitor, NSAID or diuretic at the time of admission, also previous, initial and follow up serum creatinine concentrations. Peak serum creatinine in the 3 cases was 1159, 989 and 765 micromol/l. None of the 3 required dialysis and all recovered renal function completely after receiving large volumes of intravenous fluid. In the cohort study, 89 of 2398(3.7%) admissions had serum creatinine >/=200 micromol/l. Nine were regular dialysis patients. Of the remaining patients, 30 (37.5%) were taking an ACE inhibitor. Six of 30 (20%) gave a history of diarrhoea and/or vomiting. Median creatinine concentration in this group was 135 (range 111-209) micromol/l before admission, 292 (216-724) micromol/l when first seen in hospital, and 134 (94-219) micromol/l following the withdrawal of drug therapy and fluid replacement. In conclusion, volume depletion causing acute renal failure in patients taking ACE inhibitors is not uncommon. Such patients and their general practitioners should be aware that reversible renal impairment may occur during intercurrent illnesses, particularly if characterised by diarrhoea and/or vomiting.",2003.0,0,0
532,12764406,Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension.,S G Chrysant; T C Marbury; T D Robinson,"The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents. This randomized, double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate (amlodipine) in subjects with mild-to-moderate hypertension. Following a 4-week, single-blind, placebo run-in period, 440 subjects aged >/=18 years were randomized to the starting dose of olmesartan medoxomil (20 mg/day), amlodipine (5 mg/day), or placebo for 8 weeks. Subjects were evaluated by 24-h ambulatory blood pressure monitoring (ABPM) and by seated cuff blood pressure (BP) measurements at trough. The primary end point was the change from baseline in mean 24-h diastolic blood pressure (DBP) by ABPM at Week 8. Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure (SBP) at 8 weeks, change from baseline in mean seated trough cuff DBP and SBP measurements, and response and control rates for DBP <90 and <85 mmHg. Control rates for SBP <140 and <130 mmHg were also calculated. Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo. Mean reductions in ambulatory and seated BP were similar between the two active agents; however, in the olmesartan medoxomil group, significantly more patients achieved the SBP goal of <130 mmHg and the DBP goal of <85 mmHg. Both drugs were well tolerated at the recommended starting dose. Although amlodipine was associated with a higher incidence of oedema, this did not reach statistical significance. Olmesartan medoxomil is an effective antihypertensive agent, with BP-lowering efficacy at the starting dose similar to that of amlodipine, and is associated with more patients achieving the rigorous BP goals of SBP <130 mmHg and DBP <85 mmHg.",2003.0,0,0
533,12767538,Restoration of nocturnal dip in blood pressure is associated with improvement in left ventricular ejection fraction. A 1-year clinical study comparing the effects of amlodipine and nifedipine retard on ambulatory blood pressure and left ventricular systolic function in Chinese hypertensive type 2 diabetic patients.,Gary T C Ko; Hamish C K Chan,"We assessed the effects of amlodipine and nifedipine retard on 24-h blood pressure (BP) control, nocturnal fall in BP and their significance on left ventricular systolic functions in 54 Chinese hypertensive type 2 diabetic patients. Patients being recruited were openly randomised to amlodipine or nifedipine retard. Ambulatory 24-h BP and echocardiogram (in 42 patients) were measured before and 1 year after treatment. At the end of study, there was 17% reduction in systolic BP; 17% reduction in diastolic BP and 12% reduction in mean arterial pressure (MAP) (no difference between amlodipine and nifedipine). Of the 42 subjects underwent echocardiograms, eight became 'new-dippers' at the end of study (non-dippers before treatment and restored nocturnal fall of MAP> or =10% after treatment). The other 34 patients were either non-dippers before and after treatment (n=27); dippers before and after treatment (n=3) or dippers before treatment and non-dippers after treatment (n=4). The eight 'new-dippers' had improved ejection fraction (69.6+/-7.2 to 75.8+/-7.4%, P<0.05) and increased left ventricular diastolic diameter (43.7+/-7.9 to 47.9+/-8.8 mm, P<0.05) after the 1-year treatment of calcium antagonist. Compared to the other 34 subjects, the eight 'new-dippers' showed significant improvement in ejection fraction (9.4+/-10.9 vs. -1.2+/-11.8%, P<0.05). In conclusion, both amlodipine and nifedipine retard are effective in controlling the 24-h BP in Chinese hypertensive type 2 diabetic patients. For those who have restored nocturnal dip in BP have significantly increased left ventricular systolic ejection fraction after 1-year treatment of long acting calcium antagonists. The clinical significance and underlying mechanisms require further studies.",2003.0,0,0
534,12767649,The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial (AIRCRAFT).,Rukshen Weerasooriya; Michael Davis; Anne Powell; Tamas Szili-Torok; Chetan Shah; David Whalley; Logan Kanagaratnam; William Heddle; James Leitch; Ann Perks; Louise Ferguson; Max Bulsara,"The Australian Intervention Randomized Control of Rate in Atrial Fibrillation Trial was a multicenter trial of atrioventricular junction ablation and pacing (AVJAP) compared with pharmacologic ventricular rate control (medication [MED]) in patients with mild to moderately symptomatic permanent atrial fibrillation (AF). There have been very few prospective randomized trials, undertaken in highly symptomatic patients, comparing AVJAP with pharmacologic methods of ventricular rate control for patients with permanent AF. There were 99 patients (70 men, mean age 68 +/- 8.6 years) at five centers. Forty-nine patients were randomized to AVJAP while 50 patients were randomized to pharmacologic control. The primary end point was cardiac function measured by echocardiography and exercise tolerance. The secondary end points were ventricular rate control, evaluated by 24-h ambulatory electrocardiographic monitoring, and quality of life. Data were collected at randomization and then at one month, six months, and 12 months post-randomization. At 12 months follow-up there was no significant difference in left ventricular ejection fraction (AVJAP: 54 +/- 17%; MED: 61 +/- 13% [p = ns]) or exercise duration on treadmill testing (AVJAP: 4.1 +/- 2 min; MED: 4.6 +/- 2 min [p = ns]); however, the peak ventricular rate was lower in the AVJAP group during exercise (112 +/- 17 beats/min vs. 153 +/- 36 beats/min, p < 0.05) and activities of daily life (117 +/- 16 beats/min vs. 152 +/- 37 beats/min, p < 0.05). The CAST quality-of-life questionnaire revealed that patients in the AVJAP group had fewer symptoms at six months (p = 0.003) and at 12 months (p = 0.004). The observed relative risk reduction in symptoms at 12 months was 18%. Global subjective semiquantitative measurement of quality of life using the ""ladder of life"" revealed that the AVJAP group reported a 6% better quality of life at six months (p = 0.011). In this trial, AVJAP for patients with mild to moderately symptomatic permanent AF did not worsen cardiac function during long-term follow-up, and quality of life was improved.",2003.0,0,0
535,12770652,"The dilemma of immediate preoperative hypertension: to treat and operate, or to postpone surgery?",Natan Weksler; Motti Klein; Gabriel Szendro; Vsevolod Rozentsveig; Markus Schily; Silviu Brill; Alexandre Tarnopolski; Leon Ovadia; Gabriel M Gurman,"To evaluate the efficacy and complications of immediate preoperative reduction of arterial blood pressure (BP) in patients with well-controlled hypertension but with diastolic blood pressure (DBP) between 110 and 130 mmHg on arrival at the operating room (OR). Prospective, randomized, large-sample study. University-affiliated, 550-bed community hospital. 989 patients with well-controlled hypertension, who were scheduled for surgery, and who had no previous myocardial infarction, unstable or severe angina pectoris, renal failure, pregnancy induced hypertension, left ventricular hypertrophy, previous coronary revascularization, aortic stenosis, preoperative dysrhythmias, conduction defects, or stroke. Patients with DBP between 110 and 130 mmHg were randomly allocated to two groups: 400 patients in the control group and 589 patients serving as the study group. The control group had their surgery postponed and they remained in hospital for BP control, and the study patients received 10 mg of nifedipine intranasally delivered. The patients were observed for cardiovascular and neurological complications during the intraoperative period and over the first three postoperative days. The two groups were similar in age, gender, type of surgery, duration of anesthesia, and intraoperative fluid administration. There were no statistically significant differences in postoperative complications. The hospitalization time was considerable shorter in the study group than in the control group. Immediate preoperative reduction of DBP with intranasal nifedipine is safe in patients with well-controlled arterial hypertension but they presented with severe to very severe hypertension for patients in the OR. We were able to avoid unnecessary surgery postponement and attendant costs.",2003.0,0,1
536,12774892,Interaction of alcohol and drugs in fatal poisonings.,Anna Koski; Ilkka Ojanperä; Erkki Vuori,"In Finnish data from 1995-2000, 1006 fatal poisonings due to alcohol (ethanol), a single drug or both were statistically analysed in retrospect to evaluate the interaction between alcohol and drugs. In 53% of these cases, low concentrations of some common benzodiazepines were present. The median postmortem blood alcohol concentration (BAC) was 3.3 percent per thousand (w/w) in the 615 alcohol poisonings, but significantly lower, ranging from 1.3 to 1.7 percent per thousand, when promazine, doxepin, amitriptyline or propoxyphene were found together with alcohol. When levomepromazine, temazepam or zopiclone were present, the median BAC was also significantly lower, 2.5-2.7 percent per thousand. Citalopram and diltiazem did not exhibit a significant effect. The median BAC was significantly lower in cases with high concentrations than in those with low concentrations of a drug (excluding citalopram), suggesting a positive concentration-effect relationship. Fatal toxicity indices (FTIs) were calculated by relating the number of deaths caused by a drug to the corresponding sales figures. Promazine had an extremely high FTI, followed by levomepromazine, propoxyphene, doxepin and amitriptyline. The other drugs had relatively low FTIs. The results reflect not only the acute toxicity of a given drug-alcohol combination but also the manners of use and abuse of these drugs.",2003.0,0,0
537,12780888,A prospective randomized trial of diltiazem and glyceryltrinitrate ointment in the treatment of chronic anal fissure.,K Bielecki; M Kolodziejczak,"The aim of this study was to compare prospectively diltiazem with GTN ointment in the treatment of anal fissure. Of 43 outpatients with chronic anal fissure, 22 patients were randomized to topical diltiazem (2%) ointment and 21 patients to glyceryltrinitrate (GTN) (0.5%) ointment twice daily for 8 weeks. During the course of treatment each patient was seen three times. Side-effects and healing were recorded. Healing occurred in 19 of 22 patients treated with diltiazem and 18 of 21 patients were cured with GTN (P = 0.95). Those who were treated with nitroglycerin ointment developed headache and dizziness developed after GTN in 33.3% of cases while no patient had any side-effects after diltiazem. Diltiazem and glyceryltrinitrate (GTN) were equally effective in healing anal fissure but the former resulted in fewer side-effects.",2003.0,0,0
538,12785021,The importance of von Willebrand factor level and heart rate changes in acute coronary syndromes: a comparison with chronic ischemic conditions.,Gülümser Heper; Mehmet Bayraktaroğlu,"The pathogenesis of acute coronary syndrome (ACS) and transient myocardial ischemia (TMI) is not completely understood. Therefore, the authors studied the biological indicators of thrombogenesis and sympathetic activity. The study was conducted on 50 patients with acute coronary syndrome and 30 patients with stable angina pectoris. Treatment was standardized with low-molecular-weight heparin and 300 mg aspirin/day but with no IIb/IIIa inhibitors, an oral beta-blocker, diltiazem 60 mg tid, glyceryl trinitrate i.v. in patients with ACS but with mononitrates orally and low-molecular-weight heparin in patients with stable angina. Twenty-four-hour continuous ECG monitoring and ST segment analysis were performed on day 2 of admission and heart rate analysis was performed 10, 5, and 1 minute before and during the myocardial ischemia periods. Blood sampling for von Willebrand factor (vWf) determination was performed through a peripheral vein at 8 AM, noon, 6 PM and 10 PM and half an hour after the description of angina. The patients with ACS were grouped as transient myocardial ischemia positive (n = 20) and negative (n = 30). The patients with stable angina were designated as the control group (n = 30). The detected vWf levels at 4 different daytime periods in patients with ACS were significantly higher than those in patients with stable angina. At the 6 PM to 10 PM period, the vWf level increase was significantly higher in patients with TMI than in the patients without TMI. At the 8 AM to noon period, the detected vWf levels decreased significantly in both TMI groups. During the nocturnal ischemia periods, the increase in vWf levels immediately after angina was significantly more apparent than the detected changes during daytime ischemia. Analysis showed that heart rates before the ischemia during stable angina episodes were significantly higher than those in TMI (-) (silent) angina. The heart rate difference between 10 minutes before and during the ischemia in the angina group was significantly different from that during TMI (-) (silent) ischemia. The heart rates at the times related to ischemia in the nocturnal period were significantly lower than those in the daytime period. The heart rate differences between the ischemia-related times and during the ischemia were significantly higher in daytime ischemic attacks than in nocturnal ischemic attacks. The study confirms that the vWf level, which is an indicator of thrombogenesis, was significantly increased in patients with ACS. Nocturnal ischemia is associated with thrombogenesis. Daytime ischemia is associated with increased sympathetic activity, and symptomatic ischemia is usually associated with increased sympathetic activity.",2003.0,0,0
539,12790914,The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy.,N Griffin; A G Acheson; M Jonas; J H Scholefield,"The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia. This is thought to improve anal mucosal blood flow and promote healing of the fissure. This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN). Forty-seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre. Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals. Patients were asked to report side-effects throughout the study period. Healing of the fissure was assessed after 8 weeks of treatment. Forty-six patients completed treatment; of these, 22 had healed fissures (48%). Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment. Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery. This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.",2003.0,0,0
540,12790921,Treatment of resistant anal fissure with advancement anoplasty.,N J Kenefick; A S Gee; P Durdey,"The primary aim of this study was to assess the outcome of advancement anoplasty in the treatment of chronic anal fissure, resistant to conventional therapy. The secondary aim was to evaluate the anal resting pressure in these patients with resistant fissures. Over a five-year period eight patients (2 male, median age 55 years, range 20-74) with resistant anal fissure were referred from 6 centres. They had endured symptoms for a median of 8 years (range 2-20) and had undergone a median of 2 previous surgical procedures (range 1-3), including lateral sphincterotomy and anal dilatation. Anorectal physiological testing was performed on all patients who then underwent advancement anoplasty. The outcome was analysed retrospectively. Pre-operative anorectal physiological testing showed a significantly lowered median maximal anal resting pressure of 42 mm H2O (range 12-72 mm H2O, normal range > 60 mm), P=0.03. All patients underwent advancement anoplasty. At a median of seven months follow-up (range 2-22) seven of eight patients had healed their fissure and were asymptomatic. The median healing time was four months (range 2-6). Patients with chronic anal fissure, resistant to conventional therapy, may be successfully treated by advancement anoplasty. Healing time however, may be prolonged. In this series patients had a decreased anal resting pressure rather than anal hypertonia.",2003.0,0,0
541,12794583,Topical nifedipine vs. topical glyceryl trinitrate for treatment of chronic anal fissure.,Tiberiu Ezri; Sergio Susmallian,"Nifedipine (administered orally or applied topically) has been effective for nonsurgical treatment of anal fissure. We compared the efficacy of nifedipine vs. glyceryl trinitrate for chemical sphincterotomy of anal fissure. In a prospective, double-blind trial, 52 patients suffering from chronic anal fissure were randomly and equally allocated to receive either glyceryl trinitrate or nifedipine, both applied topically to the perianal region. The end point of the study was healing within a predetermined period (6 months). Variables assessed included demographic data (age, gender), symptoms associated with the fissure, duration of treatment, percentage of healing, untoward effects of treatment, pain scores, duration of follow-up, recurrence, and need for complementary means of treatment. Descriptive data are presented as mean +/- standard deviation and quantal data as percentage. Inference analysis was performed using the Student's t-test for the descriptive data and the chi-squared or Fisher's exact test for nominal variables. No significant differences were recorded with regard to age, gender, symptoms associated with the fissure, or duration of treatment. Healing rate was higher (P < 0.04) with nifedipine (89 percent) as compared with glyceryl trinitrate (58 percent). Treatment side effects (headache, flushing) were more frequent (P < 0.01) with glyceryl trinitrate (40 percent) as compared with nifedipine (5 percent). Pain scores were significantly lower (P < 0.03) on completion of treatment in both groups (3.2 in glyceryl trinitrate and 3.4 in nifedipine vs. 6.2 and 6.1, respectively), but did not differ between the two groups. Recurrence occurred in 31 percent of patients treated with glyceryl trinitrate and 42 percent of those treated with nifedipine after a mean period of 18 +/- 3 weeks and 12 +/- 4 weeks, respectively. Topical application of nifedipine for management of chronic anal fissure was more effective and had fewer side effects than topical glyceryl trinitrate. Recurrence was frequent with both drugs.",2003.0,0,0
542,12796754,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
543,12796759,Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study.,Bjørn Jørgensen; Erik Thaulow; Coronary Angioplasty Amlodipine Restenosis Study,"Despite successful coronary angioplasty (PTCA), patients may have ischemia after the procedure because of the overall coronary disease and luminal renarrowing at the lesion sites. The aim of this study was to examine the effects of the calcium-channel blocker amlodipine on post-PTCA ischemia. In a prospective, double-blind design, patients were randomized to receive 10 mg of amlodipine or placebo 2 weeks before angioplasty. Exercise tests and 48-hour ambulatory electrocardiography recordings were performed in 405 patients, 2 weeks before and 2 and 20 weeks (early and late) after PTCA. There were no differences in clinical and angiographic baseline characteristics between the treatment groups. Ischemia and angina were equally distributed before PTCA, and no difference in restenosis was found between the groups at follow-up. The incidence of angina was significantly lower in the amlodipine group compared with the placebo group both early and late after PTCA (P =.04 and.03). Exercise-induced ischemia was reduced by 40% (P =.009) early and 34% (P =.02) late after PTCA in the amlodipine group, and ischemia on ambulatory electrocardiography was reduced by 18% early and 28% late after PTCA compared with placebo (P =.06 and P =.009). Ischemia and angina occurred after successful PTCA and were significantly reduced by amlodipine.",2003.0,0,0
544,12797102,Braxton-Hicks contractions can alter uteroplacental perfusion.,S Bower; S Campbell; S Vyas; C McGirr,"Color flow imaging was used to study the effect of spontaneous low-amplitude uterine contractions (Braxton-Hicks) on flow velocity waveforms obtained from the main uterine artery in 13 women between 26 and 34 weeks' gestation. Eight women had abnormal waveforms, as defined by the presence of an early diastolic notch, and five women had normal waveforms. In the former group, three women with chronic hypertension were started on the calcium antagonist nifedipine during this study. Contractions, which were monitored by external tocography, occurred more frequently in the group with abnormal waveforms and were temporally associated with an increase in impedance to blood flow. This effect occurred to the same degree in both normal and abnormal groups, but in the abnormal group the already impaired blood flow to the intervillous space was further diminished, resulting in absence of forward flow in diastole. Such acute reductions of flow in response to frequent, impalpable uterine contractions may cause a prolonged and silent insult to uteroplacental perfusion, which could hasten fetal compromise. This effect appeared to be abolished in patients on nifedipine, suggesting a possible therapeutic role for this drug in uteroplacental insufficiency.",2003.0,0,0
545,12798560,Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE).,Dariush Mozaffarian; Regina Nye; Wayne C Levy,"Our aim was to examine the relationships between serum hematocrit (Hct) and risk of all-cause mortality among patients with severe heart failure (HF). Anemia occurs with increased frequency in severe HF. However, few studies have examined the impact of anemia on mortality in this population. Using a prospective cohort design, we evaluated the relationships between baseline serum Hct and mortality among 1,130 patients with left ventricular EF <30% and New York Heart Association functional class IIIB or IV HF treated with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Mortality was ascertained by centralized adjudication. The mean Hct was 41.8% (range 25.4% to 58.8%). Over 15 months of mean follow-up, there were 407 deaths (29 per 100 person-years). After adjustment for potential confounders, those in the lowest quintile of Hct (range 25.4% to 37.5%) had a 52% higher risk of death (hazard ratio 1.52, 95% confidence interval 1.11 to 2.10), compared with the highest quintile (range 46.1% to 58.8%). Within the lowest quintile of Hct, each 1% decrease in Hct was associated with an 11% higher risk of death (p < 0.01), whereas within the four higher quintiles of Hct, Hct was not associated with total mortality. Evaluation of different causes of death indicated that a lower Hct was strongly associated with death from progressive HF, rather than sudden death or other deaths. Among patients with severe HF, anemia is a significant independent risk factor for death, with a progressively higher risk with increasing severity of anemia. Further investigation of the etiologies, prevention, and treatment of anemia in severe HF is warranted.",2003.0,0,0
546,12800857,Expert consensus document on management of cardiovascular diseases during pregnancy.,Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology,,2003.0,0,0
547,12801442,Optimal medical management of angina.,Brian Noronha; Edward Duncan; Jonathan A Byrne,"Coronary artery disease remains one of the principal causes of disability worldwide. Its most common manifestation is angina pectoris. Angina occurs due to an imbalance between myocardial oxygen demand and supply; it is classically precipitated by physical activity, emotion, eating, or cold weather. It is defined as stable when its frequency, severity, duration, time of appearance, and precipitating factors remain unchanged for 60 days. Treatment of patients with stable angina targets a number of factors that underlie its pathophysiology: aspirin as an antiplatelet agent, b-blockade to reduce myocardial oxygen demand, and additional antianginal drugs when symptoms are incompletely controlled by b-blockers alone. Furthermore, aggressive treatment of risk factors for the development of coronary artery disease confers a significant mortality benefit. Unstable angina is defined as symptoms developing at rest, on minimal exertion, and of increasing severity, duration, or frequency. It is associated with significant mortality; consequently, early assessment and intervention is essential to prevent worsening ischemia. Treatment includes close in-patient monitoring, administration of antiplatelet and antithrombotic drugs, and a combination of b-blockers, calcium antagonists, and intravenous nitrates where appropriate. Coronary revascularization should be considered in high-risk patients, and when conservative management strategies fail.",2003.0,0,0
548,12809816,Concepts in pathogenesis and treatment of chronic anal fissure--a review of the literature.,M J Utzig; A J Kroesen; H J Buhr,"Chronic anal fissures are associated with a persistent hypertonia and spasm of the internal anal sphincter. Classic treatment is surgical sphincterotomy to reduce the anal tone and eliminate sphincteric spasm. However, concerns have been raised about the incidence of fecal incontinence after surgery. Therefore, pharmacological means to treat chronic anal fissures have been explored. We conducted a literature review on MEDLINE database. All treatments address the anomaly of a high anal pressure. Several studies have investigated the effect of topical glyceryl trinitrate ointment. Healing rates range from 30% to 86%. Therapy is limited because of a high incidence of moderate to severe headaches in up to 84% of patients. Comparable results are observed after injection of botulinum toxin into the anal sphincter (43-96%). Minor incontinence for flatus and soiling has been reported in up to 12% of patients. Further pharmacological approaches including treatment via calcium channel blockade and treatment with alpha-adrenoceptor antagonists are still at a developmental stage. Topical glyceryl trinitrate ointment and injection of botulinum toxin into the anal sphincter are advocated as the first-line treatment for chronic anal fissure. Lateral sphincterotomy should be offered to patients with relapse and therapeutic failure of prior pharmacological treatment.",2003.0,0,0
549,12814338,Isotretinoin use and subsequent depression and suicide: presenting the evidence.,Peter R Hull; Carl D'Arcy,"The growing number of reported cases of depression and suicide associated with isotretinoin (a retinoid receptor agonist) use in patients with acne has prompted concern among dermatologists, patients, and their relatives and has triggered new warnings from regulators including depression-related, patient-informed consent forms. In establishing a cause-effect relationship, it is useful to judiciously consider whether there is an association, what is the nature of that association, if there is a plausible biological mechanism of action, the validity and reliability of measures used and the strength of study designs. Hoffmann-La Roche estimates that by April 2001 approximately 12 million patients worldwide have used isotretinoin, with 5 million patients in the US.A MEDLINE search between January 1966 and May 14 2003 of the published medical literature found 24 documented cases of isotretinoin-associated depression, with 3 suicides. One additional patient committed suicide during the fourth month of isotretinoin treatment and 3 further patients attempted suicide by taking an overdose of isotretinoin. The US FDA's Adverse Event Reporting System (AERS) contains almost 23,000 reports for isotretinoin from its approval in 1982 to December 2002. As of November 30, 2002, AERS contained 3,104 reports (US and foreign) with at least one reported psychiatric event. The FDA is aware of 173 reports of suicide (both US and foreign) in association with isotretinoin. Reports of positive dechallenge and rechallenge present a strong signal pointing to an association between isotretinoin and depression. A Hoffmann-La Roche sponsored epidemiological study failed to find any evidence of an association between isotretinoin and depression or suicide. However, the design of the study was flawed and the evidence was deemed inconclusive. Further studies using strong study designs, reliable and valid measures, and adequate sample sizes may bring us closer to the answer. The evidence suggesting a relationship between isotretinoin and depression needs to be weighed against the increasing prevalence of depression among adolescents and young adults and the psychological impact of acne. The literature contains credible evidence that isotretinoin treatment may reduce the psychosocial impact of acne in some patients. At the present time, there is no known pharmacological mechanism that would account for psychiatric symptomatology as a result of isotretinoin treatment; however, retinoid receptors are widely distributed in the brain and more research is needed to ascertain whether they have a role in depression. In the meantime, for the practitioner, the obvious benefit of isotretinoin in treating acne should encourage continued use. However, patients and their relatives must be informed and depressive symptoms should be actively assessed at each visit and, if necessary, referral to a psychiatrist, antidepressant therapy or discontinuation of isotretinoin should be considered.",2003.0,0,0
550,12826782,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
551,12826783,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
552,12826793,,,,,0,0
553,12827029,Prevention of carotid artery thrombosis after oral administration of the glycoprotein IIb/IIIa antagonist CRL42796.,James K Hennan; David E Willens; Edward M Driscoll; Ting-Ting Hong; Thierry Giboulot; Benedict R Lucchesi,"This study investigates the effect of the glycoprotein IIb/IIIa receptor antagonist CRL42796 in a canine model of carotid artery thrombosis. Both carotid arteries developed occlusive thrombosis in each of the five control animals (time to occlusion: right carotid artery, 92.6 minutes; left carotid artery, 89.0 minutes). A single oral dose of CRL42796 (3 mg/kg) prevented occlusive thrombosis in 4 of 6 vessels and increased time to thrombosis, albeit not significantly (right carotid artery, 134.1 minutes; left carotid artery, 145.0 minutes). When the initial dose of CRL42796 was followed by a second oral dose (3 mg/kg) 2 hours later, 10 of 10 carotid arteries remained patent throughout the period of electrolytic injury. CRL42796 reduced thrombus weight in both treatment protocols. Ex vivo platelet aggregation with arachidonic acid (AA) or adenosine diphosphate (ADP) was reduced at 120, 240, and 360 minutes after two doses of CRL42796. A single oral dose reduced ADP-induced responses at 240 and 360 minutes, but significant effects were not observed with AA. Bleeding time increased 360 minutes after two oral doses of CRL42796, but not at 120 minutes. Bleeding time was unchanged with the single dose of CRL42796. The results demonstrate that oral administration of CRL42796 prevents carotid artery thrombosis in response to deep vessel wall injury and may have potential value to be characterized in extended preclinical and clinical study.",2003.0,0,0
554,12828661,Immunohistochemical analysis of Th1/Th2 cytokine profiles and androgen receptor expression in the pathogenesis of nifedipine-induced gingival overgrowth.,W-T Huang; H-K Lu; H-H Chou; Mark Y P Kuo,"Numerous studies have demonstrated that gingival overgrowth may be associated with androgen and cytokine expression in tissues. The aim of this study was to compare the expression of androgen receptor-presenting cells (AR+ cells) and Th1/Th2 cytokine [Th1: interleukin (IL)-2, interferon-gamma (IFN-gamma); Th2: IL-4, IL-10, IL-13] expression cells in tissue sections of patients with gingival overgrowth. Tissue samples were collected from patients with healthy periodontium (H group), adult periodontitis (P group), surgically extracted teeth (S group), and nifedipine-induced gingival overgrowth (NIGO group). The clinical periodontal parameters of pocket depth (PD), bleeding on probing (BOP), and plaque control record (PCR) were measured around selected sample teeth. Gingival biopsies were further processed by immunohistochemical staining method. The expressions of cells positive for AR, IL-2, IFN-gamma, IL-4, IL-10, and IL-13 were counted by predetermined semiquantitative methods. Our results indicated that AR, IL-2, IFN-gamma, IL-4, IL-10, and IL-13 were intensively expressed in the nuclei of inflammatory cells and fibroblasts of gingival connective tissue. Stronger expressions of AR, IL-2, and IFN-gamma were found in the NIGO group. The AR+ cells/0.01 mm2 in gingival fibroblasts were significantly higher in the NIGO group (80.2 +/- 10.7) than those of the periodontitis group (52.5 +/- 11.8) and control group (37.4 +/- 11.3) (P < 0.05). The cytokine expression of the NIGO group showed a trend towards Th1-type expression (IL-2; P = 0.0001). In the surgically extracted tooth group, a stronger expression of Th2-type cytokine (IL-4, Il-10, IL-13; P < 0.05) was found in inflammatory cells. In a comparison of the IL-2/IL-4-labeled cell ratio of the four groups, a descending sequence was discovered as NIGO group (0.92 +/- 0.97) > H group (0.81 +/- 0.61) > P group (0.77 +/- 0.82) > S group (0.58 +/- 1.77). Our data support the following: (i) taking nifedipine may elevate the expression of AR in susceptible oral tissue, e.g. gingiva; (ii) the cytokine profile of T-cells in NIGO tissue indicates a trend preferentially towards Th1 activity; and (iii) elevation of AR expression cells and prominent Th1 cytokine-labeled cells are two significant factors in the pathogenesis of NIGO.",2003.0,0,0
555,12834362,Current treatment of patients with hypertension: therapeutic implications of INSIGHT.,Stefano Taddei; Lorenzo Ghiadoni; Antonio Salvetti,"When planning treatment for patients with hypertension, current guidelines emphasise the importance of risk stratification, based on blood pressure, the presence of end-organ damage and other cardiovascular risk factors. Because the beneficial effect of antihypertensive therapy seems to be linked to the degree of blood pressure reduction, guidelines recommend reducing blood pressure below 140/90mm Hg, with a lower target in patients who are young or who have diabetes mellitus (with or without nephropathy) or non-diabetic nephropathy. Blood pressure reduction can be achieved with several classes of drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists and calcium channel antagonists. Calcium channel antagonists have been shown to reduce the risk of stroke and major cardiovascular events. However, it is still controversial whether different treatment regimens based on different drug classes can offer advantages beyond similar degrees of blood pressure control in preventing cardiovascular morbidity and mortality. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) was a controlled clinical trial aimed at comparing the efficacy of a long-acting calcium channel antagonist, nifedipine gastrointestinal-transport-system (GITS), versus co-amilozide, a combination of the diuretics hydrochlorothiazide (HCTZ) and amiloride, on morbidity and mortality in high-risk hypertensive patients. Nifedipine GITS and HCTZ/amiloride were equally effective at reducing blood pressure and the risk of primary outcomes (a composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction and heart failure). Results from other studies indicate that there may be greater benefits for stroke and smaller benefits for coronary artery disease with calcium channel antagonist-based regimens than with diuretic or beta-blocker-based regimens. However, there is at present insufficient evidence to recommend a specific drug choice based on patient risk profile. Thus, the choice of antihypertensive drug(s) should be according to efficacy and tolerability. In addition to the reductions in cardiovascular risk, two substudies of INSIGHT showed that nifedipine GITS was able to prevent the progression of intima media thickness in the common carotid artery and slow the progression of coronary calcification. The clinical significance of this effect in the prevention of cardiovascular events still remains to be established.",2003.0,0,0
556,12836810,Safety and efficacy of sibutramine in overweight Hispanic patients with hypertension.,Guillermo Fanghänel; Leonides Cortinas; Leticia Sánchez-Reyes; Rosario Gómez-Santos; Enrique Campos-Franco; Arturo Berber,"This 6-month randomized study evaluated the safety and efficacy of sibutramine in 57 overweight Hispanic patients with hypertension. Following a 2-week washout to confirm the diagnosis of hypertension, antihypertensive medication was adjusted to achieve a blood pressure less than 140/90 mm Hg before institution of either sibutramine 10 mg or placebo once a day. A body mass index in excess of 27 kg/m2 was required for entry. At study end, weight had changed from 75.4+/-9.6 to 70.0+/-9.5 kg in the sibutramine group and from 77.9+/-9.0 to 74.5+/-9.4 kg in the placebo group. In the sibutramine group, systolic blood pressure was 127.8+/-5.8 mm Hg after stabilization and 125.2+/-8.5 mm Hg after completion of the trial; respective values for diastolic blood pressure were 82.4+/-3.7 and 81.5+/-4.6 mm Hg. With placebo, blood pressure dropped from 129.0+/-7.1/80.9+/-4.9 mm Hg to 122.8+/-9.7/80.3+/-5.4 mm Hg at the same timepoints. In the sibutramine group, 14 patients reported 21 adverse events, most frequently headache (n=5), constipation (n=4), and dry mouth (n=4). In the placebo group, 13 patients had 20 adverse events. Sibutramine is safe and effective in overweight Hispanic patients with hypertension, but monitoring of blood pressure and titration of antihypertensive medication are necessary.",2003.0,0,0
557,12842240,Effect of elevated heart rate preceding the onset of ventricular tachycardia on antitachycardia pacing effectiveness in patients with implantable cardioverter defibrillators.,Claude Kouakam; Bénédicte Lauwerier; Didier Klug; Moustapha Jarwe; Christelle Marquié; Dominique Lacroix; Salem Kacet,"The incorporation of antitachycardia pacing (ATP) into implantable cardioverter defibrillators (ICDs) has provided a better tolerated alternative to shocks. ATP has been shown to be effective in terminating approximately 80% to 90% of spontaneous ventricular tachycardia (VT) episodes. Although ATP is routinely used, little is known about predictors of ATP failure. Based on the evaluation of stored electrograms, we aimed to prospectively follow patients with ICDs, and to analyze parameters affecting ATP effectiveness. One hundred eighteen consecutive patients received ICDs for standard indications. Before discharge, empirical, standardized ATP therapy was programmed in all patients within VT zones. A total of 1,218 spontaneous tachycardia episodes occurred in 51 patients during a mean follow-up of 24.5 +/- 12 months. Among these, 888 VTs were diagnosed. One hundred four fast VTs were detected in the ventricular fibrillation zone and treated with primary shock delivery. ATP was attempted 881 times in the remaining 784 VT episodes. ATP terminated 640 VTs successfully, ATP failed in 55 VTs finally reverted by shocks, and 89 VTs converted to a slower VT outside the VT zone. Fifty-one of these slower VTs reverted spontaneously, and 38 were redetected and treated. Finally, in primary intention-to-treat basis, ATP was successful in 691 VTs (88%) and unsuccessful in 93 VTs (12%). There was no influence of VT cycle length on ATP success rate. Furthermore, ATP efficacy was similar between patients with left ventricular ejection fraction < or =35% or >35%, between daytime and nighttime, as well as between patients with ischemic or nonischemic cardiomyopathy. A faster heart rate immediately preceding the onset of VT (103 +/- 19 vs 78 +/- 14 beats/min, respectively, hazard ratio 4.08, 95% confidence interval 2.11 to 7.89, p <0.001), and absence of beta-blocker therapy (82% vs 93%, respectively, hazard ratio 2.71, 95% confidence interval 1.72 to 4.29, p = 0.02) were found, by Cox proportional-hazard analysis, to be the sole independent predictors of ATP ineffectiveness in ICD recipients. Thus, the present study identified both preceding sinus tachycardia (reflecting an increased sympathetic tone) and lack of beta-blocker use as independent risk factors for reduced success of ATP therapy in terminating VT. Therefore, modification of sympathetic tone may be beneficial for patients with ICDs.",2003.0,0,0
558,12844463,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
559,12846347,Levosimendan: a new dual-action drug in the treatment of acute heart failure.,A Mebazaa; L Erhardt,"Levosimendan is a new agent for the treatment of acute heart failure. Levosimendan acts via complementary mechanisms; it enhances contractility by sensitising cardiac myofilaments to calcium and dilates blood vessels by opening ATP-dependent potassium channels. In contrast to traditional inotropes (beta-agonists or phosphodiesterase inhibitors), levosimendan does not raise myocyte calcium levels and is therefore less likely to elicit arrhythmias or to impair diastolic relaxation. The clinical efficacy of levosimendan is supported by four key clinical studies, including more than 900 patients hospitalised for cardiac decompensation due to acutely worsened chronic heart failure or to heart failure following myocardial infarction. When given as short-term therapy, levosimendan enhances cardiac output, reduces systemic vascular resistance and lowers pulmonary capillary wedge pressure. At 31 days post-treatment, mortality rates were halved in decompensated chronic heart failure patients who received levosimendan, compared with those on dobutamine--an advantage sustained at 180 days. Similar survival gains were observed among acute failure patients treated with levosimendan following myocardial infarction. With its substantial haemodynamic and survival benefits, levosimendan is well suited to be part of routine management for patients with acutely decompensated heart failure.",2003.0,0,0
560,12848639,Preterm delivery: an overview.,Kjell Haram; Jan Helge Seglem Mortensen; Anne-Lone Wollen,"Preterm delivery is the leading factor causing neonatal mortality and morbidity. We have conducted a PubMed literature search to obtain an update on the etiology, diagnostic problems and therapeutic considerations of preterm delivery. Approximately 5-10% of all births are premature. Preterm labor is associated with preterm rupture of membranes, cervical incompetence, polyhydramnion, fetal and uterine anomalies, infections, social factors, stress, smoking, heavy work and other risk factors. The diagnosis is made on the patients presenting symptoms, clinical findings and of progressive effacement and dilatation of the cervix. Biochemical markers of preterm delivery are of minor importance in daily clinical work. Measurement of the cervix, however, is a practical and valuable tool to predict preterm delivery. Cervical cerclage can be useful in selected cases. Antibiotics may help to prevent preterm labor in cases of known etiologic agents (e.g. preterm rupture of membranes and urinary infection). The use of tocolytic agents such as beta-sympathetic receptor stimulators can be advocated for a few days. There is evidence that their long-term use is not beneficial and could even be harmful to the fetus. Calcium channel blockers (nifedipine) and a new selective oxytocin receptor antagonist, atosiban, appear to be as effective as beta-sympathomimetic drugs on uterine contractions with fewer side-effects. Prostaglandin synthetase inhibitors such as indomethacin may prevent uterine contractions and can be used prior to the 32nd week of pregnancy. A single course of corticosteroid treatment in two doses of 12 mg betamethasone or 6 mg of dexamethasone is important for the prevention of respiratory distress between the 24th and 34th weeks of pregnancy. Multiple doses may be harmful and should be avoided. In these cases management should depend on gestation age (fetal maturity). Uterine contractions after 34 weeks' gestation are not an indication for tocolytic treatment.",2003.0,0,0
561,12850387,"VALUE trial: Long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk.",Stevo Julius; Sverre E Kjeldsen; Hans Brunner; Lennart Hansson; Francis Platt; Steffan Ekman; John H Laragh; Gordon McInnes; Anthony M Schork; Beverly Smith; Michael Weber; Alberto Zanchetti; VALUE Trial,"The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study compares cardiovascular outcomes in 15,314 eligible patients from 31 countries randomized to valsartan or amlodipine-based treatment. The blood pressure (BP) trends are analyzed in 13,449 of VALUE study patients who had baseline BP and 24 months BP and treatment data. In a cohort of 12,570 patients, baseline 24 and 30 months BP, but not 30 months treatment data, were available. Of 13,449 patients, 92% (N = 12,398) received antihypertensive therapy at baseline. The baseline BP was 153.5/86.9 mm Hg in treated compared to 168.1.8/95.3 mm Hg in 1051 untreated patients. After 6 months both groups had indistinguishable BP values. At 12 months the BP decreased to 141.2/82.9 mm Hg (P <.0001 for systolic BP and diastolic BP versus baseline), at 24 months to 139.1/80 mm Hg (P <.0001 v 12 months), and to 138/79 mm Hg at 30 months (P <.0001 v 24 months). The systolic BP control (<140 mm Hg) at 30 months increased from 21.9% at baseline to 62.2%, the diastolic BP (< 90 mm Hg) from 54.2% to 90.2% and the combined control (<140 and <90 mm Hg) from 18.9% to 60.5%. At 24 months 85.8% of patients were on protocol drugs: monotherapy = 39.7%, added hydrochlorothiazide = 26.6%, add-on drugs = 15.1%, and protocol drugs in nonstandard doses = 4.3%. The achieved BP control exceeds values reported in most published large-scale trials. The VALUE study is executed in regular clinical settings and 92% of the patients received antihypertensive drugs at baseline. When an explicit BP goal is set, and a treatment algorithm is provided, the physicians can achieve better control rates than in their regular practice.",2003.0,0,0
562,12850627,Diagnosis and management of gestational hypertension and preeclampsia.,Baha M Sibai,"Gestational hypertension and preeclampsia are common disorders during pregnancy, with the majority of cases developing at or near term. The development of mild hypertension or preeclampsia at or near term is associated with minimal maternal and neonatal morbidities. In contrast, the onset of severe gestational hypertension and/or severe preeclampsia before 35 weeks' gestation is associated with significant maternal and perinatal complications. Women with diagnosed gestational hypertension-preeclampsia require close evaluation of maternal and fetal conditions for the duration of pregnancy, and those with severe disease should be managed in-hospital. The decision between delivery and expectant management depends on fetal gestational age, fetal status, and severity of maternal condition at time of evaluation. Expectant management is possible in a select group of women with severe preeclampsia before 32 weeks' gestation. Steroids are effective in reducing neonatal mortality and morbidity when administered to those with severe disease between 24 and 34 weeks' gestation. Magnesium sulfate should be used during labor and for at least 24 hours postpartum to prevent seizures in all women with severe disease. There is an urgent need to conduct randomized trials to determine the efficacy and safety of antihypertensive drugs in women with mild hypertension-preeclampsia. There is also a need to conduct a randomized trial to determine the benefits and risks of magnesium sulfate during labor and postpartum in women with mild preeclampsia.",2003.0,0,0
563,12860503,"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
564,12860576,Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension.,Norman K Hollenberg; Gordon H Williams; Richard Anderson; Kasem S Akhras; Richard M Bittman; Scott L Krause,"Although there has been increasing recognition that a substantial part of the cardiovascular, central nervous system, and renal conditions induced by renin-angiotensin-aldosterone system activation reflects an action of aldosterone, the potential influence of therapy designed to block aldosterone has been limited by the fact that spironolactone (until recently the only aldosterone antagonist available) exerts a substantial array of adverse effects. We sought to compare the magnitude of the distress induced by a widely used calcium channel blocking agent, amlodipine, and a new aldosterone antagonist, eplerenone, in patients treated for systolic hypertension. A total of 269 patients older than 50 years with systolic hypertension were randomized to either eplerenone, 50 mg/d, or amlodipine, 2.5 mg/d, and titrated to a maximum 200-mg eplerenone dose or 10-mg amlodipine dose. Patients were followed up for 24 weeks. Quality-of-life questionnaires (SF-36 Health Survey) and a validated instrument for assessing symptom distress (Symptom Distress Index) were administered at randomization and 24 weeks after starting treatment. The systolic blood pressure response to eplerenone and amlodipine did not differ (eplerenone = -20.5 mm Hg and amlodipine = -20.1 mm Hg). For the quality-of-life analysis, 119 patients were randomized to eplerenone and 122 to amlodipine. No significant treatment group differences in the Symptom Distress Index were detected at baseline. There was an overall significant treatment effect on symptom distress in favor of eplerenone (P =.03). Indeed, Symptom Distress Index showed significant worsening distress in 36 of 71 symptoms in the amlodipine arm and none in the eplerenone arm. Significant treatment effect in favor of eplerenone was observed in 5 symptoms: ankle swelling, weight gain, nocturia, increased urination, and shortness of breath. Patients with symptom distress also showed an erosion of psychosocial measures of quality of life (P<.001). The aldosterone antagonist eplerenone is substantially better tolerated than the widely used calcium-channel blocking agent amlodipine, with comparable reductions in systolic blood pressure. This feature should improve therapeutics in patients in whom blockade of aldosterone's effect would be helpful.",2003.0,0,0
565,12860866,Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study.,J A Dens; W J Desmet; P Coussement; I K De Scheerder; K Kostopoulos; P Kerdsinchai; C Supanantaroek; J H Piessens,"Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of > or = 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.",2003.0,0,1
566,12867222,Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension.,Massimo Volpe; Zhu Junren; Thomas Maxwell; Aldo Rodriguez; Raul Gamboa; Pablo Gomez-Fernandez; Ginés Ortega-Gonzalez; Norberta Matadamas; Freddy Rodriguez; Badal Dass; Chris Kyle; Laurent Clarysse; Alfonso Bryce; Ernesto Moreno-Heredia; Giuseppe Germano; Leen Gilles; Ronald D Smith; John E Sanderson; CDSP-944 Study Group,"Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH. The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH. This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire. Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine). In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.",2003.0,0,0
567,12891198,Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine.,H C Wijeysundera; M S Hansen; E Stanton; A S Cropp; C Hall; N S Dhalla; J Ghali; J L Rouleau; PRAISE II Investigators,"The purpose of this study was to assess the effects of amlodipine on neurohormones and oxidative stress in nonischemic cardiomyopathy, and determine the relationship between baseline and posttreatment levels of these markers with survival. Neurohormones and oxidative stress are important in the pathophysiology of heart failure. Calcium-channel blockers are associated with poor outcomes in patients with heart failure, in part due to neurohormonal activation. In contrast, amlodipine, a second-generation dihydropyridine, has a more favorable clinical profile. In the Prospective Randomized Amlodipine Survival Evaluation 2 (PRAISE-2) trial, a subset of 181 patients with nonischemic cardiomyopathy were randomized to amlodipine (10 mg/day) or placebo. Blood samples were evaluated at baseline, 2 weeks and 26 weeks for norepinephrine, epinephrine, angiotensin II, dopamine, N-terminal pro-atrial natriuretic peptide (Nt-pro-ANP), brain natriuretic peptide (BNP), adrenolutin and malondialdehyde. There was no difference in levels of neurohormones or oxidative stress markers between the amlodipine and placebo groups at the different times. Both Nt-pro-ANP and BNP decreased at 2 weeks and at 26 weeks. Baseline Nt-pro-ANP correlated with survival in multivariate analysis (P =.001). A strong relationship was found between a reduction in BNP at 26 weeks and survival, with a hazard ratio of 0.153 (95% CI 0.051-0.461, P =.017). No relationship was found between markers of oxidative stress and survival. We conclude that amlodipine does not affect circulating neurohormones and oxidative stress markers in patients with nonischemic cardiomyopathy treated with angiotensin-converting enzyme inhibitors, digoxin and diuretics. In addition, low circulating Nt-pro-ANP and a reduction in BNP over time confers a good prognosis.",2003.0,0,0
568,12899808,Do irbesartan and amlodipine reduce cardiovascular events in diabetic patients?,Peter S Millard,"When added to antihypertensive treatment in patients with diabetes and nephropathy, neither the angiotensin receptor blocker (ARB) irbesartan nor the calcium channel blocker amlodipine reduced the overall occurrence of cardiovascular events. However, irbesartan decreased the rate of heart failure and amlodipine reduced the rate of acute myocardial infarction.",2003.0,0,0
569,12901461,"A comparative analysis of amlodipine and felodipine in a military outpatient population: efficacy, outcomes, and cost considerations.",Steven J Blivin; Julie Pippins; Laura G Annis; Farris Lyons,"This retrospective study compared the efficacy, tolerability, and cost of two dihydropyridine calcium channel blockers. Charts of patients who had been on continuous antihypertensive therapy with amlodipine or felodipine for at least 6 months were reviewed. Analyses include mean changes in blood pressure, percentage of patients achieving blood pressure (BP) < 140/90 mm Hg, average dose, and cost per day of the two calcium channel blockers, average cost of additional medication, total medication cost per day, and cost to achieve BP control. Eighty-seven percent of amlodipine-treated patients achieved BP control compared with 33% of felodipine-treated patients. Total medication cost to achieve BP control was 0.87 dollars per day for patients on amlodipine compared with 1.79 dollars per day for patients on felodipine. Amlodipine produced BP control in a greater percentage of patients than did felodipine at a lower total cost to achieve BP control. When evaluating the total cost of antihypertensive treatment, the cost of a drug alone can be misleading.",2003.0,0,0
570,12908497,Statins: new data in secondary prevention and diabetes. Pravastatin and simvastatin are the best-assessed statins.,,"The efficacy of pravastatin and simvastatin was first shown several years ago in patients with coronary heart disease. Other trials have since been published. In the HPS trial, which studied patients with coronary heart disease, other cardiovascular conditions, or diabetes, simvastatin significantly reduced the risk of death, coronary events and stroke when compared with placebo. In the ALLHAT-LLT trial, in patients with treated hypertension, pravastatin did not reduce overall mortality. In the PROSPER trial, in patients aged over 70 with cardiovascular disease or cardiovascular risk factors, pravastatin reduced the incidence of coronary events relative to placebo, but did not reduce overall mortality. Pharmacovigilance studies suggest there is no difference between these four statins in terms of their potential to cause rhabdomyolysis. Taken together, these trials show that statin use can be extended to patients with levels of LDL-cholesterol over 2.4 mmol/l (0.9 g/l) if they have coronary heart disease (and no hypercholesterolaemia), a history of ischaemic stroke, or lower-limb arterial disease. Statins can also be prescribed for diabetic patients with no signs of cardiovascular disease but whose LDL-cholesterol exceeds 3.4 mmol/l (1.3 g/l). Clinical trial data support the use of pravastatin or simvastatin in these situations, at a dose of 20 or 40 mg daily. Plasma creatine phosphokinase assay should be done if muscle symptoms occur or if the patient has a particular risk of rhabdomyolysis.",2003.0,0,0
571,12930035,,,,,0,0
572,12933374,Calcium channel blockers for reducing cardiac morbidity after noncardiac surgery: a meta-analysis.,Duminda N Wijeysundera; W Scott Beattie,"Cardiac complications are the leading cause of death after noncardiac surgery. Despite theoretical benefits, calcium channel blockers (CCB) are not widely used in the perioperative setting. This systematic review assessed the efficacy of CCBs during noncardiac surgery. MEDLINE, EMBASE, Science Citation Index, PubMed, and reference lists were searched without language restriction for randomized controlled trials (RCT) evaluating CCBs during noncardiac surgery. Two reviewers independently abstracted data on death, myocardial infarction (MI), ischemia, supraventricular tachyarrhythmia (SVT), and congestive heart failure (CHF). Treatment effects were calculated as relative risks (RR) with 95% confidence intervals (CI). Eleven studies (1007 patients) were included. CCBs significantly reduced ischemia (RR, 0.49; 95% CI, 0.30-0.80; P = 0.004) and SVT (RR, 0.52; 95% CI, 0.37-0.72; P < 0.0001). CCBs were associated with trends towards reduced death and MI. In post hoc analyses, CCBs significantly reduced death/MI (RR, 0.35; 95% CI, 0.15-0.86; P = 0.02) and major morbid events (MME), defined as death, MI, or CHF (RR, 0.39; 95% CI, 0.17-0.89; P = 0.02). In subgroup analyses, diltiazem significantly reduced ischemia, SVT, death/MI, and MMEs. This meta-analysis shows CCBs significantly reduced ischemia, SVT, and combined end-points in the setting of noncardiac surgery. The majority of these benefits are attributable to diltiazem, suggesting the need for further evaluation of this drug in a large RCT.",2003.0,0,0
573,12939564,"Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study.",Roberta Romito; Maria Ida Pansini; Francesco Perticone; Gianfranco Antonelli; Mariavittoria Pitzalis; Paolo Rizzon,"This multicenter, double-blind, parallel-group study compared the effects of three dihydropyridine calcium channel blockers (lercanidipine, felodipine, and nifedipine gastrointestinal therapeutic system) on blood pressure and heart rate in 250 patients with mild to moderate hypertension (diastolic blood pressure > or =95 and 109 mm Hg). Patients were randomized to 4 weeks of treatment with once-daily doses of lercanidipine 10 mg, felodipine 10 mg, or nifedipine gastrointestinal therapeutic system 30 mg. After 4 weeks of treatment, the dose was doubled in nonresponding patients. At 8 weeks, no significant differences in blood pressure were observed among the three groups. Increases in heart rate in all three groups induced by stressful conditions before and after treatment were not exacerbated during active treatment. The incidence of adverse drug reactions was lower in the lercanidipine and nifedipine groups than in the felodipine group (p<0.05); in particular, the incidence of edema for lercanidipine was 5.5% vs. 13% for felodipine and 6.6% for nifedipine.",2003.0,0,0
574,12959273,A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects.,S Ueda; P A Meredith; C A Howie; H L Elliott,"1 This study in normotensive subjects compared the duration and consistency of action of amlodipine (5 mg) and nifedipine GITS (60 mg) by assessment of the attenuation of pressor responses to noradrenaline and angiotensin II. 2 Both drugs significantly attenuated pressor responses to both vasoconstrictors at 6 and 24 h post-dose with rightward shifts of up to 2.3-fold in the dose-response curves. 3 There was significantly less pharmacokinetic variability with amlodipine: for example, intra-subject variability was 33% with amlodipine and 59% with nifedipine GITS. 4 There were no significant differences in the pressor dose ratios up to 48 h post-dose with amlodipine whereas there was a significant and progressive reduction in the pressor dose ratios with nifedipine. 5 These results suggest that both drugs are broadly comparable as once daily treatments but amlodipine displayed less intra- and inter-subject variability and provided a significantly more sustained effect with a reserve of pharmacological activity up to 48 h post-dose.",2003.0,0,0
575,12959309,A comparison of the acute haemodynamic effects of nisoldipine and nifedipine during treatment with atenolol in patients with coronary artery disease.,K M Donaldson; K D Dawkins; D G Waller,"1. The acute haemodynamic effects of intravenous nisoldipine (1, 2, 4 microg kg(-1)) and nifedipine (2.5, 5, 10 microg kg(-1)) were compared in a randomised, within-patient crossover study. Fifteen male patients with stable angina pectoris treated with atenolol were studied after undergoing routine cardiac catheterisation. 2. Nisoldipine caused a dose-related fall in systemic vascular resistance (maximum 22%) associated with an increase in heart rate and cardiac index (18%) and a fall in mean arterial pressure (7%). 3. By contrast, nifedipine was associated with a significant increase in heart rate but systemic vascular resistance, cardiac index and mean arterial pressure remained unaltered. 4. At doses with equivalent effects on heart rate (2 microg kg(-1) nisoldipine; 10 microg kg(-1) nifedipine) acute dosing with nisoldipine caused a significantly greater fall in systemic vascular resistance and increase in cardiac index, whilst nifedipine caused a greater reduction in stroke volume index and left ventricular stroke work index. 5. The results suggest that, when combined with atenolol, acute dosing with nisoldipine may have a more complementary haemodynamic profile than nifedipine. The implications of this finding for chronic oral dosing in patients with impaired left ventricular function should be evaluated.",2003.0,0,0
576,12959310,The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension.,A D Bainbridge; R J Macfadyen; S Stark; K R Lees; J L Reid,"1. The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril (2.5 mg) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine (5 mg) were assessed in a double-blind, double dummy placebo controlled, randomised, crossover study in 20 patients (mean age 55.4 years; range 46-69) with uncomplicated mild to moderate hypertension (supine diastolic > 90 mmHg < 115 mmHg after 4 weeks of single-blind wash-out on placebo). The four randomised, double-blind, crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo, monotherapy with each drug and the combination. Noninvasive ambulatory blood pressure monitoring (Spacelabs 90207) was performed for 24 h at the end of each phase. 2. The mean 24 h ambulatory blood pressure (mmHg) was 147.9/92.0 following placebo, 141.3/87.8 following monotherapy with ramipril 2.5 mg, 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg. All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo. The antihypertensive efficacy of the combination was additive. 3. The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER.",2003.0,0,0
577,12963858,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
578,12967735,Prolongation of the QT interval in palliative care patients.,Georgina Walker; Andrew Wilcock; Ann Marie Carey; Cathann Manderson; Rebecca Weller; Vincent Crosby,"Prolonged QT interval on the electrocardiogram (ECG) is associated with an increased risk of cardiac arrhythmia and sudden death. Many drugs used in palliative medicine increase the QT interval and several have had their licenses withdrawn or severely restricted. The relative importance of prolonged QT interval will increase for palliative medicine physicians when dealing with patients with longer prognoses and especially cardiac disease. Given these safety concerns, the aim of this study was to determine the prevalence of a prolonged QT interval in palliative care patients who were not in the terminal stage and were referred to a specialist service. Of 300 patients, 47 (16%) had prolonged QTc but only two had QT >500ms. The presence of coexistent cardiac disease or high levels of serum alkaline phosphatase appear to be the clinical features most robustly associated with a prolonged QTc. Although prolonged QTc is relatively common in patients referred to a specialist palliative care service, severely prolonged QT is rare.",2003.0,0,0
579,12969931,Recent developments in obstetrics.,Andrew H Shennan,,2003.0,0,0
580,13679697,[Drugs associated with acute generalized exanthematic pustulosis].,E-H Saissi; F Beau-Salinas; A-P Jonville-Béra; G Lorette; E Autret-Leca; Centres Régionaux de Pharmacovigilance,"Acute generalized exanthematous pustulosis is a severe eruption which is usually drug related. If the causative drug is discontinued, acute generalized exanthematous pustulosis resolves spontaneously in ten days. The aim of this study was to compare drugs suspected of causing acute generalized exanthematous pustulosis reported to French Pharmacovigilance centres and those reported in the literature. All cases of ""pustular eruption"" qualified as ""serious"" reported to the French Pharmacovigilance Centers between January 1985 and December 2001 were analyzed. Cases for which the diagnosis of acute generalized exanthematous pustulosis was not clearly identified were reviewed by a dermatologist. The relationship between acute generalized exanthematous pustulosis and drug exposure was re-examined by one of us. An exhaustive review of the literature was also performed. Review of the data base revealed 207 cases of serious acute generalized exanthematous pustulosis leading to death in 4 cases (2%). Of these cases of acute generalized exanthematous pustulosis, only one drug was suspected in 107 cases (51.6%). The main drugs involved were: pristinamycin (18 cases), amoxicillin (+/- clavulanic acid) (16 cases), hydroxychloroquine (8 cases) and a combination of spiramycin + metronidazole (5 cases). The most frequent causal drugs in our study and in the literature are: amoxicillin +/- clavulanic acid, pristinamycin, hydroxychloroquine, ampicillin, diltiazem, co-trimoxazole, terbinafine, carbamazepine and spiramycin +/- metronidazole. Only pristinamycin and diltiazem have information in their summary of product characteristics regarding the risk of acute generalized exanthematous pustulosis. Because it is essential to discontinue the causative drug as soon as possible if a pustular eruption occurs, physicians must be informed of the risk, which should be added to the ""adverse events"", and ""warnings"" sections of the summary of product characteristics of the drugs concerned. Our results show the relevance of notification of side effects by physicians to pharmacovigilance centres, leading to the identification of a signal and public health dissemination of warnings.",2003.0,0,0
581,14508839,Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65-79 years.,Christopher I Li; Kathleen E Malone; Noel S Weiss; Denise M Boudreau; Kara L Cushing-Haugen; Janet R Daling,"Limited data are available regarding the incidence of breast carcinoma among users of relatively recently introduced forms of antihypertensive therapy. Although it has been suggested that women who have taken calcium channel blockers (CCBs) have an increased risk and that women who have taken angiotensin-I-converting enzyme (ACE) inhibitors have a decreased risk, currently, no conclusions can be drawn. A population-based case-control study of women ages 65-79 years was conducted in western Washington State. The responses of 975 women who were diagnosed with invasive breast carcinoma during 1997-1999 were compared with the responses of 1007 women in a control group. Associations between use of different types of antihypertensive medications and breast carcinoma incidence were evaluated using logistic regression. Overall, women who had ever used CCBs, beta-blockers, or ACE inhibitors did not have an altered risk of breast carcinoma relative to women who had never used antihypertensive medications. Although the use of immediate-release CCBs, thiazide diuretics, and potassium-sparing diuretics was associated with modestly increased risks of breast carcinoma (odds ratio [OR], 1.5; 95% confidence interval [95% CI], 1.0-2.1; OR, 1.4; 95% CI, 1.1-1.8; and OR, 1.6; 95% CI, 1.2-2.1, respectively), the absence of any trend in the size of excess risk with increasing duration or with current versus former use of these agents argues for a cautious interpretation. The use of particular types of antihypertensive medications, including immediate-release CCBs and certain diuretics, may increase the risk of breast carcinoma among older women. Additional studies are warranted to clarify these potential associations. Cancer 2003;98:1504-13.",2003.0,1,1
582,14509142,Pulmonary arterial hypertension--the primary pulmonary hypertension syndromes.,Jamie C Hey; Steven M Scharf,,2003.0,0,0
583,14513044,Current trends in large cell lymphoma.,R I Fisher; P Shah,"For the last decade, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the best available standard of care for aggressive non-Hodgkin's lymphoma (NHL), based on equivalent therapeutic results with other multiagent chemotherapy accompanied by lower costs and lesser toxicity. However, only 40-45% of these patients are cured with CHOP. New treatment strategies have been employed, including the addition of Rituximab to CHOP in elderly patients; dose escalation using granulocyte-colony-stimulating factor; overcoming the multidrug resistance phenotype with infusional chemotherapeutic regimens and use of some newer agents. Furthermore, the International Prognostic Factor index (IPI) has permitted identification of subsets of patients with large variations in prognosis, allowing prognosis specific therapy to be tested. There is now accumulating evidence that the clinical behavior of certain NHL can be profiled by the expression of certain molecular markers, which will undoubtedly play a role in the development of new prognostic models that may refine our ability to identify poor-risk patients. Regardless, there is still significant opportunity for improving survival in large cell lymphomas.",2003.0,0,0
584,14514004,Glucagon in beta-blocker and calcium channel blocker overdoses: a systematic review.,Benoit Bailey,"Glucagon is usually accepted as part of the standard treatment in the management of patients with beta-blocker and calcium channel blocker overdoses. A systematic review was done in order to evaluate the evidence supporting glucagon use in beta-blocker and calcium channel blocker overdoses. Studies evaluating glucagon for those uses were identified using the Cochrane Database of Systematic Reviews, the Cochrane Controlled Trials Register, MedLine, ToxLine, and EMBASE searches, as well as reviewing medical toxicology textbooks and references of identified articles. Only controlled studies of human or animal studies were included, the latter only when it was an in vivo model of acute poisoning. The quality of the included studies was assessed. The search found no study in humans but identified 30 in animals. In the five studies of animal models of beta-blocker overdose included, glucagon appeared to consistently increase the heart rate at least transiently but appeared to have no effect on mean arterial pressure even though it possibly increased cardiac output. Its effect on the survival rate in animal models of beta-blocker overdose was unclear. In the six studies of animal models of calcium channel blocker overdose included, glucagon appeared to increase heart rate and cardiac output and reverse second and third degree AV blocks, all at least transiently. There appeared to be no effect of glucagon on mean arterial pressure although it did increase in one model. Glucagon appeared to have no effect on survival rate. The included studies for both overdoses were not blinded, had limited numbers of animals, and some had inadequate glucagon regime. The evidence supporting the use of glucagon in the management of patients with beta-blocker and calcium channel blocker overdoses is limited to animal studies.",2003.0,0,0
585,14517164,"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
586,14567007,Medications and sexual function.,David R Thomas,"There seems to be a reluctance to self-report sexual dysfunction during clinical interviews. The rate of reported sexual dysfunction increases when information is sought aggressively in the clinical interview. The relationship to a specific therapeutic agent, however, can be clouded by the patient's perception and coexisting morbidity. Most of the data relating sexual dysfunction to specific drugs are anecdotal. The strongest proof of a casual effect is improvement in sexual function after withdrawal of the medication. Most of the adverse sexual effects of commonly used medications can be predicted from a simplified understanding of the human sexual response and physiologic mediators. Alternative therapeutic agents can be substituted by understanding these physiologic mechanisms and a careful clinical interview. Although polypharmacy is a problem for older persons, in some cases sildenafil can be used to correct drug-induced impotence.",2003.0,0,0
587,14597462,"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
588,14657064,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.",2003.0,1,1
589,7477146,Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.,P F Kokkinos; P Narayan; J A Colleran; A Pittaras; A Notargiacomo; D Reda; V Papademetriou,"The prevalence of hypertension and its cardiovascular complications is higher in African Americans than in whites. Interventions to control blood pressure in this population are particularly important. Regular exercise lowers blood pressure in patients with mild-to-moderate hypertension, but its effects in patients with severe hypertension have not been studied. We examined the effects of moderately intense exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension. We randomly assigned 46 men 35 to 76 years of age to exercise plus antihypertensive medication (23 men) or antihypertensive medication alone (23 men). A total of 18 men in the exercise group completed 16 weeks of exercise, and 14 completed 32 weeks of exercise, which was performed three times per week at 60 to 80 percent of the maximal heart rate. After 16 weeks, mean (+/- SD) diastolic blood pressure had decreased from 88 +/- 7 to 83 +/- 8 mm Hg in the patients who exercised, whereas it had increased slightly, from 88 +/- 6 to 90 +/- 7 mm Hg, in those who did not exercise (P = 0.002). Diastolic blood pressure remained significantly lower after 32 weeks of exercise, even with substantial reductions in the dose of antihypertensive medication. In addition, the thickness of the interventricular septum (P = 0.03), the left ventricular mass (P = 0.02), and the mass index (P = 0.04) had decreased significantly after 16 weeks in the patients who exercised, whereas there was no significant change in the nonexercisers. Regular exercise reduced blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.",1995.0,0,0
590,7483123,,,,,0,0
591,7486271,[Comparison of vascular effects of magnesium sulfate and nicardipine during extracorporeal circulation].,A Delhumeau; J C Granry; C Cottineau; J G Bukowski; J J Corbeau; X Moreau,"To evaluate the hypothesis that magnesium sulphate (SO4Mg), usually administered for protecting the myocardium and decreasing the rate of arrhythmias in cardiac surgery, was able to control the hypertensive peaks occurring during cardiopulmonary bypass (CPB), as efficiently as nicardipine (N). Randomized controlled trial. Forty patients were allocated into two groups when hypertensive peaks occurred during CPB. The patients of the N group were then given nicardipine 0.016 mg.kg-1 and those of the SO4Mg group received magnesium sulphate 50 mg.kg-1. Anaesthesia technique was identical and during normothermic CPB the flow remained constant at 2.4 L.min-1, during the 10 min following N or SO4Mg administration. The usual haemodynamic variables were monitored. Both N and SO4Mg decreased significantly the MAP and the SVR over the 9 min following their administration. The decrease was more marked after SO4Mg. As the flow of the pump was unchanged after their injection the decrease can be attributed to the relaxing effect of these agents on the smooth vascular muscles. SO4Mg permits to treat hypertensive peaks occurring during CPB as efficiently as N. Three grammes of SO4Mg have an hypotensive effect equivalent to that of 1 mg of nicardipine. However repetitive injections of SO4Mg cannot be recommended because of the risk for hypermagnesemia.",1995.0,0,0
592,7487236,Calcium antagonists should continue to be used for first-line treatment of hypertension.,M Epstein,,1995.0,0,0
593,7489530,Comparative efficacy of two long-acting formulations of nifedipine in the treatment of hypertension. The Switch Study Investigators.,M G Myers; C B Toal,"To compare the antihypertensive effects and incidence of side effects of two formulations of nifedipine: a prolonged action (PA) tablet bid and a gastrointestinal therapeutic system (GITS) tablet once daily. Patients with controlled hypertension (diastolic blood pressure less than 90 mmHg) on nifedipine-PA 10 mg (n = 74) or 20 mg (n = 99) bid were enrolled into an open label study consisting of six weeks of previous nifedipine-PA followed by six weeks of nifedipine-GITS therapy. Nifedipine-GITS was increased from 30 mg to 60 mg daily if the patient's diastolic blood pressure increased by at least 10 mmHg compared with the value after six weeks of nifedipine-PA. Blood pressure after six weeks of nifedipine-PA 10 mg (142 +/- 1/86 +/- 1 mmHg) decreased (P < 0.01) after conversion to nifedipine-GITS 30 mg (137 +/- 1/84 +/- 1 mmHg). Blood pressure values for nifedipine-PA 20 mg patients were unchanged after conversion to nifedipine-GITS; 74 patients received nifedipine-GITS 30 mg and 14 patients required titration up to nifedipine-GITS 60 mg daily. Sixteen patients withdrew on nifedipine-PA and five withdrew on nifedipine-GITS, mostly for reasons unrelated to drug therapy. Twenty-three patients experienced adverse events on nifedipine-PA versus 20 patients on nifedipine-GITS therapy. Patients whose hypertension is controlled by nifedipine-PA 10 or 20 mg bid can be successfully converted to nifedipine-GITS with most patients remaining normotensive on 30 mg daily.",1995.0,0,0
594,7503006,"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.",1995.0,1,1
595,7504141,Bepridil improves left ventricular performance in patients with angina pectoris.,R M Zusman; J Higgins; D Christensen; C A Boucher,"Patients with coronary artery disease and angina pectoris have abnormalities of left ventricular (LV) diastolic performance. These abnormalities, which exist when the patients are at rest and not experiencing angina, are presumably secondary to abnormalities of intracellular calcium metabolism. Twenty-three patients with chronic exertional angina pectoris participated in a placebo-controlled, randomized, cross-over trial of bepridil hydrochloride. Angina frequency, nitroglycerin (NTG) consumption, and treadmill exercise capacity were assessed, and each patient underwent first-pass radionuclide cineangiography while receiving placebo or bepridil to assess LV performance. Bepridil decreased angina frequency from 8.5 +/- 0.6 to 4.4 +/- 1.5 episodes per week (p < 0.01) and NTG consumption from 7.2 +/- 2.4 to 3.6 +/- 1.5 tablets per week (p < 0.01). Total treadmill exercise time, time to onset of angina, and time to 1-mm ST segment depression increased significantly during bepridil therapy. Cardiac output (CO), stroke volume (SV), and ejection fraction (EF) increased at rest and during peak upright bicycle exercise. Peak ejection rate and peak filling rate increased, and time to peak ejection rate and time to peak filling rate decreased at rest and at peak exercise during bepridil therapy. In addition, early diastolic filling fraction increased and atrial filling volume decreased during bepridil treatment. Bepridil is effective as monotherapy for treatment of patients with exertional angina; its use is associated with increased exercise capacity and decreased angina frequency and NTG consumption as well as improved LV systolic and diastolic performance at rest and during peak exercise.",1993.0,0,1
596,7505351,Comparative evaluation of the antihypertensive efficacy of once-daily amlodipine versus nitrendipine with 24-hour ambulatory blood pressure monitoring in essential hypertension.,A Coca; M J Picado; A De la Sierra; M T Aguilera; M Sánchez; M M Lluch; A Urbano-Márquez,"We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.",1993.0,0,0
597,7506652,Sotalol. An updated review of its pharmacological properties and therapeutic use in cardiac arrhythmias.,A Fitton; E M Sorkin,"Sotalol is a nonselective beta-adrenoceptor antagonist which prolongs cardiac repolarisation independently of its antiadrenergic action (class III antiarrhythmic properties). The antiarrhythmic action of sotalol appears to arise predominantly from its class III properties, and the drug exhibits a broader antiarrhythmic profile than the conventional beta-blockers. Sotalol is effective in controlling paroxysmal supraventricular tachycardias and the ventricular response to atrial fibrillation/flutter in Wolff-Parkinson-White syndrome, in maintaining sinus rhythm after cardioversion of atrial fibrillation/flutter, and in preventing initiation of supraventricular tachyarrhythmias following coronary artery bypass surgery. Sotalol shows promise in the control of nonmalignant and life-threatening ventricular arrhythmias, particularly those associated with ischaemic heart disease. It is effective in suppressing complex forms of ventricular ectopy, displaying superior antiectopic activity to propranolol and metoprolol. The acute efficacy of sotalol in preventing reinduction of sustained ventricular tachyarrhythmias and suppressing spontaneous episodes of these arrhythmias on Holter monitoring is translated into long term prophylactic efficacy against arrhythmia recurrence in approximately 55 to 85% of patients with refractory life-threatening ventricular arrhythmias. In addition, sotalol offers the advantage over the class I agents of reducing cardiac and all-cause mortality in the high risk population with life-threatening ventricular arrhythmias. The adverse effects of sotalol are primarily related to its beta-blocking activity and its class III property of prolonging cardiac repolarisation. Sotalol is devoid of overt cardiodepressant activity in patients with mild or moderate left ventricular dysfunction. The overall arrhythmogenic potential is moderately low, but torsade de pointes may develop in conjunction with excessive prolongation of the QT interval due to bradycardia, hypokalaemia or high plasma concentrations of the drug. In summary, sotalol displays a broad spectrum of antiarrhythmic activity, is haemodynamically well tolerated, and confers a relatively low proarrhythmic risk. It is likely to prove particularly appropriate in the treatment and prophylaxis of life-threatening ventricular tachyarrhythmias.",1993.0,0,0
598,7512483,Postinfarct treatment with verapamil. Effect of verapamil in patients with hypertension.,J F Hansen,"In the Danish Verapamil Infarction Trial II (DAVIT II), treatment with verapamil 360 mg/day improved reinfarction-free survival compared with administration of placebo. Verapamil appears to effectively prevent reinfarction and sudden death, i.e. sudden events (hazard ratio 0.78 compared with placebo, 95% confidence limits 0.62 to 0.99). In a retrospective analysis of data from DAVIT II, verapamil treatment in patients with systemic hypertension prevented reinfarction significantly better than placebo (15 of 149 verapamil recipients compared with 27 of 152 placebo recipients reinfarcted, p = 0.04). Similarly, first cardiovascular events, i.e. first reinfarction, first stroke or death, were prevented more effectively by verapamil treatment than by administration of placebo (29 verapamil recipients vs 42 placebo recipients had first cardiovascular events, p = 0.07).",1993.0,0,1
599,7521487,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
600,7523788,"Effect of isradipine and nifedipine on diastolic function in patients with left ventricular dysfunction due to coronary artery disease: a randomized, double-blind, nuclear, stethoscope study.",E Wout van den Toren; R J de Vries; M C Portegies; P K Blanksma; W H van Gilst; H J Hillege; D J van Veldhuisen; K I Lie,"To elucidate the effect of isradipine and nifedipine on left ventricular (LV) systolic and diastolic function, each drug was given intravenously (i.v.) in equihypotensive doses to 10 patients accepted for coronary arteriography for stable angina pectoris. All 20 patients had LV ejection fraction (LVEF) of < 40% owing to previous myocardial infarction (MI). Systolic and diastolic function was assessed by standard hemodynamic parameters and pressure-volume relations measured by nuclear stethoscope. All measurements were taken at rest and during ischemia caused by right atrial pacing. Both systolic and diastolic parameters improved equally with isradipine and nifedipine. LVEF and cardiac output (CO) increased owing to peripheral vasodilatation. A decrease in P/Vmax, indicating a negative inotropic effect, was noted in patients at rest with both medications, but not during pacing-induced ischemia. With either medication, the time constant of relaxation and the end-diastolic elasticity constant decreased during pacing, indicating improvement in diastolic function, probably owing to relief of myocardial ischemia.",1994.0,0,0
601,7526065,Felodipine versus placebo in stable effort-induced angina pectoris in patients inadequately controlled with metoprolol--a dose-finding study.,H Emanuelsson; P Ahlström; V Kujacic; L Lundkvist; U Rosenqvist; A Tisell; K Angman,"We compared the antianginal and antiischemic effect and tolerability of four different doses of felodipine extended-release (ER) tablets with placebo in patients with stable effort-induced angina pectoris treated with beta-blocker [metoprolol controlled release (CR) 100 mg once daily, o.d.]. Seventy-five patients were enrolled in the study. At the end of a 2-week single-blind period, all patients performed two exercise tests. If total exercise time did not vary by > 15% between the two tests and both tests were limited by anginal discomfort and concomitant ST depression of at least 1 mm, the patients were randomized to double-blind treatment (66 patients). Each patient received three of the following treatments: felodipine 2.5, 5, 10, or 20 mg, or placebo. The treatments were given o.d. in a cross-over, balanced incomplete block design with three of 3-week treatment periods. Exercise tests were performed 12 and 24 h after dose intake at the end of each treatment period. Fifty-nine patients completed the study. Twelve hours after dose administration, 10 and 20 mg felodipine increased time to onset of anginal pain by 60 and 63 s on the average, respectively, as compared with placebo (p = 0.001). Time to 1-mm ST depression was prolonged by 29 s after 10 mg (p = 0.14) and by 30 s after 20 mg (p = 0.13) felodipine. Time to end of exercise was increased by 28 s (p = 0.07) and 15 s (p > 0.20), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
602,7533703,The 24-hour efficacy of a new once-daily formulation of nifedipine. Italian Nifedipine GITS Study Group.,A Zanchetti,"Nifedipine GITS (Gastro-Intestinal Therapeutic System) is a recently launched long-acting formulation of nifedipine. The aim of the Italian Nifedipine GITS Study was to determine the duration of the antihypertensive effect of once-daily nifedipine GITS in outpatients with essential hypertension. After a 2-week placebo run-in period, 126 patients with mild to moderate essential hypertension (diastolic BP95 to 114mm Hg) were randomised to receive nifedipine GITS 30mg (n = 42), nifedipine GITS 60mg (n = 42) or placebo (n = 42), once daily in a double-blind fashion for 4 weeks. At the end of the run-in and treatment periods, ambulatory BP monitoring was performed (Spacelabs 90202 or 90207 device) to provide regular 15-minute BP readings for 24 to 36 hours. In the 81 patients with at least 24 hours of valid ambulatory BP data, the average systolic and diastolic BP changes after treatment with nifedipine GITS 30mg (n = 25), nifedipine GITS 60mg (n = 28) and placebo (n = 28) were -16.5/-10.8, -16.3/-10.0 and +0.4/+0.9mm Hg, respectively. BP changes with nifedipine GITS differed significantly (p < 0.01) from those with placebo. Heart rate was not significantly altered by nifedipine GITS. The effects of nifedipine GITS and placebo on ambulatory BP 24 hours and 36 hours after the last dose were evaluated in 56 patients with complete 36-hour ambulatory BP profiles. After 24 hours, both doses of nifedipine GITS caused significant (p < 0.01) reductions in systolic and diastolic BP.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
603,7546494,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
604,7546497,Differential effects of felodipine and nifedipine on 24-h blood pressure and left ventricular mass.,M G Myers; F H Leenen; J Tanner,"1,4-Dihydropyridine calcium antagonists, which have a rapid onset and short duration of action, tend to increase sympathetic activity, which may limit the regression of left ventricular hypertrophy when used for the treatment of hypertension. This study compares the effects of the shorter-acting formulation of nifedipine (PA) with longer-acting felodipine (ER) on 24-h blood pressure and left ventricular mass in patients with uncomplicated essential hypertension. Subjects were randomly allocated to receive nifedipine (n = 52) or felodipine (n = 56) over 8 weeks at increasing doses until the sitting office diastolic blood pressure (DBP) was < 90 mm Hg. An ambulatory blood pressure (ABP) recording and echocardiogram were performed at baseline and upon completion of the study. At the end of the dosing interval, felodipine lowered office DBP (mm Hg) by -18 +/- 12/14 +/- 1 compared to -14 +/- 2/11 +/- 1 for nifedipine (P < or = .05). Mean 24-h ABP was reduced (P < .001) by felodipine (-15 +/- 1/-10 +/- 1 mm Hg) and nifedipine (-15 +/- 1/-9 +/- 2 mm Hg). However, nifedipine caused an apparent biphasic response with felodipine reducing (P < .05) blood pressure more in the early afternoon compared to nifedipine. Left ventricular mass index was significantly reduced (P < .01) by felodipine (-6 +/- 1 g/m2), but not by nifedipine. Once-daily administration of felodipine achieves a more consistent control of blood pressure compared to twice-daily nifedipine and may be associated with a greater reduction in left ventricular mass.",1995.0,0,0
605,7546498,Time-dependent effect of isradipine on the nocturnal hypertension in chronic renal failure.,F Portaluppi; L Vergnani; R Manfredini; E C degli Uberti; C Fersini,"Nocturnal hypertension is frequently observed in chronic renal failure and contributes to the risk of target organ damages. We assessed whether antihypertensive therapy may restore a nocturnal blood pressure (BP) fall in this condition. A sustained-release oral formulation (SRO) of isradipine was used, and the possible differences in the response to morning nu evening dosing were also investigated. Sixteen hypertensive patients with chronic renal failure due to parenchymal kidney disease were studied after 2 weeks of single-blind placebo runin. According to the double-blind, randomized, cross-over design, they received 5 mg isradipine SRO at 08:00, or at 20:00 for 4 weeks, separated by a single-blind placebo period of 2 weeks. A 24-h BP monitoring at 10-min intervals was carried out at the end of each treatment using a SpaceLabs 90207 instrument. Under placebo, blunt BP profiles were observed, whereas HR showed a mean nocturnal fall of 17.4%, which remained unaltered after isradipine. Both isradipine treatments were equally effective in reducing the mean 24-h BP levels. However, the evening regimen showed a more pronounced effect during the night. The mean nocturnal fall in systolic/diastolic BP represented 4.8/8.7% and 7.5/10.9% of the corresponding daytime mean after morning and evening dosing, respectively. Only the evening administration reset the normal synchronization of the 24-h BP and HR profiles. Our findings demonstrate that antihypertensive treatment may restore a nocturnal BP fall in renal patients. An evening regimen of isradipine SRO seems more apt than a morning regimen to obtain this therapeutic goal.",1995.0,0,0
606,7555159,Changes in wall motion in patients treated for unstable angina. A suggestion of the stunned and hibernating myocardium in humans. UNASEM Collaborative Study Group. Unstable Angina Study Using Eminase.,C de Zwaan; F W Bär; W R Dassen; F Vermeer; H J Wellens,"A double-blind, placebo-controlled study using anistreplase was performed in 159 patients with unstable angina. All patients had a history of unstable angina combined with typical ECG changes and without evidence of a previous, recent, or ongoing myocardial infarction. The purpose of the present study was to analyze the relationship between the patency of the culprit artery and the behavior of the ischemia-related regional left ventricular (LV) wall motion. On entry to the study, all patients received conventional drug therapy: i.v. nitroglycerin therapy, an oral beta-blocking agent, and a calcium antagonist. Baseline angiography was carried out within 3 h after randomization, a mean of 4.2 +/- 3.0 h (range, 1 to 17 h) after the last attack of chest pain. Treatment with trial medication was withheld in 33 cases. Sixty-five patients with coronary artery disease received anistreplase (30 U/5 min)/heparin and 61 patients heparin-only therapy. Angiography was repeated 20.6 +/- 4.6 h (mean +/- SD; range, 12 to 39 h) after the baseline angiographic study. To assess changes in regional myocardial wall motion, the LV wall was divided into seven segments. The ischemia-related coronary artery stenosis was calculated quantitatively and related to the quantitatively assessed mean regional left ventricular ejection fraction (RLVEF) of the ischemia-related segments. In 118 of 126 patients who received trial medication, we found that anistreplase/heparin therapy leads to a significantly (p < 0.01) greater reduction in coronary artery diameter stenosis than heparin-only therapy (n = 63, mean +/- SD, 11 +/- 22, vs n = 55, mean +/- SD, 3 +/- 11%). Anistreplase/heparin therapy was related to a larger significant improvement of the ischemia-related RLVEF than heparin-only therapy, although the latter association was not statistically significant (n = 63, mean +/- SD, 7 +/- 15, vs n = 55, mean +/- SD, 5 +/- 14%). The effects of change of coronary artery stenosis on regional LV wall motion were also determined. A paradoxical finding was that a persistently occluded vessel or a vessel showing an increase in coronary artery stenosis was associated with a greater improvement of the ischemia-related RLVEF than a reopened vessel or a vessel with a reduction in coronary artery stenosis (n = 15, mean +/- SD, 7 +/- 11, vs n = 41, mean +/- SD, 8 +/- 13, vs n = 15, mean +/- SD, 1 +/- 12, vs n = 47, mean +/- SD, 5 +/- 16%, NS). One day after the last attack of chest pain, the regional LV wall motion was still abnormal in about 20% of patients. In these patients with unstable angina, the LV wall motion improved both in the treated and the control group at follow-up angiography 1 day later. Improved coronary arterial anatomy was associated with a lesser improvement of the LV contractile function than when worsening of the coronary angiographic appearance occurred. There is no rational explanation of these results. This is a beginning of an effort to elucidate the clinical significance of the stunned and hibernating myocardium in humans.",1995.0,0,0
607,7555530,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
608,7562881,Determination of systemic haemodynamic alterations induced by slow-release nifedipine in elderly hypertensive patients using a non-invasive method: double-blind cross-sectional random study.,S R Ferreira-Filho; H Dorneles,"We evaluated the systemic haemodynamic alterations induced by slow-release nifedipine administered to elderly hypertensive patients, 20 mg twice daily by the oral route for 4 weeks. A non-invasive chest electrical bio-impedance method was used to detect changes in stroke volume and cardiac output. The random, double-blind, crossover study showed variations in measurements made in the supine and in the standing position: delta -18.0% (P < 0.001) and delta -14.9% (P < 0.001) for mean arterial pressure; delta -16.5% (P < 0.01) and delta -34.9% (P < 0.01) for total peripheral resistance; and delta +8.1% (P < 0.05) and delta +12.6% (P < 0.01) for heart rate, respectively. In contrast, cardiac output and stroke volume were the same when measured in the supine and standing positions both when compared with the placebo period and when compared with each other. We conclude that slow-release nifedipine is effective in reducing systemic blood pressure levels of elderly subjects and that this phenomenon occurs without reductions in cardiac output.",1995.0,0,0
609,7564348,"Acute thrombogenicity of arterial prostheses exposed to reduced blood flow in dogs: effects of heparin, aspirin, and prostacyclin.",Y Merhi; J Bernier; Y Marois; R Guidoin,"Thrombogenesis is considered the principal cause of early failure of arterial grafts. Although antithrombotic drugs are recommended, their efficiency under low blood flow conditions is still being debated. In this study, we evaluated the ability of three drugs to modify the thrombotic properties of blood and, consequently, to influence platelet and fibrin deposition on the luminal surface of polyester arterial prostheses. In dogs receiving saline (control, n = 10), heparin (100 U/kg, n = 5), aspirin (325 mg, n = 5), or prostacyclin (15 ng/kg/min, n = 5), a 30-cm, woven, loop-shaped, DeBakey arterial prosthesis was implanted as a substitute for the infrarenal aorta and exposed to reduced blood flow (50 ml/min) for 4 h. The parameters of the blood measured included activated clotting time (ACT) and platelet aggregation with collagen, determined before and after each treatment. Blood deposits were quantified using 111In labeled platelets and 125I-labeled fibrinogen. The ACT was significantly prolonged only after heparin treatment, and platelet aggregation, which was decreased by 35% (p < 0.05) after heparin treatment, was almost abolished after aspirin and prostacyclin treatments. As compared with the control group, both platelet and fibrin uptake on the luminal surface of the prostheses were reduced significantly by heparin by 87 and 37%, respectively. Despite their inhibition of platelet aggregation in vitro, aspirin and prostacyclin induced no significant change in platelet and fibrin deposition on the luminal surface of the woven polyester arterial prostheses under low blood flow conditions. Under such conditions, however, thrombin generation with subsequent platelet-fibrin deposition was prevented by use of heparin anticoagulant therapy.",1995.0,0,0
610,7564371,Clinical efficacy and safety of once-daily diltiazem in patients with stable angina pectoris switched from twice-daily diltiazem.,D Savard; J Lenis; M Juneau; C Jacob; A P Boulet,"The maintenance of angina control was assessed in this multicenter (three sites), randomized, double-blind, parallel-group study. Patients with stable angina pectoris receiving twice-daily sustained-release (SR) diltiazem were switched to equivalent doses of once-daily controlled-delivery (CD) diltiazem or to diltiazem SR. Patients who were switched from diltiazem SR to diltiazem CD (n = 28) experienced a 5% increase in time to termination (p = 0.0004) on the exercise tolerance test (ETT), as well as an 8% improvement in time to onset of angina (p < 0.0001) on the ETT. A similar trend was observed in patients randomized to diltiazem SR (n = 7), which suggested a training effect, and, therefore, equal efficacy between diltiazem SR and diltiazem CD. During exercise testing in the diltiazem SR baseline phase, 77% of the patients did not experience angina, whereas 60% of the patients did not experience ST-segment depression. Following transfer to diltiazem CD, 79 and 61% of patients, respectively, remained angina- and ST-segment depression free. No significant changes in the number of angina attacks, nitroglycerin use, or any hemodynamic-related parameters were observed following transfer to diltiazem CD. Eleven percent of the patients receiving diltiazem CD experienced treatment-related adverse events, which were limited to headache and abdominal pain; these adverse events did not lead to discontinuation of treatment. These findings suggest that patients whose angina is controlled with twice-daily diltiazem SR can be safely and effectively switched to an equivalent daily dose of the once-daily diltiazem CD.",1995.0,0,1
611,7572595,Three-period crossover trial with ambulatory blood pressure monitoring for evaluating antihypertensive therapy.,S Meeves; K Hafner; G Park; M Weber,"A double-blind, three-period, crossover trial used 24-hour ambulatory blood pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with placebo. Patients with hypertension (N = 43) were randomly assigned to one of four crossover treatment sequences of three treatment periods each. Ambulatory blood pressure was obtained at the end of each 4-week treatment period. Diltiazem CD significantly decreased diastolic and systolic blood pressure at bihourly ambulatory blood pressure evaluations (p < 0.05, all). However, when all ambulatory blood pressure monitoring data were combined into one statistical model, blood pressure reductions were quantifiably similar to those in the overall bihourly analysis, but with a consistent 24-hour antihypertensive effect for both diastolic and systolic blood pressure relative to that with placebo (i.e., parallel blood pressure profiles) and with increased precision. Mean +/- SE changes in diastolic and systolic blood pressure across the 24-hour dosing interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001, both). Therefore, by using a crossover design with ambulatory blood pressure monitoring, we showed diltiazem CD to reduce blood pressure consistently throughout a 24-hour dosing interval in comparison with placebo in patients with hypertension.",1995.0,0,0
612,7572650,Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris.,J Brouwer; J W Viersma; D J van Veldhuisen; A J Man in 't Veld; P Sijbring; J Haaksma; W A Dijk; K I Lie,"We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
613,7574861,A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension.,I Moncica; P I Oh; I ul Qamar; D Scolnik; G S Arbus; D Hebert; J W Balfe; G Koren,"In a crossover design, control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension. Compliance with once daily felodipine was higher than with nifedipine, at 95.6 (SEM 2.7)% v 78.9 (6.0)% (p = 0.02). Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine, at 77.6 (2.4) v 84.4 (2.8) mm Hg (p = 0.05). Similarly, blood pressure load (the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age) was lower for felodipine than for nifedipine: 43.5 (5.5)% v 61.3 (6.3)%. There was an opposite trend during the night, though this did not reach statistical significance. These data suggest that once a day felodipine is effective in children with hypertension. This may be because of improved compliance.",1995.0,0,0
614,7585281,Calcium channel blockers for heart rate control in atrial fibrillation complicated by congestive heart failure.,J T Heywood,"To review the safety and efficacy of verapamil and diltiazem with respect to ventricular response in atrial fibrillation (AF) in the setting of left ventricular (LV) systolic dysfunction. Pertinent articles were identified through a MEDLINE search of the English language literature from 1984 to 1993, followed by a manual search of the bibliographies of pertinent articles. Studies selected were case reports, controlled trials, review articles and editorials. Effects of verapamil and diltiazem on hemodynamics, ventricular response in AF, clinical parameters and mortality were reviewed. There are limited data about the effects of verapamil and diltiazem on ventricular function in patients with congestive heart failure. In vitro diltiazem has fewer negative inotropic effects than verapamil. Clinically there are some reports of hemodynamic and clinical deterioration in patients with significant LV dysfunction given verapamil although most patients improve with verapamil. There are more data concerning diltiazem in the setting of AF complicated by congestive heart failure. The drug does not appear to exacerbate heart failure, although hypotension can result. In chronic AF complicated by heart failure, there is concern that diltiazem may increase mortality. Options for therapy are digoxin, beta-blockers and atrioventricular node ablation. Calcium channel blockers may have a role in the acute reduction of ventricular response in patients with AF complicated by congestive heart failure; however, their safety in chronic heart rate control remains to be proven.",1995.0,0,1
615,7585759,Antihypertensive efficacy of optimally titrated doses of once-daily sustained-release diltiazem: a placebo-controlled trial. DILPLACOMP Study Group.,J P Ollivier; A Wajman; A Stalla-Bourdillon,"This study assessed once-daily sustained-release (o.d. SR) diltiazem in essential hypertension; 158 patients with supine diastolic blood pressures (BP) of 95-115 mm Hg were randomized to 200 mg diltiazem or placebo, then optimally titrated, at 2-week intervals, to 200, 300 or 400 mg to achieve supine diastolic BP < 90 mm Hg or a > or = 10 mm Hg fall from baseline. BP was measured at trough level, 24 h after dosing. After 2 weeks at the dose of 200 mg, supine diastolic BP was significantly reduced (from 101 to 92 mm Hg) compared with placebo (from 101 to 98 mm Hg; p < 0.001), and yielded 57% of responders with diltiazem against 22% with placebo (p < 0.001). Titration allowed supine diastolic BP normalization with diltiazem (88 mm Hg) compared with placebo (93 mm Hg; p < 0.001) and yielded 78% of responders with diltiazem against 37% with placebo (p < 0.01). The safety profile was similar to placebo. 200 and 300 mg o.d. SR diltiazem formulations enable safe and close regimen adjustments in mild-to-moderate essential hypertension.",1995.0,0,1
616,7589766,Comparative evaluation of the antihypertensive efficacy of once-daily sustained-release isradipine and lacidipine using 24-hour ambulatory blood-pressure monitoring.,M Galderisi; A Petrocelli; M Garofalo; A Celentano; A Alfieri; O de Divitiis,"In this single-blind crossover study the antihypertensive efficacies of two dihydropyridine calcium antagonists, sustained-release isradipine and lacidipine, were compared using clinic and ambulatory blood-pressure measurements. After a 2-week placebo wash-out, 34 patients (19 men, 15 women, mean age 49 years) with mild to moderate hypertension (diastolic blood pressure range 95-110 mmHg) were treated with 5 mg sustained-release isradipine for 4 weeks and 4 mg lacidipine for 4 weeks in a random order. Medications were taken once daily at 08.00 h. Clinic and ambulatory blood pressures were recorded at the end of each placebo or treatment period. Two patients stopped isradipine and six lacidipine because of severe adverse effects. Clinic systolic and diastolic blood pressures decreased by an average of 17/14 mmHg with isradipine and 17/13 mmHg with lacidipine, compared with placebo (P < 0.01 in both cases), without a change in heart rate. Mean ambulatory 24-h and daytime systolic and diastolic blood pressure were significantly reduced by sustained-release isradipine and lacidipine (P < 0.05 and P < 0.01, respectively). At night systolic blood pressure fell compared with placebo (P < 0.05 with both drugs) whereas the reduction in diastolic blood pressure was not statistically significant. Mean 24-h heart rate remained unchanged. Blood-pressure variability did not differ significantly between the two drugs or between either drug and the placebo. The antihypertensive effects of sustained-release isradipine and lacidipine were similar, but the tolerability of isradipine appears to be greater since it caused fewer withdrawals.",1995.0,0,0
617,7591321,Streptokinase-induced transient aggravation of myocardial injury.,M A Arstall; S Stewart; M A Haste; J D Horowitz,"We examined the relationship between streptokinase infusion, intensity of myocardial injury and systemic hypotension in patients receiving streptokinase for treatment of evolving acute myocardial infarction. Twenty consecutive patients treated with streptokinase for evolving acute myocardial infarction received continuous blood pressure and S-T segment monitoring of the 12 lead electrocardiogram (ECG) for at least 5 h, commencing prior to commencement of the streptokinase infusion. Aggravation of injury, manifested both by episodic increases in S-T segment elevation on the electrocardiogram (ECG) (P < 0.001), and in mean S-T segment elevation (P < 0.05) occurred within the first 20 min after initiation of streptokinase infusion. Hypotension also occurred transiently in most patients, with a mean minimum systolic blood pressure of 92 +/- 22 (S.D.) mmHg occurring 16 +/- 5 min after commencement of streptokinase. There was no correlation between the extent of aggravation of injury and that of hypotension. All patients showed ECG evidence of reperfusion, with a reduction of S-T elevation in the reference lead to 50% of maximal value, after a median of 62 min (range 9-174 min). It is concluded that streptokinase aggravates injury prior to reperfusion, although probably not via the induction of hypotension: It is possible that this effect contributes to the 'early hazard' of thrombolytic therapy.",1995.0,0,0
618,7594429,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
619,7601014,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
620,7603180,New occupational risk factors for chronic renal failure.,G D Nuyts; E Van Vlem; J Thys; D De Leersnijder; P C D'Haese; M M Elseviers; M E De Broe,"Occupational pollutants may have a role in development of chronic renal failure (CRF). Most epidemiological studies have been cross-sectional, limited to certain renal diagnoses, or concentrated on early transient renal effects. In a case-control study, we examined the association between CRF and occupational exposure. Occupational histories of 272 men and women with CRF (of all types) were compared with those of 272 controls matched for age, sex, and region of residence. Exposures were assessed and degree and frequency were scored independently by three industrial hygienists unaware of case/control status. Significantly increased risks of CRF were found for exposure to lead (odds ratio 2.11 [95% CI 1.23-4.36]), copper (2.54 [1.16-5.53]), chromium (2.77 [1.21-6.33]), tin (3.72 [1.22-11.3]), mercury (5.13 [1.02-25.7]), welding fumes (2.06 [1.05-4.04]), silicon-containing compounds (2.51 [1.37-4.60]), grain dust (2.96 [1.24-7.04]), and oxygenated hydrocarbons (5.45 [1.84-16.2]). The frequencies of various occupational exposures were high among patients with diabetic nephropathy. This epidemiological study confirms previously identified risk factors and suggests that additional occupational exposures, for which there is some other experimental evidence, may be important in the development of CRF. The role of grain dust and the association between occupational exposure and diabetic nephropathy merit further investigation.",1995.0,0,0
621,7606987,Are calcium antagonists harmful in hypertensive patients? Distinguishing hype from reality.,G B Habib,,1995.0,0,0
622,7608309,Diltiazem: ten years of clinical experience in the treatment of hypertension.,M R Weir,"Diltiazem hydrochloride is a benzothiazepine derivative calcium-channel blocker with proven antianginal and antihypertensive capabilities. Its primary mechanism of action is vasodilatation, which results in diminished vascular resistance and improved perfusion to various vascular beds and target organs. The antihypertensive efficacy of diltiazem in various demographic groups has been studied and compared with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and other calcium-channel blockers. These studies have shown that the antihypertensive effect of diltiazem is similar to that of the other therapies. Diltiazem does not adversely affect electrolytes or carbohydrate or lipid metabolism, and it may have beneficial effects on the heart and kidneys. Diltiazem reduces myocardial hypertrophy and exerts antianginal effects on the heart through coronary vasodilation and reduction in the blood pressure double product. Diltiazem improves renal perfusion and attenuates proteinuria. These effects may be helpful in limiting the progression of renal injury. Overall, the efficacy and tolerability of diltiazem, as well as its salutary effects on the heart and kidneys, make it an important therapeutic consideration for patients with hypertensive disease.",1995.0,0,0
623,7608311,Sustained blood pressure control with controlled-release isradipine (isradipine-CR).,S G Chrysant; M Cohen,"The safety and efficacy, as measured by peak/trough blood pressure reduction, of a new, once-daily, controlled-release formulation of isradipine (isradipine-CR, ICR) were evaluated in patients with mild to moderate essential hypertension during a nine-week trial. After a 3-week placebo washout period, patients with a sitting diastolic blood pressure between 100 and 114 mm Hg were randomized to either 1 of 4 ICR treatment groups or placebo. Of 402 randomized patients, 384 completed the study (placebo = 77, ICR-5 mg = 76, ICR 10 mg = 76, ICR-15 mg = 78, and ICR-20 mg = 77). Peak and trough post-dose blood pressure responses and heart rates were monitored for both the sitting and upright positions. Blood chemistries, urinalyses, complete blood counts, and electrocardiograms were done during the study. Both sitting and upright blood pressure decreased with the 5-(P < .05), 10-, 15-, and 20-mg (P < .001) once-daily ICR doses. The peak blood pressure reduction for all ICR doses occurred at 8 to 10 hours post-dose. Maximum peak/trough blood pressure response, achieved with the 10-mg dose, was similar with that of 15 and 20 mg of ICR. No serious clinical or metabolic side effect were noted, except ankle edema, which was dose dependent but did not require discontinuation of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
624,7608428,"Addition of zatebradine, a direct sinus node inhibitor, provides no greater exercise tolerance benefit in patients with angina taking extended-release nifedipine: results of a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The Zatebradine Study Group.",W H Frishman; C J Pepine; R J Weiss; W M Baiker,"We examined the antianginal and anti-ischemic effects of oral zatebradine, a direct sinus node inhibitor that has no blood pressure-lowering or negative inotropic effects in patients with chronic stable angina pectoris taking extended-release nifedipine. Heart rate reduction is considered an important pharmacologic mechanism for providing anginal pain relief and anti-ischemic action in patients with chronic stable angina, suggesting a benefit for sinus node-inhibiting drugs. In a single-blind placebo run-in, randomized double-blind, placebo-controlled, multicenter study, patients already receiving extended-release nifedipine (30 to 90 mg once a day) were randomized to receive zatebradine (5 mg twice a day [n = 64]) or placebo (n = 60). All subjects had reproducible treadmill exercise-induced angina at baseline, and after randomization they performed a serial exercise test 3 h after each dose for 4 weeks. Zatebradine reduced rest heart rate both at 4 weeks ([mean +/- SEM] 12.9 +/- 1.23 vs. 2.3 +/- 1.6 [placebo] beats/min, p < 0.0001) and at the end of comparable stages of Bruce exercise (16.7 +/- 1.2 vs. 3.4 +/- 1.2 [placebo] beats/min, p < 0.0001). Despite the significant effects on heart rate at rest and exercise, there were no additional benefits of zatebradine from placebo baseline in measurements of total exercise duration, time to 1-mm ST segment depression or time to onset of angina. Subjects taking zatebradine also had more visual disturbances as adverse reactions. Zatebradine seems to provide no additional antianginal benefit to patients already receiving nifedipine, and it raises questions regarding the benefit of heart rate reduction alone as an antianginal approach to patients with chronic stable angina.",1995.0,0,1
625,7610735,Intravenous administration of diltiazem in the treatment of supraventricular tachyarrhythmias.,G Boudonas; N Lefkos; A P Efthymiadis; I G Styliadis; G Tsapas,"The aim of the study was to investigate the efficacy of diltiazem bolus intravenous administration, compared to disopyramide, in the treatment of various types of paroxysmal supraventricular tachyarrhythmias. Fifty patients (23 males, 27 females, mean age 47.7 +/- 15.2 years) with paroxysmal supraventricular tachyarrhythmia (20 with paroxysmal atrial tachycardia, 23 with paroxysmal atrial fibrillation and rapid ventricular response and 7 with atrial fluttering) were studied. Diltiazem at a dose of 0.25-0.30 mg/kg BW or disopyramide at a dose of 50 mg were given bolus IV. If conversion of the arrhythmia to sinus rhythm could not be achieved with the initial drug, the alternate was given. The order of administration of the drugs was random, independent of the type of the arrhythmia. Before and during drug administration detailed clinical examination and frequent blood pressure (BP) measurements were performed. Twenty-four hour Holter monitoring was done in all patients, starting with the administration of the antiarrhythmic drug. 1) Paroxysmal atrial tachycardia: diltiazem administration converted the arrhythmia to sinus rhythm in all patients while disopyramide in only 1 of 9 patients who received this drug. 2) Paroxysmal atrial fibrillation: disopyramide converted the arrhythmia in 5 patients without significant change in ventricular response in the others. Diltiazem did not convert the arrhythmia though it caused significant decrease in ventricular response (< 100 bpm) and in 1 patient an important bradycardia (45 bpm). 3) Atrial fluttering: disopyramide converted the arrhythmia to sinus rhythm in 1 patient without significant change in the ventricular response in the others. Diltiazem caused significant decrease in the ventricular response without conversion to sinus rhythm. During conversion to sinus rhythm an AV junctional rhythm of short duration (< 1 min) was noticed in 5 patients and a short pause (< 2 sec) with or without an initial premature contraction in the remaining 21. Disopyramide administration was not associated with side effects. Diltiazem administration cause small (< 20 mm Hg), transient (< 30 min) decrease of BP without symptoms with the exception of the patient with bradycardia in whom the BP decrease was significant (90/60 from 160/80 mm Hg) followed by intense symptoms which lasted for six hours. Diltiazem administration is extremely effective in conversion of paroxysmal atrial tachycardia to sinus rhythm. In addition it retards ventricular response in patients with atrial fibrillation and fluttering. Compared to disopyramide these effects of diltiazem are more pronounced and clinically pertinent.",1995.0,0,0
626,7614530,The efficacy and safety of once-daily nifedipine administered without food: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate hypertension. Nifedipine Study Group.,S P Glasser; S R Ripa; K S Allenby; L A Schwartz; B M Commins; S Jungerwirth,"A parallel-group, randomized, double-blind, forced-titration, multicenter study was done to compare the efficacy and safety of once-daily nifedipine coat-core (NIF CC) and once-daily nifedipine gastrointestinal therapeutic system (NIF GITS) dosed in the fasting state in patients with mild-to-moderate essential hypertension. Both formulations have been shown to effectively and safely lower blood pressure in placebo-controlled trials. After a 4-week placebo run-in period, 228 patients were randomized to 4 weeks of treatment with either NIF CC 30 mg daily or NIF GITS 30 mg daily. This period was followed by a forced-titration period to nifedipine 60 mg daily for an additional 4 weeks of double-blind therapy. After the 30-mg treatment period (the primary time point), there were no statistically significant differences between treatment groups in mean change from baseline in trough supine diastolic blood pressure, the primary efficacy variable (NIF CC patients, -7.0 mm Hg; NIF GITS patients, -8.4 mm Hg; P = 0.139). Also, because the upper bound of the treatment difference confidence interval was < 3.0 mm Hg, equivalence--as defined in the protocol--was established. After the 60-mg treatment period, the change from baseline in trough supine diastolic blood pressure was significantly greater for patients treated with NIF GITS than for patients treated with NIF CC (NIF GITS patients, -12.0 mm Hg; NIF CC patients, -8.4 mm Hg; P < 0.001). Because the upper bound of the confidence interval was > 3 mm Hg, equivalence cannot be claimed. No statistically significant differences were noted for the comparison of mean 24-hour ambulatory blood pressure monitoring changes. Both formulations were well tolerated.",1995.0,0,0
627,7619356,"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
628,7619669,Twenty-four hour efficacy of two dose levels of a once daily sustained-release diltiazem formulation in stable angina: a placebo-controlled trial. The Dildurang Study Group.,Y Frances; S Gagey; A Stalla-Bourdillon,"1. This placebo-controlled study assessed once daily sustained-release (SR) diltiazem, 200 and 300 mg, in 182 stable angina patients with positive exercise test. 2. Exercise testing was performed at baseline after a 7 day placebo run-in period, and repeated after 7 days of treatment, 25.0 +/- 0.1 h postdose. 3. Diltiazem (200 and 300 mg) produced respectively a 68% and a 64% decrease in weekly angina episodes, and placebo a 15% decrease (P < 0.05). Similarly, both dose levels produced a 70% decrease in nitroglycerin consumption, whereas no difference was obtained with placebo (P < 0.01). The increase in time to ischaemic threshold was significantly superior for 200 mg and 300 mg diltiazem when compared with placebo (75.2 and 91.5 s respectively vs 47.0 s) (P < 0.05); increase in time to anginal threshold was also significantly greater for diltiazem when compared with placebo (84.6 and 85.9 s respectively vs 43.9 s) (P < 0.05). 4. Only one patient experienced worsening of angina and had to be withdrawn from the study. 5. This study demonstrates 200 and 300 mg SR diltiazem is effective when given once-a-day in the prophylaxis of stable exertional angina. This once daily formulation should improve patients' compliance and comfort.",1995.0,0,1
629,7620692,Signalling drug-induced rash with 36 drugs recently marketed in the United Kingdom and studied by Prescription-Event Monitoring.,K Kubota; N Kubota; G L Pearce; P Prescott; R D Mann,"This study examines skin rash, as a reported event, in the patients who used one of the 36 drugs recently released to the UK market and studied by Prescription-Event Monitoring between 1985 and 1992. The results are also compared to the voluntary reports on rash as a possible adverse drug reaction sent to the Committee on Safety of Medicines (CSM). Specific types of skin rash (e.g. exfoliative dermatitis) are excluded. The rate of rash has been calculated for 2 periods, the first month (T1) and the subsequent 5 months (T2) after the first prescription for the drug. Despite the heterogeneity of the patient groups, the rate for rash between the 2nd and 6th months was consistent in the 36 drugs and probably represented the baseline rate of rash due to a variety of nonspecific causes. This rate (T2) was around 1 per 1,000 patients per month (ranging from 0.5 to 2 per 1,000 patients per month). On the other hand, in the first month after the first prescription for the drug, the rate (T1) varied substantially from 0.9 to 6.4 per 1,000 patients per month. Diltiazem had the highest first monthly rate. These rates are listed for the 36 drugs. The difference of the rates was tested by 2 methods: a standard statistical test assuming a Poisson model and a method based on the ratio of the rates for the 2 periods. When the 2 rates (T1 and T2) were similar to each other, drug induced rash was considered to be rare.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
630,7621840,Vasodilation-related adverse events in diltiazem and dihydropyridine calcium antagonists studied by prescription-event monitoring.,K Kubota; G L Pearce; W H Inman,"The incidence of vasodilation-related events (flushing, headache, dizziness and oedema) was determined in a total of 37,670 patients treated with diltiazem, nicardipine, isradipine or amlodipine and studied by Prescription-Event Monitoring between 1984 and 1991. Event rates are expressed as the percentage of patients who experienced these events during the six months after the first prescription. The rates for all these events with the newer vasoselective dihydropyridines (nicardipine, isradipine and amlodipine) were higher than those with diltiazem. Among the three dihydropyridines, there were large individual differences in the rates. With nicardipine, the frequency of each of the four vasodilation-related events were similar to one another (approximately 3%). With isradipine, the rates were also similar to one another but all were approximately twice those measured in the nicardipine study (approximately 6%). These differences may have been due to confounding factors such as the publicity about adverse drug reactions, the indication for use by individual patients or the doses actually being used at the time the event occurred. With amlodipine, in contrast, the rate for oedema was two to four times larger than the rates for flushing, headache or dizziness.",1995.0,1,1
631,7631621,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)",1995.0,1,1
632,7632029,[Value of the combination of trimetazidine (Vastarel 20 mg) with diltiazem (Tildiem 60 mg) in stable effort angina. A double-blind versus placebo multicenter study].,S Lévy,"Trimetazidine is a cytoprotective anti-ischaemic agent whose antianginal efficacy has been demonstrated in monotherapy versus placebo and versus reference products, and in combination with beta-blockers and nifedipine. As coprescription with diltiazem has not been previously studied, the objective of this study was to evaluate the benefit of the addition of trimetazidine (60 mg/24 h) to diltiazem (180 mg/24 h) in the stable exertional angina insufficiently improved by calcium channel blocker alone. This multicentre double-blind placebo-controlled study was conducted over a period of 6 months. The inclusion criteria were stable angina with electrically positive stress test, which remained positive despite a 15-day treatment with diltiazem (180 mg/24 h). It was conducted in 67 patients randomized into two groups: diltiazem-placebo (group I: 35 patients) and diltiazem-trimetazidine (group II: 32 patients). The follow-up consisted of clinical assessment and a stress test on inclusion and at 6 months. The two groups were similar on inclusion for all ergometric parameters, excepted for the time to onset of the ischaemic threshold of 1 mm and the total duration of effort, which were significantly longer in the placebo group. Comparison of the stress tests performed at the sixth month and on inclusion between groups I and II showed that the ischaemic threshold of 1 mm was significantly delayed by 2 minutes 41 seconds in the trimetazidine group (p < 0.001) versus 42 seconds in the placebo group (NS). Similarly, the work performed at this threshold was significantly increased by 1446 kpm in the trimetazidine group (p < 0.001) versus 564 kpm in the placebo group (p = 0.012). The difference between the two groups was significant for these two parameters, p = 0.008 and p = 0.018, respectively. At maximum effort, the total duration and the total work also increased significantly in the trimetazidine group, by 50 seconds (p = 0.006) and 570 kpm (p = 0.004), respectively, versus 16 seconds and 221 kpm in the placebo group (NS). The [double product (SBP x HR)/load (in watts)] ratio at the ischaemic threshold of 1 mm reached at M0, decreased significantly in the trimetazidine group by 69.9 (p < 0.001) versus 20.3 in the placebo group (NS). The difference between the two groups was significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
633,7636536,Phase I/II trial of dexverapamil plus vinblastine for patients with advanced renal cell carcinoma.,R J Motzer; P Lyn; P Fischer; P Lianes; R L Ngo; C Cordon-Cardo; J P O'Brien,"The reduced cardiac toxicity of the dextro-(d-) stereoisomer of verapamil (dexverapamil; Knoll Pharmaceuticals, Whippany, NJ) warrants its study as a potential multidrug-resistance (MDR) reversal agent. Twenty-three patients with advanced renal cell carcinoma (RCC) were treated with vinblastine at a dose of 0.11 mg/kg intravenous (IV) bolus injection on days 1 and 2 every 21 days. Dexverapamil was added to subsequent cycles after resistance had been demonstrated. Dexverapamil treatment was begun 18 hours before day 1 of vinblastine administration and was given orally every 6 hours for 12 doses. Patients in group A were treated with a dose of 120 mg/m2, and those in group B were treated with 180 mg/m2 plus dexamethasone; plasma concentrations achieved in patients were correlated with in vitro effects. Toxicities included hypotension, asymptomatic bradycardia, and mild atrioventricular conduction delays, although one patient had dexverapamil discontinued for grade IV congestive heart failure. There were no partial or complete responses. The mean day-1 serum dexverapamil plus norverapamil plasma concentrations were 2,575 ng/mL (range, 697 to 6,015 ng/mL) for group A and 1,654 ng/mL (range, 710 to 4,132 ng/mL) for group B at the time of vinblastine administration. These concentrations were in the range of those that reversed vinblastine resistance in vitro. The advantage of dexverapamil as an MDR reversal agent is its potential for achieving desired blood levels with substantially less toxicity than the racemic mixture of verapamil. Based on tolerability, it is a suitable drug for further study in clinical trials of malignancies other than RCC that attempt to achieve MDR reversal. The dose of 120 mg/m2 given orally every 6 hours, with dose escalation based on individual tolerance, represents a feasible schedule to be considered for such studies.",1995.0,0,0
634,7636894,The efficacy and tolerability of amlodipine and hydrochlorothiazide in Nigerians with essential hypertension.,A A Ajayi; A O Akintomide,"The efficacy and safety of the novel calcium antagonist Amlodipine (Pfizer Laboratories, New York, New York) and hydrochlorothiazide were evaluated and compared in a randomized, single-blind, parallel group study in black Africans with essential hypertension. Twenty Nigerians with newly diagnosed mild to moderate essential hypertension were randomized to receive ascending doses of Amlodipine (5 mg and 10 mg) or hydrochlorothiazide (25 mg or 50 mg), and blood pressure and heart rate were measured at baseline and at 2, 4, and 6 weeks of therapy. Both Amlodipine and hydrochlorothiazide significantly reduced supine and erect blood pressure. Supine blood pressure on Amlodipine fell from a mean of 190/104 mm Hg to 150/79 mm Hg, and on thiazide from 180/103 mm Hg to 141/84 mm Hg. There was, however, no significant difference between both drugs in antihypertensive efficacy. Neither drug induced a reflex increase in heart rate. The fall in blood pressure on both agents was associated with an increase in plasma urea. Amlodipine induced no change in plasma potassium, but hydrochlorothiazide caused hypokalemia. Both agents were well tolerated, and Amlodipine should undergo further study in the treatment of hypertension in blacks.",1995.0,0,0
635,7637142,The risk of myocardial infarction associated with antihypertensive drug therapies.,B M Psaty; S R Heckbert; T D Koepsell; D S Siscovick; T E Raghunathan; N S Weiss; F R Rosendaal; R N Lemaitre; N L Smith; P W Wahl,"To assess the association between first myocardial infarction and the use of antihypertensive agents. We conducted a population-based case-control study among enrollees of the Group Health Cooperative of Puget Sound (GHC). Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infarction from 1986 through 1993 among women and from 1989 through 1993 among men. Controls were a stratified random sample of hypertensive GHC enrollees, frequency matched to the cases on age, sex, and calendar year. All 623 cases and 2032 controls had pharmacologically treated hypertension. Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors. Antihypertensive therapy was assessed using the GHC's computerized pharmacy database. The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease. Compared with users of diuretics alone, the adjusted risk ratio of myocardial infarction was increased by about 60% among users of calcium channel blockers with or without diuretic (risk ratio = 1.62%; 95% confidence interval [Cl], 1.11 to 2.34; P = .01). The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker. Among these subjects, the use of calcium channel blockers compared with beta-blockers was associated with about a 60% increase in the adjusted risk of myocardial infarction (risk ratio = 1.57; 95% Cl, 1.21 to 2.04; P < .001). While high doses of beta-blockers were associated with a decreased risk of myocardial infarction (trend P = .04), high doses of calcium channel blockers were associated with an increased risk (trend P < .01). In this study of hypertensive patients, the use of short-acting calcium channel blockers, especially in high doses, was associated with an increased risk of myocardial infarction. Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies, including calcium channel blockers, on several important cardiovascular end points. Until these results are available, the findings of this study support the current guidelines from the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated, unacceptable, or not tolerated.",1995.0,0,1
636,7639163,Nocturnal dosing of a novel delivery system of verapamil for systemic hypertension. Verapamil Study Group.,W B White; R J Anders; J M MacIntyre; H R Black; D A Sica,"To evaluate the efficacy and safety of a novel delivery system of physiologic pattern release (PPR)-verapamil administered nocturnally to patients with stages I and II hypertension using ambulatory blood pressure (BP) monitoring, we performed a multicenter (17 centers), double-blind, randomized, placebo-controlled, parallel-group trial with placebo and 120, 180, 360, and 540 mg of verapamil in 287 randomized patients. The delivery system has a delay in the release of verapamil for 4 to 6 hours, and then delivers the drug from an osmotic pumping system for approximately 12 hours. Patients were dosed at 10 P.M. The primary end point was change from baseline in trough diastolic BP assessed by ambulatory BP monitoring from 6 to 10 P.M. after 8 weeks of therapy, whereas secondary measures included changes from baseline in peak, early morning (6 to 10 A.M.) systolic and diastolic BP, trough clinic BP, and 24-hour average daytime (8 A.M. to 8 P.M.) and nighttime (8 P.M. to 8 A.M.) BP. The 180, 360, and 540 mg verapamil doses achieved statistically significant reductions in trough (6 to 10 P.M.) diastolic BP (-3.9 +/- 1.0, -7.8 +/- 1.2, and -10.6 +/- 1.1 mm Hg, respectively). Reductions in peak early morning (6 to 10 A.M.) diastolic BP were greater (-4.6 +/- 0.9, -13.3 +/- 1.2, and -19.0 +/- 1.2, for 180, 360, and 540 mg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
637,7639642,Changes in extracellular matrix macromolecules in human gingiva after treatment with drugs inducing gingival overgrowth.,M Bonnaure-Mallet; S Tricot-Doleux; G J Godeau,"It is generally agreed that gingival overgrowth results from an increase in the levels of gingival extracellular macromolecules infiltrated with various numbers of inflammatory cells. The relative amounts of extracellular matrix macromolecules observed in 12 cases of gingival hyperplasia associated with the use of cyclosporin, hydantoin or nifedipine were compared with those obtained in a control group on the basis of histological and immunohistochemical investigations. From tissue sections, the quantification was by computerized morphometric analysis on a BFM 186 microcomputer to which were implemented the transformations of mathematical morphology. The area fractions (AA%) occupied by total collagen, type III and type IV collagen, vessels, fibroblasts, fibronectin and elastic fibres were estimated and compared. The overall histological aspects of drug-induced gingival overgrowth were similar, but quantification of different extracellular matrix components showed differences. In the nifedipine and cyclosporin groups, the area occupied by fibroblasts were not significantly greater than in healthy gingiva and chronic gingivitis. The area occupied by collagen was significantly greater in the nifedipine group than in the other pathological groups. Fibronectin was also strongly expressed in the nifedipine group, and the elastic fibre network was preserved in this group.",1995.0,0,0
638,7642847,Asymptomatic Cardiac Ischemia Pilot (ACIP) study: impact of anti-ischemia therapy on 12-week rest electrocardiogram and exercise test outcomes. The ACIP Investigators.,B R Chaitman; P H Stone; G L Knatterud; S A Forman; G Sopko; M G Bourassa; C Pratt; W J Rogers; C J Pepine; C R Conti,"This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study examines differences in the magnitude of reduction of myocardial ischemia as determined by exercise treadmill testing in patients randomized to three different treatment strategies: angina-guided medical therapy, ischemia-guided medical therapy and coronary revascularization. No prospective randomized clinical trials in patients with exercise electrocardiographic (ECG) abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have compared the impact of different treatment strategies, including coronary revascularization, in terms of reducing myocardial ischemia. The ACIP exercise protocol was used. Exercise variables measured included final exercise stage; presence of exercise-induced angina or ischemia; time to angina; time to 1-mm ST segment depression; number of exercise ECG leads with abnormalities; maximal depth of ST segment depression in any lead; sum of ST segment depression; ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST segment depression and at peak exertion. Peak exercise time was increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided, ischemia-guided and coronary revascularization strategies, respectively, from the qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6 +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies, respectively. At the 12-week visit, the sum of exercise-induced ST segment depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the three treatment strategies, respectively. Each treatment strategy resulted in a significant reduction in all exercise-induced variables of myocardial ischemia measured at 12 weeks. Coronary revascularization significantly reduced the extent and frequency of exercise-induced myocardial ischemia compared with either medical strategy. The prognostic impact of these observations should be evaluated in a large-scale multicenter clinical trial.",1995.0,0,0
639,7648646,Nifedipine and mortality. Grave defects in the dossier.,L H Opie; F H Messerli,,1995.0,0,0
640,7648648,Calcium antagonists in coronary artery disease and hypertension. Time for reevaluation?,S Yusuf,,1995.0,0,0
641,7648682,Nifedipine. Dose-related increase in mortality in patients with coronary heart disease.,C D Furberg; B M Psaty; J V Meyer,"The purpose of this study was to assess the effect of the dose of nifedipine, a dihydropyridine calcium antagonist, on the increased risk of mortality seen in the randomized secondary-prevention trials and to review the mechanisms by which this adverse effect might occur. We restricted the dose-response meta-analysis to the 16 randomized secondary-prevention trials of nifedipine for which mortality data were available. Recent trials of any calcium antagonist and formulation were also reviewed for information about the possible mechanisms of action that might increase mortality. Overall, the use of nifedipine was associated with a significant adverse effect on total mortality (risk ratio, 1.16, with a 95% CI of 1.01 to 1.33). This summary estimate fails to draw attention to an important dose-response relationship. For daily doses of 30 to 50, 60, and 80 mg, the risk ratios for total mortality were 1.06 (95% CI, 0.89 to 1.27), 1.18 (95% CI, 0.93 to 1.50), and 2.83 (95% CI, 1.35 to 5.93), respectively. In a formal test of dose response, the high doses of nifedipine were significantly associated with increased mortality (P = .01). While the mechanism of this adverse effect is not known, there are several plausible explanations, including the established proischemic effect, negative inotropic effects, marked hypotension, recently reported prohemorrhagic effects attributed to antiplatelet and vasodilatory actions of calcium antagonists, and possibly proarrhythmic effects. In patients with coronary disease, the use of short-acting nifedipine in moderate to high doses causes an increase in total mortality. Other calcium antagonists may have similar adverse effects, in particular those of the dihydropyridine type. Long-term safety data are lacking for most calcium antagonists.",1995.0,0,1
642,7649665,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
643,7651666,Emergent management of the patient in preterm labor.,C A Sullivan; J C Morrison,"Clinicians who treat PTL should realize that side effects rarely occur when tocolytic medications are properly used. The beneficial effects of tocolytic therapy vastly outweigh the risks associated with their use for the prolongation of gestation. Even a short extension of in utero life for a few days or weeks can significantly and positively affect neonatal survival and long-term outcome. Although the opponents of tocolytic therapy argue that no reduction in the PTB rate has occurred since their introduction, this argument does not consider that the large majority of PTBs are not eligible for tocolytic intervention. If patients with clear indications for tocolysis could be compared with those that were not treated (which most studies have not done), a substantial beneficial effect of tocolytic administration probably would be demonstrated. Based on available data, we consider MgSO4 and terbutaline to be first-line tocolytics. Magnesium is used more often because of its lower side-effect profile. Indomethacin and nifedipine should be reserved for difficult or refractory preterm labor, and should only be used for intervals of < or = 48 hours. We have attempted to present a method of decision analysis which should be followed for every patient who is admitted to the obstetric care unit for a presumptive diagnosis of premature labor. We realize that many of the issues included here are controversial, however, we hope that by developing a decision tree (see Fig. 1), a more complete management scheme will be created and lead to improved care of the patient undergoing premature labor.",1995.0,0,0
644,7654482,Amlodipine induces a flow and pressure-independent vasoactive effect on the brachial artery in hypertension.,J L Megnien; J Levenson; M Del-Pino; A Simon,"1. The objectives of this study were to study the flow-dependent arterial reactivity and pressure-independent arterial compliance of the calcium antagonist amlodipine in hypertensive men. 2. Twenty-one hypertensive patients were randomized to receive 2 months treatment with placebo (n = 10) or 5-10 mg amlodipine (n = 11) once a day. Non-invasive measurement of brachial artery mean blood pressure, diameter and flow (pulsed Doppler) and compliance (arterial mechanography and logarithmic elastic model) were obtained before and after drug administration. Vasoreactivity was studied by means of response of the brachial artery during exclusion of the hand and hyperaemia post-ischaemia. 3. Compared with placebo, amlodipine reduced mean blood pressure (% change +/- s.e. mean 11 +/- 1% vs 4 +/- 3%, P < 0.05), and increased arterial compliance at prevailing pressure (44 +/- 13%, vs 1 +/- 8%, P < 0.05) and at isobaric pressure (26 +/- 10% vs -3 +/- 6%, P < 0.05). A significant % change increase from baseline in brachial artery diameter between placebo and amlodipine was observed at rest (-2 +/- 3 vs 8 +/- 3%; P < 0.05), after wrist occlusion (-3 +/- 3 vs 6 +/- 2%; P < 0.05) and during reactive hyperaemia (-5 +/- 3 vs 18 +/- 5%; P < 0.05). No significant differences between amlodipine and placebo groups were observed in blood velocity after forearm manoeuvres before and after treatment. 4. No differences were observed between groups in brachial flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
645,7657848,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.",1995.0,0,0
646,7662226,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.",1995.0,0,1
647,7669481,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
648,7674688,Contemporary management of atrial fibrillation.,Z A Ukani; M D Ezekowitz,"The incidence of atrial fibrillation approximately doubled for every 10-year increment in age in the Framingham Heart Study cohort; thus physicians will be faced with an increasing patient population with atrial fibrillation. Hypertension is observed to be the most common associated risk factor in both sexes. The management of patients with atrial fibrillation is evolving as a result of a number of published studies. Calcium channel blockers and beta-blockers are emerging as the preferred choices for rate control rather than digoxin. Low-dose anticoagulation therapy has shown beneficial effects not only in primary prevention, but also for secondary prevention of thromboembolism. Thus, patients who cannot be successfully cardioverted should be anticoagulated if there are no contraindications (Table 3) and if they do not fall into the low-risk group--defined as patients under the age of 65 without risk factors (hypertension, diabetes, previous stroke). Patients not eligible for anticoagulation should be on aspirin therapy. Patients with lone atrial fibrillation are not at higher risk for thromboembolism than the general population; therefore, they can be managed without anticoagulation or antiplatelet therapy. Antiarrhythmic treatment should be approached cautiously; amiodarone in low doses is the most effective and safe treatment, but this remains controversial.",1995.0,0,0
649,7702799,Effect of isradipine in black patients with very severe hypertension. 24-hour ambulatory blood pressure monitoring and echocardiographic evaluation.,J Skoularigis; J Weinberg; V Strugo; J Davis; D Skudicky; C Zambakides; P Sareli,"Fifty consecutive black patients with very severe hypertension (sitting diastolic blood pressure > or = 120 mm Hg and systolic > or = 210 mm Hg by the conventional cuff method) were treated in an open-label study (without a placebo or active drug control group) for 3 months with a long-acting preparation of isradipine (Dynacirc SRO), during which time serial changes in 24-h ambulatory blood pressure monitoring (ABPM), left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-h ABPM was reduced from 184 +/- 13/119 +/- 6 to 148 +/- 18/96 +/- 11 mm Hg at 3 months (P < .0001). The reduction in BP was sustained for 24 h after dosing. Simultaneous BP measurements using a conventional cuff method and Dinamap were significantly different from the ABPM pre- and posttherapy, suggesting a marked ""white coat"" pressor effect. LV mass index regressed from 143 +/- 36 to 122 +/- 32 g/m2 at 3 months (P < .02). Heart rate and mean body weight were unchanged. Left ventricular performance was not adversely affected. Cardiac index and fractional shortening changed insignificantly, from 2.6 +/- 0.6 to 2.7 +/- 0.5 L/min/m2, and from 28 +/- 6 to 31 +/- 7%, respectively. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. We conclude that in this group of patients long-acting isradipine 1) showed a marked and sustained antihypertensive action demonstrated by 24-h ABPM; and 2) was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
650,7710563,Three-month efficacy and safety of once-daily diltiazem in chronic stable angina pectoris.,C Nadeau; D Hilton; D Savard; Y Morin; M Baird; M Alexander; G Langer; D Roth; A P Boulet; L Larivière,"The 3-month efficacy and safety of a once-daily controlled formulation of diltiazem (180 to 360 mg/day) were assessed in a study of 54 patients with angina pectoris. This multicenter study was a nonrandomized, placebo run-in, open-label, 3-month trial followed by a 1-week, double-blind, randomized period during which most patients (89%) received placebo. There were only minimal changes in the time to termination (mean change +/- SEM -5.8 +/- 9.6 seconds), time to onset of angina (10.5 +/- 12.2 seconds), and the time to 1 mm ST-segment depression (2.9 +/- 12.5 seconds) from the end of the titration phase to the end of the open-label study. There were, however, statistically significant differences between the end of the 3-month treatment phase and the end of the 1-week randomized placebo phase for those 3 efficacy parameters (-37.3 +/- 11.2, -58.6 +/- 13.6, and -45.6 +/- 16.4 seconds, respectively). Diltiazem significantly decreased the frequency of anginal attacks and nitroglycerin use at the end of the 3-month treatment phase compared with results at the end of the randomized double-blind placebo phase. No new or unusual adverse events were reported during treatment. The present results suggest that there is no loss of efficacy of once-a-day diltiazem when administered for a long period to patients with chronic stable angina pectoris.",1995.0,0,1
651,7717013,[Increased vagal activity after administration of the calcium antagonist diltiazem in patients with coronary heart disease].,A W Frey; C Müller; M Dambacher; K Theisen,"The effects of the calcium channel blockers diltiazem on the parasympathetic nervous system were studied by using spectral analysis of heart rate variability, and were compared with the effects of the beta-receptor blocker metoprolol. The area under the curve of the high-frequency range (f = 0.18-0.35 Hz) during controlled respiratory rate (f = 0.25 Hz) was used as a quantitative index of parasympathetic activity. Twenty-four male patients with proven coronary artery disease and normal left ventricular function (LVEF > 60%) were studied 2 weeks after chronic treatment with diltiazem (3 x 60 mg daily) or metoprolol (3 x 50 mg daily) before and after administration of the drug. Twelve patients received diltiazem and 12 patients metoprolol. After administration of diltiazem the peripheral systolic blood pressure was reduced, but the parasympathetic activity was significantly higher than compared with the initial measurement. The same effect was seen for metoprolol, but a significant lower heart rate was present after administration. The relative area under the high-frequency range significantly increased at rest, by 110% after diltiazem and 70% after metoprolol. Diltiazem and metoprolol enhance the vagal influence at the heart, thereby leading to an enhancement of barosensitivity and of the respiratory sinus arrhythmia. This action may contribute to the beneficial effects of both drugs in patients with coronary artery disease.",1995.0,0,0
652,7717281,"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
653,7721406,Effectiveness of enalapril versus nifedipine to antagonize blood pressure and the renal response to endothelin in humans.,K A Kaasjager; H A Koomans; T J Rabelink,"Endothelin-1 infusion into humans to obtain pathophysiological plasma levels causes mild hypertension, strong renal vasoconstriction, and sodium retention. We studied whether oral use of the angiotensin-converting enzyme inhibitor enalapril (20 mg BID) or the calcium channel blocker nifedipine (60 mg OD) could attenuate these effects of endothelin-1 (2.5 ng/kg per minute for 90 minutes) in six healthy volunteers. Endothelin infusion alone increased plasma endothelin from 3.0 +/- 0.3 to 8.8 +/- 1.0 pmol/L (P < .05). Blood pressure rose by approximately 6 mm Hg (P < .05). Renal function changes were relatively large: Renal blood flow decreased from 941 +/- 76 to 729 +/- 118 mL/min (P < .05) and glomerular filtration rate from 105 +/- 9 to 92 +/- 10 mL/min (P < .05); renal vascular resistance increased from 101 +/- 7 to 152 +/- 20 mm Hg.min/L (P < .05); and sodium excretion decreased from 158 +/- 54 to 86 +/- 27 mumol/min (P < .05). Enalapril treatment reduced blood pressure from 94 +/- 2 to 87 +/- 3 mm Hg (P < .05) and prevented the hypertensive response to endothelin. By contrast, despite renal predilatation, endothelin reduced renal blood flow strongly (from 1063 +/- 127 to 763 +/- 100 mL/min, P < .05), although maximal renal vascular resistance was numerically lower (124 +/- 11 mm Hg.min/L) than during endothelin alone (P < .05). Glomerular filtration rate fell from 118 +/- 11 to 108 +/- 11 mL/min (P < .05). Enalapril did not alter the antinatriuretic effect of endothelin.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
654,7723358,,,,,0,0
655,7731143,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
656,7731301,[Effect of 3 hypertensive++ agents on ventricular geometry and function].,C Gómez Pajuelo; M A Gómez Sánchez; R Marín Ruiz; F Lombera Romero; M Sanz Julve; J Tascón Pérez; C Sáenz de la Calzada,"To assess the prevalence of left ventricular hypertrophy in hypertensive patients referred to an outpatient cardiology unit, and to assess its evolution under antihypertensive treatment. One hundred and seven mild to moderate hypertensive patients were randomized to receive either xipamide, verapamil or atenolol. Cross-sectional echocardiography was performed in order to assess left ventricular mass and function. Mean age was 56 years, with a 4:1 female/male ratio. Mean follow-up was 120 days. Left ventricular hypertrophy was very common (65%) and decreased to 54% under antihypertensive treatment. Left ventricular mass decreased from 134.3 g/m2 to 118.1 g/m2 (p < 0.001). Concentric hypertrophy was the most common geometric pattern (42%), decreasing to 30% with treatment. Xipamide decreased ventricular mass by decreasing left ventricular diameters, while verapamil and atenolol decreased left ventricular thickness, mainly in septal wall. Systolic function was not modified during the treatment period. Diastolic function was not modified by xipamide and verapamil, and improved with atenolol. Left ventricular hypertrophy is very frequent when determined by echocardiography and all three drugs produced regression of left ventricular hypertrophy in a different way with respect to left ventricle geometry, an effect which could have potential therapeutic implications.",1995.0,0,0
657,7732981,"Evaluation of the efficacy and safety of oral nicardipine in treatment of urgent hypertension: a multicenter, randomized, double-blind, parallel, placebo-controlled clinical trial.",G B Habib; L M Dunbar; R Rodrigues; A C Neale; K J Friday,"This study was a prospective, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of oral nicardipine for the treatment of urgent hypertension in the emergency department. Of 57 patients with urgent hypertension 53 patients were enrolled: 36 men and 17 women, 43 black and 10 white, age range 48 +/- 11 years, and diastolic blood pressure 128 +/- 7 mm Hg. Patients were randomly assigned to receive 30 mg nicardipine or placebo in blind fashion followed by 30 mg open-label nicardipine in nonresponders. Responders to one or two doses of nicardipine received 30 or 40 mg nicardipine three times a day for 1 week after discharge from the emergency department. Adequate blood pressure reduction, defined as a reduction of diastolic blood pressure to less than 100 mm Hg or by at least 20 mm Hg, was achieved in 65% and 22% of patients who received 30 mg nicardipine or placebo (p = 0.002). Adequate blood pressure reduction after administration of open-label nicardipine occurred in 76% of the nonresponders to placebo. Blood pressure reductions were maintained at 1 week after discharge. The drug was well tolerated, and no significant adverse events occurred. We conclude that oral nicardipine is a safe and effective drug for the initial treatment of urgent hypertension.",1995.0,0,0
658,7734104,Sustained blood pressure control with controlled-release isradipine.,S G Chrysant; M Cohen,"The efficacy and safety of different doses of a new controlled release formulation of isradipine (isradipine-CR, ICR) were evaluated in patients with mild to moderate (stages 1 and 2) essential hypertension in a placebo-controlled study. Of 402 randomized patients, 384 completed the study (placebo = 77, 5 mg ICR = 76, 10 mg ICR = 76, 15 mg ICR = 78, 20 mg ICR = 77). All doses of ICR decreased the blood pressure and the effect was greater with doses of 10, 15, and 20 mg once daily (P < .001). The most common clinical side effect was mild ankle edema, which was dose dependent, occurring in 35.5% of the patients taking the 20-mg ICR dose. This study showed that ICR is long acting, effective, and well tolerated.",1995.0,0,0
659,7736741,,,,,0,0
660,7738211,Calcium-channel entry blocker therapy for hypertensive patients with concomitant renal impairment: a focus on isradipine.,W H Frishman,"In the treatment of hypertension in renally impaired patients, normalization of blood pressure alone may not be sufficient to prevent significant morbidity to the kidneys. Treatment must reduce pressure in the renal vasculature, otherwise glomerular filtration rate and renal plasma flow will continue to deteriorate. Isradipine a dihydropyridine calcium-channel blocker, has been investigated as a suitable treatment in this setting. Isradipine maintains glomerular filtration rate, preserves or enhances renal plasma flow, decreases renal vascular resistance, maintains or reduces filtration fraction, and exerts a sustained natriuretic effect, all of which may enable isradipine to slow the rate of progression of renal deterioration. In addition, isradipine may decrease proteinuria and may decrease glomerular capillary pressure by dilating both the efferent and afferent arterioles. Unlike older calcium-channel blockers, isradipine exhibits minimal cardiodepressant activity and is not associated with any negative inotropic effects. It is metabolized in the liver and dosage adjustments may not be necessary when administered to patients with renal insufficiency. Isradipine has a favorable renal effect profile and also has several properties that meet the requirements of other patient populations where an extra measure of antihypertensive safety is required, such as diabetics, dialysis patients, and transplant recipients. Side effects with isradipine are usually mild and transient, occurring in a dose-dependent manner.",1994.0,0,0
661,7744087,"24 h anti-anginal and anti-ischaemic effects with once daily felodipine. A double-blind comparison with nifedipine, twice daily, and placebo in patients with stable exercise induced angina pectoris.",K L Schulte,"The effects, as monotherapy, of felodipine ER 10 mg o.m. and nifedipine SR 20 mg b.d. were compared in a double-blind, randomized, placebo-controlled, three-way cross-over trial in 43 patients with stable exercise-induced angina pectoris. The exercise tests were performed at the end of dosage interval (i.e. 24 h after felodipine ER, 12 h after nifedipine SR) and at the expected peak time of 3 h post dose. Felodipine and nifedipine improved exercise duration by 66 and 50 s, respectively, (P < 0.001) compared with placebo at the end of the dosing interval. Time to the end of exercise showed no statistically significant difference between the two calcium antagonists. The onset of anginal pain and time to 1 mm ST depression were significantly more delayed by felodipine ER than nifedipine SR (22 s and 19 s, respectively, P < 0.05). Both felodipine and nifedipine decreased the pain score and rate pressure product at the highest comparable work load. Overall tolerability was good for both drugs.",1995.0,0,1
662,7748048,The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil.,M C Houston; M Weir; J Gray; D Ginsberg; C Szeto; P M Kaihlenen; D Sugimoto; M Runde; M Lefkowitz,"Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, central alpha-agonists, and other vasodilators. Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal. A three-phase, randomized, double-blind, placebo-controlled multicenter study included 162 patients aged 18 to 75 years with essential hypertension. After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride, patients received ibuprofen, naproxen, or placebo matching capsules for 3 weeks, and blood pressure, heart rate, weight, and adverse effects were evaluated. A general linear model with 95% confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group. No significant differences in sitting, standing, or supine blood pressure were noted with naproxen or ibuprofen compared with placebo. The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar. Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies. Changes in pulse rate were not significant. The incidence of adverse effects was similar across all three treatment groups. The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure. Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy.",1995.0,0,0
663,7750891,"[Treatment of hypertension with a fixed calcium antagonist-diuretic combination. Observations from treatment of 5,595 patients].",D Klaus,"In an observational study lasting 6 months, 5,595 patients with essential hypertension were treated with a combination of a calcium antagonist and a diuretic, with the aim of testing the efficacy and safety of the drug. Some 63.8% oft the patients had already received anti-hypertensive treatment; 67.3% of the patients also had accompanying diseases. Treatment was begun with a single daily tablet comprising 160 mg verapamil, 50 mg triamterene and 25 mg hydrochlorothiazide (Veratide), and the dose could be reduced to one-half or increased to two daily as indicted by the response of the blood pressure. At the end of 6 months of treatment, the overall groups showed a decrease in both systolic and diastolic blood pressure of 15.2% (26/15 mmHg). Breakdown oft the patients into various age groups revealed no differences in the results. Responder rates varied between 62.0 and 71.8%. Among patients with isolated systolic hypertension, the response rate was 66.4%. In this form of hypertension only the systolic blood pressure was lowered. During the course of treatment, 6.8% of the patients developed side effects, which were severe in 0.9% of the cases. In only 143 of the 5,595 patients did the treatment have to be broken off. The efficacy and safety oft the combination preparation investigated have been confirmed under doctor's office conditions. The decrease in diastolic blood pressure was more marked among smokers than among non-smokers.",1995.0,0,0
664,7751431,"Dose-ranging study of a new, once-daily diltiazem formulation for patients with stable angina.",N R Cutler; J Eff; G Fromell; E P Brass; S Archer; S G Chrysant; R Fiddes,"A double-blind safety and efficacy dose-ranging study was conducted with a new, once-daily, extended-release (XR) diltiazem hydrochloride formulation (Dilacor XR, Rhône-Poulenc Rorer, Collegeville, PA) in 189 patients with chronic stable angina pectoris. After a 2-week placebo lead-in phase, the patients were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: placebo, XR diltiazem 120 mg, 240 mg, or 480 mg. Extended-release diltiazem, at 240-mg and 480-mg once-daily doses, significantly improved (P < .05) total exercise time during treadmill exercise tolerance testing after 2 weeks of treatment when assessed 24 hours after the previous dose. These increasing doses of XR diltiazem were associated with incremental improvements in exercise tolerance. Outpatient function, as assessed by frequency of anginal attacks, nitroglycerin use, and ambulatory electrocardiogram (Holter, Scole Engineering Culver City, CA) monitoring of ischemic events, was also improved by XR diltiazem. This extended-release diltiazem formulation can be clinically titrated within the 120- to 480-mg dosing range, permitting effective once-daily administration for treating chronic stable angina.",1995.0,0,1
665,7752176,"Metabolic effects of anti-hypertensive treatment with nifedipine or furosemide: a double-blind, cross-over study.",L Lind; C Berne; T Pollare; H Lithell,"To evaluate the metabolic effects of two anti-hypertensive agents with different actions, nifedipine 20 mg twice daily and furosemide 60 mg twice daily, 23 patients with untreated essential hypertension performed a double-blind, cross-over study in treatment periods of 5 months. Metabolic effects were evaluated by serum lipoprotein determinations, the intravenous glucose tolerance test and the hyperinsulinaemic euglycaemic clamp technique. Nifedipine and furosemide reduced blood pressure to the same extent (-14 to -15 mm Hg for supine SBP and -9 to -10 mm Hg for supine DBP, both P < 0.0001). Whereas both drugs significantly increased the levels of glycolysated haemoglobin (HbA1c, +0.24%, P < 0.005 for nifedipine and +0.43%, P < 0.001 for furosemide), only furosemide increased fasting blood glucose (+0.3 mmol/L, P < 0.01) and fasting insulin (+2.2 mU/L, P < 0.05) but impaired the early insulin response to i.v. glucose (-15 mU/L, P < 0.05). Insulin sensitivity on the other hand was significantly impaired by nifedipine treatment only (-1.6 mg/kg/min, P < 0.01). Whereas treatment with nifedipine did not change serum lipids, furosemide caused an increase in serum cholesterol (+0.2 mmol/L, P < 0.05) because of a rise in the LDL fraction (+0.32 mmol/L, P < 0.001). The insignificant change in heart rate induced by nifedipine treatment correlated with the change in HbA1c (r = 0.50, P = 0.05) and was inversely related to the change in insulin sensitivity (r = -0.56, P < 0.05). In conclusion, both furosemide and nifedipine caused abnormalities in glucose metabolism. In the nifedipine group the effects on glucose metabolism were related to the occurrence of tachycardia suggesting that sympathetic nerve activation could be involved in the metabolic impairments.",1995.0,0,0
666,7752177,Do changes in dietary salt influence blood pressure of hypertensive patients pharmacologically controlled with verapamil? The Salt-Switching-Study (SSS).,J Redón; J V Lozano; M de la Figuera; J C Rodriguez; J Garrido; J E Alés-Martínez; I Alvarez-Cantalapiedra; J Velasco-Quintana,"To study how changes in dietary salt influence the blood pressure (BP) of pharmacologically controlled hypertensive patients, we have selected from a large multicenter trial two subgroups of 14 and 16 patients who attained BP control (office DBP < 90 mm Hg) after a 4-week treatment with verapamil SR 240 mg once daily, either under an unrestricted salt diet (high-salt; 14 patients) or under a moderately restricted salt diet (low-salt; 16 patients). All of them were switched to the opposite dietary salt regimen and continued on verapamil for 4 more weeks (Salt-Switching-Period). Office BP and ambulatory blood pressure monitoring (ABPM) were registered before and after the Salt-Switching-Period. Salt intake was checked by urinary sodium excretion (UNa). Patients switching from high- to low-salt reduced UNa from 180.9 +/- 22.9 to 89 +/- 28 mM Na/24h (P < 0.001) and patients switching from low- to high-salt increased UNa from 85 +/- 38.4 to 175.8 +/- 57.5 mM Na/24h (P < 0.001). No significant changes in BP were found by ABPM either in the group switching from high- to low-salt or in the group switching from low- to high-salt. In the latter group, a significant increase was observed in office DPB but not in SBP. Short-term changes in salt intake seem to have little influence on the BP of patients pharmacologically controlled with verapamil.",1995.0,0,0
667,7753427,[The efficacy and safety of slow-release nicardipine vs nifedipine in angina].,C Villanova; F Maddalena; C G Rocco,"This controlled, double-blind, completely randomized study assessed the efficacy and safety of nicardipine and nifedipine, both in slow-release formulations, in patients with unstable angina. Thirty patients (28 M, 2F) were included in the final analysis, mean age 56.5 +/- 9.1 years (SD), mean weight 73.5 +/- 9.2 kg, mean height 171.5 +/- 6.5 cm, all with unstable angina. Nicardipine was given at a daily dosage of 80-120 mg, and nifedipine 40-60 mg, for up to one month. At the end of treatment with nicardipine supine systolic and diastolic blood pressure (SBP and DBP) dropped respectively 7.7% and 5.5% at 8 am and 8.6% and 7.1% at 8 pm. Nifedipine reduced SBP and DBP by respectively 6.5% and 13.1% at 8 am and 5.3% and 9.4% at 8 pm. There was no clinical or statistical difference between the treatments. Heart rate did not change appreciably during either treatment. On completion of nicardipine treatment, 87.5% of patients had suffered no angina attacks, compared with 66.7% for nifedipine. The remaining 12.5% of patients treated with nicardipine presented only one mild angina attack per day, while the other 33.3% of the nifedipine patients had one moderate angina attack per day. No untoward effects were reported with nicardipine; one patient receiving nifedipine presented cardiopalmus and another complained of headache. These results indicate that nicardipine is at least as safe and effective as nifedipine in the treatment of unstable angina.",1994.0,0,0
668,7754414,Pharmacologic management of preterm labor.,M Monga; R K Creasy,,1995.0,0,0
669,7755476,,,,,0,0
670,7755939,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.",1995.0,0,1
671,7755941,Combined terazosin and verapamil therapy in essential hypertension. Hemodynamic and pharmacokinetic interactions.,M L Lenz; J L Pool; A R Laddu; A Varghese; W Johnston; A A Taylor,"alpha-Blockers and calcium antagonists are commonly used in the treatment of hypertension, but few data are available concerning first dose or steady state (SS) hemodynamic and pharmacokinetic effects of these drugs when they are used in combination therapy. To examine these interactions, we measured supine and standing blood pressure (BP), heart rate (HR), and cardiac index (CI) for 6 h in 24 hypertensive patients after 2 weeks of placebo, again after the first dose or 3 weeks of therapy (SS) with either 120 mg verapamil (V) twice a day, or 1 mg terazosin (T) titrated weekly to 5 mg daily, and finally when T was added to V (group VT) or V added to T (group TV), acutely and at SS. Changes in supine hemodynamics when T was added to V or when V was added to T were similar and included a further reduction in BP, a transient increase in HR, and little or no change in CI. Both groups experienced significant decreases in standing blood pressure, especially 0.5 to 2 h following initiation of combination therapy despite significant increases in standing HR and CI. Standing BP tended to be lower in group TV after the first dose, but minimum standing systolic BP was not significantly different between groups (group TV 97 mm Hg at 1 h; group VT 109 mm Hg at 1.5 h, P > .05). Four patients in group TV and two in group VT experienced symptomatic orthostatic hypotension with the first dose of double-agent treatment. Pharmacokinetic interactions, including an increase in the bioavailability of T when V was added, did not correlate with the degree of orthostasis. After 3 weeks of combined therapy, the orthostatic change in BP had attenuated and symptoms had improved in all patients. We conclude that T and V represent an effective combination for the treatment of essential hypertension, but that orthostasis may result when initiating combination therapy. The orthostasis seen in some patients appears to be due to the combined vasodilatory effects rather than negative ionotropic or chronotropic effects.",1995.0,0,0
672,7755942,Assessment of blood pressure during naproxen therapy in hypertensive patients treated with nicardipine.,D K Klassen; L H Jane; D Y Young; C A Peterson,"Nonsteroidal antiinflammatory drugs (NSAIDs) are known to attenuate the antihypertensive effects of a variety of antihypertensive agents including diuretics, beta-blockers, and vasodilators. Because of their unique mechanisms of actions, calcium channel blockers may not be subject to this interaction. This multicenter, double-blind, randomized, placebo-controlled study was designed to assess the effect of NSAID therapy on blood pressure control in stable hypertensive patients treated with a calcium channel blocker. One hundred patients with stable blood pressure control on 30 mg nicardipine three times a day were treated with 375 mg naproxen twice a day or placebo for 4 weeks. The mean diastolic blood pressures and estimated mean arterial pressures in both groups changed < 1 mm Hg during the 4 weeks of study drug treatment. None of the changes was significantly different from baseline and the two treatment groups were not significantly different from each other. Body weight in the placebo-treated patients did not change significantly whereas body weight in the naproxen-treated patients increased significantly, from 90.3 +/- 3.2 kg to 91.0 +/- 3.2 kg (mean = 0.7, P = .0003). At 4 weeks there was a mean loss of 0.1 kg in the placebo group and a mean gain of 0.4 kg in the naproxen group compared to baseline weights, neither of which was statistically significant (P = .60 and P = .071, respectively). These results indicate that despite a significant increase in body weight, the antihypertensive action of the calcium channel blocker nicardipine is not significantly affected by cotreatment with naproxen.",1995.0,0,0
673,7758054,The efficacy and safety of once-daily nifedipine: the coat-core formulation compared with the gastrointestinal therapeutic system formulation in patients with mild-to-moderate diastolic hypertension. Nifedipine Study Group.,S P Glasser; A Jain; K S Allenby; T Shannon; K Pride; P P Pettis; L A Schwartz; E P MacCarthy,"The efficacy and safety of two sustained-release formulations of nifedipine, the coat-core system (NIF CC) and the gastrointestinal therapeutic system (NIF GITS), were examined in 228 patients with mild-to-moderate essential hypertension in this 16-week, multicenter, randomized, double-blind study. The coadministration of food affects the nifedipine pharmacokinetics with differing magnitudes for the two formulations. To evaluate drug safety under the most rigorous circumstances, all medication was given with food. After a 4-week placebo lead-in period, eligible patients were randomized to a parallel-group treatment period of either NIF CC or NIF GITS. 30 mg daily with food for 4 weeks, followed by forced titration to nifedipine 60 mg daily for an additional 4 weeks. For the final 4-week period, half of the patients receiving each formulation were switched to the alternate formulation at a dose of 60 mg daily. Within treatment groups, all four blood pressure variables (systolic and diastolic measurements for both trough and 24-hour periods) demonstrated significant reductions (P < 0.05) from baseline (established after the placebo lead-in period) for both formulations at every subsequent visit and end point. When comparing the two formulations, the mean change from baseline in 24-hour systolic and diastolic blood pressure measurements, determined by using ambulatory monitoring, was not statistically different for both doses (P > 0.05). The mean change in trough blood pressure from baseline during the parallel-group treatment period was statistically significant in favor of NIF GITS for both the 30-mg and 60-mg doses (P < 0.05). The treatment-emergent adverse-event rates for both formulations were similar during the parallel-group period, with the exception of dizziness, which was higher for patients receiving NIF CC. Both formulations were well tolerated and reduced blood pressure over the 24-hour dosing interval even when coadministered with food. When half of the patients receiving NIF GITS 60 mg daily were randomly crossed over to NIF CC 60 mg daily, there were no significant changes in either the trough or 24-hour mean blood pressure measurements (P > 0.05), adverse events, or dropout rates. When patients receiving NIF CC 60 mg were crossed over to NIF GITS 60 mg daily, they exhibited no significant change in diastolic blood pressure (P > 0.05). This study demonstrated that when given with food, both NIF CC and NIF GITS reduce 24-hour mean blood pressure measurements similarly.(ABSTRACT TRUNCATED AT 400 WORDS)",1995.0,0,0
674,7758057,The costs and effects of switching calcium channel blockers: evidence from Medicaid claims data.,W R Simons; J A Rizzo; M Stoddard; M E Smith,"This study used Medicaid claims data from Pennsylvania to examine the costs and effects of changing calcium channel blocker therapies. Specifically, we compared Procardia XL with Adalat CC. They are the only once-daily-dosed, extended-release forms of nifedipine available. These drugs were interesting to compare for several reasons. First, because the frequency of treatment regimens has been shown to be the most important determinant of long-term compliance with calcium channel blocker medications, it was desirable to compare drugs having identical dosing regimens. Second, switching from one to the other should be quite feasible in most patients. Third, Adalat CC is priced (ie, average wholesale price) less than Procardia XL. The results indicate that prescription prices were lower when patients were switched from Procardia XL to Adalat CC, with no apparent effects on blood pressure control, the incidence of adverse drug reactions, or nonprescription health care costs. The potential savings to Medicaid from switching patients from Procardia XL to Adalat CC appears to be large, more than $2.5 million annually for Procardia XL-treated Medicaid patients in the state of Pennsylvania. Our study also demonstrates that large retrospective databases can be used to evaluate economic and clinical outcomes for specific therapy alternatives. Such evaluations are increasingly relevant to third-party payers, health maintenance organizations, and other parties involved in managed care.",1995.0,0,1
675,7759701,Selection of medical treatment in stable angina pectoris: results of the International Multicenter Angina Exercise (IMAGE) Study.,D Ardissino; S Savonitto; K Egstrup; K Rasmussen; E A Bae; T Omland; P M Schjelderup-Mathiesen; P Marraccini; P A Merlini; I Wahlqvist,"The present study was designed to investigate which characteristics of anginal symptoms or exercise test results could predict the favorable anti-ischemic effect of the beta-adrenergic blocking agent metoprolol and the calcium antagonist nifedipine in patients with stable angina pectoris. The characteristics of anginal symptoms and the results of exercise testing are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacologic approach in individual patients. In this prospective multicenter study, 280 patients with stable angina pectoris were enrolled in 25 European centers. After baseline evaluation, consisting of an exercise test and a questionnaire investigating patients' anginal symptoms, the patients were randomly allocated to double-blind treatment for 6 weeks with either metoprolol (Controlled Release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) according to a parallel group design. At the end of this period, exercise tests were repeated 1 to 4 h after drug intake. Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels; the improvement was greater in the patients receiving metoprolol (p < 0.05). Multivariate analysis revealed that low exercise tolerance was the only variable associated with a more favorable effect within each treatment group. Metoprolol was more effective than nifedipine in patients with a lower exercise tolerance or with a higher rate-pressure product at rest and at ischemic threshold. None of the characteristics of anginal symptoms or exercise test results predicted a greater efficacy of nifedipine over metoprolol. The results of a baseline exercise test, but not the characteristics of anginal symptoms, may offer useful information for selecting medical treatment in stable angina pectoris.",1995.0,0,1
676,7762493,"Placebo-controlled evaluation of three doses of a controlled-onset, extended-release formulation of verapamil in the treatment of stable angina pectoris.",N R Cutler; R J Anders; S S Jhee; J J Sramek; N A Awan; J Bultas; A Lahiri; M Woroszylska,"This double-blind, placebo-controlled, parallel-group, multicenter study was designed to evaluate the safety and efficacy of a new controlled-onset, extended-release formulation of verapamil hydrochloride called physiologic pattern release (PPR) verapamil. The study was conducted at 24 sites (13 United States, 5 Canada, 6 overseas; see Appendix). Following a 1- to 3-week single-blind placebo lead-in period, 278 patients with chronic stable angina pectoris (247 males, 31 females, mean age 60.8 years, range 32 to 78) were randomly assigned to 1 of 4 once-daily, fixed-dose treatment groups: verapamil 180, 360, or 540 mg, or placebo. PPR verapamil at all doses significantly increased (p < 0.05) time to moderate angina and symptom-limited exercise duration, and verapamil 360 mg significantly increased (p < 0.05) time to > or = 1 mm ST-segment depression, after 4 weeks of treatment when assessed 24 hour after the previous dose. Larger doses of verapamil were associated with proportionately greater improvements in exercise tolerance. Frequency of anginal attacks was also reduced by verapamil. The most frequently observed adverse events were dizziness, headache, constipation, and nausea. The incidence of constipation was high (20.9%) within the 540 mg treatment group. This verapamil formulation can be clinically titrated within a 180 to 540 mg dosing range, permitting effective once-daily administration for the treatment of chronic stable angina.",1995.0,0,1
677,7766339,Low dose combination antihypertensive therapy. Additional efficacy without additional adverse effects?,A M MacConnachie; D Maclean,,1995.0,0,0
678,7768250,Efficacy and safety of the 200-300 mg sustained release formulation of diltiazem administered once daily in patients with stable angina.,B Trimarco; D Radzik; W Van Mieghem; E Neveux; A Wajman; P Attali; J Ponsonnaille,"The aim of this multicentre randomised double blind study was to compare the efficacy and safety of the 200-300 mg sustained release diltiazem formulation administered once daily (200-300 SR) with standard diltiazem (D) given three or four times daily to patients with stable angina. Patients aged 59 years, with a reproducible exercise test on placebo, were randomised to 4 weeks of treatment with 200-300 SR (n = 70) or D (n = 74). The initial dosage was 200 mg in the 200-300 SR group and 60 mg t.i.d. in the D group, increased to 300 mg once daily or 60 mg q.i.d., respectively, if ergometric parameters, which were always measured at the end of the dosing period, had not improved after two weeks. After 4 weeks of treatment, the antianginal efficacy at rest was comparable in the 200-300 SR and the D group; there was a prolongation of the total duration of exertion of 14% and 18% respectively (P < 0.01 vs placebo for both groups with no intergroup difference). A dose-effect relation was found with both formulations. The 200-300 SR formulation gave full 24 hour anti-ischaemic protection when administered once daily. Its efficacy and safety were comparable to those of standard diltiazem t.i.d. or q.i.d. in patients with stable angina. The once daily administration should improve treatment compliance.",1995.0,0,1
679,7774991,"Comparison of efficacy of nisoldipine, metoprolol, and isosorbide dinitrate in patients with stable exertional angina: a randomized, cross-over, placebo-controlled study.",H Ogawa; H Yasue; N Nakamura; H Fujii; H Miyagi; K Kikuta,"We evaluated the acute antianginal effect of oral nisoldipine (10 mg), metoprolol (40 mg), and long-acting isosorbide dinitrate (20 mg) in 15 patients with stable exertional angina. The patients performed symptom-limited treadmill exercise at 2 h after the administration of placebo (Placebo stages 1 and 2) and each of the active drugs. After Placebo stage 1, the patients were randomized for cross-over evaluation of the acute effect of a single oral dose of placebo (Placebo stage 2), nisoldipine, metoprolol, or long-acting isosorbide dinitrate. All 15 patients developed angina during all of exercise tests and their exercise tests were terminated at the onset of angina. The time until development of 0.1 mV ST segment depression was increased by all three drugs compared to placebo, and it was significantly longer with metoprolol than with isosorbide dinitrate. Similarly, the time to ceasing exercise because of angina was also prolonged by all three drugs. The exercise time was longer with nisoldipine and metoprolol compared to isosorbide dinitrate, but there was no significant difference between nisoldipine and metoprolol. In conclusion, metoprolol and nisoldipine more effectively prolonged exercise compared to long-acting isosorbide dinitrate in patients with stable exertional angina.",1995.0,0,1
680,7783096,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
681,7783099,Assessment of effects of two anti-hypertensive regimens on overall cardiovascular risk.,G L Jennings; K Sudhir; E Laufer; P Korner; C Reid,"Anti-hypertensive drugs differ in their effects on other cardiovascular risk factors. To date there have been few attempts to quantitate the impact of such differences. Twenty five unmedicated patients with primary hypertension were randomised to initial therapy with either the calcium antagonist, felodipine, or a diuretic and doses titrated to achieve similar levels of blood pressure (BP). Second drugs were added if needed (metoprolol and prazosin, respectively). The aim was to determine over 1 year whether similar anti-hypertensive effects were associated with differences in a multivariate index of overall cardiovascular risk. The target supine diastolic blood pressure (DBP) (85 mm Hg) required the second agent in four of 13 evaluable patients in the felodipine group and six of 10 in the diuretic group. There was a significant rise in serum cholesterol and a fall in serum potassium in the diuretic group, but not in the felodipine group. Cardiovascular risk scores were ranked in percentiles in relation to the age-matched general population. This score fell to a greater degree in felodipine patients particularly over the first 6 months, but remaining lower at 12 months. Left ventricular hypertrophy assessed by echocardiography, another measure of cardiovascular risk, was generally unchanged by either regimen. At equivalent blood pressure levels, the calcium antagonist-based regimen had a greater benefit on cardiovascular risk, particularly in the first 6 months of therapy. This method may be widely applicable in the assessment of anti-hypertensive therapy.",1995.0,0,0
682,7786657,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.",1995.0,1,1
683,7788902,AHA president's letter.,S C Smith,,2001.0,0,0
684,7789289,Hypertension in pregnancy. Practical management recommendations.,E D Gallery,"Hypertension is a common and potentially serious complication of human pregnancy. It can be a marker of underlying maternal disease processes aggravated by pregnancy, or it can be directly related to the pregnancy (pre-eclampsia). It is associated with increased risks of fetal growth retardation and, if severe, can cause both maternal and fetal problems. The risks to both mother and neonate can be reduced by appropriate supervision and therapy. Close monitoring of maternal and fetal welfare will help to determine the optimum time for delivery. Maternal hypertension should be controlled with agents considered to be well tolerated in pregnancy. Following the index pregnancy, all patients with early and/or severe hypertension should be investigated for an underlying cause. Provided that there is clinical resolution of acute pregnancy-related hypertension, investigations are usually postponed until at least 3 months following delivery.",1995.0,0,0
685,7789292,Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension.,R N Brogden; E M Sorkin,"Since the earlier review in Drugs substantial additional data have accumulated regarding the antihypertensive efficacy of isradipine in various clinical situations, as well as data on its clinical effects in atherosclerosis. Recent therapeutic trials confirm that the efficacy of isradipine in the treatment of patients with mainly mild to moderate hypertension, when administered orally as a conventional or modified release preparation, is similar to that of titrated dosages of amlodipine, felodipine, nifedipine, diltiazem, captopril, methyldopa, metoprolol, prazosin and hydrochlorothiazide. A further decrease in blood pressure can be expected when isradipine is combined with another antihypertensive drug in patients who have not responded adequately to monotherapy. Initial studies have shown that intravenous isradipine is effective in controlling hypertension following coronary artery bypass graft surgery and that it appears useful in the treatment of intraoperative hypertension and hypertensive crisis, and in hypertensive disorders in pregnancy, when administered orally or intravenously. A large study, the Multicentre Isradipine Diuretic Atherosclerosis Study (MIDAS), was designed to compare the efficacy of isradipine and hydrochlorothiazide in reducing the rate of progression of carotid artery wall thickness, measured by B-mode ultrasound, as a surrogate for early atherosclerosis. Results indicated that wall thickness increased significantly less with isradipine than hydrochlorothiazide after 6 months of therapy. Thereafter the rate of progression remained parallel for the remainder of the 3-year trial. The confirmation of its antihypertensive efficacy, along with its favourable haemodynamic profile and reversal of left ventricular hypertrophy, minimal effect on glucose and lipid metabolism, preservation of quality of life and good tolerability, makes isradipine a suitable drug for the treatment of most patients with mild to moderate hypertension.",1995.0,0,0
686,7794578,Clinical efficacy of force titrated doses of diltiazem extended-release. A placebo controlled study.,Y Lacourcière; L Poirier; J Lefebvre; R G Burford,"Thirty patients with clinical and ambulatory essential hypertension were treated in a double-blind fashion with force titrated doses of placebo or diltiazem once daily (OD) extended-release (ER) 120, 240, 360, and 540 mg to characterize the full-dose range of the new formulation. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters. Doses of > or = 240 mg significantly decreased clinic diastolic blood pressure, whereas systolic blood pressure was significantly lowered by the 540-mg dose. Moreover, compared with placebo, ambulatory blood pressure was significantly decreased by the 360- and 540-mg dose levels. Trough/peak ratios for systolic and diastolic blood pressures were 50% and higher at dose levels of 240 mg and above. Adverse reactions with diltiazem OD ER were generally mild and similar to those observed with placebo. The findings of this study indicate that the most favorable effects of diltiazem OD ER were observed in response to the 360- and 540-mg dose levels. The dose escalation forced titration study design appears to be a valuable tool in obtaining rigorous dose-response data of new antihypertensive agents.",1995.0,0,0
687,7798508,"Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial comparing bisoprolol and nifedipine. The TIBBS Investigators.",T von Arnim,"We compared the effects of bisoprolol on transient myocardial ischemia with those of nifedipine in patients with chronic stable angina. Both beta-adrenergic blocking agents and calcium antagonists reduce transient ischemic episodes, but comparisons of these agents have been made in only a few larger studies. The Total Ischemic Burden Bisoprolol Study (TIBBS) was a randomized double-blind controlled study with two parallel groups; 330 patients from 30 centers in seven European countries with stable angina pectoris, a positive exercise test and more than two transient ischemic episodes during 48 h of Holter monitoring (central evaluation) were included. Of these patients 161 were randomized to receive bisoprolol and 169 to receive nifedipine slow release. There were two treatment phases of 4 weeks each, with 48-h Holter monitoring after each phase. During phase 1, patients received either 10 mg of bisoprolol daily or 2 x 20 mg of nifedipine slow release. During phase 2, they received either 20 mg of bisoprolol daily or 2 x 40 mg of nifedipine slow release. In phase 1 of the trial, 4 weeks of bisoprolol therapy (10 mg daily) reduced the mean [+/- SD] number of transient ischemic episodes from 8.1 +/- 0.6 to 3.2 +/- 0.4/48 h. Nifedipine (2 x 20 mg) reduced transient ischemic episodes from 8.3 +/- 0.5 to 5.9 +/- 0.4/48 h. Total duration of ischemia was reduced from 99.3 +/- 10.1 to 31.9 +/- 5.5 min/48 h with bisoprolol and from 101 +/- 9.1 to 72.6 +/- 8.1 min/48 h with nifedipine. Reductions were statistically significant for both drugs; the difference between bisoprolol and nifedipine was also significant (p < 0.0001). Bisoprolol reduced the heart rate at onset of episodes by 13.7 +/- 1.4 beats/min from a baseline value of 99.5 +/- 1.2 beats/min (p < 0.001). Heart rate was unchanged with nifedipine. Bisoprolol had significantly higher responder rates than nifedipine. Doubling of the dose in phase 2 of the trial had small additive effects. Only bisoprolol showed a marked circadian effect by reducing the morning peak of transient ischemic episodes (by 68% at peak time, 8:00 to 8:59 AM). Both bisoprolol and nifedipine reduced the number and duration of transient ischemic episodes in patients with chronic stable angina. Bisoprolol was significantly more effective than nifedipine in both doses tested and reduced the morning peak of ischemic activity.",1995.0,0,1
688,7801876,Efficacy and safety of digoxin alone and in combination with low-dose diltiazem or betaxolol to control ventricular rate in chronic atrial fibrillation.,K K Koh; K S Kwon; H B Park; S H Baik; S J Park; K H Lee; E J Kim; S H Kim; S K Cho; S S Kim,,1995.0,1,1
689,7803945,"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
690,7814301,Long-term clinical effect of nilvadipine in patients with chronic heart failure: a double-blind placebo-controlled study.,M Hori; H Sato; M Karita; K Kodama; N Hoki; T Hayashi; M Naka; S Nanto; Y Yamada; T Kamada,"The long-term effect of calcium channel blockers on chronic heart failure is disappointing, probably because of reflex sympathetic activation through arterial vasodilation. However, nilvadipine may be beneficial for treatment of chronic heart failure since this drug has minimal effects on sympathetic activation. In this study, the effects of 12-week administration of nilvadipine or placebo on symptoms of heart failure and cardiac function were investigated in 23 patients with mild-to-moderate chronic heart failure in a double-blind trial. The patients were randomly assigned to either a nilvadipine group (16 mg daily) or a placebo group. Intergroup comparisons did not show significant differences in any parameters. Serious adverse effects were not observed during the study. Thus, this study failed to show any beneficial effect of nilvadipine in the long-term treatment of patients with chronic heart failure. We conclude that the long-term administration of nilvadipine (16 mg daily) is neither effective nor harmful in the treatment of patients with chronic heart failure.",1994.0,0,0
691,7828296,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
692,7828793,[Isradipine versus diltiazem in the treatment of stable effort angina pectoris: ergometric evaluation in a crossover double-blind study].,F Perticone; D A Borelli; R Maio; R Costa; F Pugliese; L Torchia; S Caristo; P L Mattioli,"To evaluate the effects of isradipine (ISR) and diltiazem (DIL) on exercise tolerance and ischemic ST depression in patients with stable effort angina. Fourteen out-patients, 9 males and 5 females, aged 46-65 years (mean +/- SD = 57 +/- 8), with ischemic heart disease and reproducible ST-segment depression on two consecutive exercise stress tests in baseline conditions, underwent a study consisting of 4 periods: 1 and 3 placebo, 2 and 4 at random ISR (5 mg b.i.d.) and DIL (120 mg b.i.d.). At the end of each period a multistage treadmill exercise stress test (Bruce protocol) was performed. Both drugs significantly (p < 0.001) increased ischemia time (IT) (0.1 mV ST depression) as compared to placebo, from 438 +/- 132 s. to 620 +/- 164 s. (ISR) and 583 +/- 147 s. (DIL) without statistical difference between two drugs (p = 0.2), and significantly reduced (p < 0.002) the maximal ST depression, from -0.20 +/- 0.11 mV to -0.07 +/- 0.07 mV (ISR) and -0.09 +/- 0.11 mV (DIL). At the IT, systolic blood pressure increased (p = 0.02), from 180 +/- 19 mm Hg to 187 +/- 15 mm Hg (ISR) and 191 +/- 15 mm Hg (DIL); similarly, heart rate increased from 133 +/- 24 bpm to 144 +/- 18 bpm (ISR: p = 0.002) and 140 +/- 17 bpm (DIL: p = NS). ISR and DIL, at the above dosage have showed an important and significant anti-ischemic effect (IT = +41.5% during ISR and +33.1% during DIL).",1994.0,0,0
693,7830324,Effect of two different therapeutic approaches on total and cardiovascular mortality in a Cardiovascular Study in the Elderly (CASTEL).,E Casiglia; P Spolaore; A Mazza; G Ginocchio; G Colangeli; C Onesto; G Di Menza; L Pegoraro; G B Ambrosio,"Although limited numbers of elderly subjects have occasionally been included in population-based studies, only a few studies have been conducted specifically on elderly hypertensives, and practically none at a population level. We studied 655 hypertensive subjects from a cohort of 2,254 elderly subjects. The intervention consisted of the creation of a Hypertension Outpatients' Clinic under our auspices but with complete co-operation from general practitioners, randomizing the identified hypertensive patients into pre-established therapeutic drug regimens, and early follow-up recording of mortality for 7 years. The drugs used were clonidine (n = 61), nifedipine (n = 146) and the fixed combination of atenolol+chlorthalidone (n = 144); 304 subjects underwent ""free therapy"" by their personal physicians without any special intervention. There were 1,404 normotensive subjects. Overall 7-year follow-up mortality was 34.9% in the hypertensive subjects receiving ""free therapy"", 22.5% in those receiving ""special care"", and 24.2% in the normotensives. Cardiovascular mortality was respectively 23.7%, 12.2%, and 12.0%. Overall and cardiovascular annual cumulative mortality were significantly lower in the < special therapy > than in the < free therapy > group. The fixed combination of atenolol and chlorthalidone reduced mortality below that of the normotensives, independent of other cardiovascular risk factors.",1994.0,0,0
694,7832144,Effects of isosorbide dinitrate and nicardipine hydrochloride on postprandial blood pressure in elderly patients with stable angina pectoris or healed myocardial infarction.,C M Connelly; C Waksmonski; M M Gagnon; L A Lipsitz,,1995.0,0,0
695,7833223,"At equipotent doses, isradipine is better tolerated than amlodipine in patients with mild-to-moderate hypertension: a double-blind, randomized, parallel-group study.",L Hermans; A Deblander; P De Keyser; I Scheys; E Lesaffre; K J Westelinck,"1. The objective of this double-blind parallel-group study was to compare the tolerability of isradipine and amlodipine, specifically, the side-effects known to be related to the use of dihydropyridine calcium antagonists. 2. A total of 205 patients with mild-to-moderate essential hypertension were randomized to receive either the sustained-release (SRO) formulation of isradipine (n = 103) or amlodipine (n = 102), both at dosages of 5 mg once daily. Blood pressure measurements were taken at the end of the dosing interval to assess the antihypertensive efficacy of the two drugs. 3. Adverse reactions were assessed in two ways: a) spontaneously reported adverse events were recorded and investigated in depth for severity, duration, relation to the study drug, and outcome; b) a questionnaire was used to elicit specific adverse reactions known to be related to the use of dihydropyridine calcium antagonists which were evaluated for severity, duration, relation to the study drug, and outcome. 4. After 6 weeks of active treatment, both isradipine and amlodipine reduced mean sitting systolic/diastolic blood pressure: from 165.1/100.1 to 145.2/89.7 mm Hg with isradipine; and from 164.1/100.6 to 145.7/90.5 mm Hg with amlodipine. There was no difference in antihypertensive effect between isradipine and amlodipine (95% CI: -3.73 to 4.73 and -1.89 to 3.49 for differences in systolic and diastolic blood pressure, respectively). 5. The number of patients spontaneously reporting adverse events was significantly higher (P = 0.02; 95% CI: 3.1 to 26.7%) with amlodipine (33.3%) than with isradipine (18.4%).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
696,7840400,[Esmolol as a bolus for prevention of sympathetic adrenergic reactions following induction of anesthesia].,J Schäffer; C Karg; S Piepenbrock,"In addition to laryngoscopy, endotracheal intubation, and other stressful intraoperative phases, hypertension occurs during recovery from anaesthesia, provoking post-operative complications like bleeding and increased intracranial or intraocular pressure. Furthermore, these hypertensive reactions result in life-threatening complications, especially in patients with pre-existing cardiovascular diseases. In this study, the effect of the new, short-acting beta-blocker esmolol given as a single bolus for preventing the increases in blood pressure and heart rate during recovery from anaesthesia and extubation in patients with hypertension was investigated. PATIENTS AND METHODS. Sixty-three patients with a history of hypertension over a period of more than 6 months and blood pressure (BP) more than 150/90 mm Hg undergoing intervertebral-disc, otolaryngologic, or eye surgery were included in the study. The operations were performed during thiopentone-induced isoflurane anaesthesia with relaxation by atracurium. The patients were assigned to three groups after giving witnessed oral informed consent. During the study period they received the study drug twice: (A) 30-90 s before turning off the nitrous oxide; and (B) 20-90 s before extubation. Group I (placebo) received placebo each time, group II (100 mg esmolol) placebo at A and 100 mg esmolol i.v. at B, and group III (200 mg esmolol) 100 mg esmolol i.v. each time. After each medication the cardiovascular parameters were measured noninvasively over a period of 10 min every minute and in the following 2 h every 15 min. RESULTS. After the first medication systolic and diastolic BP, heart rate (HR), and rate-pressure product (RPP) were lower in patients receiving 100 mg esmolol (Group III) than in groups I and II. After the second injection the blood pressure was lower in the two groups receiving 100 mg esmolol, than the placebo group (I: 180.1 +/- 7.4/100.7 +/- 3.6; II: 152.8 +/- 5.8/87.9 +/- 3.4; III: 157.9 +/- 5.3/91.5 +/- 3.6 mm Hg [mean 2 min +/- SEM]). The changes in HR (I: 88.2 +/- 3.8; II: 75.6 +/- 2.6; III: 72 +/- 3.1 min-1) and RPP (I: 15,800 +/- 900; II: 11,700 +/- 700; III: 11,400 +/- 600) were similar. In 8 of the 20 patients in group III the HR dropped below 60.min-1, but in none of these patients did the BP become instable. CONCLUSIONS. The sympathoadrenergic reaction during recovery from anaesthesia and extubation can be treated by beta-blocking agents, but such therapy is not without risk because of the long half-life and effects of the therapy on other factors such as postoperative loss of intravascular volume. Esmolol is a new, short-acting, cardioselective beta-blocker with a very short plasma distribution time and a elimination half-life of 9.2 min. Thus, the potential risks of beta-blockers due to half-life are minimised. The results of this study show that a dangerous increase in BP and HR with increased myocardial oxygen consumption can be prevented by a single bolus, and better by a double bolus of 100 mg esmolol. Although bradycardia with HR below 50.min-1 in 8 patients might indicate a risk of cardiac instability, the systolic BP did not fall below 100 mm Hg, and the episode of bradycardia was so short that there was no risk to the patients.",1994.0,0,0
697,7840730,[Fasting and postprandial lipids and lipoproteins during the chronic administration of antihypertensive drugs].,V Granados; S Ichazo; J Chávez; J Zamora; C Ochoa; G Cardoso; C Posadas,"To evaluate the effect of various antihypertensive drugs on fasting and postprandial lipids and lipoproteins, we studied 39 normolipidemic hypertensive patients, 28 men and 11 women aged 52.3 +/- 9.0 and 58.5 +/- 7 years, respectively. After four weeks of placebo administration, lipids and lipoproteins were measured in the fasting state and every three hours for a period of nine hours after intake of a standardized fat mixed load (65 g/m2). Following this test, the patients were randomly assigned to one of four treatment groups: group I metoprolol (n = 10), 100 mg/day; group II nicardipine (n = 9), 90 mg/day; group III captopril (n = 11), 75 mg/day. At the end of week four of treatment the fasting and postprandial lipid measurements were repeated. Blood pressure mean values were significantly (p < 0.05) reduced in the four treatment groups. We found no statistically significant lipids or lipoproteins changes neither in the fasting nor in the postprandial state, but a trend toward lower concentrations in the postprandial lipemia after treatment was observed in three groups (metoprolol, nicardipine and captopril), whereas no change was observed in the chlorthalidone group. These data confirm that fasting lipids and lipoproteins in normolipidemic hypertensive patients are not unfavorably changed by low doses of the drugs studied. In addition, we inform that postprandial lipemia is not affected by these four drugs in the doses used.",1994.0,0,0
698,7846938,[Amiodarone and verapamil/quinidine in treatment of patients with chronic atrial fibrillation].,M Zehender; T Meinertz; H Just,"Rapid, reliable and safe reestablishment of sinus rhythm is the major aim of pharmacologic treatment in patients with chronic atrial fibrillation. The mainstay of therapy in this arrhythmia has been quinidine. More recently, amiodarone was shown in noncomparitive studies to be superior to class IA agents under certain conditions. In 40 patients with atrial fibrillation persisting for 4 weeks up to 2 years, the efficacy and safety of either quinidine and verapamil (days 1 to 3, quinidine 1,500 mg/day; days 4 to 6, quinidine 1,500 mg+verapamil 240 mg/day) or amiodarone therapy (days 1 to 3, amiodarone 1,200 mg/day intravenously; days 4 to 14, amiodarone 800 mg/day orally) were randomly examined. Responders continued on their effective medication for 3 months. Thereafter, all patients were treated with a fixed regimen of quinidine (480 mg/day) plus verapamil (240 mg/day) for up to 2 years. During atrial fibrillation, quinidine reduced mean ventricular cycle length by 40 ms (-5%), quinidine and verapamil increased mean cycle length by 57 ms (8%) and amiodarone by 192 ms (28%, p < 0.01). In addition, quinidine and verapamil had a characteristic ""rate-smoothing"" effect on atrioventricular conduction during atrial fibrillation. The rhythm was converted to sinus rhythm after quinidine in 5 (25%) of 20 patients and after the combination of quinidine and verapamil in 11 (55%) of 20 patients. Amiodarone restored sinus rhythm in 12 (60%) of 20 patients. Overall, a shorter duration of atrial fibrillation (p < 0.05) and a smaller left atrial size (p < 0.01) were predictive of successful conversion of the arrhythmia.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
699,7846939,[Sotalol and quinidine/verapamil (Cordichin) in chronic atrial fibrillation--conversion and 12-month follow-up--a randomized comparison].,D Kalusche; J Stockinger; P Betz; H Roskamm,"Atrial fibrillation is one of the most common arrhythmias, leading at least in a subset of patients to severe symptoms (palpitations, weakness, syncope), and to hemodynamic impairment especially in the clinical setting of left ventricular dysfunction. Thus, in many cases restauration of sinus rhythm is indicated because of the negative effects of reduced cardiac output. Quinidine has been the first line drug for many years and has been proven to be highly effective especially when combined with Verapamil. But there is growing concern about using quinidine and other class I-anti-arrhythmic agents because of some hints in clinical trials for increased longterm mortality on these drugs. This study was undertaken to test the efficacy of Sotalol, a beta-blocker with additional strong class-III antiarrhythmic action, compared to a fixed combination of Quinidine and Verapamil for conversion of chronic atrial fibrillation and maintenance of sinus rhythm after medical or electrical cardioversion. To avoid early proarrhythmic effects, potassium values in the range of ""high""-normal values (> 4.3 mval/L) were tried to be obtained. 82 patients were randomly assigned to receive either Sotalol or Quinidine/Verapamil. There was no difference between the groups as far as the underlying heart disease, duration of atrial fibrillation (mean 219 days) and other clinical features including echocardiographic parameters were concerned. The dose of the drug was weight-related individually adjusted, and the drug was continued thereafter. If sinus rhythm could not be established at that time, electric cardioversion was performed and the drug was continued in lower dosage thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
700,7848623,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
701,7848788,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
702,7850818,Postoperative antiarrhythmic effects of diltiazem in patients undergoing coronary bypass grafting.,M el-Sadek; E Krause,"Hemodynamic problems resulting from cardiac arrhythmias often occur in patients undergoing coronary bypass grafting in the early postoperative period. Therefore, in this study the antiarrhythmic effects of the calcium channel antagonist diltiazem were evaluated in coronary bypass grafting. Forty patients were randomly assigned either to a therapy with diltiazem or nitroglycerin. Hemodynamic measurements were established by Swan-Ganz catheter, and long-term ECG analyses were performed preoperatively and 1, 3 and 5 days after operation. There were significantly fewer ventricular arrhythmias (Lown class IV) in the diltiazem groups than in the nitroglycerin groups (p < 0.05). Supraventricular tachycardias were significantly more often observed in the nitroglycerin groups on all 3 days (p < 0.05). As a result, the calcium channel antagonist diltiazem is recommended as a standard adjunct to perioperative medication in cardiac surgery.",1994.0,0,1
703,7852749,"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
704,7860905,"Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.",R F Davies; H Habibi; W P Klinke; P Dessain; C Nadeau; D C Phaneuf; S Lepage; S Raman; M Herbert; K Foris,"This study compared the effects of amlodipine, atenolol and their combination on ischemia during treadmill testing and 48-h ambulatory monitoring. It is not known whether anti-ischemic drugs exert similar effects on ischemia during ambulatory monitoring and exercise treadmill testing. Patients with stable coronary artery disease and ischemia during treadmill testing and ambulatory monitoring were randomized to receive amlodipine (n = 51) or atenolol (n = 49). Each group underwent a counterbalanced, crossover evaluation of single drug and placebo, followed by evaluation of the combination. Amlodipine and the combination prolonged exercise time to 0.1-mV ST segment depression by 29% and 34%, respectively (p < 0.001) versus 3% for atenolol (p = NS). During ambulatory monitoring, the frequency of ischemic episodes decreased by 28% with amlodipine (p = 0.083 [NS]), by 57% with atenolol (p < 0.001) and by 72% with the combination (p < 0.05 vs. both single drugs; p < 0.001 vs. placebo). Suppression of ischemia during exercise testing and ambulatory monitoring was similar in patients with and without exercise-induced angina. Exercise time to angina improved by 29% with amlodipine (p < 0.01), by 16% with atenolol (p < 0.05) and by 39% with the combination (p < 0.005 vs. placebo, atenolol and amlodipine). In patients with angina, total exercise time improved by 16% with amlodipine (p < 0.001), by 4% with atenolol (p = NS) and by 19% with the combination (p < 0.05 vs. placebo and either single drug). In those patients without angina, no therapy significantly improved total exercise time. Ischemia during treadmill testing was more effectively suppressed by amlodipine, whereas ischemia during ambulatory monitoring was more effectively suppressed by atenolol. The combination was more effective than either single drug in both settings.",1995.0,0,1
705,7862585,"[Use of nifedipine in elderly patients with essential hypertension: patient compliance, safety and efficacy of therapy].",K Kawecka-Jaszcz; J Kocemba; D Czarnecka; T Grodzicki; B Gryglewska,"The aim of the study was to evaluate chronic treatment with Cordafen (nifedipine) in the out-patients over 60 years of age with established arterial hypertension. Out of 100 out-patients aged 60-83 years 69 subjects completed one-year study. The main reasons of drop-outs were: lack of patient compliance (12%), severe side effects (11%), ineffective monotherapy (5%) and other (3%). Less severe adverse effects were found in further 20 subjects. After one-year therapy hematological and biochemical parameters of the homeostasis did not deteriorate except an increase in alkaline phosphatase. Regular drug intake in a dose of 20-80 mg/daily (mean = 46.0) produced a significant decrease in the blood pressure level and an improvement of cardiac function indices (CO nad EF). In contrast Cordafen did not reduce the differences between extreme blood pressure values recorded automatically, and it did not produce a significant regression of left ventricular mass and cardiac arrhythmias. Nifedipine in mild or moderate hypertension in the elderly patient any be an adequate form of monotherapy in about 70% of them. Higher motivation for treatment in this age group and better drug tolerance may further improve this efficacy.",1994.0,0,0
706,7866597,"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)",1994.0,0,1
707,7867240,Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients.,S G Chrysant; E Miller,"The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single-blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance test by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem-SR is effective and well tolerated, (2) it decreases the 24-h BP load, (3) it does not interfere with exercise capacity.",1994.0,0,0
708,7867683,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
709,7872184,Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial.,M D Ezekowitz; K Hossack; J L Mehta; U Thadani; D J Weidler; W Kostuk; N Awan; W Grossman; W Bommer,"The efficacy and safety of amlodipine, 10 mg, a new long-acting calcium antagonist, was compared with placebo in 103 patients with stable angina pectoris in a multicenter double-blind crossover study. The trial consisted of an initial 2-week single-blind placebo period followed by a first period of 4 weeks of double-blind therapy, which was followed by a 1 week washout period and then a second 4-week double-blind period after treatments were crossed over. Twenty-four-hour Holter electrocardiographic monitoring was carried out in 12 patients at three centers. In the first double-blind period amlodipine produced a significantly greater increase in symptom-limited exercise duration (amlodipine 478.5 to 520.6 vs placebo 484.6 to 485.2 seconds; change +8.8% vs +0.1%, respectively; p = 0.0004) and total work (amldipine 2426 to 2984 vs placebo 2505 to 2548 kilopondmeters; change +24% vs +1.7%, respectively; p = 0.0006) and a decrease in angina attack frequency (from 3 to 1 per week; p = 0.016) and nitroglycerin consumption (from 2 to 0.5 tablets/wk; p = 0.01) compared with placebo. Holter monitoring revealed significant reductions in numbers (amlodipine 4.65 to 2.22 vs placebo 1.84 to 1.54; change -52% vs +84%, respectively; p = 0.06), absolute total area (amlodipine 87.66 to 11.43 vs placebo 5.76 to 35.24; change -87% vs +513%, respectively; p = 0.02), and duration (amlodipine 12.29 to 2.95 vs 1.66 to 7.74 seconds; change -76% vs +367%, respectively; p = 0.008) of ST-segment depressions after treatment with amlodipine compared with placebo. After the treatments were crossed over changes continued to favor amlodipine.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,1
710,7878283,[Adenosine triphosphate in the treatment of supraventricular paroxysmal tachycardia: a comparison with verapamil].,J Gil Madre; S Lázaro Rodríguez; G Sentenac Merchán; M A Sepúlveda Berrocal; J M Alises Moraleda; S Cortés Bermejo; J García de Pedro; N Laín Teres,"There are multiple drugs options in the treatment of Paroxysmal Supraventricular Tachycardia (PST) after inefficacious vagal stimulus. In this study we compare two of these treatments: verapamil versus adenosin triphosphate (ATP). Fifty patients with PST were randomly treated with either Verapamil (5 to 10 mg) or ATP (5 to 20 mg). The basal features of each group, and the efficacy and safety of the two drugs were compared. Verapamil failures were treated with ATP and vice versa. The characteristics of both groups of treatment were similar. 86% of PST episodes were resolved with Verapamil use, versus 83% after ATP administration. Finally all patients were successfully treated with these drugs. No adverse effects were observed with Verapamil, whereas these effects were frequent with ATP use, but in any case requiring specific intervention. Both Verapamil and aTP are an equally safe and effective treatment of PST, but transient and minor side effects are frequent after ATP administration.",1995.0,0,0
711,7884790,One year experience of elderly hypertensive patients with isradipine therapy.,G H Stein; B P Hamilton; J H Hamilton; J L Holtzman; W M Kirkendall; A Abrams; G Neri; R Culter; K Matthews,"This is the first report of long-term use (one year) of isradipine, a new dihydropyridine calcium channel blocker, in the treatment of elderly patients with essential hypertension. Patients completing a three month, double-blind, multicentre study comparing isradipine to hydrochlorothiazide (HCTZ) were eligible to enroll in this open-label, continuation study. At initial baseline, patients were at least 60 years of age and had DBP from 95 mmHg to 120 mmHg. Patients were titrated when necessary every two weeks with isradipine, 5 mg to 15 mg once daily or 2.5 mg to 10 mg twice daily, to maintain sitting DBP < or = 90 mmHg. HCTZ, 12.5 mg to 50 mg once daily, could be added for better BP control. A total of 136 patients completed the one year, open-label phase. One hundred and fourteen patients (84%) received isradipine as monotherapy (mean dose, 9.7 mg/day); 22 received concomitant HCTZ therapy at one year. Reduction in DBP was significant and similar among all age groups and races (mean change of -19 mmHg). Reduction in SBP was similar among all age groups. Ninety-four per cent of those receiving isradipine monotherapy achieved BP control during the last four months of treatment. Twenty-six patients (16%) withdrew from the study: 11 (7%) had adverse reactions (one with headache, two with pedal oedema, eight with other problems); 11 (7%) had nondrug-related problems; and in four (2%), the drugs were ineffective. Based on these observations, isradipine is a well-tolerated, safe and effective agent for long-term BP control in elderly patients with essential hypertension.",1994.0,0,0
712,7887361,,,,,0,0
713,7894213,Morning versus evening administration of nifedipine gastrointestinal therapeutic system in the management of essential hypertension.,P Greminger; P M Suter; D Holm; R Kobelt; W Vetter,"The nifedipine gastrointestinal therapeutic system (GITS) is a recently developed controlled-release formulation for once-a-day dosing. We evaluated the influence of morning versus evening administration of the drug in a randomized double-blind cross-over study including 15 essential hypertensives. Five patients had to be excluded from blood pressure analysis because of noncompliance (three cases) or intolerable side effects (two cases). To assess the exact duration of the antihypertensive efficacy noninvasive automatic ambulatory blood pressure monitoring was performed. After a placebo period patients were given 30 mg nifedipine GITS either at 1000 or 2200 hours. Twenty-four-hours systolic and diastolic blood pressure profiles documented a sustained antihypertensive effect of both nifedipine regimens throughout the whole period without affecting the circadian rhythm. Statistical analysis revealed no significant difference between morning and evening administration. Two patients stopped their medication because of intolerable side effects (fatigue and muscle cramps, respectively). Two more cases suffered from mild reversible headache which provoked no discontinuation of the drug. In conclusion our results document a sustained antihypertensive efficacy of 30 mg nifedipine GITS in patients with moderate essential hypertension. Time of administration has no impact on day- and nighttime blood pressure control.",1994.0,0,0
714,7900385,[Use of isoptin SR-240 in treatment of hypertension].,K Knypl; E Brym; J Wacławek-Maczkowska,"The effectiveness of hypotensive action and tolerance of Isoptin SR-240 were studied in 20 patients with primary arterial hypertension. The drug was used in doses 240-360 mg daily (mean dose 324 mg daily). Blood pressure returned to normal values in 12 (60%) out of 20 patients. In the remaining eight cases no blood pressure normalization was achieved. Side effects occurred in five patients. General worsening of wellbeing and easy tiring were most frequently observed. The results of the present work indicate that Isoptin SR-240 is an effective hypotensive drug, useful in the treatment of mild and moderate arterial hypertension.",1993.0,0,0
715,7903069,Atrial fibrillation and atrial flutter.,D R Geraets; M G Kienzle,"The epidemiology, pathophysiology, diagnosis, evaluation, and treatment of atrial fibrillation (AF) and atrial flutter (AFl) are reviewed, and recent developments and controversies in the approach to these arrhythmias are addressed. AF and AFl are the arrhythmias most frequently encountered in clinical practice. Although occasionally unaware of their arrhythmia, patients usually complain of palpitations, weakness, dyspnea, and decreased exercise tolerance. The initial goal of therapy is control of the ventricular rate. Rate control is accomplished with atrioventricular node-blocking agents such as digoxin, calcium-channel blockers, or beta-adrenergic blockers. Along with a rapid, irregular ventricular response, other detrimental outcomes of AF and AFl include compromised hemodynamics and increased vulnerability to thromboembolism. After the cause of the patient's arrhythmia has been evaluated, pharmacologic treatment is directed at converting the rhythm to normal sinus rhythm and maintaining it. Antiarrhythmic drugs have proved effective in about 50% of cases but may be associated with increased mortality. More effective and safer forms of drug therapy for AF and AFl are needed. Nonpharmacologic alternatives to antiarrhythmic medications for refractory AF and AFl include radio-frequency catheter ablation of the bundle of His with pacemaker placement and surgery. Patients who remain in AF despite therapy should receive long-term warfarin treatment. Drugs may be used to control the ventricular response in patients with AF and AFl, terminate and prevent the arrhythmias, and prevent thromboembolism. Nonpharmacologic treatments are reserved for patients whose arrhythmias are poorly controlled by drugs.",1993.0,0,0
716,7905413,"Pharmacokinetics and additional anti-ischaemic effectiveness of amlodipine, a once-daily calcium antagonist, during acute and long-term therapy of stable angina pectoris in patients pre-treated with a beta-blocker.",G Lehmann; G Reiniger; A Beyerle; W Rudolph,"Amlodipine 10 mg was evaluated for additional anti-ischaemic and anti-anginal efficacy in 14 patients pre-treated with a beta-blocker who had documented coronary artery disease, stable angina pectoris, and > or = 2 mm of exercise-induced ST segment depression. For 2 days the patients received open-label amlodipine and then, according to a randomized, placebo-controlled, cross-over and double-blind protocol, they were treated with amlodipine or placebo, respectively, once a day for 3 weeks each. Exercise tests and blood sampling for plasma concentrations of amlodipine were performed at 8 and at 24 h after dosing on both days of acute testing as well as on day 18 of chronic treatment. During chronic treatment, when plasma concentrations fluctuated between 23.5 ng.ml-1 at 8 h and 14 ng.ml-1 at 24 h post-dosing, ST segment depression at an individually comparable workload was significantly decreased by 28% compared with placebo (P < 0.005) at both points in time. Increases in ischaemia-free workload capacity amounted to 76% (P < 0.005) and to 81% (P < 0.01) at 8 and at 24 h, respectively. The number of anginal attacks was reduced by 39% (P < 0.05). Conversely, after initial dosing, i.e. when plasma concentrations declined from 4.7 ng.ml-1 to 3.9 ng.ml-1, influences upon ischaemic parameters compared to control values were markedly less at 24 h as opposed to 8 h. There were no untoward side effects observed at any point in time.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,1
717,7908691,Clinical and pharmacologic study of multidrug resistance reversal with vinblastine and bepridil.,S C Linn; C K van Kalken; O van Tellingen; P van der Valk; C J van Groeningen; C M Kuiper; H M Pinedo; G Giaccone,"To achieve an adequate plasma concentration of bepridil, a calcium channel blocker, which reverts multidrug resistance (MDR) in vitro, when administered in combination with vinblastine in patients with advanced colorectal cancer, a tumor characterized by high MDR1 gene expression. To study the pharmacokinetics of both drugs, tolerability and antitumor activity in relation to the MDR1 expression in tumor tissue. Sixteen colorectal cancer patients entered the study. Bepridil was administered by central venous catheter as 5-mg/kg bolus over 30 minutes, followed by 12 mg/kg for 12 hours and 5 mg/kg for 24 hours. Vinblastine 5 mg/m2 was administered as an intravenous (i.v.) bolus 24.5 hours after the start of bepridil. MDR1/P-glycoprotein (Pgp) expression was assessed in 14 tumor samples by immunohistochemistry and RNase protection assay. The bepridil plasma level was greater than 2 mumol/L at the time of vinblastine administration in all patients investigated. At the dose used in the study, bepridil produced a QTc-prolongation more than 50 ms, which prevented further dose escalation. However, cardiac toxicity was asymptomatic in all treated patients, and other side effects were mild. MDR1/Pgp expression was positive in nine of 14 cases. Of fifteen patients assessable for response, one complete remission of 8 months' duration and 14 progressions were observed. The responding patient attained complete remission again when re-treated on progression with vinblastine alone. Bepridil plasma concentrations needed in vitro to modulate MDR could be achieved in this study with tolerable toxicity; however, despite most tumors being MDR1/Pgp-positive, no response was obtained that could be attributed to the drug combination. Mechanisms of drug resistance other than MDR are probably implicated in drug resistance of colorectal cancer.",1994.0,0,0
718,7909677,Calcium channel blocking drug overdose: an Australian series.,D M Howarth; A H Dawson; A J Smith; N Buckley; I M Whyte,"1. A descriptive case study of calcium channel-blocking drug (CCB) overdoses in the Hunter Region of NSW was performed to analyse the in-hospital morbidity and mortality of CCB drug overdoses in an Australian population. 2. The patients were admitted to major hospitals within the Hunter Region and treated initially with gastrointestinal decontamination, including the use of oral activated charcoal. Further management was required in most cases and included intravenous calcium, atropine and inotropic support. 3. Of the 15 CCB overdoses, four patients died. Noncardiogenic pulmonary oedema occurred in two other cases. Cardiac conduction defects occurred in 11 cases. 4. Atropine was found to be effective only after intravenous calcium had been administered. 5. Overdose with slow-release verapamil required prolonged treatment with intravenous calcium salts. 6. Overdose with verapamil or diltiazem in doses greater than 300 mg carries a significant risk of death and potentially life threatening arrhythmias occur with lower doses. 7. Recommended initial management includes early, effective gastrointestinal decontamination. High dose intravenous calcium salts should be given to reverse hypotension and bradycardia. Atropine and inotropic support are frequently required.",1994.0,0,0
719,7911271,Antianginal and anti-ischemic efficacy of immediate-release nisoldipine in chronic stable angina pectoris.,S P Glasser; N Bittar; D G Labreche; B Singh; R Katz; P Schulman,"A double-blind, randomized, placebo-controlled, crossover study tested peak and trough efficacy of immediate-release nisoldipine (20 mg twice daily) added to existent beta-adrenergic blocking therapy. Patients were randomized with a history of chronic stable angina, while receiving a stable regimen of a beta-blocking agent, with exercise test-induced angina in association with 1 mm horizontal or downsloping ST-segment depression and exercise test reproducibility of +/- 15%. Ambulatory electrocardiographic monitoring (48-hour) was performed at 3 of 5 centers (44 patients). Efficacy was achieved in 53 patients (26 taking immediate-release nisoldipine/placebo in sequence and 27 taking placebo/immediate-release nisoldipine in sequence). Total exercise time increased compared with placebo at peak, but only a trend was seen at trough. Time to 1 mm ST-segment depression at peak and trough and ambulatory electrocardiographic parameters were also improved. Adverse effects were mild. This trial confirms that immediate-release nisoldipine when added to existent beta-blocker therapy is an active antianginal and anti-ischemic agent, but that the immediate-release formulation loses its antianginal effect at the end of its dosing interval (9 to 14 hours). This drug is therefore being examined in a new extended-release formulation (Coat-Core).",1994.0,0,1
720,7915067,[Anti-ischemia effects of gallopamil and esmolol in an intra-individual comparison in patients with coronary heart disease].,V Mitrovic; E Oehm; C Minge; P Thürmann; M Schlepper,"To compare the hemodynamic, antiischemic, metabolic, and neurohumoral effects of intravenous esmolol (beta 1 blocking agent) and gallopamil (verapamil-like calcium channel blocker), 14 patients with angiographically proven CAD and reproducible ST segment depression were studied at rest and during exercise under control conditions and after an intravenous bolus injection of esmolol (0.5 mg/kg/1 min, followed by an infusion with 0.2 mg/kg/min) or gallopamil (0.025 mg/kg/3 min). In contrast to gallopamil, esmolol significantly reduced systolic blood pressure (175.7 vs. 160 mm Hg) and heart rate (107.4 vs. 96.9 min-1) during exercise as well as cardiac output (11.57 vs. 9.38 l/min) and significantly enhanced systemic vascular resistance both at rest (1241 vs. 1479 dynes.s.cm-5) and during exercise (805 vs. 947 dynes.s.cm-5). On the other hand, exercise filling pressures and lactate levels (3.66 vs. 3.05 mmol/l) were significantly reduced by gallopamil only. Thus, the significant improvement of exercise tolerance by both esmolol and gallopamil is based on different mechanisms of action: esmolol improves myocardial ischemia by appreciably reducing myocardial oxygen consumption, whereas gallopamil primarily improves oxygen supply and ventricular performance. Plasma catecholamines, atrial natriuretic factor, and aldosterone levels as well as plasma renin activity were identically influenced by esmolol and gallopamil, respectively. A reflex activation of the sympathetic system did not occur.",1994.0,0,0
721,7917158,"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
722,7923305,,,,,0,0
723,7925519,Duration and extent of antianginal effects of a sustained-release formulation of nifedipine in angina.,M Yokota; F Saito; H Izawa; T Matsunami; J Yoshida; H Inagaki; I Sotobata,"Twenty-four patients with chronic stable exertional angina pectoris were randomized in a double-blind, placebo-controlled, crossover trial to assess the efficacy and durability of a newly developed, sustained-release formulation of nifedipine (nifedipine CC) in a single 40-mg oral dose. Symptom-limited graded treadmill exercise tests were performed just before, and at 4, 7, and 24 h after a single administration of the drug or the placebo was given. Exercise tolerance at 4, 7, and 24 h after the drug were compared with the corresponding placebo values. Data could be analysed for 19 patients. Maximal exercise time, time to the onset of angina, and time to 1 mm ST segment placebo. The average maximal exercise time was significantly increased by 72, 76, and 37 s at 4, 7, and 24 h. Rate-pressure product at rest and at peak exercise showed significant changes only at 24 h compared with placebo (both P < 0.05). The maximal increase in exercise tolerance was most marked at 7 h nifedipine CC, at which time plasma drug concentration was 99.4 +/- 14.0 ng.ml-1. Thus, in patients with chronic stable exertional angina pectoris, nifedipine CC showed a prolonged improvement in exercise tolerance up to 24 h after a single oral administration.",1994.0,0,1
724,7932518,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
725,7940807,Long-term protective effect of a calcium antagonist on renal function in hypertensive renal transplant patients on cyclosporine therapy: a 5-year prospective randomized study.,J M Morales; E Rodriguez-Paternina; A Araque; A Andres; E Hernandez; L M Ruilope; J L Rodicio,,1994.0,0,1
726,7941918,A comparative study of long acting diltiazem (Tildiem LA) with sustained release nifedipine (nifedipine SR) and bendrofluazide in the treatment of mild to moderate hypertension.,J Hosie; M A Nasar; G P Belgrave; E G Walters,"The therapeutic efficacy of long acting diltiazem 300 mg od (Tildiem LA) was compared with sustained release nifedipine 20 mg bd and bendrofluazide 5 mg od in a multicentre study with 230 patients diagnosed with mild to moderate essential hypertension, with 77, 77 and 76 randomized to the diltiazem, nifedipine SR and bendrofluazide groups respectively. Patients were entered into this randomised, single (investigator) blind, parallel-group multicentre study if the systolic and diastolic blood pressures were > or = 145 mm Hg and/or 95 mm Hg respectively at the admission visit. Twenty-one general practitioners and two hospital physicians monitored patients at baseline and at four and eight weeks of continuous dosing. After eight weeks of therapy, clinically acceptable control of blood pressure was seen in all groups: reductions were 19.2/13.5 mm Hg, 20.4/14 mm Hg and 18.5/10.8 mm Hg for the Tildiem, nifedipine and bendrofluazide groups respectively. Significant differences were shown between bendrofluazide and the other two groups on diastolic pressures (p = 0.01). The non-significant trend was for systolic pressures to mirror these effects. Significantly higher withdrawals caused by adverse events were seen with nifedipine. These were as follows: 14 patients receiving nifedipine (18%), 5 patients receiving diltiazem (6%) and 4 patients receiving bendrofluazide (5%). The difference in this withdrawal rate between treatments was statistically significant (p = 0.01). Post hoc tests revealed that both diltiazem and bendrofluazide had statistically significant lower withdrawals for adverse events than the nifedipine group (p = 0.047). Nifedipine was associated with a marginal increase in standing apex pulse rate and only diltiazem LA significantly maintained serum potassium levels. These results indicate that diltiazem 300 mg is an effective antihypertensive agent and is equivalent in efficacy to nifedipine SR 20 mg and both are superior to bendrofluazide. Nifedipine SR was however the worst tolerated and had the highest withdrawal rate (p = 0.013).",1994.0,0,0
727,7942536,Effects of intracoronary felodipine versus nifedipine on left ventricular contractility and coronary sinus blood flow in stable angina pectoris.,J J Koolen; H B Van Wezel; J Piek; R van Liebergen; A Swaan; C A Visser,,1994.0,0,0
728,7944997,[Inefficacy of diltiazem in restenosis prevention after coronary angioplasty].,L F Tanajura; A G Sousa; F Feres; T Atallah; I M Pinto; M P Centemero; A J Chaves; L A Mattos; H C Martins; R L Abud,"To evaluate the efficacy of diltiazem in preventing restenosis after balloon angioplasty (PTCA). Eighty-nine patients who were undergone to successful PTCA, were divided them in 2 groups (G): A) 44 patients (50%) who received diltiazem (180 mg tid) immediately after PTCA and were kept on it for 6 months); B) 45 patients (50%) who received placebo. Fifty two lesions were dilated in GA and 54 in GB. Patients were excluded from analysis for several reasons, including: necessity of diltiazem or others calcium channel blockers use; heart failure, bradicardia, AV block of any degree, PTCA to chronic total occlusion, ostial lesions and AMI less than 30 days prior to PTCA. Patients were randomized to either the active drug or placebo in a double blind fashion. Restenosis was defined as a 50% lesion. Patients underwent late angiography either at 6 months or sooner if clinically indicated. Both G were similar to age > 70 years (A = 7% vs B = 4%-p = NS), sex (A = 13% vs B = 11%-p = NS), stable angina (A = 43% vs B = 51%), unstable angina (A = 57% vs B = 49%-p = NS) and single vessel (A = 91% vs B = 87%-p = NS) or multivessel (A = 9% vs B = 13%-p = NS) PTCA. We studied 39/44 (89%) patients in GA and 43/45 (96%) in GB (p = NS). We observed restenosis in 17/39 (43%) in GA and 16/43 (37%) in GB (p = NS). The restenosis rate per lesion was 39% in GA and 31% in GB (p = NS). Diltiazem was ineffective in the prevention of restenosis following PTCA.",1994.0,0,0
729,7946164,A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension.,J M Neutel; D H Smith; D Wallin; E Cook; C V Ram; E Fletcher; K E Maher; P Turlepaty; S Grandy; R Lee,"The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside (SNP) in patients with severe hypertension. The study was conducted in 121 patients with severe hypertension (diastolic blood pressure [BP] > 120 mm Hg, or systolic BP > 200 mm Hg). Patients were randomized to receive intravenous nicardipine or SNP. Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period. Sixty-one patients were randomized to intravenous nicardipine and 60 to SNP. Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg, respectively. Therapeutic response (diastolic BP < 100 mm Hg, or a decrease of > 15 mm Hg; systolic BP < 180 mm Hg, or a decrease of > 20 mm Hg) was achieved in 98% (60/61) of patients treated with nicardipine and 93% (56/60) of patients treated with SNP. The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine, and 59 mm Hg and 38 mm Hg after 4 h of SNP. The mean increases in heart rate also were similar in both groups (nicardipine, 12 beats/min; SNP 10 beats/min). The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower (P < .01) in the nicardipine-treated patients (0.5 +/- 0.1 times per hour) than in the SNP-treated patients (1.5 +/- 0.2 times per hour).(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
730,7954234,A phase I trial of intrahepatic verapamil and doxorubicin. Regional therapy to overcome multidrug resistance.,L Saltz; B Murphy; N Kemeny; J Bertino; W Tong; D Keefe; Y Tzy-Jun; Y Tao; D Kelsen; J P O'Brien,"Verapamil can modulate multidrug resistance in vitro, but only at levels that are not tolerable when administered systemically. Regional strategies of drug administration may permit the delivery of high concentrations of a drug to specific areas with lower systemic levels. Colorectal cancers typically express the multidrug resistance phenotype. A Phase I trial was performed to determine the maximum tolerable dose (MTD) and dose limiting toxicities of verapamil by hepatic artery infusion, together with doxorubicin, to patients with hepatic metastases of colorectal cancer. Fourteen patients with metastatic colorectal cancer received a 14-hour intrahepatic infusion of verapamil. Six hours after the start of the infusion, a fixed dose of doxorubicin (50 mg/m2) was given, also via the hepatic artery, over a 30-minute period. Patients were followed by cardiac telemetry but were not in an intensive care setting, and no invasive monitoring was used. All patients had received prior intrahepatic chemotherapy. The MTD of intrahepatic verapamil on this schedule in this patient population was 1.2 mg/kg/hour. Hypotension was the dose limiting toxicity. No major objective responses were noted in this heavily pretreated patient population. A dose of 1.0 mg/kg/hour is recommended for Phase II trials. Based on estimations of normal hepatic artery blood flow, the estimated concentration of verapamil delivered to the hepatic tumors at 1.0 mg/kg/hour is 3.6 micrograms/ml (7.3 microM), which is comparable to concentrations at which an in vitro reversal of MDR is seen. This study demonstrates that the systemic toxicities of an MDR reversal agent can be overcome by regional drug delivery, establishing this approach as an important model system for further study of MDR modulation.",1994.0,0,0
731,7956631,The effects of enalapril and nifedipine on carbohydrate and lipid metabolism in NIDDM.,J C Chan; V T Yeung; D H Leung; B Tomlinson; M G Nicholls; C S Cockram,"To compare the effects of nifedipine and enalapril on carbohydrate and lipoprotein metabolism in Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. A 12-week, double-blind, randomized study of plasma lipid levels and glycemic control in patients treated with nifedipine (n = 52) or enalapril (n = 50) was conducted. None of the patients were treated with insulin. Diet and dosages of oral hypoglycemic agents remained unchanged during the 12-week treatment period. Mean arterial pressure was reduced more by nifedipine than by enalapril (23.1 vs. 11.1 mmHg, P < 0.001). Similar reductions in body mass index and plasma triglycerides and increases in apolipoprotein A-I were seen with both treatments, but HbA1 was reduced more during treatment with enalapril than with nifedipine (0.49 vs. 0.20%, P = 0.035) and serum apolipoprotein B (apoB) also declined more with enalapril than with nifedipine (8.2 vs. 2.3 mg/dl, P = 0.009). Twelve weeks of treatment with enalapril in hypertensive NIDDM patients was associated with greater improvement in glycemic control and greater reduction in serum apoB concentration, although the reduction in blood pressure was less than with nifedipine. These changes in cardiovascular risk profile warrant investigation for a longer term.",1994.0,0,0
732,7968872,[Does long-term blood pressure reduction in patients with essential hypertension improve concomitant metabolic disorders?].,H Hauner; C Meissner,"Aim of this study was to investigate the occurrence of metabolic abnormalities in patients with newly diagnosed essential hypertension and to assess the effects of a blood pressure lowering drug therapy on the respective variables. Twenty-six hypertensive subjects (12 female, 14 male) were included in the study. Twenty-one normotensive subjects (9 female, 12 male) served as a control group. During an oral glucose tolerance test the hypertensive subjects had higher blood glucose and serum insulin levels than the controls. The hypertensive patients also showed higher triglyceride concentrations and a more abdominal pattern of body fat distribution. In addition, the women with essential hypertension exhibited a higher free androgen index (32.2 +/- 14.8 vs 20.1 +/- 15.0%, p < 0.05) than the women of the control group. After a 3 to 6 month treatment period with nifedipine or nitrendipine the elevated blood pressure of the hypertensives was significantly reduced. In a second glucose tolerance test carried out in 13 patients blood glucose, serum insulin and triglyceride concentrations were significantly lower compared to the pretreatment period. The other metabolic and hormonal variables remained unchanged. This observation raises the question, whether a long-term vasodilatating antihypertensive therapy can improve the metabolic abnormalities found in patients with essential hypertension.",2000.0,0,0
733,7977065,Efficacy of metoprolol and diltiazem in treating silent myocardial ischemia.,M C Portegies; P Sijbring; E J Göbel; J W Viersma; K I Lie,"Recent studies strongly support the prognostic importance of transient silent ischemia. Because patients with silent ischemia are at higher risk of a cardiac event, they are likely to benefit not only from control of symptoms, but also from treatment directed at prevention of ischemia. The efficacy of controlled-release metoprolol 200 mg once daily and diltiazem 60 mg 4 times daily was assessed in a randomized, double-blind, crossover study in 32 patients with proven coronary artery disease, predominantly asymptomatic myocardial ischemia, positive bicycle exercise test results, and > or = 5 minutes of asymptomatic ST-segment depression on a 24-hour screening ambulatory electrocardiogram (ECG). At the beginning and at the end of both 3-week treatment periods, an exercise test was performed and a 72-hour ambulatory ECG was recorded. Both active treatment periods were preceded by a 2-week placebo phase. Both treatments effectively reduced and postponed exercise-induced ST depression and reduced the total ischemic integral on the ambulatory ECG. Only metoprolol significantly reduced the mean number of ischemic episodes (54%, p = 0.0003, vs 31% for diltiazem, p = NS) and the mean duration of ischemia (51%, p = 0.012, vs 27% for diltiazem, p = NS) compared with baseline values. Metoprolol strongly blunted the morning and afternoon peak in the circadian distribution of ischemia, whereas diltiazem did not change the circadian distribution of ischemia at all.",1994.0,0,1
734,7977090,Comparison between felodipine and isosorbide mononitrate as adjunct to beta blockade in patients > 65 years of age with angina pectoris.,R J de Vries; P H Dunselman; D J van Veldhuisen; A F van den Heuvel; R P Wielenga; K I Lie,"Coronary artery disease is an increasingly common medical problem in the elderly, and relatively few studies investigating drug therapy focus on this population. To assess the efficacy and safety of the calcium channel blocker, felodipine, and isosorbide mononitrate (ISMN), as adjunct to optimal beta-blocker therapy in elderly patients, a placebo-controlled, double-blind study was conducted in 46 patients, aged between 65 and 80 years, with documented stress-induced angina pectoris and myocardial ischemia. With use of a latin-square design, with 3 periods of 4 weeks each, exercise testing was performed after each period. Felodipine, 5 mg once daily, significantly improved both time to ischemic threshold and pain threshold (p = 0.02 and p = 0.003, respectively, vs placebo), and tended to increase total exercise time (p = 0.06 vs placebo). In contrast, ISMN, 20 mg twice daily, did not significantly affect these parameters. Comparison of the 2 active treatment arms showed that, overall, felodipine was more effective than ISMN, with a statistically significant difference for time to ischemic threshold (p = 0.02). With regard to safety, felodipine was also better tolerated than ISMN, which led to more patients discontinuing study medication with ISMN (p < 0.05 between ISMN and felodipine). It is concluded that in elderly patients who are treated with optimal beta blockade, felodipine, but not ISMN, leads to an additional significant reduction in ischemic parameters during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
735,7977118,Intravenous diltiazem for the treatment of patients with atrial fibrillation or flutter and moderate to severe congestive heart failure.,I F Goldenberg; W R Lewis; V C Dias; J T Heywood; W R Pedersen,"The objective of this multicenter, randomized, double-blind, placebo-controlled study was to determine the safety and efficacy of intravenous diltiazem in the treatment of 37 patients with rapid (ventricular rate, mean +/- SD 142 +/- 17 beats/min) atrial fibrillation or flutter and moderate to severe congestive heart failure (ejection fraction, mean +/- SD 36 +/- 14%; New York Heart Association class III [23 patients], class IV [14 patients]). During the double-blind portion of the study, patients received either intravenous diltiazem, 0.25 mg/kg over 2 minutes, or placebo followed 15 minutes later by diltiazem or placebo, 0.35 mg/kg over 2 minutes, if the first dose was tolerated but ineffective. Placebo nonresponders were given open-label intravenous diltiazem in a similar fashion as in the double-blind portion of the study. In the double-blind part of the study, 21 (18 with 0.25 mg/kg, 3 with an additional 0.35 mg/kg) of the 22 patients (95%) responded to diltiazem, and 0 of 15 patients (0%) responded to placebo (p < 0.001). All 15 patients (13 with 0.25 mg/kg and 2 with an additional 0.35 mg/kg) who received placebo during the double-blind period had a therapeutic response to diltiazem during open-label therapy. Overall, 36 of 37 patients (97%) had a therapeutic response to intravenous diltiazem. Heart rate response to diltiazem after the 2-minute bolus infusions consisted of a > or = 20% decrease in heart rate from baseline in 36 patients; in addition, 17 patients also had heart rates decreased to < 100 beats/min, whereas no patient had conversion to sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
736,7980076,[Comparative and double-blind study of the efficacy and safety of cilazapril compared to nifedipine retard in the treatment of mild and moderate arterial hypertension].,I F Velasco-Cornejo; D Mion Júnior; L C Martin; T Tinucci; M Sampaio; I J Pascoal; R C Athanázio-Heliodoro; M Marcondes; R J Franco,"To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmHg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 +/- 14/103 +/- 5 - nifedipine 157 +/- 17/108 +/- 7mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 +/- 9 - nifedipine 96 +/- 11mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no difference inter groups. BP normalization was obtained in 58% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. Cilazapril 2.5 to 25mg normalized BP in 58% of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects.",1994.0,0,0
737,7982251,Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension.,T C Fagan; B E Haggert; C Liss,"The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild-to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once-daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension.",1994.0,0,0
738,7982252,"A large, prospective, open-label study of isradipine in patients with essential hypertension. The Isradipine Investigators Group.",R J Weiss,"Isradipine is a dihydropyridine calcium-entry blocker. Previous controlled and blinded trials have demonstrated the safety and efficacy of isradipine in lowering blood pressure in patients with hypertension. The purpose of this study was to reassess this safety and efficacy in a large number of patients in an open-label, long-term, multicenter trial. A total of 501 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) received 5 to 10 mg/d of isradipine in two divided doses for a period of 32 weeks. The mean dose used was 7.4 mg/d with titration at week 4 from 5 mg/d (2.5 mg BID) to 10 mg/d (5 mg BID) if the diastolic pressure was still > 90 mm Hg. After 32 weeks of isradipine treatment, systolic blood pressure decreased from 154.9 +/- 16.4 mm Hg to 140.2 +/- 13.9 mm Hg (P < 0.001) and diastolic pressure from 101.2 +/- 5.2 mm Hg to 86.6 +/- 7.9 mm Hg (P < 0.001). This monotherapy was successful in reducing diastolic blood pressure > 10 mm Hg in 62.5% of the patients. Significant adverse effects were noted in 92 (18.4%) of the 501 patients; only 30 (6.0%) withdrew from the study because of adverse events. In this large, long-term, community-based study, isradipine was effective and well tolerated in most patients.",1994.0,0,0
739,7983235,Controlled study with a new sustained-release formulation of nifedipine in essential hypertensive patients.,F Galletti; G Barba; A Nardecchia; P Strazzullo; P Scagliusi; A Pirrelli; M Mancini,"The authors studied the antihypertensive effect and tolerability of a new sustained-release formulation of nifedipine 50 mg once a day, in comparison with nifedipine retard 20 mg twice a day in patients with mild or moderate primary arterial hypertension. Both treatments significantly lowered blood pressure with no difference in daily blood pressure profile. At steady state, the two drugs determined comparable plasma levels of nifedipine as measured immediately before the morning dose. After a 12-month treatment, the new formulation of nifedipine still displayed satisfactory blood pressure control in both supine and standing positions, with no change in tolerability throughout the study. In conclusion, this new sustained-release formulation of nifedipine has similar efficacy and tolerability to conventional treatment with nifedipine retard 20 mg twice a day.",1994.0,0,0
740,7986459,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
741,7988629,Conventional and controlled release diltiazem. Bioavailability in healthy volunteers and anti-anginal effects in combination with metoprolol in stable angina pectoris.,L Brorson; A Arvill; P Löfdahl; E Jörgensen; T Fraser; H Larsson; A M Olsson; S O Olsson,"Diltiazem CR tablets 120 mg b.i.d. for 1 week were compared with plain tablets 60 mg q.i.d. in 13 healthy male volunteers in a study of pharmacokinetic variables. Their antianginal efficacy was also compared in 23 patients with stable angina pectoris who were already on metoprolol. Both studies were of randomised, cross over design, and the clinical study was double blind. The pharmacokinetic variables of the two formulations were very similar except for the longer tmax of 4.4 h for diltiazem CR in comparison to 2.9 h for the plain tablets. The mean relative bioavailability of diltiazem CR in comparison with plain tablets was 1.14. The clinical study showed that after four weeks on diltiazem CR 120 mg b.i.d. or diltiazem plain tablets 60 mg q.i.d. in addition to metoprolol, there were significant decreases in weekly anginal attacks from 11 to 5 attacks/week, the number of nitroglycerin tablets consumed from 6 to 3 tablets/week, and an increase in the maximum workload from 116 to 126 and 123 W for diltiazem CR and plain diltiazem tablets, respectively, as compared to placebo. Five of the patients were angina free during diltiazem treatment. No difference in anti-anginal efficacy between the two preparations was seen. It was concluded that CR 120 mg b.i.d. appears bioequivalent to plain diltiazem tablets 60 mg q.i.d.",1994.0,0,0
742,7995312,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
743,7998047,[Lisinopril and nifedipine have neutral effects on lipids].,K Gisholt; B Bratland; B Dahlöf; I Os; J O Syvertsen; S Tretli,"In a randomized, double blind, parallel-group, multicentre study in Norway, 97 patients with mild to moderate hypertension (mean blood pressure 159/104 mm Hg) were treated with either lisinopril 10-40 mg or nifedipine 20-80 mg and the effects on blood lipids were evaluated. Complete results of laboratory analyses are given for 80 patients. After a 4 week run-in and placebo period, antihypertensive treatment was given for the next 10 weeks. During treatment with lisinopril the changes in lipids were +2.1% for total cholesterol, +0.7% for HDL-cholesterol, +3.8% for triglycerides and -6.1% for ratio HDL/cholesterol-HDL. For nifedipine the corresponding values were -2.4% for cholesterol, -5.8% for HDL-cholesterol, +8.0% for triglycerides and +3.2% for ratio. None of these changes was statistically significant. Both lisinopril and nifedipine lowered the blood pressure significantly, 18.1/12.0 mm Hg with lisonopril (p < 0.01 for both systolic and diastolic pressure) and 8.0/8.5 mm Hg with nifedipine (p < 0.01 for both respectively). Both drugs were well tolerated. In conclusion, neither lisinopril nor nifedipine had any negative impact on lipid levels.",1994.0,0,0
744,8004839,Double-blind comparison of amlodipine and hydrochlorothiazide in patients with mild to moderate hypertension.,C V Ram; R P Ames; W B Applegate; J F Burris; M E Davidov; W J Mroczek,"In the final analysis of this study at Week 26, 26% of the patients randomized to receive amlodipine attained blood pressure control with amlodipine alone compared with 33% of the patients allocated to hydrochlorothiazide (HCTZ). Neither amlodipine nor HCTZ produced clinically significant changes in pulse rate or in the electrocardiogram. Amlodipine treatment did not appear to produce clinically significant changes in blood lipids; HCTZ, however, produced an increase in total plasma cholesterol (delta 22.9 +/- 8.6 mg/dl). The incidence of side effects and the rate of patient withdrawal in the amlodipine and HCTZ groups were comparable. As expected, HCTZ therapy caused well-recognized biochemical alterations in cholesterol and potassium levels, whereas amlodipine was metabolically neutral.",1994.0,0,0
745,8005121,Antihypertensive efficacy and tolerability of different drug regimens in isolated systolic hypertension in the elderly.,F Avanzini; C Alli; G Bettelli; R Corso; F Colombo; G Mariotti; M Radice; V Torri; G Tognoni,"The pharmacological treatment, mainly based on diuretics, of isolated systolic hypertension (ISH) has recently been shown to reduce the risk of stroke and coronary heart disease in the elderly. The purpose of this study was to compare the antihypertensive effect and tolerability of different drug regimens in elderly subjects with ISH (systolic blood pressure--SBP-- > or = 160 mmHg and diastolic blood pressure--DBP-- < 90 mmHg). A multicentre, randomized, controlled open trial was planned in the general practice setting. Four widely used treatment schedules were tested: hydrochlorothiazide 25 mg plus amiloride 2.5 mg (H+Am), nifedipine slow release 20 mg (N), atenolol 50 mg (At) and atenolol 25 mg plus chlorthalidone 6.25 mg (At+C). After a baseline evaluation, 308 patients (76.3% female, mean age 75.3 +/- 7.1 years) were randomized and followed up for 6 months. After 3 months the drug dosage was doubled if the systolic blood pressure goal (SBP < 160 mmHg and SBP reduction of at least 20 mmHg) had not been reached. Ninety-four subjects (30.5%) presented contraindications to beta-blockers. At the 3rd- and 6th-month visits all treatment groups, except At, showed a significant reduction in SBP compared to the control group; DBP showed no significant reduction in any group at any time. At the end of the follow-up the percentage of hypertensives who had reached the BP goal was 14.6% in the control group, 52.9% in H+Am, 54.8% in N, 28.6% in At and 52.2% in At+C.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
746,8005130,The prognostic significance of post-infarction angina pectoris and the effect of verapamil on the incidence of angina pectoris and prognosis. The Danish Study Group on Verapamil in Myocardial Infarction.,C M Jespersen; J F Hansen; L S Mortensen,"The prognostic significance of angina pectoris and the effect of intervention with verapamil on the incidence of angina pectoris were studied in patients recovering from myocardial infarction and included in the Danish Verapamil Infarction Trial II. During the second week after admission patients were doubly-blindly randomized to treatment with verapamil 360 mg.day-1 or placebo. Treatment was continued for up to 18 months. At discharge angina pectoris was reported in 11% of 869 patients randomized to verapamil and in 12% of 888 randomized to placebo (ns). One month after discharge a significant increase in the prevalance of angina pectoris was reported in both the verapamil (33%) (P < 0.001) and the placebo groups (39%) (P < 0.001). The one month prevalence of angina pectoris (P = 0.03) and the 18 months overall incidence of angina pectoris (P = 0.002) were both significantly lower in the verapamil group compared with placebo. Stable angina pectoris during the first month of follow-up was a significant predictor of major events (i.e. death or reinfarction) (hazard ratio = 1.45; 95% confidence limits: 1.10, 1.89). As verapamil significantly reduced the incidence of angina pectoris during daily activities, and thereby the number of patients at high risk, the beneficial effect of verapamil in reducing major events in patients recovering from myocardial infarction is likely to be due to abolishing myocardial ischaemia.",1994.0,0,0
747,8006249,"The Asymptomatic Cardiac Ischemia Pilot (ACIP) study: design of a randomized clinical trial, baseline data and implications for a long-term outcome trial.",C J Pepine; N L Geller; G L Knatterud; M G Bourassa; B R Chaitman; R F Davies; P Day; J E Deanfield; A D Goldberg; R P McMahon,"The primary objectives of the Asymptomatic Cardiac Ischemia Pilot were 1) to compare the 12-week efficacy of three treatment strategies to suppress cardiac ischemia, and 2) to assess the feasibility of a prognosis trial in patients with asymptomatic cardiac ischemia. Cardiac ischemia has been associated with increased morbidity and mortality. However, most cardiac ischemia is asymptomatic, and although therapeutic strategies ranging from no medication to revascularization are being used to treat ischemia, no prospective study evaluating different treatment strategies has been reported. Patients with angiographically documented coronary artery disease and ischemia on exercise and ambulatory electrocardiogram (ECG) in 11 clinical units were randomized to receive angina-guided medical therapy, angina-guided plus ambulatory ECG ischemia-guided medical therapy or revascularization (coronary angioplasty or bypass surgery). Patients were also randomized to receive either diltiazem plus isosorbide dinitrate or atenolol plus nifedipine when possible. After anti-ischemic medication adjustment to control angina, blinded medication was adjusted in the medical therapy groups to eliminate ischemia in the ischemia-guided group. The primary outcome was the absence of ischemia at 12 weeks. Follow-up was scheduled for 1 year. A total of 1,959 patients were screened by ambulatory ECG monitoring; 982 (49%) had asymptomatic ischemia, and 618 (65%) were enrolled in the study. Most patients were men, were > 60 years old and had two or more ischemic episodes, early positive exercise tests and multivessel disease. Design and baseline data for a pilot study of ischemia treatment strategies are described.",1994.0,0,0
748,8006252,Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.,G L Knatterud; M G Bourassa; C J Pepine; N L Geller; G Sopko; B R Chaitman; C Pratt; P H Stone; R F Davies; W J Rogers,"The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was initiated to determine the feasibility of a large trial in evaluating the effects of treatment of ischemia on outcome (mortality and myocardial infarction). The study was designed to examine the effects of medical treatment to control angina compared with treatment strategies guided by ambulatory electrocardiographic (ECG) ischemia or coronary anatomy. Treatments to suppress ischemia (asymptomatic and symptomatic) have not been evaluated in a large prospective, randomized trial. Before undertaking such a trial, issues about recruitment and treatment strategies must be addressed. The 618 enrolled patients had coronary artery disease suitable for revascularization, ischemia on stress test and asymptomatic ischemia on ambulatory ECG. Patients were assigned randomly to one of three treatment strategies: 1) angina-guided medical strategy with titration of anti-ischemic medication to relieve angina (angina-guided strategy); 2) angina-guided plus ambulatory ECG ischemia-guided medical strategy with titration of anti-ischemic medication to eliminate both angina and ambulatory ECG ischemia (ischemia-guided strategy); and 3) revascularization by angioplasty or bypass surgery (revascularization strategy). Ambulatory ECG ischemia was no longer present at the week 12 visit in 39% of patients assigned to the angina-guided strategy, 41% of patients assigned to the ischemia-guided strategy and 55% of patients assigned to the revascularization strategy. All strategies reduced the median number of episodes and total duration of ST segment depression during follow-up ambulatory ECG monitoring. Revascularization was the most effective strategy. Treadmill test results were concordant with those of ambulatory ECG monitoring. For most patients in the two medical strategies, angina was controlled with low to moderate doses of anti-ischemic medication, and the majority of patients (65%) in the revascularization strategy did not require medication for angina. This pilot study demonstrated that cardiac ischemia can be suppressed in 40% to 55% of patients with either low or moderate doses of medication or revascularization and that a large trial is feasible.",1994.0,0,0
749,8013763,[Comparison of nisoldipine and diltiazem in the treatment of effort angina pectoris].,L de Caprio; M Sestito; E Pandolfi; F Santamaria; A di Palma; L Lombardi; A Voza; M L De Rosa; A M Cicatiello; F Rengo,"In order to evaluate the benefits of a calcium-antagonist medium-term treatment, 20 patients with effort stable angina pectoris were treated with nisoldipine in comparison to diltiazem. Twenty patients with stable effort angina completed a double-blind, placebo controlled trial, comparing 10 twice daily nisoldipine per os and diltiazem 120 three times daily per os for 28 days. After wash-out, placebo and drug period, ergometer stress tests were performed. Exercise tolerance, angina frequency, nitrate consumption and side effects were evaluated. Our results showed that both drugs significantly increased exercise tolerance. Exercise duration was 330 +/- 107 sec after placebo, 397 +/- 106 sec after nisoldipine (p < 0.05) and 378 +/- 99 sec after diltiazem (p < 0.05). Effort angina episodes decreased from 20 after placebo to 8 after nisoldipine and diltiazem. Both drugs reduced rate-pressure product at submaximal exercise in comparison to placebo. There were no differences at peak exercise between placebo or drug periods. Both drugs similarly reduced nitrate consumption and weekly effort angina attacks. No patients referred serious side-effects. nisoldipine, like diltiazem, is an effective drug in the treatment of stable effort angina. Moreover, the therapeutic effects of nisoldipine during medium-term treatment are probably related to decrease in oxygen consumption.",1994.0,0,1
750,8017316,Dose-response evaluation of once-daily therapy with a new formulation of diltiazem for stable angina pectoris. Diltiazem CD Study Group.,U Thadani; S Glasser; N Bittar; C L Beach,"Diltiazem hydrochloride in a once-daily capsule formulation (DCD) has recently been approved in the United States for the treatment of mild to moderate hypertension and chronic stable angina pectoris. This trial evaluated the dose response of DCD in patients with chronic stable angina pectoris. In a multicenter, randomized, double-blind, parallel-design trial, the effects and tolerability of once-daily therapy with placebo or DCD (60, 120, 240, 360, or 480 mg) were evaluated 24 hours after dosing, following 3 weeks of therapy in 227 patients with reproducible stable exertional angina pectoris. A significant linear dose trend (p = 0.004) was present across the 6 treatment groups for the primary end point--time to exercise termination at 24 hours after dosing--using a standard Bruce treadmill exercise test. A significant linear dose trend was also seen for time to 1 mm ST-segment depression at 24 hours after dosing. Similar effects on exercise parameters were also seen at 4 hours after dosing. A linear dose trend (p = 0.04) was noted relative to the overall anginal attacks during daily activities and for anginal attacks during exercise (p = 0.02). Overall frequency of treatment-related adverse effects was dose-related and occurred in 24.4% and 17.5% of patients treated with DCD and placebo, respectively. At a dose up to 240 mg/day, improvement in exercise tolerance was achieved without an associated increase in the rate of treatment-related adverse events compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
751,8021331,The use of confidence intervals to describe the precision of trough/peak ratios for diltiazem CD in the treatment of hypertension.,S G Meeves; G D Park,"Once-daily diltiazem hydrochloride, CARDIZEM CD (diltiazem CD) 300 mg, was evaluated for safety, efficacy, and the relationship between peak and trough antihypertensive effects in a multicenter, placebo-controlled, parallel design trial. After a 4- to 6-week placebo baseline period, 111 patients with essential hypertension were randomized to receive placebo or diltiazem CD for a 4-week treatment period. Diltiazem CD 300 mg lowered supine diastolic and systolic blood pressure at trough significantly more than placebo (-7.5 mm Hg vs. -1.3 mm Hg, P = 0.0001 and -6.4 mm Hg vs. 0.5 mm Hg, P = 0.0051, respectively). Supine blood pressure was also measured hourly from 6 to 10 hours after the dose to assess peak effect and trough/peak ratios. Using the largest residual drug effect of -8.3 mm Hg at 6 hours as peak and the 24-hour residual drug effect of -5.9 mm Hg as trough, the trough/peak ratio was estimated to be 71%, with a lower one-sided 95% confidence limit of 50%. The precision of the trough/peak ratio is estimated by the lower confidence limit of 50%, which establishes the trough/peak ratio as statistically > or = 50%. No statistically significant differences in supine DBP were noted between the peak effect hours, indicating a plateau of the peak antihypertensive effect from 6 to 10 hours postdose. Diltiazem CD therapy was well tolerated, with no serious treatment-related adverse events reported during the trial and no patients discontinuing the trial due to a treatment-related adverse event.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
752,8021573,Short-term effects of felodipine in hypertensive type II diabetic males on sulfonylurea treatment.,T Kjellström; E Blychert; F Lindgärde,"To study the effects on blood pressure and glucose homeostasis of felodipine, a calcium antagonist. A double-blind randomized cross-over study comparing felodipine ER and placebo. A university centre of diabetic care in Malmö, Sweden. Seventeen hypertensive type II diabetic males on oral sulfonylurea (glibenclamide) treatment. Four-week treatment periods separated by a 2-week wash-out period. Felodipine 10-20 mg once daily was given. Blood pressure, heart rate, HbA1c and response to oral glucose tolerance test; glucose, insulin and c-peptide. Measured before randomization and at the end of each double-blind treatment period. Blood pressure was significantly reduced during felodipine treatment and heart rate slightly increased. Felodipine did not influence insulin or c-peptide levels. There was no significant change in glucose levels but an increase in HbA1c. The study demonstrated that felodipine is an effective agent for type II diabetic patients on glibenclamide treatment. The effect on HbA1c is noteworthy even if not of clinical significance in the short term. Controlled long-term studies in diabetic patients are needed to fully evaluate antihypertensive agents.",1994.0,0,0
753,8021907,"Effects of long-acting propranolol and verapamil on blood pressure, platelet function, metabolic and rheological properties in hypertension.",Y A Ding; T C Chou; K C Lin,"The newly developed antihypertensive drugs, the long-acting beta-blocker propranolol and the sustained release calcium antagonist verapamil, are compared in their antihypertensive, platelet function, rheological properties and metabolic effects. The trial was a double-blind, randomised, placebo-controlled cross-over study. Thirty patients with mild to moderate hypertension received propranolol (40-120 mg) or verapamil (80-200 mg) once daily in two separate ten week courses. After ten weeks treatment both drugs had significantly reduced both SBP and DBP. Beta-thromboglobulin (beta-TG) concentration, reflecting the status of platelet activation in vivo, was significantly decreased after propranolol (129.6 +/- 13.5 vs. 77.9 +/- 8.6 ng/ml) and verapamil (129.6 +/- 13.5 vs. 90.7 +/- 10.1 ng/ml) treatments while platelet aggregation induced by ADP, collagen, arachidonic acid or adrenaline and the production of thromboxane B2 (TXB2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and platelet cyclic 3'-5' adenosine monophosphate (C-AMP) concentration were not affected. Significant alterations in rheological parameters such as plasma and whole blood viscosity, fibrinogen level and red cell deformability were not found. Higher cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels were observed after propranolol treatment but not in verapamil treatment. Side-effects were mild, tolerated and no patient had to be withdrawn from the study. In conclusion, propranolol and verapamil are generally effective antihypertensive as well as rheologically safe drugs. Compared with the metabolic effect on serum lipid, verapamil may be a better choice. Both drugs possess the tendency to inhibit platelet properties which is desirable in hypertension treatment.",1994.0,0,0
754,8021910,Double-blind crossover study of once daily nifedipine coat core in essential hypertension.,C G Missouris; F P Cappuccio; N D Markandu; D R Singer; G A MacGregor,"Nineteen patients with essential hypertension on regular treatment with nifedipine tablets 20 mg twice daily and whose DBP was < 95 mmHg on at least two occasions two weeks apart were entered in a double-blind randomised crossover study of three weeks treatment with nifedipine coat core (new formulation) either as 30 mg one daily or as 60 mg once daily dose. BP and plasma nifedipine levels were measured at 24, two, four and six hours after dosing. The pattern of BP response to both doses was similar over the 24h period. However, a greater BP lowering effect was achieved with 60 mg compared with 30 mg. The BP lowering effect of both doses was less at 24h after the last dose compared with peak effect. Plasma nifedipine levels were significantly associated with the BP lowering effect in the group as a whole (i.e. the higher the nifedipine levels, the lower the BP) and were significantly less at 24 hours compared with peak. Nifedipine in the coat core formulation is effective in lowering BP in patients with essential hypertension. The 60 mg dose is more effective than the 30 mg dose and induces higher nifedipine levels which are associated with greater BP lowering effect. However, the maximum BP lowering effect is not maintained up to 24 hours.",1994.0,0,0
755,8024162,,,,,0,0
756,8031548,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.",1994.0,1,1
757,8031705,"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.",1994.0,1,1
758,8046120,Treatment of hypertensive emergency. Comparison of a new dosage form of the calcium antagonist nitrendipine with nifedipine capsules.,G Rohr; P Reimnitz; P Blanke,"To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency. Multicenter randomized double blind clinical study. 23 study centres (hospitals) in Germany. 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200-250 mmHg, diastolic between 110-140 mmHg) with and without concomitant clinical symptoms. Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure. Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values < 180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups. The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.",1994.0,0,0
759,8048393,Addition of pentoxifylline plus nifedipine to chemotherapy in patients with cisplatin-resistant cancers of the lung and other sites.,D J Stewart; W K Evans; D Logan,"Eight evaluable patients with cisplatin-resistant non-small cell lung cancer (6 patients), small cell lung cancer (1 patient), or both breast and ovarian cancer (1 patient) were entered on a study to determine whether the addition of nifedipine plus pentoxifylline to cisplatin-based chemotherapy would result in increased chemotherapy efficacy. No patient responded to treatment. Myelosuppression may have been augmented by the nifedipine and pentoxifylline (median granulocyte nadir, 0.3 x 10(9)/L). Two patients developed febrile neutropenia. Nifedipine and pentoxifylline had to be stopped in two evaluable patients due to hypotension, and three additional inevaluable patients withdrew from the study due to nifedipine-pentoxifylline toxicity before receiving their chemotherapy. There was no indication that other types of chemotherapy toxicity were increased by the addition of nifedipine and pentoxifylline. A major problem with the strategy followed in this protocol was that patients whose tumors had failed to respond to cisplatin-based regimens were often too ill to tolerate additional cisplatin, particularly when accompanied by nifedipine-associated hypotension.",1994.0,0,0
760,8058074,Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function.,R Scognamiglio; S H Rahimtoola; G Fasoli; S Nistri; S Dalla Volta,"Vasodilator therapy with nifedipine reduces left ventricular volume and mass and increases the ejection fraction in asymptomatic patients with severe aortic regurgitation. To assess whether vasodilator therapy reduces or delays the need for valve replacement, we randomly assigned 143 asymptomatic patients with isolated, severe aortic regurgitation and normal left ventricular systolic function to receive either nifedipine (20 mg twice daily, 69 patients) or digoxin (0.25 mg daily, 74 patients). By actuarial analysis, we determined that after six years a mean (+/- SD) of 34 +/- 6 percent of the patients in the digoxin group had undergone valve replacement, as compared with only 15 +/- 3 percent of those in the nifedipine group (P < 0.001). In the digoxin group, valve replacement (in a total of 20 patients) was performed because of left ventricular dysfunction (ejection fraction < 50 percent) in 75 percent, left ventricular dysfunction plus symptoms in 10 percent, and symptoms alone in 15 percent. In the nifedipine group, all six patients who underwent valve replacement did so because of the development of left ventricular dysfunction. In addition, all the patients in both groups who underwent aortic-valve replacement had an increase of 15 percent or more in the left ventricular end-diastolic volume index. After aortic-valve replacement, 12 of the 16 patients (75 percent) in the digoxin group and all six patients in the nifedipine group who had had an abnormal left ventricular ejection fraction before surgery had a normal ejection fraction. Long-term vasodilator therapy with nifedipine reduces or delays the need for aortic-valve replacement in asymptomatic patients with severe aortic regurgitation and normal left ventricular systolic function.",1994.0,0,0
761,8058230,Nicardipine versus metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial.,D Jannet; B Carbonne; E Sebban; J Milliez,"To compare the effects of treatment with nicardipine and metoprolol in patients with hypertension during pregnancy. One hundred pregnant patients with mild or moderate hypertension followed at the Centre Hospitalier Intercommunal de Créteil (France) were randomly allocated to treatment with either nicardipine or metoprolol. Changes in maternal blood pressure (BP), laboratory indices, umbilical Doppler velocimetry, and neonatal outcome were compared by means of Student t test, chi 2 test, and analysis of variance. Nicardipine decreased maternal systolic and diastolic BP more than metoprolol (P < .001). Umbilical artery resistance was lower in nicardipine-treated patients (P < .001). Plasma uric acid and creatinine concentrations were increased less markedly in the nicardipine group (P < .05 and P < .01, respectively). The incidence of cesarean delivery for fetal distress was lower in the nicardipine group (P < .01). There was a trend toward higher birth weights in the nicardipine group but no significant difference in neonatal outcome. Nicardipine is more effective than metoprolol in decreasing maternal BP; neonatal outcome is not significantly different.",1994.0,0,0
762,8059624,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
763,8060578,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)",1994.0,0,1
764,8060584,Comparison of effects of nicardipine and trichlormethiazide on insulin sensitivity in hypertensive patients.,S Kageyama; J Yamamoto; A Mimura; K Ishibashi; T Sakurai; K Yokota; Y Isogai; T Fujita,"We performed a randomized, crossover study comparing the effects of nicardipine and trichlormethiazide on insulin sensitivity in 8 untreated essential hypertensive patients. They were treated either with nicardipine or trichlormethiazide for 12 weeks, after which they were treated with the alternative drug for a further 12 weeks. Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp technique. Nicardipine had no adverse effect on insulin sensitivity. Trichlormethiazide decreased insulin sensitivity index by 12%. As nicardipine does not have an adverse effect on insulin sensitivity, it should be preferred in patients who have a proven metabolic abnormality.",1994.0,0,0
765,8062317,"Blood pressure control with diltiazem XR, a novel extended-release formulation of diltiazem HCl, in mature and elderly hypertensive patients.",R Fiddes; H Heym; W Hilty; A J Lewin; J Codispoti; C McNally; A Stokes; L Gilderman,"The safety and efficacy of an extended-release form of diltiazem HCl (diltiazem XR) in patients 55 years or older with mild-to-moderate essential hypertension were examined in a multi-center, double-blind, randomized, placebo-controlled, parallel-group study involving 350 patients with supine diastolic blood pressure (DBP) between 95 mm Hg and 114 mm Hg. Patients were randomized to a once-daily dose of diltiazem XR (240 mg) or placebo; 261 patients received diltiazem XR and 89 received placebo. After 4 weeks, the dose was doubled (to 480 mg) in patients whose supine DBP was > 90 mm Hg, and treatment was continued for another 4 weeks. Diltiazem XR consistently reduced blood pressure (BP) in the study population. At end-point, the mean reduction in supine DBP was 8.65 mm Hg in the diltiazem XR group and 2.75 mm Hg in the placebo group (P < 0.0001). Subgroup analysis confirmed the efficacy of diltiazem XR in men, women, patients between the ages of 55 and 64 years, patients 65 years or older, and non-black patients. Other BP values (supine systolic, standing diastolic, and standing systolic) also were significantly reduced in patients treated with diltiazem XR. BP reduction (supine DBP < or = 90 mm Hg or by > or = 10 mm Hg) was achieved in 58% of patients receiving diltiazem XR compared with 27% of patients receiving placebo. Decreases in apical heart rate were minimal and similar in both groups. No significant differences were noted in adverse events in the diltiazem XR and placebo groups: 36.4% of patients in the diltiazem XR group and 37.1% in the placebo group had no adverse experiences, and 63.6% and 62.9%, respectively, had at least one adverse event. Physical examination findings and laboratory values were clinically unremarkable and comparable in the diltiazem XR and placebo groups. Diltiazem XR given once daily at doses of 240 mg and 480 mg was safe and effective in lowering blood pressure in mature and elderly patients with mild-to-moderate hypertension.",1994.0,0,0
766,8066309,[Effect of verapamil and nitrendipine on the left ventricular mass and function (systolic and diastolic) in arterial hypertension].,J R González-Juanatey; J M García-Acuña; C Calvo Gómez; A Amaro Cendón; J A Fernández-López; M Gil de la Peña,"To evaluate the effect of two calcium antagonists (verapamil and nitrendipine) on the regression of left ventricular mass and function (systolic and diastolic) by echocardiography-Doppler, in not treated hypertensive subjects. 31 hypertensive subjects were studied in a randomized, placebo controlled, prospective and double blind trial. Verapamil (120-240 mg/day) was administered in 16 and nitrendipine (10-20 mg/day) in 15. The active drug therapy phase was 12 months with rest and effort tensional evaluation. Echo-Doppler was performed in the placebo phase, 6 and 12 months, evaluating left ventricular structure (septal and posterior-wall thicknesses, diameters and mass) and function (systolic and diastolic). Tensional control at rest and under effort was similar with both drugs, heart rate decreased only with verapamil. Left ventricular mass index decreased with verapamil and nitrendipine, due to reduction in the wall thicknesses (with verapamil from 158.5 +/- 31 to 135.7 +/- 20 g/m2 and with nitrendipine from 167.3 +/- 26 to 146.9 +/- 21 g/m2, p < 0.05). Left ventricular systolic function was not modified during the follow-up with both drugs. Only in the verapamil group some left ventricular diastolic function parameters improved (E from 0.82 +/- 0.11 to 0.95 +/- 0.14 and E/A/Age from 0.013 +/- 0.005 to 0.017 +/- 0.005; p < 0.05). Verapamil and nitrendipine exerts a similar tensional control at rest and under effort and left ventricular mass regression. The improvement of some diastolic function parameters in the verapamil group was probably due to bradycardia.",1994.0,0,0
767,8071397,Quality of life and cost-effectiveness in the treatment of hypertension.,I Wiklund,"By and large, the results of the different studies on quality of life in hypertension suggest that among beta-blockers only the nonselective beta-blocker propranolol has a negative effect on well-being, being associated with depression and side-effects. The findings on diuretics are comparatively few, and mainly observed as an adverse impact on sexual function. If one broadens the treatment scenario to include mortality and morbidity, evidence of a beneficial impact has only been proven for beta-blockers and diuretics. With the primary aim of antihypertensive drug therapy given as a reduction in cardiovascular risk factors, the aim with regard to quality of life is that quality of life be maintained. The new guidelines on the management of mild hypertension issued in the United States highlight the danger of relaxing the concern for risk reduction and costs in favour of surrogate end-points, even though these may carry great significance in the individual patient.",1994.0,0,0
768,8083368,Intracellular ionic consequences of dietary salt loading in essential hypertension. Relation to blood pressure and effects of calcium channel blockade.,L M Resnick; R K Gupta; B DiFabio; M Barbagallo; S Mann; R Marion; J H Laragh,"To study the ionic basis of salt sensitivity in hypertension, 19F-, 13P-, and 23Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Cai), pH (pHi), free magnesium (Mgi), and sodium (Nai) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low- (UNaV < 50 meq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t.i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Cai and Nai while suppressing Mgi and pHi; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (delta diastolic BP [high-low salt vs placebo] = 5 +/- 2 vs 14 +/- 2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cai and elevating Mgi and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Cai (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pHi (r = -0.754, P < 0.001), and the salt-induced change in Mgi (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake.",1994.0,0,0
769,8083787,Comparative metabolism of 3H-glucosamine by fibroblast populations exposed to cyclosporine.,E J Zebrowski; S P Pylypas; O Odlum; R B Johnson,"Cyclosporine and nifedipine therapy produces gingival overgrowth in many patients. Neither the mechanism underlying this undesirable side effect nor the possibility of synergism between these drugs is known, although many renal transplant patients receive both drugs. This study compared the rates of 3H-glucosamine utilization by three groups of fibroblasts: untreated gingival fibroblasts, fibroblasts from gingival overgrowth tissue of a patient receiving both cyclosporine and nifedipine, and normal gingival fibroblasts exposed to cyclosporine-A in vitro. Significant differences in the rates of deposition of 3H-glucosamine into the extracellular matrix by each group of gingival fibroblasts were demonstrated, suggesting that increased rates of deposition of proteoglycans into the gingival extracellular matrix by fibroblasts should be further investigated as a biologic mechanism for gingival overgrowth.",1994.0,0,0
770,8088691,[Effect of nilvadipine on nifedipine-induced edema of the lower leg. Results of a double-blind randomized comparative study].,M Vollmuth; W Schmitt,"Evaluation of the effects of nilvadipine on nifedipine-induced lower-leg edema. multicenter, randomized, double-blind study. 61 outpatients suffering from essential hypertension with diastolic blood pressure adjusted to < or = 95 mmHg by nifedipine, and simultaneous lower-leg edema. First phase: wash-out--placebo b.i.d.; Second phase: slow-release nifedipine 20 mg b.i.d.; Third phase: slow-release nifedipine 20 mg b.i.d. or nilvadipine 8 mg (mornings) and placebo (evenings). Lower leg volume, blood pressure, heart rate, weight, laboratory investigations, undesired effects, assessment of effectiveness and tolerability by the physician, subjective patient assessment. Patients treated with nilvadipine immediately following nifedipine therapy showed a significant decrease in lower-leg volume as compared with those continuing to receive nifedipine. In about half of the patients receiving nilvadipine, nifedipine-induced lower-leg edema disappeared completely. No differences were seen between the two substances in terms of effectiveness or tolerability.",1994.0,0,0
771,8111804,"A double-blind, placebo-controlled trial of sustained-release diltiazem in patients with angina. Sustained-Release Diltiazem Study Group.",R J Weiss; D Hicks; N Bittar; J Bowers; A Shah,"The efficacy of a new sustained-release formulation of diltiazem was examined in a placebo-controlled, double-blind trial in patients with stable angina. Doses of 60 mg BID, 90 mg BID, 180 mg BID and 240 mg BID were compared with placebo in 208 patients at 3 hours and 12 hours after dosing. Diltiazem, in doses of 90 mg BID and 180 mg BID, was statistically superior to placebo with respect to increasing total exercise time. Treadmill exercise time at 3 hours postdose increased with placebo from 356.1 +/- 118.7 sec to 375.7 +/- 119.8 sec (NS); with 90 mg BID, 382.7 +/- 111.8 sec to 445.4 +/- 117.5 sec (P < 0.005); and with 180 mg BID, 386.8 +/- 145.9 sec to 467.2 +/- 166.2 sec (P < 0.0001). At 12 hours postdose, treadmill exercise time with placebo increased from 357.6 +/- 128.3 sec to 383.8 +/- 128.7 sec (NS); with 90 mg BID, 395.2 +/- 119.4 sec to 449.7 +/- 123.1 sec (P = 0.053); with 180 mg BID, 395.3 +/- 141.4 sec to 476.6 +/- 165.6 sec (P < 0.0001). Time to onset of angina was also increased by the 180-mg-BID dose both at 3 hours postdose (257.3 +/- 126.8 sec to 354.3 +/- 158.7 sec; P < 0.0001) and at 12 hours postdose (274.7 +/- 131.2 sec to 377.4 +/- 186.2 sec; P < 0.0001). Sustained-release diltiazem is effective and safe in treating patients with chronic stable angina.",1993.0,0,1
772,8111807,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
773,8111816,The efficacy and safety of once-daily nifedipine coat-core in the treatment of mild-to-moderate hypertension. Adalat CC Cooperative Study Group.,P U Feig; L Gibson; E P Mac Carthy; P P Pettis; L Schwartz,"The efficacy and safety of once-daily nifedipine coat-core, a new, extended-release formulation, were examined in 245 patients with essential hypertension in this 10-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Mean net reductions in trough supine diastolic blood pressure at endpoint were 6.5 mmHg, 7.7 mmHg, and 11.7 mmHg at 30, 60, and 90 mg/day of nifedipine, respectively. All reductions were statistically significant, compared with placebo. Trough-to-peak ratios for supine diastolic blood pressure change following the 30, 60, and 90 mg/day doses were 49%, 67%, and 61%, respectively. Adverse events were generally mild or moderate, and most reflected the vasodilatory properties of the drug (eg, headache, edema). Reports of adverse events decreased as treatment progressed. The nifedipine coat-core tablet provided good control of blood pressure for the entire 24-hour dosing interval and was well tolerated by the majority of patients in the study.",1993.0,0,0
774,8111817,The safety and efficacy of once-daily nifedipine coat-core in combination with atenolol in hypertensive patients. Adalat CC Cooperative Study Group.,E P Mac Carthy; P P Pettis; L Gibson; L Schwartz; P U Feig,"The efficacy and safety of once-daily nifedipine coat-core when added to a regimen of atenolol (ATN; 50 mg/day) were compared with ATN and placebo in 251 patients with essential hypertension in this 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Mean net reductions (ATN effect subtracted) in supine diastolic blood pressure at endpoint were 7.9 mmHg, 9.4 mmHg, and 9.9 mmHg at 30, 60, and 90 mg/day of nifedipine coat-core, respectively, and 4.1 mmHg on ATN+placebo. Beyond the first week of double-blind therapy, all reductions produced by nifedipine coat-core combined with ATN were statistically significant (P < 0.05) compared with ATN+placebo. On ambulatory blood pressure monitoring, trough-to-peak ratios of the change in diastolic blood pressure for the 30, 60, and 90 mg/day doses were 41%, 68%, and 78%, respectively. Adverse events were generally mild or moderate and most reflected the vasodilatory properties of nifedipine (eg, edema, headache). Nifedipine coat-core, when combined with ATN in patients not controlled by ATN alone, had significant antihypertensive activity for the entire 24-hour dosing interval and was well tolerated by the majority of patients in the study.",1993.0,0,0
775,8113575,Safety of placebo-controlled trials in vasospastic angina.,S Savonitto; D Ardissino,,1994.0,0,1
776,8115311,Pharmacokinetics and dynamic response of plain and slow release isradipine formulations in moderately hypertensive patients.,H R Christensen; K Simonsen; J P Kampmann,"The pharmacokinetic variables and antihypertensive effect of the calcium antagonist isradipine, were investigated in 30 hypertensive patients. Isradipine was given orally in parallel group design in plain and slow release formulations in doses of 2.5 mg twice daily and 5.0 mg once daily, respectively. Isradipine concentration in serum was measured by a sensitive RIA method after the first dose and after 6 weeks of treatment. The pharmacokinetics and concentration/effect relationship after the first dose and after 6 weeks of treatment were compared. No differences in pharmacokinetics were observed between single and multiple dosing. Data were in accordance with results from studies in healthy volunteers. Rate, but not extent of bioavailability differs between the two isradipine formulations. Antihypertensive efficacy of the two formulations was similar (16/11 and 19/15 mmHg), and a significant time dependent increase in Emax from 10/3 mmHg to 23/14 mmHg after 6 weeks of treatment was observed.",1993.0,0,0
777,8117550,,,,,1,1
778,8121567,Are the calcium antagonists really useful in cerebral aneurysmal surgery? A retrospective study.,P Mercier; G Alhayek; T Rizk; D Fournier; P Menei; G Guy,"From 1983 to 1990, 234 patients with one or several cerebral arterial aneurysms were surgically treated in our department. Since 1983, we have been performing surgery as early as possible. As soon as the subarachnoid hemorrhage diagnosis is confirmed by computed tomography (or if unconfirmed, by lumbar puncture), we assume that each patient may have an aneurysm. Between 1987 and 1990, 111 patients were treated by vascular volume expansion (maintenance of central venous pressure above 5 cm H2O with 4% albumin or Ringer-lactate or, if necessary, with 20% albumin), which we supplemented with calcium antagonists (nimodipine in 60 patients and nicardipine in 51 patients). Two months after being discharged, each patient is examined by a neurosurgeon and, on the same day, is subjected to a neuropsychological evaluation and a computed tomographic scan of the brain. A few months after this consultation, a working-position/family-activities questionnaire is issued to the patient. All of the results studied on the basis of postoperative mortality, second-month computed tomographic scan ischemia, neuropsychological evaluation, and return to work show no significant difference between the groups with or without calcium antagonists or between the nimodipine and nicardipine subgroups.",1994.0,0,0
779,8127455,Nicardipine in heart failure: distinguishing its acute beneficial from its chronic effects.,J Sy; A Vitarelli; M Gheorghiade,"Concern over negative inotropic effects has limited the use of calcium blockers in patients with congestive heart failure. Nicardipine, a second generation dihydropyridine calcium channel blocker, has demonstrated positive hemodynamic effects in short-term therapy in patients with congestive heart failure. Prolonged use of calcium channel blockers remains contraindicated in patients with congestive heart failure due to the potential for activation of the renin-angiotensin system. However, acute intravenous nicardipine administration has important clinical applications (as in the management of surgical hypertension or hypertensive emergencies). Nicardipine may be safely used for these indications even in the presence of congestive heart failure.",1993.0,0,0
780,8129540,[Is placebo necessary in a clinical trial on ambulatory blood pressure?].,N P Chau; X Chanudet; D Mestivier; G Nguyen,"Placebo has only a slight effect on ambulatory blood pressure (ABP). Some authors have suggested that the use of a placebo is not necessary in a study on the drugs effect on ABP. We demonstrate that even if placebo effect is small, the use of a placebo group is still necessary. Effects of one daily dose of 50 mg atenolol + 20 mg slow-released nifedipine (AN) were investigated. Patients with office DBP 90-110 mmHg received, in a double-blind protocol, either AN (group AN, n = 31) or a placebo (group P, n = 26). Ambulatory BP (ABP) and HR were measured (Spacelabs or Diasys systems) for 24 h before and one month after treatment. The 2 groups were comparable before treatment. After 1 month under treatment, ABP was significantly lower in the AN group, compared to the P group, and this over the whole day (p = 0.03 to p < 0.0001). The effect was the most important between 10-17 h (p < 0.0001). HR was significantly lower in the AN group during daytime (6-22 h), but not during the night (22-6 h). Over the whole group, placebo effect was not significant. However, ABP did decrease under placebo in subjects with high initial pressure. As a result, an analysis without data from the placebo group led to an overestimation of the effects of the drug.",1993.0,0,0
781,8129541,[Treatment of arterial hypertension after surgery of the abdominal aorta: comparison of captopril and nifedipine administrated sublingually].,M Leeman; J P Degaute,"Treatment of high blood pressure after abdominal aortic surgery requires, because of adynamic ileus, the use of intravenously or sublingually (SL) administered drugs. The hemodynamic responses to captopril 25 mg SL (n = 10) and to nifedipine 10 mg SL (n = 10) were studied for 2 hours in patients (mean age 66 years) with arterial hypertension (mean blood pressure, Pa > or = 115 mmHg) the day after abdominal aortic surgery. Patients with bilateral renal artery stenoses, identified with the preoperative angiogram, were excluded. Systemic arterial pressure and pulmonary vascular pressures were measured using a femoral catheter and a pulmonary artery catheter respectively. Cardiac output (Q) was determined by thermodilution. [table: see text] Captopril and nifedipine significantly decreased pulmonary artery pressure, pulmonary artery occlusion pressure and right atrial pressure. No deterioration of renal function was observed. In conclusion, captopril and nifedipine SL are effective and well tolerated for the treatment of high blood pressure after abdominal aortic surgery.",1993.0,0,0
782,8132851,Verapamil and nifedipine in combination for the treatment of hypertension.,W H Kaesemeyer; A A Carr; P B Bottini; L M Prisant,"The authors examined the efficacy and safety of the combination of verapamil and nifedipine in the control of hypertension. Retrospective analysis of blood pressures was obtained on 50 patients who had historically documented essential hypertension and were receiving verapamil and nifedipine. The patients had moderate to severe hypertension; 27 of 50 (54%) were uncontrolled on prescribed regimens of two or more separate classes of drugs. Control was defined by the ability to maintain a blood pressure of < or = 160/90 by providing doses of verapamil (max: 480 mg/day) and nifedipine (max: 180 mg/day). Twenty-nine (58%) were black and 21 (42%) were white. Ages ranged from 16 to 84 years. Mean duration of therapy was 1-2 years. Only 3 of 50 (6%) were control failures after providing verapamil and nifedipine. Three of 50 (6%) were discontinued because of side effects--reversible hepatitis (2) and rash (1). There were no serious adverse events, i.e., CHF or arrhythmias. Manageable ankle edema was seen in 14 of 50 (28%) patients. Verapamil and nifedipine, a combination of a dihydropyridine and a non-dihydropyridine calcium antagonist, was effective and safe in this group of patients with difficult-to-manage hypertension.",1994.0,0,0
783,8133022,"The use of self-measured blood pressure determinations in assessing dynamics of drug compliance in a study with amlodipine once a day, morning versus evening.",T Mengden; B Binswanger; T Spühler; B Weisser; W Vetter,"To test whether the time of administration influences the therapeutic response to a calcium antagonist taken once a day. Also, the dynamics of drug compliance and its impact on blood pressure control were investigated. Twenty outpatients with mild-to-moderate hypertension were included in a randomized, placebo-controlled open study. In a crossover design, all of the patients received 5 mg amlodipine, either in the morning or in the evening, during two consecutive 4-week treatment periods. Blood pressure was taken by casual measurement, ambulatory 24-h monitoring (SpaceLabs 90202) and self-measurement at home, performed with a semi-automatic oscillometric device during the whole study period. Compliance was assessed using the Medication-Event-Monitoring System (MEMS). Neither casual nor ambulatory day- or night-time readings detected a significant difference between morning and evening administration. However, self-measurement documented significantly greater blood pressure reductions for morning than for evening administration. The MEMS showed different compliance on the days of ambulatory monitoring (100% with both drug regimens) compared with the whole treatment period. The number of days with missed medication was thus significantly higher for the evening dosing regimen. The difference in self-measured blood pressure between the two regimens was lost if the days with missed medication were removed from the statistical analysis. Time of once-a-day amlodipine administration does not influence its efficacy for 24-h blood pressure control. Furthermore, the use of self-measurement and the MEMS may provide useful additional information on the pharmacodynamic impact of different dosing patterns in hypertensive patients.",1993.0,0,0
784,8135425,"Hemodynamic effects of 3,4-diaminopyridine in a swine model of verapamil toxicity.",M C Plewa; T G Martin; J J Menegazzi; D C Seaberg; A B Wolfson,"3,4-Diaminopyridine (3,4-DAP) may reverse the hemodynamic effects of severe verapamil toxicity. A nonblinded acute animal preparation. Eighteen chloralose-anesthetized and instrumented swine were poisoned with verapamil at 10 mg/kg/hr for five minutes and then 5 mg/kg/hr until a systolic blood pressure of 55 mm Hg was achieved. Heart rate, lead II ECG, mean arterial pressure, left ventricular dP/dT max, and cardiac index were monitored. Nine control animals received 0.2 mL/kg/min infusion of normal saline, and nine treatment animals received similar volumes of 1 mg/kg/min 3,4-DAP until systolic blood pressure reached 100 mm Hg, an elapsed time of 30 minutes, or death. Verapamil toxicity was produced in all animals following an average dose of 1.38 +/- 0.44 mg/kg verapamil, and resulted in diminished mean arterial pressure, dP/dT max, cardiac index, and heart rate to average values of 47%, 32%, 46%, and 88% of baseline values, respectively. Transient atrioventricular dissociation was noted in only 22% of cases. 3,4-DAP treatment (with an average dose of 14 +/- 5.6 mg/kg) resulted in significant increases in mean arterial pressure, dP/dT max, cardiac index, and heart rate to 136%, 298%, 149%, and 158% of baseline values, respectively. Mortality was unchanged (22% in both groups). 3,4-DAP treatment was complicated by muscle twitching, tachycardia (rate of more than 180) and hypertension (diastolic blood pressure of more than 110 mm Hg) each in 44% of cases. Although 3,4-DAP reversed the hypotensive and negative inotropic effects of verapamil toxicity, it failed to improve survival and resulted in several complications including muscle twitching, tachycardia, and hypertension.",1994.0,0,0
785,8135450,Calcium antagonist-induced gingival hyperplasia.,R M Steele; A A Schuna; R T Schreiber,,1994.0,0,0
786,8136093,A comparison of the effects of nifedipine and verapamil on exercise performance in patients with mild to moderate hypertension.,A K Halperin; M V Icenogle; C O Kapsner; T W Chick; J Roehnert; G H Murata,"Twenty-four patients completed a double-blind, randomized clinical trial comparing the effects of nifedipine GITS (N) and verapamil SR (V) on blood pressure (BP) control and exercise performance. After a 2-week placebo phase, all subjects had measurements of VO2max, maximal workload, and endurance time. They were then randomized to either N (30 to 90 mg/day) or V (240 to 480 mg/day) and retested when BPs had stabilized. At rest, N lowered systolic (S) BP by 12 mm Hg (P = .02 compared to baseline) and diastolic (D) BP by 11 mm Hg (P = .001). V lowered SBP by 8 mm Hg (P = .013) and DBP by 11 mm Hg (P = .002). Neither drug affected resting heart rate. V significantly decreased resting epinephrine (P = .05) and there was a tendency for V to reduce norepinephrine (P = .07) and dopamine (P = .08). N tended to increase plasma renin activity (P = .07). During graded cycle ergometry N, compared with placebo, significantly lowered DBP at all exercise levels (P = .011), but had no significant effect on heart rate (HR), SBP, or heart rate pressure product (HRPP). Pulse pressure (PP) was significantly increased (P = .045), which was most noticeable at high exercise levels. Compared with placebo, V caused a marked reduction of exercise HR (P < .001), which was more pronounced at high levels, SBP (P = .004), DBP (P = .004), mean arterial pressure (MAP) (P = .001), and HRPP (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
787,8136109,,,,,0,1
788,8142195,Verapamil treatment after coronary angioplasty in patients at high risk of recurrent stenosis.,E Hoberg; R Dietz; U Frees; H A Katus; B Rauch; A Schömig; G Schuler; F Schwarz; H Tillmanns; J Niebauer,"To evaluate the efficacy of high-dose verapamil treatment (240 mg twice daily) in the prevention of angiographic restenosis after primary successful coronary angioplasty in patients at high risk of recurrent obstruction. A placebo controlled, double blind trial in which patients with stable angina pectoris and patients with unstable angina or non-Q wave infarction treated with 330 mg aspirin and 75 mg dipyridamole twice daily were randomised to a verapamil group or a control group. Follow up angiography was performed 6 months after angioplasty or sooner if signs of recurrent ischaemia developed. University department of cardiology. 196 consecutive patients undergoing coronary angioplasty from the beginning of April 1987 to the end of March 1989 and meeting the selection criteria that included the presence of at least one of six predefined risk factors for restenosis. At the time of coronary angioplasty 113 patients had unstable angina or non-Q wave infarction and 83 had stable angina pectoris. In 89 (91%) patients in the verapamil group and in 83 (85%) control patients follow up angiograms were available. The restenosis rate was lower in the verapamil group (48.3%) than in the placebo group (62.7%) (odds ratio 0.56, 95% confidence interval (CI) 0.303 to 1.025 p = 0.059). Of the 172 patients in whom follow up angiograms were available, 24 (13 taking verapamil and 11 taking placebo) did not comply with the trial for more than 40 (34) days (mean (1 SD)). For the remaining 148 patients the restenosis rate was 47.4% in the verapamil group and 63.9% in the placebo group (odds ratio 0.52, 95% CI 0.271 to 0.993, p = 0.046). In the 97 patients with unstable angina or non-Q wave infarction the restenosis rate was not significantly influenced by verapamil (55.8% with verapamil v 62.2% with placebo, odds ratio 0.77, 95% CI 0.339 to 1.728, p = 0.520). In the 75 patients with stable angina pectoris the restenosis rate dropped from 63.2% with placebo to 37.8% with verapamil (odds ratio 0.36, 95% CI 0.137 to 0.917, p = 0.038). The observed beneficial effect of high-dose verapamil treatment on the angiographic restenosis rate in patients with stable angina pectoris and at increased risk of recurrent obstruction requires confirmation in further prospective studies.",1994.0,0,1
789,8146352,[Experience with amlodipine (Norvasc) in the management of arterial hypertension].,N Rodríguez; B Domínguez,"The authors report the results of therapy with amlodipine in 20 patients with mild or moderate hypertension (diastolic pressure between 95 and 115 mmHg). Amlodopine was administered in a dose of either 5 or 10 mg once a day for 12 weeks. None of the patients had a history of congestive heart failure. Eleven patients were men between 27 and 89 years of age (average age was 52.6 years). There was a significant decrease in systolic blood pressure (from 161 to 141 mm Hg or -12.4%) and in diastolic blood pressure (from 103 to 86 mm Hg or -16.5%). Heart rate remained between 78 and 77 beats per minute. Only one patient experienced palpitations and two complained of mild, transient giddiness while on this therapy.",1993.0,0,0
790,8147070,[Effect of nisoldipine and diltiazem on systolic and diastolic function of the left ventricle in patients with coronary heart disease].,W Fehske; A Niedeggen; H Omran; L Pizzulli; M Manz; B Lüderitz,"Calcium channel blockers have a negative inotropic effect and protract the relaxation of the normal myocardium. These effects may vary in patients with coronary artery disease (CAD) and with the different kinds of calcium antagonists. In the present study we therefore compared the hemodynamic effects of intravenously given equihypotensive dosages of diltiazem (D) and nisoldipine (N) in patients with CAD. Each group contained 10 patients. After administration of a bolus of 300 micrograms/kg (D) and 5 micrograms/kg (N) respectively and following continuous infusion of 5.4 micrograms/kg/min (D) and 0.2 micrograms/kg/min (N) respectively, the mean arterial pressure was reduced by 15.5 +/- 6.0 (D) and 16.6 +/- 4.1 (N) mm Hg. Atrial pacing was performed in all patients to avoid reflectory heart rate effects. The pulmonary artery pressure decreased slightly with both drugs, whereas the cardiac index increased only with the use of N from 3.44 l/min x m2 to 3.93 l/min x m2. A significant change in the maximal rate of rise of left ventricular pressure (dP/dt max) as an index for inotropy was not detected for N or for D. The parameters of the diastolic function (the time constant of ventricular relaxation (tau) and the maximum rate of left ventricular isovolumic pressure decline (dP/dt min)) also did not indicate unequivocal drug effects. Doppler echocardiography of the mitral valve flow was performed simultaneously with invasive pressure measurements. The flow propagation derived from the color-M-mode correlated significantly with tau and was slightly improved by D.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
791,8147945,"Antihypertensive efficacy of a slow release nifedipine tablet formulation given once daily in patients with mild to moderate hypertension. A placebo-controlled, double-blind parallel-group trial.",S Harder; S Rietbrock; P Thürmann,"In a double-blind, randomized parallel-group, multi-center study the antihypertensive efficacy of a slow release tablet containing 60 mg nifedipine (Aprical long, CAS 21829-25-4) has been investigated. After two-weeks wash-out of previous antihypertensive medication and a two-weeks placebo run-in period, 88 patients of both gender with a diastolic blood pressure between 95 and 115 mmHg received either nifedipine or placebo for 8 weeks. Blood pressure was measured at the end of the dose interval at rest by a semi-automatic, auscultatory device. Control measurements were recorded using a standard cuff sphygmomanometer. Primary efficacy criterion was the drop in diastolic blood pressure (DBP, measured semi-automatically) after 8 weeks therapy. 88 patients were randomized to nifedipine or placebo. 86 patients completed the protocol (42 nifedipine, 44 placebo). However, only in 73 patients BP measurements were recorded appropriately with the semi-automatic device (36 nifedipine, 37 placebo). In the nifedipine group, blood pressure fell from 152 (+/- 18)/102 (+/- 6) mmHg to 139 (+/- 16)/91 (+/- 10) mmHg. Blood pressure under placebo was determined to 149 (+/- 20)/102 (+/- 8) mmHg before treatment and 146 (+/- 18)/100 (+/- 10) mmHg at the end of the study. Heart rate was not affected under both treatments. The 90% confidence interval of the difference between the mean fall in DBP ranged from 5.0 to 12.5 mmHg, the point estimator was 8.8 mmHg. At the end of the study, 21 of 36 patients under nifedipine and 10 of 37 patients under placebo had a DBP below 90 mmHg and/or a decrease in DBP > 10 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
792,8149520,Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia.,,"Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established. Patients (n = 1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P = NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P = .04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P = .06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P = NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower. In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.",1994.0,0,0
793,8150546,Long-term open evaluation of amlodipine vs hydrochlorothiazide in patients with essential hypertension.,A B Adolphe; N D Vlachakis; B A Rofman; D Brescia; S R Zellner,"The long-term efficacy and safety of amlodipine (2.5 to 10 mg) once daily was compared with that of hydrochlorothiazide (HCTZ) (25 to 100 mg) daily in 139 patients with mild-to-moderate hypertension. The study was a randomized, open-label, parallel comparison of 50 weeks' duration. Patients were randomized in a 2:1 ratio (amlodipine n = 92: HCTZ n = 47). Atenolol was added at week 12 if monotherapy was inadequate. At week 12, the mean reductions for supine and standing systolic and diastolic blood pressure values with amlodipine were found to be -15.2/-12.3 mmHg and -14.0/-11.6 mmHg respectively, as compared to -15.5/-11.1 mmHg and -16.1/-10.1 mmHg after treatment with HCTZ. The percentage of patients responding to treatment at week 12 was 74% on amlodipine and 70% on HCTZ. The addition of atenolol in those patients not adequately controlled on monotherapy produced additional mean reductions in supine and standing systolic and diastolic pressures in both the amlodipine-atenolol group and in the HCTZ-atenolol group. The incidence of adverse effects was 47% with amlodipine and 26% with HCTZ at 12 weeks. Overall, six patients were discontinued because of side effects while receiving amlodipine monotherapy and one from the HCTZ monotherapy group; none were discontinued because of side effects on combination therapy. Laboratory test abnormalities were reported by 16% of amlodipine-treated patients compared with 63% of patients on HCTZ. The antihypertensive effects of amlodipine and hydrochlorothiazide appeared to be comparable and were maintained during long-term therapy.",1993.0,0,1
794,8151095,Effects of vasopressin and nicardipine on hemodynamics and liver function in patients with cirrhosis: comparison with vasopressin alone.,T Iwao; A Toyonaga; M Ikegami; K Oho; M Sumino; M Sakaki; H Shigemori; M Nakayama; E Sasaki; K Tanikawa,"The effects of a combination of vasopressin and a calcium channel blocker (nicardipine) on portohepatic hemodynamics and liver function were compared with the effects of vasopressin alone in 18 patients with portal hypertension. Nine patients received 0.4 units/min of vasopressin and 9 patients received the same dose of vasopressin plus 0.3 mg/min of nicardipine for 40 min. Vasopressin plus nicardipine induced a significant reduction in both free portal venous pressure and the portal venous pressure gradient. These effects were similar to the changes with vasopressin alone (-14% vs. -16% in free portal venous pressure; -29% vs. -31% in portal venous pressure gradient). Vasopressin decreased both hepatic blood flow (-34%, P < 0.01) and intrinsic clearance of indocyanine green (-22%, P < 0.05). In contrast, these two parameters did not significantly change after vasopressin plus nicardipine (-8% and -3%, respectively). These results suggest that the addition of nicardipine improves hepatic impairment induced by vasopressin but causes no further reduction on portal pressure.",1993.0,0,0
795,8151609,Double-blind comparison of amlodipine and nifedipine retard in the treatment of mild to moderate hypertension.,A R Lorimer; J A Anderson; M S Laher; J Davies; J H Lazarus; S H Taylor; S Sanghera,"The efficacy and safety profiles of amlodipine (5-10 mg once daily) and nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a randomised double-blind parallel group study. BP was measured 22-24 hours after the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard. Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were no clinically significant changes in heart rate with either treatment. Three patients in the amlodipine group and five patients in the nifedipine retard group could not be considered in analysis. The total numbers of adverse events (considered related or possibly related to treatment) (42 vs. 36) as well as the numbers of patients experiencing such events (22 vs. 22) were similar in the amlodipine and nifedipine retard treated groups, respectively, but with a greater incidence of headaches in response to nifedipine retard and of oedema in response to amlodipine. Five patients in each treatment group discontinued therapy due to such events. Overall the results showed once daily amlodipine as equivalent to twice daily nifedipine retard in the management of mild to moderate hypertension.",1994.0,0,0
796,8163757,Efficacy of flecainide in patients with supraventricular arrhythmias and respiratory insufficiency.,F Barranco; M Sanchez; J Rodriguez; M Guerrero,"Evaluation of efficacy of intravenous flecainide to revert supraventricular arrhythmias to sinus rhythm in patients with respiratory insufficiency. Comparative randomized prospective trial. ICU in a University Hospital. 30 patients with acute respiratory insufficiency or acute exacerbation of chronic respiratory insufficiency and supraventricular arrhythmias. Intravenous flecainide was administered to 15 patients (Group A) (2 mg/kg for 10 min and continuous perfusion of 1.5 mg/kg for 1 h). Intravenous verapamil was administered to 15 patients (Group B) (0.15 mg/kg for 5 min and continuous perfusion of 0.005 mg/kg/min for 1 h). The categories of patients' arrhythmias were: Group A-atrial fibrillation (AF) in 5 cases, atrial flutter (AFl) in 2, multifocal atrial tachycardia (MAT) in 4 and other supraventricular tachycardia (SVT) in 4. Group B-AF in 6 cases, AFL in 2, MAT in 2 and SVT in 5 cases. Flecainide reverted arrhythmias to sinus rhythm in 12 out of 15 cases (80%); of these 12, 11 reverted with the initial bolus. Verapamil reverted 5 out of 12 cases (33.3%, p < 0.01). No significant secondary adverse effects were detected. Intravenous flecainide is an effective antiarrhythmic drug to treat acute supraventricular arrhythmias in patients with respiratory insufficiency.",1994.0,0,0
797,8172482,[Comparative study of the efficacy and tolerability of bepridil and diltiazem in unstable angina. 277 patients].,M Bory; L Quilliet,"Bepridil has been used only rarely in unstable angina since its long half-life could imply a delayed action. A loading dose could deal with this disadvantage. In order to confirm this hypothesis, a randomised trial was undertaken involving a 5 day comparison of bepridil at the dose of 300 mg/day after a loading dose (900 mg on D1, 500 mg on D2 and D3) with diltiazem 360 mg/day in 277 patients: 210 men and 67 women, with a mean age of 62.1 +/- 9.5, suffering from unstable angina confirmed by an ECG during symptomatic events showing reversible ST depression. A continuous 72 hour ECG record was obtained in 82 patients. Because of 69 inclusion errors, only 208 patients provided evaluable data (110 with bepridil and 98 with diltiazem), including 55 with continuous ECGs. Mortality (4.5% bepridil v. 3.1% diltiazem) and premature treatment terminations for therapeutic inefficacy (4.5% bepridil v. 7.1% diltiazem), myocardial infarction (3.6% bepridil v. 3% diltiazem), adverse events (3.6% bepridil v. 3% diltiazem) or at the patient's request (0.9% bepridil) were similar between the 2 groups. Efficacy regarding angina was similar, with 18.2% recurrences with bepridil and 21.4% with diltiazem during the first 72 hours, persisting without any difference beyond 72 hours. Resulting treatment adjustments concerning nitrates were identical in the 2 groups. Among the 55 patients with an evaluable continuous ECG (27 bepridil and 28 diltiazem, NS), 18 had recurrent ischemic episodes (9 bepridil and 9 diltiazem), 72.2% of which were clinically silent. Their total number, total duration and maximum amplitude of ST depression were similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
798,8173689,Improved antihypertensive efficacy of the felodipine-metoprolol extended-release tablet compared with each drug alone.,B Dahlöf; L Jönsson; O Borgholst; G Ekblad; C Engstrand; I Grundestam; A Lindh,"In this double-blind, randomised, three-way crossover (latin square design), multicentre study, the aim was to compare the efficacy and tolerability of the fixed combination of felodipine and metoprolol with the individual components as monotherapy. A total of 58 patients with supine diastolic blood pressure of 100-115 mmHg were treated with (1) a fixed combination of felodipine plus metoprolol 5/50-10/100 mg (FM), (2) felodipine 5-10 mg (F) or (3) metoprolol 50-100 mg (M), for 12 weeks each. All treatments were extended-release formulations administered once daily and blood pressure was measured 24 h after dosing. Dose titration was performed after 6 weeks if diastolic blood pressure was > 90 mmHg. After 12 weeks of active treatment, the mean supine blood pressures were 153/89, 159/93 and 163/94 mmHg with FM, F and M, respectively. The mean differences in systolic/diastolic blood pressure were -5.6/-3.1 mmHg (p = 0.007/p = 0.002), -10.2/-4.4 mmHg (p < 0.0001/p < 0.0001) and -4.6/-1.4 mmHg (p = 0.03/p = 0.15) for FM vs F, FM vs M, and F vs M, respectively. Blood pressure control (supine diastolic blood pressure < or = 90 mmHg) after 12 weeks was achieved in a significantly greater proportion of patients during treatment with FM than with F or M; 71%, 45% and 40% were controlled with the respective treatments. With FM, 45% of the patients were taking the higher dose after 12 weeks of treatment. The corresponding figures for F and M were 60% and 67%, respectively. Thirteen of the 58 patients (22%) were controlled only with FM.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
799,8173698,,,,,0,0
800,8173702,The Nordic Diltiazem Study (NORDIL). A prospective intervention trial of calcium antagonist therapy in hypertension.,,"NORDIL--the Nordic diltiazem intervention study was started in September 1992. This trial is a prospective randomized open blinded-endpoint (PROBE) multicenter, parallel-group study conducted in Norway and Sweden. The study is designed to evaluate the potential preventive effects of diltiazem compared with conventional antihypertensive drug treatment. Primary endpoints are cardiovascular mortality defined as fatal acute myocardial infarction, fatal acute cerebrovascular disease (stroke), sudden death and other fatal cardiovascular disease as well as cardiovascular morbidity defined as myocardial infarction and cerebrovascular disease (stroke). Secondary endpoints are total mortality, the development or deterioration of ischaemic heart disease, congestive heart failure, atrial fibrillation, transient ischaemic attacks, diabetes mellitus and renal insufficiency. Male and female patients, aged 50-69, with primary hypertension are randomly allocated to therapy starting with either diltiazem (180-360 mg daily) or conventional treatment (diuretics or beta-adrenergic blockers). Add-on therapy in the conventional treatment group excludes all types of calcium antagonists. The goal of treatment will be a target diastolic blood pressure of < or = 90 mmHg or a 10% diastolic blood pressure reduction. The NORDIL study will allow the detection of a 20% difference in cardiovascular mortality between the two groups with a power of 80% at the 5% significance level (two-sided test). A total of 12,000 patients will be recruited from about 480 primary Health Care Centers or hospital based Hypertension Units. Patients will be treated for an average period of 5 years.",1993.0,0,0
801,8176999,[Comparison of amlodipine and the nifedipine retard preparation in the treatment of arterial hypertension].,N Pivac; J Dobovisek; J Bagatin; V Gros Furek; Z Rumboldt; A Janezić; R Kveder; V Sjerobabski; M Simunić; S Sardelić,"The efficacy and acceptability of amlodipine (5-10 mg o.d.) and sustained-release nifedipine (20-40 mg b.i.d.) were compared in a multicenter, double-blind clinical trial. After a two-week placebo period, 71 essential hypertensives of both sexes, aged 51.7 +/- 8.5 years, having diastolic blood pressure of 95-114 mmHg were randomly allocated to either amlodipine 5 mg once daily (group A) or nifedipine 20 mg twice daily (group B). With respect to the blood pressure response, the initial dose was doubled after two weeks. No significant differences in blood pressures recorded at baseline and at the end of the placebo period were demonstrated. A significant reduction in both systolic and diastolic blood pressures in the supine position was observed already two days after the start of treatment. In the group A it decreased from 163.2 +/- 21.4/102.7 +/- 8.5 to 155.7 +/- 20.7/98.2 +/- 8.9 mm Hg (p < 0.05) and in the group B from 160.5 +/- 16.2/100.5 +/- 12.2 to 152.2 +/- 17.0/95.4 +/- 9.5 mm Hg (p < 0.05). The similar changes of blood pressure were observed in the standing position, as well. At the end of the study, the overall reduction of the supine diastolic blood pressure was 12.5% in the group A versus 5.2% in the group B (p < 0.05). In the standing position, amlodipine decreased diastolic blood pressure by 8.8% and nifedipine by 6.4% (p < 0.05). Furthermore, amlodipine decreased the standing diastolic blood pressure to a greater extent (8.8% versus 6.4%; p < 0.05) than nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
802,8193733,Twenty-four hour profile of the anti-hypertensive action of isradipine in essential hypertension.,C J Low; S G Foy; H Chaudhary; I G Crozier; S Baskaranathan; H Ikram,"Isradipine, 2.5 mg twice daily and placebo were administered for 4 weeks to 11 untreated essential hypertensives in a double-blind, random order, crossover study. At the end of each phase patients were assessed by 36 h of continuous intra-arterial blood pressure monitoring, surface electrocardiography, and measurement of endogenous creatinine clearance, serum biochemistry and plasma renin activity. Arterial pressure was significantly reduced by isradipine, with mean reduction in systolic blood pressure of 11.0 mmHg and diastolic pressure of 13.2 mmHg over 24 h. There was no significant change in heart rate, endogenous creatinine clearance, serum biochemistry or plasma renin activity.",1993.0,0,0
803,8195441,Clinical assessment of gingival hyperplasia in patients treated with nifedipine.,P Bullon; G Machuca; A Martinez-Sahuquillo; J V Rios; J Rojas; J R Lacalle,"Gingival hyperplasia caused by the use of nifedipine has been extensively reported. In this paper, the gingiva of 18 patients suffering from cardiopathy and treated with nifedipine were compared with those of 10 patients with cardiac disorders who had not been treated with calcium antagonists and with a no-treatment group of 12 patients. Nifedipine produced gingival hyperplasia, although patients who had not been treated with calcium antagonists also had mild hyperplasia. Hyperplasia first appeared in the interproximal areas, an observation which may be important for early detection. There was a direct correlation between the degree of hyperplasia and the bacterial plaque score. When we studied the influence of administration time and dose of nifedipine with the degree of hyperplasia, no statistically significant differences were found.",1994.0,0,0
804,8198031,Effects of bepridil on silent myocardial ischemia and eicosanoid metabolism in chronic stable angina pectoris after healing of myocardial infarction.,B Takase; A Kurita; H Hikita; A Uehata; T Nishioka; T Maruyama; K Mizuno; H Nakamura; Y Kanda,"To investigate the effects of bepridil on silent myocardial ischemia and on eicosanoid metabolism, 10 patients with chronic stable angina underwent exercise treadmill testing and 48-hour ambulatory electrocardiographic monitoring both before and after 4 weeks of bepridil administration (150 mg/day). Fasting venous levels of thromboxane B2, 6-keto-prostaglandin F1 alpha, and leukotriene C4 were measured by radioimmunoassay. Bepridil decreased heart rate responses to daily activities during ambulatory monitoring, and significantly (p < 0.05) reduced the median frequency and duration of silent myocardial ischemic episodes (from 5.5 to 0 events/48 hours and from 86 to 0 minutes/48 hours respectively). Bepridil significantly decreased the blood pressure heart rate product at peak exercise and significantly prolonged the mean exercise tolerance time (from 456.6 to 527.0 second). Bepridil also significantly decreased the plasma levels of thromboxane B2 and leukotriene C4 at rest. These results suggest that bepridil may reduce silent myocardial ischemic episodes either by the reduction of cardiac oxygen demand during daily activities and exercise stress, or by controlling coronary and systemic vasomotor tone. The drug also has a salutary effect on eicosanoid metabolism, to which its efficacy on silent myocardial ischemic episodes may be related.",1994.0,0,0
805,8199723,"Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly.",L M Wing; A E Russell; A L Tonkin; A J Bune; M J West; J P Chalmers,"This study compared with placebo the efficacy and tolerability of optimised doses of felodipine 5-20 mg daily, metoprolol 50-200 mg daily and their combination in subjects 60 years or over with isolated systolic hypertension. The study employed a randomised double-blind crossover design with allocation of treatment order within subjects by Latin squares. For each subject, after a single-blind run-in placebo phase, there were four randomised treatment phases each of six weeks duration, with a dose titration step at three weeks if necessary. Twenty-eight subjects entered the randomised phases of the study and twenty-one completed all four phases--13 male, 8 female (ages: median 71, range 59-85 years). At the end of both the felodipine and metoprolol phases systolic and diastolic pressure were reduced at 2 hours postdose compared with the placebo phase (p < 0.001), the blood pressure reduction with felodipine (-40/-20 mmHg) being greater than that with metoprolol (-15/-9 mmHg) (p < 0.01). Immediately predose (12 hours postdose) there was a persisting reduction of supine systolic blood pressure (-17 mmHg) with felodipine (p < 0.001), but there was no significant effect of metoprolol. At both measurement times the two drugs when in combination had an additive effect on blood pressure. There was a 20% increase in reported symptoms during each of the active treatment phases. Four subjects withdrew during the randomised phases because of probable drug-related adverse events and six subjects required dosage reductions during the felodipine or combination phases.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
806,8199724,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
807,8203987,Effects of calcium antagonists on renal hemodynamics and progression of nondiabetic chronic renal disease.,P M ter Wee; A G De Micheli; M Epstein,"In recent years, substantial investigative attention has focused on therapeutic regimens that could retard the progression of chronic renal insufficiency. Emphasis has been placed on the effects of antihypertensive treatment on renal hemodynamics and preservation of renal function. It has been suggested that some classes of antihypertensive agents may confer a greater renoprotective effect, especially agents that lower glomerular capillary pressure. Conversely, by virtue of their ability to preferentially dilate the afferent arteriole calcium antagonists theoretically could favor an increase in glomerular capillary pressure thereby accelerating the decline of renal function. In this review we survey the literature critically and conclude that in patients with essential hypertension and in patients with chronic renal insufficiency, calcium antagonists effectively reduce systemic blood pressure while maintaining glomerular filtration rate and effective renal plasma flow. Preliminary results from a few long-term studies suggest that calcium antagonists may even attenuate the decline in renal function of patients with chronic renal failure. The majority of studies in humans, however, have been nonrandomized, of too short duration, or confounded by investigative difficulties precluding definite conclusions whether calcium antagonists have renoprotective effects. Although the possibility that calcium antagonists may retard progression of renal disease remains to be ascertained, the available evidence indicates that calcium antagonists may be used in patients with renal functional impairment without further exacerbating renal function.",1994.0,0,0
808,8205301,Effect of isradipine on cyclosporin A-related hypertension.,M A van den Dorpel; R Zietse; J N Ijzermans; M A Schalekamp; W Weimar,"There is evidence that calcium antagonists may have a beneficial effect on cyclosporin A (CyA)-induced hypertension after organ transplantation. In a double-blind controlled trial, 50 consecutive non-diabetic first kidney-transplant recipients were randomized to receive either isradipine, a dihydropyridine calcium antagonist, or placebo. There were no significant differences in age, weight, gender, warm and cold ischaemic periods, and original renal disease between treatment groups. Treatment was started intravenously 2 h before the transplantation procedure and was subsequently continued orally for 3 months. The immunosuppressive treatment included oral CyA from day 5 after a short course of anti-T-lymphocyte immunoglobulins. Hypertension was treated with oral labetolol in combination with guanfacine if necessary. Antihypertensive medication was prescribed significantly more often (16 vs 7 patients; p < 0.05) in the placebo group. Standing systolic blood pressure was significantly lower in the isradipine group. The standing diastolic and both systolic and diastolic sitting blood pressures were similar in both groups. After 3 months, patients' mean serum creatinine was significantly lower with isradipine than with placebo (142.0 +/- 11.9 vs 164.0 +/- 10.8 mumol/l; p < 0.05). With isradipine, a significantly higher dose of CyA was needed to achieve adequate plasma levels (8.0 +/- 0.5 vs 6.2 +/- 0.5 mg/kg/day; p < 0.01). It can be concluded that isradipine is an effective antihypertensive agent after kidney transplantation and may have an influence on CyA metabolism. Furthermore, isradipine appears to ameliorate CyA-induced nephropathy.",1994.0,0,0
809,8205314,,,,,0,0
810,8205854,Amiodarone and the development of ARDS after lung surgery.,W Van Mieghem; L Coolen; I Malysse; L M Lacquet; G J Deneffe; M G Demedts,An evaluation of amiodarone as prophylactic treatment for supraventricular tachyarrhythmias after pulmonary surgery was stopped because of a high incidence of the adult respiratory distress syndrome (ARDS) after a pneumonectomy. Retrospective analysis of all cases of resection for pulmonary neoplasm in our hospital between 1987 and 1991 indicates that amiodarone may be implicated in the development of ARDS after lung surgery.,1994.0,0,0
811,8207740,"Comparison of cilazapril and nifedipine retard on ambulatory blood pressure, metabolic, rheological and platelet function in hypertensive patients.",Y A Ding; H W Law; T C Chou,"In a 12 week randomised, double-blind study, a total of 31 patients with a sitting DBP of between 95 and 115 mmHg were enrolled for comparison of the antihypertensive, metabolic and antiplatelet effects of the drugs cilazapril and nifedipine retard. A two week placebo treatment was given before either cilazapril (2.5 mg daily) or nifedipine retard (20 mg twice daily) was administered. After four weeks treatment, those patients with a sitting DBP > 90 mmHg were given a doubling of their initial doses for the next six weeks; the others were maintained at their initial doses. All patients received their drugs and reported any adverse effects every other week. Blood was taken for metabolic, rheological and platelet function tests. Ambulatory BP and heart rate were recorded at the start, fourth and tenth weeks of study. At the end of this trial, there was a significant decrease in both SBP and DBP in the cilazapril group (155 +/- 14 to 142 +/- 12 mmHg systolic, P < 0.01; 106 +/- 6 to 95 +/- 5 mmHg diastolic, P < 0.01). In the nifedipine group, there was also a significant decrease in SBP and DBP (161 +/- 18 to 139 +/- 5 mmHg, systolic, P < 0.01; 101 +/- 6 to 88 +/- 9 mmHg diastolic, P < 0.05) but with a significant increase in heart rate (79 +/- 14 to 91 +/- 10 beats/minute, P < 0.05). There were no significant changes in the biochemical or metabolic parameters in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,0
812,8207744,Effect of verapamil on reinfarction and cardiovascular events in patients with arterial hypertension included in the Danish Verapamil Infarction Trial II. The Danish Study Group on Verapamil in Myocardial Infarction.,C M Jespersen; J F Hansen,"An increased incidence of reinfarction and cardiovascular events has been reported in patients with hypertension recovering from acute myocardial infarction. We studied the effect of intervention with verapamil on the development of myocardial infarction and cardiovascular events in 301 patients with hypertension enrolled in the Danish Verapamil Infarction Trial II. During the second week after the index infarct, patients were randomly assigned to treatment with verapamil 360 mg per day (n = 149) or placebo (n = 152) and followed-up to 18 months (mean 16 months). The 18 months first reinfarction rates were 12.5% in verapamil and 19.8% in placebo treated patients (hazard ratio 0.53, 95% confidence limits 0.28-1.00, P = 0.04). The first cardiovascular event rates were 21.8% in the verapamil and 29.3% in the placebo group (hazard ratio 0.66, 95% confidence limits 0.41-1.06, P = 0.07). In this retrospective analysis of patients with hypertension included in the Danish Verapamil Infarction Trial II, intervention with verapamil reduced cardiovascular events primarily due to a substantial reduction in reinfarctions.",1994.0,0,1
813,8208641,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
814,8247194,"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
815,8247308,[Antihypertensive action of nicardipine retard in 24 hours and its effect on stress].,R De Cesaris; G Ranieri; A Andriani; V Filitti; M V Bonfantino; G Lamontanara; A Ferrieri,"Thirty-six patients (17 males and 19 females), aged between 40 and 70 years old (mean age 55.9), suffering from slight or moderate arterial hypertension, were monitored for four weeks after 14 days of placebo treatment. In a double-blind and random study 24 patients were treated with Nicardipine Retard (40 mg twice a day) whereas a further 12 received placebo twice a day. Sphigomanometric controls carried out after two and four weeks showed a significant reduction in arterial pressure only in those patients receiving active treatment. 24-hour out-patient monitoring of arterial pressure, carried out using Spacelabs 5300, showed a reduction in both systolic and diastolic arterial pressure throughout the day in subjects treated with calcium-antagonists compared to the placebo group. The normal physiological 24-hour trend of arterial pressure was always taken into account. The pressure response to a cold pressor test, mental arithmetic test, isometric and dynamic effort tests, measuring using a cycloergometer, was not modified by anti-hypertensive treatment, thus confirming the preservation of normal physiological behaviour during daily activities. There was no significant change in heart rate and the drug was well tolerated.",1993.0,0,0
816,8258265,[The assessment of glucose tolerance in hypertensive subjects treated with amlodipine].,D Panuccio; A Romani; M R Trabatti; R Romanelli; R Nardi,"The authors studied the side effects of amlodipine on glucose metabolism, carrying out an oral glucose tolerance test before and after 8-10 days of treatment, in a group of subjects with normal glucose tolerance. No significant variation in the average plasma glucose and insulin levels was observed. Nevertheless, in some cases, during amlodipine therapy, a decrease in glucose plasma level was found.",1993.0,0,0
817,8262084,Atenolol versus the fixed combination of atenolol and nifedipine in stable angina pectoris.,R A Foale,"One hundred and fourteen patients (94 male) with chronic stable angina who had a positive exercise test after 4 weeks on atenolol alone were randomized to receive either atenolol alone or the fixed combination of atenolol and nifedipine slow release formulation for 4 weeks in a double-blind cross-over manner. Exercise stress testing (Bruce protocol) at the end of each treatment period demonstrated that the time to the onset of pain and occurrence of 1 mm ST segment depression improved significantly (P < 0.05 and P < 0.001 respectively) whilst on the fixed combination compared to atenolol alone. In order to achieve sufficient sensitivity in the analysis of the exercise times, novel statistical methods based on survival analysis were used. Maximum ST segment depression was 0.13 mm less (P < 0.04) while on the fixed combination. The incidence of withdrawals and adverse effects was similar on both treatments.",1993.0,0,1
818,8274062,[Acute effects of nicardipine on the vascular reactivity of oxygen in patients with respiratory insufficiency and pulmonary hypertension].,A Saadjian; F Philip-Joët; F Paganelli; M Saadjian; S Lévy,"Pulmonary vascular response to the inhalation of various concentrations of oxygen (FIO2) was studied under basal conditions and after nicardipine in 10 patients with pulmonary hypertension secondary to chronic bronchitis. Hemodynamic data and blood gases were measured during inhalation of 3 gas mixtures: hypoxia (FIO2 = 0.15), normoxia (FIO2 = 0.21) and hyperoxia (FIO2 = 0.30). Each gas mixture was administered for 20 minutes, initially during an infusion of placebo and then of nicardipine giving a steady plasma concentration of 29 +/- 4 ng/ml. This was obtained by continuous I.V. infusion of 0.06 mg/kg/hour. Under basal conditions with placebo, the heart rate, cardiac output and pulmonary hypertension increased with decreasing concentrations of inhaled oxygen. The systemic blood pressure was unchanged with hypoxia but decreased during hyperoxia. Nicardipine increased the heart rate and the cardiac output but reduced the blood pressure with every inhaled oxygen mixture. The blood pressure was independent of FIO2 and the reduction observed during hyperoxia with placebo no longer occurred with nicardipine. However, the pulmonary hypertension was unaffected. At the dosage used in this study, nicardipine modified the systemic vascular response to oxygen but not the pulmonary vascular response. The vasodilation induced was much greater in the systemic than in the pulmonary circulation. In relation to the absence of significant pulmonary vasodilation, no changes in blood gases, due to a possible pulmonary shunting effect, were observed. At this dosage, nicardipine is ineffective in reducing pulmonary hypertension. However, its systemic hypotensive action may be used in patients with respiratory failure due to chronic bronchitis without deleterious effects on blood gases.",1993.0,0,0
819,8279372,Comparison of nifedipine gastrointestinal therapeutic system and atenolol on antianginal efficacies and exercise hemodynamic responses in stable angina pectoris.,W A Wallace; K L Wellington; M A Chess; C S Liang,"A gastrointestinal therapeutic system (GITS) of nifedipine has been developed to provide a once-daily dosing, and predictable, relatively constant plasma concentrations. This study compared the antianginal efficacy of nifedipine GITS with a once-a-day beta-receptor blocker, atenolol. Seventeen patients with documented coronary artery disease and stable stress-induced angina pectoris were studied during a 2-week, single-blind, placebo baseline phase and a 12-week randomized, double-blind, active drug crossover efficacy phase, using the bicycle exercise test and ambulatory electrocardiographic recordings. Patients exercised significantly longer with nifedipine GITS (883 +/- 47 seconds) and atenolol (908 +/- 44 seconds) than with placebo (794 +/- 41 seconds). Nifedipine GITS reduced systolic blood pressure at all stages of exercise compared with placebo but, because heart rate tended to increase more during nifedipine therapy, there was no difference in rate-pressure products between the placebo and nifedipine GITS periods. In contrast, atenolol reduced heart rate, systolic blood pressure and rate-pressure product during exercise compared with placebo. Whereas left ventricular ejection fractions (by radionuclide angiocardiography) increased with exercise, the maximal increase was smaller with atenolol than with placebo and nifedipine. The net increase in left ventricular ejection fraction at the end of exercise was greater with nifedipine than with placebo or atenolol. Ambulatory electrocardiograms showed only a small number of ischemic events. Neither nifedipine GITS nor atenolol reduced the number of ischemic events or total duration of ST-segment deviations significantly. It is concluded that nifedipine GITS is as effective an antianginal agent as atenolol, but the hemodynamic effects of the 2 agents differ.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
820,8279377,Characteristics and radiofrequency ablation therapy of intermediate septal accessory pathway.,S J Yeh; C C Wang; M S Wen; F C Lin; C C Koo; Y S Lo; D Wu,"Fourteen patients (5%) with an intermediate septal accessory pathway were identified among 283 consecutive patients with the Wolff-Parkinson-White syndrome who had electrophysiologic study and radiofrequency ablation therapy. Nine were women and 5 were men (mean age 33 +/- 13 years). The resting electrocardiogram showed ventricular preexcitation in 8 patients and normal PR interval in 6. Anterograde and retrograde mapping studies revealed that the accessory pathway was para-Hisian in 11 patients and paranodal in 3. The accessory pathway was successfully ablated in 10 patients (9 para-Hisian and 1 paranodal) and damaged in 1 (para-Hisian). Treatment of 3 patients was complicated by transient atrioventricular (AV) block, of 1 by intermittent second-degree AV block, and of another by permanent complete AV block requiring implantation of a permanent pacemaker. Six patients underwent a follow-up electrophysiologic study 84 +/- 55 days after ablation; none had induction of tachycardia even after isoproterenol infusion. It is concluded that radiofrequency ablation therapy for intermediate septal accessory pathway is feasible. However, the success rate is only modest (71%), whereas complications with heart block (36%) or complete right bundle branch block (29%) are high. Thus, the procedure should be reserved for patients with life-threatening or troublesome symptomatic tachyarrhythmias.",1994.0,0,0
821,8282290,[Monotherapy of mild to moderate hypertension. Double-blind comparative study: amlodipine versus enalapril].,H C Mehmel; R C Görne,"A double-blind multicenter study involving 89 patients with mild-to-moderate essential hypertension was performed to compare the efficacy and tolerability of amlodipine and enalapril. Following a placebo-controlled run-in phase, treatment was initiated with a daily dose 5 mg amlodipine or enalapril. In the second week of treatment, the daily dose of enalapril was increased to 10 mg. After two weeks of treatment, the amlodipine dose was increased from 5 to 10 mg, the enalapril dose from 10 to 20 mg if the diastolic seated blood pressure exceeded 90 mmHg. Mean systolic and diastolic blood pressures decreased in the amlodipine group from, respectively, 158 +/- 17/101 +/- 6 mmHg to 142 +/- 14/87 +/- 11 mmHg, and in the enalapril group from 157 +/- 15/102 +/- 5 mmHg to 140 +/- 16/88 +/- 12 mmHg. The reduction in blood pressure was statistically significant in both groups (p < 0.0001), but the difference in blood pressure lowering effect of the two treatments was not statistically significant. The target blood pressure (diastolic BP seated < 90 mmHg) was achieved in 24 patients (75%) in the amlodipine group, and 23 patients (68%) in the enalapril group. Neither group experienced any severe adverse reactions. Side effects were seen in 3 patients of the amlodipine group and in 6 of the enalapril group.",1993.0,0,0
822,8288408,Effect of metoprolol and diltiazem on the total ischaemic burden in patients with chronic stable angina: a randomized controlled trial.,R C Ahuja; N Sinha; R R Kumar; R K Saran,"We conducted a randomised controlled trial to study the effects of metoprolol and diltiazem on the total ischaemic burden--sum of symptomatic and silent myocardial ischaemia, in 146 patients with stable angina pectoris. One-hundred thirty-four completed the study protocol. Sixty-eight patients received metoprolol (100 mg twice daily, n = 52, 50 mg twice daily, n = 16) while 66 received diltiazem (90 mg three times daily, n = 50, 60 mg three times daily, n = 16). The drugs were given for 4 weeks. The primary outcome variables were frequency and duration of total ischaemic burden, silent and symptomatic myocardial ischaemia. These were measured on 48 h of Holter monitoring. The reductions in duration and frequency of total ischaemic burden by metoprolol, 76% and 40%, respectively, were significantly higher than by diltiazem, 43% and 24%, respectively (P < 0.01 and P < 0.02). The frequency and duration of silent myocardial ischaemia, which constituted more than 80% of the total ischaemic burden in the two groups showed similar results. However, the reduction in frequency of symptomatic myocardial ischaemia only was significantly greater by metoprolol (63% than diltiazem (24%) as the difference in reduction of duration of symptomatic ischaemia was insignificant (85% vs. 75%; P > 0.05). Whether a greater reduction of total ischaemic burden by metoprolol as compared to diltiazem has any implications for prognosis in patients with chronic stable angina remains to be established.",1993.0,0,1
823,8296698,Investigation of therapeutic mechanisms of atenolol and diltiazem in patients with variable-threshold angina.,A Nadazdin; G J Davies,"The effects of beta-adrenoreceptor and calcium channel-blocking agents on the balance of myocardial oxygen supply and demand were studied in 15 patients (2 women and 13 men), aged 46 to 69 (mean 62) years, with variable-threshold angina. An exercise test was performed before therapy was begun, and 24-hour ambulatory ECG monitoring was performed after 1 week of long-acting nitrate therapy, in the third week after random assignment to either atenolol or diltiazem, and in the third week after crossover. All exercise tests were positive except in one patient taking diltiazem. The exercise time to 0.1 mV ST change was 4.2 +/- 1.7 minutes with no therapy, 5.1 +/- 1.6 minutes with nitrates, 6.6 +/- 0.8 minutes with diltiazem, and 6.5 +/- 2.1 minutes with atenolol. The rate-pressure product at 0.1 mV ST change was 20.9 +/- 4.6 with no therapy and 21.2 +/- 5.7 and 22 +/- 4.6 with nitrates and diltiazem, respectively, but fell to 15 +/- 3.9 beats.min.-1 mm Hg 10(-3) after atenolol (p < 0.01). There was no significant difference in the number of anginal attacks or in nitroglycerin consumption per week. The heart rate at the onset of ST-segment change during the exercise test and during ambulatory ECG monitoring was significantly lower during atenolol than during diltiazem treatment. Both atenolol and diltiazem were of similar efficacy in increasing nonischemic exercise duration in patients with variable-threshold angina and acted primarily by slowing the resting heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)",1994.0,0,1
824,8296748,Safety and compatibility of betaxolol hydrochloride combined with diltiazem or nifedipine therapy in stable angina pectoris.,S P Glasser; R Friedman; T Talibi; L K Smith; E K Weir,"Compared with placebo, adding betaxolol 20 mg every day to nifedipine (up to 60 mg/day in divided doses) or diltiazem (up to 360 mg/day in divided doses) for a 3-week treatment period in 135 patients with stable angina pectoris significantly (p < 0.05) lengthened the time to onset of moderate angina during exercise tolerance tests at all treatment time points. The median increases in the time to onset of moderate angina at the final exercise tolerance test (end point) compared with baseline were 1.08 and 0.53 minutes for betaxolol and placebo groups, respectively (p = 0.002, betaxolol and placebo groups, respectively (p = 0.002, betaxolol vs placebo). The time to onset of 1 mm ST-segment depression increased significantly (p < 0.05) with betaxolol compared with placebo at all but 1 treatment time point (median increase [p = 0.001] 1.77 and 0.37 minutes, respectively, at end point). Duration of exercise also was increased significantly (p < 0.05) after the third week of treatment and at end point (median 0.62 and 0.50 minutes, respectively; p = 0.03). Generally comparable results were found within the diltiazem (n = 128) and nifedipine (n = 25) subgroups, although the nifedipine group was too small to detect statistically significant differences between betaxolol and placebo treatment. Resting systolic blood pressure, heart rate and the rate-pressure product, measured both when angina occurred and at the end of exercise, also were influenced significantly (p < 0.05) by the betaxolol addition. The only serious adverse effect associated with betaxolol treatment was syncope, seen in 2 patients.",1994.0,0,0
825,8297198,Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors.,L A García Rodríguez; R Williams; L E Derby; A D Dean; H Jick,"Hospitalizations for acute liver injury in the absence of a viral infection or any other well-defined pathologic finding that could have caused it is rare. In this study, we included both outpatients and hospitalized patients with acute liver injury to estimate the risk of clinically important acute liver injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to study the role of certain risk factors. This was a retrospective cohort study with secondary case-control analysis. The study included 536 general practitioners' practices in England and Wales for the period October 1987 through August 1991. A total of 625,307 persons who received more than 2 million prescriptions for one of 12 NSAIDs were followed up to estimate the risk of newly diagnosed acute liver injury. There were 23 cases of acute liver injury. The incidence of acute liver injury was 3.7 per 100,000 NSAID users or 1.1 per 100,000 NSAID prescriptions. None of the cases had a fatal outcome. Sulindac was the only NSAID with a substantially greater risk than that for the overall NSAID group. Users of NSAIDs who had rheumatoid arthritis had a 10-fold increased risk of acute liver injury compared with NSAID-treated patients with osteoarthritis. Concomitant exposure to other hepatotoxic medications also increased the risk. Transient minor increases in liver test values were not a useful predictor of diagnosed NSAID-associated acute liver injury. Although NSAIDs have been found to be associated with acute liver injury in a small number of persons, the risk is sufficiently small as to be of minimal concern for most NSAIDs.",1994.0,0,0
826,8297690,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.",1994.0,0,1
827,8299527,[The effect of angiotensin-converting enzyme inhibitors on proteinuria in chronic glomerulonephritis].,C M Erley; E Komini; T Nicaeus; N Braun; S Wolf; T Risler,"The effect of two angiotensin-converting enzyme (ACE) inhibitors, lisinopril and captopril, on proteinuria and renal haemodynamics was investigated in 11 hypertensives (9 men, 2 women; mean age 46 +/- 16 years) with proteinuria (> 1.5 g/24 h) due to chronic glomerulonephritis and impaired renal function (glomerular filtration rate < 75 ml/min). In a randomized and double-blind cross-over trial the patients received, each time for six weeks, either lisinopril (5 mg/d, sometimes increased to 10 mg/d after 3 weeks) or captopril (twice daily 12.5 mg, sometimes increased to twice 25 mg after 3 weeks). Initially and between the individual treatment phases they were on a placebo phase for 4 weeks. The following were measured: protein excretion, including fractional clearance of albumin and IgG, plasma-renin activity and renal haemodynamics. Protein excretion was not significantly reduced by either drug (placebo: 7.1 +/- 4.0 g/d; lisinopril: 5.1 +/- 2.8 g/d; captopril: 5.4 +/- 3.0 g/d). Albumin excretion and fractional albumin clearance were significantly decreased only by lisinopril (P < 0.05), not by captopril. Plasma-renin activity was increased more by lisinopril than captopril (Placebo: 1.0 +/- 0.9 ng/ml.h; lisinopril: 5.2 +/- 2.8 ng/ml.h [P < 0.05]; captopril: 1.8 +/- 1.3 ng/ml.h [P < 0.05]). The renal haemodynamics was only slightly influenced by either drug, but captopril significantly decreased the filtration fraction in the presence of chronic glomerulonephritis and renal failure. - Resulting from their influence on the renin-angiotensin-aldosterone system, ACE inhibitors have, in addition to their known action on renal haemodynamics, an independent effect on the loading barrier of the basal membrane of the kidney.",1994.0,0,0
828,8299661,Effects of amlodipine on renal haemodynamics in mild to moderate hypertensive patients. A randomized controlled study versus placebo.,G Licata; R Scaglione; A Ganguzza; G Parrinello; R Costa; G Merlino; S Corrao; P Amato,"In this study the efficacy and safety of short-term amlodipine administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduced blood pressure induced by treatment was associated with maintenance of renal function. After a run-in period with placebo, 30 hypertensive patients without cardiac or renal diseases were randomly allocated to a double-blind 4 weeks controlled study with amlodipine 10 mg once a day (15 patients) or placebo (15 patients). Renal haemodynamic measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, with methods described by Schlegel and Gates, respectively. In addition, effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. Plasma renin activity (PRA), serum aldosterone (ALD) and urinary excretion of sodium (NaU) were evaluated. At the end of amlodipine administration a significant decrease (P < 0.001) in SBP, DBP and MBP from baseline values was observed. A significant decrease (P < 0.01) in RVR and significant increases (P < 0.05) in ERPF, ERBF and in NaU were also found, without relevant changes in GFR, FF, PRA and ALD. No significant variation in clinical and renal measurements was observed in the placebo group. No relevant side effects were observed in either group. In conclusion, amlodipine was effective in lowering blood pressure in mild to moderate hypertension and exerted favourable effects on renal haemodynamics and function.",1993.0,0,0
829,8302442,[Slow-release nicardipine in the treatment of arterial hypertension: comparative study vs. an ACE inhibitor].,R De Cesaris; G Ranieri; V Bonfantino; A Adriani; V Filitti; A Ferrieri,"The anti-hypertensive activity and influence on some forms of stress of slow-release Nicardipoine and Captopril were compared using a randomized 2:1 protocol. Thirty-six patients, mean age 55.9 years, suffering from slight or moderate arterial hypertension were treated with either 40 mg of Nicardipine retard twice a day (b.i.d.), or Captopril in a dose of 25 mg (b.i.d.) for 8 weeks. A significant reduction was observed in arterial pressure, both in orthostatism and clinostatism, following both treatments in comparison to the placebo period, but the group treated with slow-release Nicardipine showed a greater and statistically significant reduction in arterial pressure. No significant change in heart rate was reported using either drug. Non-invasive out-patient monitoring of arterial pressure, performed using Spacelabs 5300, showed a significant reduction in arterial pressure using both drugs and the conservation of the normal circadian rhythm of arterial pressure. The pressure response to the cold pressor test (CPT), mental arithmetic test (MAS), and to dynamic and isometric effort was positive with both drugs, thus revealing a degree of protection offered by treatment using these two substances. In overall terms, the two drugs were well tolerated.",1993.0,0,0
830,8304366,"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.",2001.0,0,1
831,8307554,[Cardiac protection in heart surgery interventions by preventive drug administration before extracorporeal circulation. Studies with troponin T as a parameter for perioperative myocardial damage].,C Knothe; J Boldt; B Zickmann; M Ballesteros; G Häufler; F Bruns; G Hempelmann,"The present study was designed to test if prophylactic intravenous nifedipine or nitroglycerine could reduce myocardial damage after cardiopulmonary bypass. 45 patients scheduled for elective coronary artery bypass grafting were divided at random into three groups: Group 1: control; group 2: nifedipine (0.25 microgram/kg/min); group 3: nitroglycerine (1.5 micrograms/kg/min). Infusion period reached from the beginning of anaesthesia until crossclamp of the aorta. Myocardial damage was estimated by troponin T (TnT), CK-MB and ST-segment analysis of the ECG. TnT is a cardiospecific protein from the contractile apparatus of striated muscle cells. TnT-levels might provide a very sensitive marker of small amounts of cardiac muscle necrosis. It was tested with an ELISA/one-step sandwich-assay with streptavidin-technology [9]. Criteria for ischemia in the ST-segment analysis were (according to Smith et al. [19]): ST-depression > 1 mm from baseline or ST-elevation > 2 mm from baseline at J-point + 60 ms. Statistical interpretation was done by one- and two-factorial analyses of variance (including multivariate analyses of variance). Correlation between two variables was tested by regression analysis. A level of p < 0.05 was taken for indicating statistical significance. Biometrical data, circulation data and data from cardiopulmonary bypass were without significant differences among all groups (Tables 1 and 2). Starting from normal values (< 0.05 ng/ml) TnT significantly rose in all groups immediately after cardiopulmonary bypass and remained elevated until the forth day after operation (values between 0.4 and 0.6 microgram/ml) (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)",1993.0,0,0
832,8314271,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
833,8522634,Antianginal and antiischemic efficacy of monotherapy extended-release nisoldipine (Coat Core) in chronic stable angina.,S P Glasser; S Ripa; W T Garland; R Weiss; K Nademanee; S Singh; N Bittar,"A double-blind, randomized, placebo-controlled study was conducted to test the peak and trough antianginal and antiischemic monotherapy efficacy and safety of a new extended-release formulation of nisoldipine (nisoldipine Coat Core [Bayer Corporation], 20 mg, 40 mg, and 60 mg once daily compared to placebo). Study patients had a history of chronic, stable angina pectoris, exercise-induced angina in association with ST segment depression, and exercise test reproducibility. Of the 483 patients enrolled in the study, results were valid for safety analysis for 312 and for efficacy analysis for 284. There was a statistically significant improvement in total exercise time at both peak and trough for patients taking 20 mg and 60 mg of nisoldipine compared with patients taking placebo, but the group taking 60 mg was not better than the group taking 20 mg (33.9 and 33.7 seconds, respectively, at trough). The results were similar for the secondary endpoints (time to onset of angina and time to 1 mm ST segment depression). No correlation was evident between plasma nisoldipine levels and total exercise duration. Headache and peripheral edema were the most frequently reported adverse events and were dose related. There were no discontinuations due to adverse events in patients randomized to the 20-mg nisoldipine group. No deaths occurred while patients were receiving active nisoldipine therapy. Therapy with this extended-release formulation of nisoldipine is an effective once-daily treatment for chronic stable angina pectoris. It represents one of the few dihydropyridine calcium channel antagonists that has shown efficacy when administered as monotherapy to patients with angina.",1995.0,0,1
834,8522636,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.",1995.0,0,0
835,8523374,Office and ambulatory blood pressure: a comparison between amlodipine and felodipine ER. Danish Multicentre Group.,A Høegholm; N Wiinberg; E Rasmussen; P E Nielsen,"The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5, 10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients with mild-to-moderate essential hypertension in a double-blind, double-dummy, randomised, comparative study. A total of 118 patients were allocated to a 12-week, double-blind treatment with either felodipine ER (n = 57) or amlodipine (n = 61). The anti-hypertensive effect was evaluated by measuring office blood pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24 h ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment and at the end of the study. The mean office BP changes from baseline to week 12 were -13.4 (+/- 15.7)/-11.8 (+/- 6.9) mmHg for felodipine ER (mean daily dose 11.2 mg) and -15.3 (+/- 17.0)/-12.9 (+/- 7.3) mm Hg for amlodipine (mean daily dose 7.4 mg). All BP reductions were significant (P < 0.01) with respect to time, but differences between treatment groups were not significant. The mean ambulatory BP changes from baseline to end of the study were -11.6 (+/- 5.2)/-10.0 (+/- 2.0) mmHg for felodipine ER and -16.3 (+/- 4.4)/-9.6 (+/- 3.0) mm Hg for amlodipine, both significant (P < 0.01). The fall in ambulatory SBP was significantly greater (P < 0.001) in the patients treated with amlodipine compared with felodipine ER whereas there was no difference between the groups with respect to ambulatory DBP. Both drgs were well tolerated with a withdrawl rate of 12% equally distributed.(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
836,8523379,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
837,8533005,[Initial results of the HOT-study in Switzerland (hypertension optimal treatment)].,B Waeber; D Roth,"The HOT study (hypertension-optimal treatment) is an international clinical study on primary prevention of cardiovascular events in 19,193 hypertensive patients worldwide. It aims at the recognition of the optimal diastolic blood pressure value (< 90, < 85 or < 80 mmHg?) in order to maximize the possible benefit of an antihypertensive therapy. In addition, the HOT study investigates whether low doses of aspirin (75 mg/day) are able to reduce the occurrence of severe cardiovascular events. In Switzerland a total of 797 patients have been enrolled in the study. Antihypertensive therapy was initiated with felodipine = Plendil (5 mg/day). This vasoelective calcium antagonist could reduce diastolic blood pressure values to < 90 or < 80 mg/Hg, respectively, in one of two or one of three patients within the first three months. In nine or six patients, respectively out of ten a reduction of diastolic blood pressure values to < 90 or < 80 mmHg was reached within one year by combination of felodipine with other antihypertensive drugs (ACE inhibitors, beta blockers and diuretics).",1995.0,0,0
838,8535552,"Effects of felodipine, metoprolol and their combination on blood pressure at rest and during exercise and on volume regulatory hormones in hypertensive patients.",R D Gordon; S A Klemm; T J Tunny; J R Wicks; D B Elmfeldt,"The effects on blood pressure (BP) and heart rate (HR), at rest and during bicycle exercise, of the vascular selective calcium antagonist felodipine, the cardio-selective beta-blocker metoprolol, and of the two drugs in combination, were assessed in a double-blind, three-way cross-over study comprising 23 patients with essential, mild to moderate hypertension. All three treatment regimens were given to each patient in randomised order for 4 weeks after a 4 week placebo run-in period. Felodipine 10-20 mg daily, metoprolol 100-200 mg daily and the combination of felodipine 10-20 mg plus metoprolol 100 mg daily were all effective antihypertensive treatments both at rest and during exercise. The two drugs seemed to have additive effects and the effect on BP of the combination was greater than that of either drug given as monotherapy. The mean sitting BP was 148/103 mmHg at randomisation, after 4 weeks of placebo treatment, and 134/88, 134/94 and 121/84 mmHg, respectively, after 4 weeks' treatment with felodipine, metoprolol and the combination. Maximal exercise capacity was similar irrespective of treatment regimen, and the normal response to exercise BP and HR was maintained during all active treatments. Changes observed in volume regulatory hormones (PRA, aldosterone and ANP) were consistent with a direct tubular natriuretic-diuretic effect of felodipine and of beta-blocker attenuated release of renin. All treatment regimens were well tolerated and adverse events reported were usually mild and transient.",1995.0,0,0
839,8535554,The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure and tolerability. With special reference to age and gender.,L Hansson; A Zanchetti,"The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective, randomized, multicenter trial conducted in 26 countries. Its two main aims are to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients and the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 19,193 patients have been recruited and randomized and one-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability and other available data after 12 months of follow-up of all patients. Special reference will be given to the subgroup of elderly patients (> or = 65 years, n = 6,113) as compared to younger patients (< 65 years, n = 13,080). On average, the target group < or = 90 mmHg in diastolic blood pressure has reached 86 mmHg, the target group < or = 85 mmHg has reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg. The percentage of patients that has obtained their target blood pressures is 84% in the target group < or = 90 mmHg, 72% in the target group < or = 85 mmHg and 57% in the target group < or = 80 mmHg at 12 months of follow-up. In the elderly subgroup (> or = 65 years of age) the percentage of patients at target is higher for all target groups, being 86, 76 and 61%, respectively, at 12 months. Antihypertensive treatment is initiated with a calcium antagonist, felodipine, at a dose of 5 mg once 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 dose adjustments are made in accordance with a set protocol. As a fifth and final step a diuretic may be added. Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients. Only ankle edema, 2.6% and 3.0%, and coughing, 1.3% and 0.8%, in young and elderly patients, respectively, exceed a frequency of 1%, and 88% of all patients are still taking their baseline therapy felodipine after one year. The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study.",1995.0,0,1
840,8548113,"Proarrhythmia with class III antiarrhythmic drugs: definition, electrophysiologic mechanisms, incidence, predisposing factors, and clinical implications.",S H Hohnloser; B N Singh,"Antiarrhythmic drugs can and do induce unexpected and sometimes fatal reactions by either producing new symptomatic arrhythmias or by aggravating existing arrhythmias. The definition of proarrhythmia has changed since controlled clinical studies showed a dichotomy between arrhythmia suppression and mortality. The nature of proarrhythmic reactions is linked to the electrophysiologic effects of various antiarrhythmic drugs. Whereas Class I agents without accompanying effects on repolarization generally produce ventricular tachycardia (often incessant) or fibrillation, Class III agents typically produce torsades de pointes that may deteriorate into ventricular fibrillation. The precise mechanism of torsades de pointes is not fully elucidated, although early after-depolarization and increases in spatial or temporal dispersion of repolarization are likely possibilities. Proarrhythmic risk is lowest for amiodarone and is probably related to the drug's complex electrophysiologic profile. The incidence of torsades with sotalol increases with dose and the baseline values of the QT interval; the incidence with d-sotalol and other pure Class III agents remains unclear. Prospective, randomized, placebo-controlled studies to evaluate this are under way. The fact that d-sotalol increases mortality in postinfarction patients suggests that it may possibly be a common property of most, if not all, pure Class III compounds. The ongoing clinical trials with various Class III agents are likely to provide the critical information on this important therapeutic issue.",1995.0,0,0
841,8551485,Hypertension in the elderly: 24 h ambulatory blood pressure results from a placebo-controlled trial.,J M Neutel; D H Smith; M P Lefkowitz; P Cargo; D Alemayehu; M A Weber,"Calcium channel blockers are increasingly used to treat hypertension in elderly patients. To assess the effects of low-dose, long-acting verapamil on blood pressure (BP) and quality of life (QOL) in elderly patients, verapamil 120-240 mg of placebo was given once daily for 8 weeks to 76 patients aged > or = 60 years. After a 4-week placebo wash-out period, patients with a sitting DBP of 95-110 mm Hg and a mean daytime (6 am to 6 pm) ambulatory DBP > or = 90 mm Hg were entered into the study. Twenty four-hour BP monitoring as well as QOL self-assessment and digit span testing of cognitive function were performed at the end of the placebo wash-out and double-blind treatment periods. Patients treated with verapamil showed a significant decrease in mean whole-day BP, while those treated with placebo showed a small increase in BP. Treatment differences between the two groups in SBP and DBP were each statistically significant (P < 0.01). Significant differences were also seen when the 24 h period was divided into daytime and night-time readings. Both QOL and digit span testing scores were unchanged from baseline for verapamil-treated patients and were not different from the placebo-treated group. The results of this study demonstrate consistent and significant decreases in BP throughout the 24 h period with no adverse effects on QOL or cognitive function this this formulation of verapamil in elderly hypertensive patients.",1995.0,0,0
842,8551492,"Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension.",J C Chan; J A Critchley; J T Lappe; S J Raskin; D Snavely; A I Goldberg; C S Sweet,"This study investigated the anti-hypertensive efficacy and tolerability of once-daily losartan potassium (50 mg titrated to 100 mg), an angiotensin II receptor antagonist, compared with once daily felodipine extended release (ER) (5 mg titrated to 10 mg), a calcium channel blocker, after 12 weeks of therapy in elderly hypertensive patients. Following a 4-week, single-blind, placebo baseline period, qualifying patients were randomly allocated to 12 weeks of double-blind treatment with losartan potassium or felodipine ER. After 6 weeks, patients with a 24 h post-dose sitting diastolic blood pressure > or = 90 mm Hg had their dose doubled for the remaining 6 weeks. At 6 weeks, there was a greater BP response for felodipine ER than losartan potassium in elderly patients with mild to moderate hypertension. However, after 12 weeks of therapy, losartan potassium reduced BP as effectively as felodipine ER with no differences in mean BP reduction or anti-hypertensive response category between treatment groups. In this study, both treatments were well tolerated; felodipine ER was associated with a numerically higher incidence of headache and oedema while the incidence of asthenia was numerically higher in losartan-treated patients.",1995.0,0,0
843,8551821,"Randomised, double-blind trial of intravenous diltiazem versus glyceryl trinitrate for unstable angina pectoris.",E J Göbel; R W Hautvast; W H van Gilst; J N Spanjaard; H L Hillege; M J DeJongste; G P Molhoek; K I Lie,"The effect of dihydropyridines in patients with unstable angina is discouraging. To find out the effect of the non-dihydropyridine-like calcium-channel blocker diltiazem, a randomised, double-blind trial was conducted comparing diltiazem with glyceryl trinitrate, both given intravenously, in 129 patients with unstable angina. The endpoints were refractory angina or myocardial infarction, individually and as a composite endpoint. Refractory angina alone or together with myocardial infarction occurred significantly less commonly in the diltiazem group. While patients were on the trial drugs the numbers with refractory angina were 6 (10%) in the diltiazem group versus 17 (28%) in the glyceryl trinitrate group (relative risk 0.36, p = 0.02), and the numbers with refractory angina and myocardial infarction were 9 (15%) versus 23 (38%) (relative risk 0.40, p = 0.007). Over 48 h the number were: refractory angina 8 (13%) versus 18 (30%), relative risk 0.45, p = 0.03, and refractory angina and myocardial infarction 12 (20.0%) versus 25 (41%), relative risk 0.49, p = 0.02. Patients in the diltiazem group had better (p < 0.05) event-free survival while taking the drugs. Heart-rate pressure product was reduced significantly only by diltiazem (p < 0.05). The incidence of bradyarrhythmias did not differ significantly. Atrioventricular conduction disturbances occurred in 5 (8%) patients in the diltiazem group but were not seen in the glyceryl trinitrate group (p = 0.03). These disturbances could be reversed by decreasing the dose of the drug or withdrawing it. No temporary pacemakers were required. Headache requiring an analgesic or dose adjustment occurred significantly less in the diltiazem group: 3 (5%) versus 15 (25%), relative risk 0.20 (p < 0.004). These results indicate that intravenous diltiazem, compared with intravenous glyceryl trinitrate, significantly reduces ischaemic events and can be used safely in patients with unstable angina.",1995.0,0,0
844,8554947,Calcium antagonists: when the content does not justify the headline.,G Jackson,,1995.0,0,0
845,8556804,Are calcium antagonists safe?,R W Gifford,,2001.0,0,0
846,8557899,Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study.,S Savonitto; D Ardissiono; K Egstrup; K Rasmussen; E A Bae; T Omland; P M Schjelderup-Mathiesen; P Marraccini; I Wahlqvist; P A Merlini; N Rehnqvist,"This study was designed to investigate whether combination therapy with metoprolol and nifedipine provides a greater anti-ischemic effect than does monotherapy in individual patients with stable angina pectoris. Combination therapy with a beta-adrenergic blocking agent (which reduces myocardial oxygen consumption) and a dihydropyridine calcium antagonist (which increases coronary blood flow) is a logical approach to the treatment of stable angina pectoris. However, it is not clear whether, in individual patients, this combined therapy is more effective than monotherapy. Two hundred eighty patients with stable angina pectoris were enrolled in a double-blind trial in 25 European centers. Patients were randomized (week 0) to metoprolol (controlled release, 200 mg once daily) or nifedipine (Retard, 20 mg twice daily) for 6 weeks; placebo or the alternative drug was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p < 0.01); metoprolol was more effective than nifedipine (p < 0.05). At week 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p < 0.05 vs. placebo). Analysis of the results in individual patients revealed that 7 (11%) of 63 patients adding nifedipine to metoprolol and 17 (29%) of 59 patients (p < 0.0001) adding metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated with metoprolol + nifedipine and in 4 (24%) of the 17 treated with nifedipine + metoprolol. The mean additive anti-ischemic effect shown by combination therapy with metoprolol and nifedipine in patients with stable angina pectoris is not the result of an additive effect in individual patients. Rather, it may be attributed to the recruitment by the second drug of patients not responding to monotherapy.",1996.0,0,1
847,8560112,[Diltiazem versus intravenous nitroglycerin in the treatment of unstable angina pectoris. A randomized study].,P Castro; R Corbalán; I Vergara; S Kunstmann,"Prognosis of unstable angina pectoris is related to admission EKG changes and prompt symptom control. The aim of this study was to compare the clinical effects of intravenous diltiazem (DTZ) or nitroglycerin (NTG) in patients with unstable angina pectoris. We studied 43 patients admitted to the hospital with a history of rest angina within the last 48 hours, associated with EKG evidence of ischemia. All subjects received intravenous heparin and oral aspirin, 23 were randomly assigned to receive intravenous DTZ and 20 to receive intravenous NTG. Both groups had similar baseline features and the endpoints of treatment were recurrence of angina, myocardial infarction, death during hospitalization and secondary side effects. Treatment with DTZ, when compared to NTG, resulted in a significant reduction of recurrent angina (8.7 and 59% respectively; p < 0.005), number of angina episodes per patient (0.18 +/- 0.5 and 0.9 +/- 1.2 respectively; p < 0.05) and lower need for dose increment to control symptoms (3 and 9 patients respectively; p < 0.05). The most common side effects observed were cephalea with NTG (60% of patients) and asymptomatic sinus bradicardia with DTZ (28% of patients). In each group, one patient had a myocardial infarction and one patient died. It is concluded that intravenous DTZ reduces myocardial ischemia to a greater extent than NTG and can be safely used in patients with unstable angina pectoris.",1995.0,0,0
848,8561443,[Comparison of the antispastic effect of Bi-Tildiem 120 mg and Tildiem 60mg].,S Yvorra; L Desfossez; D Panagides; A De La Garoullaye; M Bory,"Diltiazem (Tildiem 60 mg) is a calcium channel blocker with demonstrated efficacy and safety in the treatment of stable angina pectoris and spastic angina. The sustained release formulation of diltiazem, allowing two daily doses (Bi-Tildiem 120 mg), is already marketed in France for the treatment of stable angina. It was therefore interesting to evaluate the efficacy and safety of this form, administered in two daily doses, in coronary spasm, versus the classical formulation, Tildiem 60 mg, given at the same daily dose, i.e. 240 mg, in three divided doses per day. We conducted a single-centre, randomized, double-blind, cross-over clinical study in twelve patients, eleven men and one woman, between the ages of 42 and 70 years, presenting with angina and normal coronary arteries and spasm documented by a positive methylergonovine (Methergin) test. They were divided into two groups of six patients receiving either Tildiem followed by Bi-Tildiem, or Bi-Tildiem followed by Tildiem. The characteristics of the two groups were comparable at the time of the selection visit. The methylergonovine test, used to assess the efficacy of the two treatments, was improved by Tildiem and Bi-Tildiem compared to the placebo test (p = 0.001 and 0.002), without any significant difference between Tildiem and Bi-Tildiem: an improvement was obtained in 11/12 and 10/12 patients, respectively. No deterioration of the test was observed with Tildiem or Bi-Tildiem compared to placebo. The coronary symptoms and blood diltiazem levels were similar with Tildiem and Bi-Tildiem. The results confirmed the safety of Bi-Tildiem. A single adverse effect was attributed to treatment: an episode of mild insomnia. No serious adverse effect were observed and none of the patients discontinued the study. The efficacy and safety of Tildiem and Bi-Tildiem are comparable in the treatment of spastic angina.",1995.0,0,0
849,8565032,Comparison of the efficacy and safety of nifedipine coat-core versus amlodipine in the treatment of patients with mild-to-moderate essential hypertension. Hypertension Study Group.,W Zidek; C Spiecker; G Knaup; L Steindl; H W Breuer,"The antihypertensive efficacy and safety of once-daily nifedipine coat-core was compared with that of once-daily amlodipine in a multicenter, prospective, double-blind, randomized, parallel-group study in which titration was based on response. The study consisted of a 2-week, single-blind, placebo run-in period followed by an 8-week double-blind treatment period. Double-blind treatment began with nifedipine coat-core 30 mg or amlodipine 5 mg. After 4 weeks of double-blind therapy, patients with a trough seated diastolic blood pressure (DBP) > or = 90 mm Hg received an increased dose of nifedipine coat-core (60 mg) or amlodipine (10 mg). A total of 207 patients received the study medication at 12 private-practice medical centers. Ambulatory blood pressure monitoring (ABPM) was performed at six medical centers with 38 nifedipine coat-core and 37 amlodipine patients. Data from 176 patients were valid for the primary efficacy analysis. Treatment groups were well matched with respect to baseline demographic and disease characteristics. During the study period, 59 (65.6%) nifedipine coat-core patients remained on their original 30-mg dose of study medication compared with 52 (60.5%) amlodipine patients who remained on the 5-mg starting dose. Mean trough blood pressure at baseline was 160.9/101.9 mm Hg in the nifedipine coat-core patients compared with 160.5/101.8 mm Hg in the amlodipine patients. Mean trough blood pressures at end point were 141.3/85.5 mm Hg and 140.7/85.9 mm Hg in the nifedipine coat-core and amlodipine groups, respectively. Equivalence between the two treatment groups was demonstrated based on the difference between amlodipine and nifedipine coat-core in the change from baseline in trough seated DBP (90% confidence interval, -0.50 to 2.59). Systolic blood pressure and 24-hour ABPM data supported the equivalent antihypertensive efficacy of the two treatments. Both drugs were well tolerated and had similar safety profiles. Nineteen patients in the amlodipine group experienced at least one adverse event compared with 12 in the nifedipine coat-core group. The amlodipine patients tended toward a later occurrence of adverse events plus a greater number of events, particularly edema and gastrointestinal symptoms. More patients in the nifedipine coat-core group (n = 3) than in the amlodipine group (n = 1) discontinued treatment because of adverse events.(ABSTRACT TRUNCATED AT 400 WORDS)",1995.0,0,0
850,8572869,[Quality of blood pressure control in general practice and in the HOT study. French Research Group HOT (Hypertension Optimal Treatment)].,C Raveau-Landon,"A previous investigation of the French League against Hypertension has shown that only 27% of the hypertensives aged below 64 years and 19% of those aged above 64 years have their BP controlled under treatment (BP < 140/90 mmHg). The international, prospective, randomised HOT study aims at assessing the optimal diastolic BP (DBP) level during active antihypertensive treatment to reduce at the best the cardiovascular morbidity and mortality. The study is on-going, with a completion of inclusions. The BP measurements are performed by oscillometric method with the D2 international BP device, HESTIA. At enrollment, only 52% of the hypertensives were treated, their mean BP level being 161/99 mmHg +/- 18/9 mmHg (n = 10,005). On randomisation, two weeks after the treatment withdrawal, BP was 170/106 +/- 15/4 mmHg. Six months later, under treatment, BP was 150/84 +/- 10/7 mmHg with a mean decrease of 11/15 mmHg compared to values under previous treatment. Depending on the randomisation groups which are defined by different DBP objectives, 87.5 to 92.2% of the patients have a BP normalisation (DBP < or = 90 mmHg) after one year of treatment. Five explanations may be proposed for the better BP control observed in the study compared to the results at inclusion, reflecting the general practice: (1) the fact that the patient is free to participate and has been informed may have improved the compliance, (2) the patient's follow-up was reinforced during the first weeks, (3) the protocol is based on the treatment initiation by a dihydropyridine with a long duration of action: felodipine, (4) the BP objectives are rigorously defined by a DBP between 80 and 90 mmHg depending on the randomisation group whereas in general practice, the physician may have a smoother objective mainly aiming at improving tolerability, (5) the larger use of a bi-therapy. CONCLUSION. The more ambitious aims of BP control (DBP < or = 90, 85, 80 mmHg) in this study have induced a treatment intensification with a better BP control.",1995.0,0,0
851,8582392,Antihypertensive treatment with verapamil and amlodipine. Their effect on the functional autonomic and cardiovascular stress responses.,P Nazzaro; M Manzari; M Merlo; R Triggiani; A M Scarano; A Lasciarrea; A Pirrelli,"Many biological and psychological factors induce haemodynamic and extra-cardiovascular functional changes mediated by the autonomic nervous system. Pharmacological blood pressure reduction, as a neurovegetative stimulus, can change the arousal of the sympathetic nervous system. We evaluated the effects of two calcium channel blockers, verapamil and amlodipine, both administered as monotherapies, upon the sympathetic stress response in 23 randomized mild-to-moderate essential hypertensives (161 +/- 2/98 +/- 1 mmHg). Patients performed four stress tests (mental arithmetic, colour word Stroop, cold pressor and handgrip) while extracardiovascular and haemodynamic functions were assessed non-invasively at every heart beat, during baseline, stress and recovery phases. The sympathetic response was evaluated by computing the 'area-under-the-curve' (value x time) measured during the psychophysiological session. The session was repeated at run-in, after placebo and during treatment. After one month's treatment, baseline blood pressure was significantly reduced in patients treated with amlodipine (139 +/- 1/84 +/- 1 mmHg; P < 0.001) and verapamil (140 +/- 2/85 +/- 1 mmHg; P < 0.001). The emotional arousal (frontalis muscular contraction, skin conductance) was unchanged, but the cutaneous vascular response was reduced (P < 0.05) in patients treated with verapamil. No changes in systolic or diastolic blood pressure were detectable, but amlodipine increased the heart rate response (P < 0.05). In contrast, verapamil reduced the heart rate (P < 0.05) without depressing the cardiac output response, which was increased with amlodipine (P < 0.05). Total vascular resistance was significantly (P < 0.001) reduced with both the treatments. Consequently, functional cardiac load, expressed by pressure-rate product and cardiac power, was significantly enhanced with amlodipine and reduced with verapamil. In conclusion, the abnormal sympathetic stress response, which characterizes the hypertensive patient, might be affected by the choice of medication. Verapamil in particular, moderated emotional arousal, the vasoconstrictive response and reduced cardiac load without lowering cardiac output demands. In contrast, in patients treated with amlodipine, in whom the cardiac output response was increased, the pattern was reversed and the functional cardiac load was also increased.",1995.0,0,0
852,8583014,Gingival overgrowth induced by nifedipine and cyclosporin A. Clinical and morphometric study with image analysis.,F O'Valle; F Mesa; J Aneiros; M Gómez-Morales; M A Lucena; C Ramírez; F Revelles; E Moreno; N Navarro; T Caballero,"In this study, we developed a quantitative method with digital image analysis to evaluate the degree of gingival overgrowth (GO), and compared GO in kidney transplant patients treated with cyclosporin A (CsA) (n = 21) or CsA+nifedipine (n = 8) and a group of healthy controls (n = 30). The method was reproducible and reliable. Our findings showed significant differences in papillary and gingival surface between controls and transplant patients treated with GO inducers. Gingival overgrowth index also differed significantly between controls and each patient group (p < 0.01, Kruskal-Wallis test). The administration of the calcium channel blocker nifedipine potentiated the adverse effect of CsA: comparison of the morphometric findings revealed significant differences between patients treated with CsA alone and CsA+nifedipine in papillary area, dental area, and GO index (p < 0.01, Mann-Whitney U-test). We conclude that the method of image analysis we developed is useful in assessing the degree of GO.",1995.0,0,0
853,8583790,Effect of amlodipine on left ventricular mass in the Amlodipine Cardiovascular Community Trial.,R A Kloner; J R Sowers; G F DiBona; M Gaffney; M Wein,"As part of the Amlodipine Cardiovascular Community Trial (ACCT), which was a large multicenter study designed to assess the effects of the calcium channel blocker amlodipine besylate (Norvasc) as monotherapy for treatment of mild to moderate hypertension, we sought to determine the effects of amlodipine on regression of left ventricular (LV) hypertrophy (LVH). The study began with a 2-week placebo run-in period (baseline), before which antihypertensive drugs had been discontinued. Amlodipine was then administered at 5-10 mg/day during a 4-week titration/efficacy period. Patients achieving a goal diastolic blood pressure (DBP) of < or = 90 mm Hg or a decrease in DBP of > or = 10 mm Hg entered a 12-week maintenance phase and had the option to continue long-term therapy thereafter. Echocardiograms were obtained in a subset of patients at the end of the baseline period. In patients with LVH at baseline, echocardiograms were repeated at the end of 16 weeks of therapy (week 18), and at 42 weeks in patients continuing long-term therapy. Thirty-seven percent of 124 hypertensive patients screened for LVH at baseline had LVH detected on echocardiograms. Blacks had a higher incidence of LVH (64%) as compared with whites (34%, p < 0.05). Patients with LVH were more likely to have a higher baseline systolic BP (SBP) and DBP. Their sitting SBP and DBP decreased significantly from a mean of 163/102 mm Hg at baseline to 139/86 mm Hg with amlodipine therapy at week 18 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)",1995.0,0,0
854,8586825,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.",1995.0,1,1
855,8590792,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
856,8606348,Ritodrine and nifedipine as tocolytic agents: a preliminary comparison.,K G van Dijk; G A Dekker; H P van Geijn,"The effectiveness of the tocolytic agent and other betamimetic drugs in the treatment of preterm labor remains controversial. Effectiveness or efficancy of ritodrine has not yet convincingly been proven. A major concern are the marked side effects of beta-mimetics. The calcium channel blocker nifedipine has been used for tocolysis shortly after its introduction in clinical practice and is considered to be a probable good alternative for ritodrine. The efficacy of nifedipine versus ritodrine in the treatment of preterm labor was assessed in a retrospective study. 32 patients received intravenous ritodrine and 29 oral nifedipine. As endpoints were used: postponement of delivery, maternal side effects and perinatal outcome. The results of this retrospective study suggest that nifedipine is more successful in postponing delivery than ritodrine. Maternal side effects seemed to occur more frequently and be more serious in patients treated with ritodrine as compared to nifedipine. Perinatal outcome seemed better in the nifedipine group than in the ritodrine group. The promising data from small prospective studies and the results of this retrospective study warrant further large prospective studies on the definitive place of nifedipine in the treatment of premature labor. Until the results of such a trial are available we advocate the use of nifedipine in case of preterm labor, especially in a patient with diabetes mellitus, ruptured membranes, cardiac disease or multiple pregnancy, in order to avoid the characteristic side effects of beta-mimetics.",1995.0,0,0
857,8606536,Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine: cross-over study.,J Carroll; A Shamiss; D Zevin; J Levi; T Rosenthal,"The lack of comparative studies of nifedipine and felodipine using 24-h blood pressure (BP) monitoring in the same patients led to the present study evaluating the antihypertensive efficacy and side effects of treatment with slow-release (SR) nifedipine (20 mg twice daily) and extended-release (ER) felodipine (10 mg once daily). In the double-blind study, subjects were randomly assigned to one of two treatment groups: 6 weeks of nifedipine SR (20 mg twice daily) followed by 6 weeks of felodipine (ER) (10 mg once daily with evening matched placebo), or vice versa. Twenty-four-hour ambulatory BP monitoring showed no significant differences in systolic BP (SBP) during the day. There were no significant differences in diastolic BP (DBP) throughout the 24 h, although the frequency of DBP recordings > 90 mm Hg was greater during nifedipine (33.1%) than felodipine (27.75%) treatment. The most common side effects were flushing, palpitations, headaches, and ankle edema; there were no adverse effect on lipid profile or glucose level.",1995.0,0,0
858,8607661,Verapamil as prophylactic treatment for atrial fibrillation after lung operations.,W Van Mieghem; G Tits; K Demuynck; L Lacquet; G Deneffe; T Tjandra-Maga; M Demedts,"Atrial fibrillation is a frequently occurring arrhythmia after thoracic operations. Preventive strategies for this complication have been extensively evaluated after cardiac operations. We performed a prospective, open randomized study, comparing intravenous verapamil and placebo in 199 patients after pneumonectomy or lobectomy at the University Hospital of Leuven. Verapamil was administered as a bolus of 10 mg over 2 minutes followed by a 30-minute infusion of 0.375 mg/min and then 0.125 mg/min for 3 days. The patients were continuously monitored in the postoperative intensive care unit. Atrial fibrillation occurred in 15% of the patients receiving placebo and in 8% of the patients receiving verapamil (difference not significant). The verapamil infusion was interrupted in 9% of the patients because of bradycardia and in 14% because of hypotension. If tolerated, continuous intravenous verapamil infusion showed only a modest prophylactic efficacy for the occurrence of atrial fibrillation after lung operations. In the dose employed the verapamil infusion was accompanied with a high incidence of side effects necessitating interruption of the therapy.",1996.0,0,0
859,8615057,Effects of gemfibrozil (Lopid) on hyperlipidemia in acitretin-treated patients. Results of a double-blind cross-over study.,C Vahlquist; A G Olsson; A Lindholm; A Vahlquist,"Hyperlipidemia is a common side-effect of oral retinoid treatment, which sometimes interferes with long-term therapy. To evaluate the safety and efficacy of the lipid-lowering drug gemfibrozil on retinoid-associated hyperlipidemia, we studied the clinical response and the plasma lipoprotein levels in 22 acitretin-treated (0.25-0.75 mg/kg) patients mainly suffering from psoriasis. Gemfibrozil or placebo was given in a double-blind cross-over fashion to 14 patients, who after 8 weeks of acitretin therapy and dietary advice exhibited hyperlipidemia (triglyceride levels > or = 50% above baseline and/or > or = 2.0 mmol/l). Serum triglycerides remained high (3.7 +/- 2.4 mmol/l) during placebo treatment but were reduced after 8 weeks of gemfibrozil treatment (p < 0.01). The total cholesterol level decreased slightly (p < 0.05) during gemfibrozil treatment, but the LDL/HDL ratio did not change significantly. No untoward effects of gemfibrozil on acitretin dose-response and clinical side-effects were noted. Gemfibrozil thus appears useful in patients prone to retinoid-induced hyperlipidemia unresponsive to dietary treatment and acitretin dose reductions.",1995.0,0,0
860,8622245,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
861,8626878,"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
862,8631565,Echocardiography in acute myocardial infarction: today and tomorrow.,S Firoozan; S Kaul,,1996.0,0,1
863,8636558,"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
864,8637188,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
865,8638195,Felodipine as an alternative to more expensive calcium antagonists in mild to moderate hypertension.,F J Landry; J D Horwhat; D Tomich; L Pinski,"We studied the therapeutic substitution of a less expensive but equally effective antihypertensive agent and assessed patient outcome. The medication of 39 patients with hypertension was changed from once-daily diltiazem hydrochloride (Cardizem CD) or nifedipine (Procardia XL) to felodipine (Plendil). Titration to a final dose was based on home and office blood pressure measurements assessed over subsequent follow-up clinic visits. Self-administered questionnaires measured different aspects of well-being and symptoms before and after the change in medication. Eighty percent of the cohort switched successfully to felodipine. Office systolic and diastolic pressures improved after the medication change (systolic: 150 mm Hg versus 144 mm Hg; diastolic: 92 mm Hg versus 87 mm Hg). No statistically significant differences were found among the 39 symptoms measured. A yearly savings potential for our institution was estimated to be $72,000.",1996.0,0,0
866,8641044,Corrections to the nifedipine meta-analysis.,C D Furberg; B M Psaty,,1996.0,0,1
867,8644661,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.",1996.0,1,1
868,8650291,[The effect of nifedipine and chlordiazepoxide on alcohol withdrawal syndrome].,J Samochowiec; K Fabiańczyk; R Reszczyński; I Czopek; J Pełka-Wysiecka; J M Horodnicki,"The aim this study was to evaluate the efficacy and tolerability of DHP calcium channel antagonist-nifedipine in human AWS in comparison to conventional treatment with chlordiazepoxide. Fifty nine hospitalized alcoholics of both sexes with diagnosis of AWS according to DSM-III-R criteria were treated for 2 weeks in monotherapy with nifedipine (Cordafen-Polfa)-60 mg/d. or with chlordiazepoxide (Elenium-Polfa)-150 mg/d. Evaluation of AWS symptoms was performed at baseline and after 3, 7, 14 days using Sandowal-Wang scale. Our original scales (37 items) were designed for measuring the depth of dependence (WGU) and the velocity of dependence syndrome appearance (WWO). The results show that both groups were similar regarding WGU and WWO before treatment. Both drugs caused an improvement of AWS symptoms after 3 and 7 days lasting till the end of hospitalization. Nifedipine was well tolerated and no side effects were observed or reported. The group and multidimensional analyses were performed using original computer program. The patients were divided into 3 subgroups. Comparison of mean values of improvement index between both drugs in those subgroups of patients according to WGU criteria, revealed that nifedipine was more effective on the 3-rd and 7-th day in 3 groups and 2 groups resp. According to WWO criteria the improvement index was significantly higher on the 3-rd and 7-th day in two groups whereas in one group chlordiazepoxide and nifedipine action was equal. The proposed method of group and multidimensional analysis enable us to compare the effectiveness of different kinds of AWS treatment. It is an useful aid of choosing the best drug treatment for a new patient.",1996.0,0,0
869,8651122,Sex- and age-related antihypertensive effects of amlodipine. The Amlodipine Cardiovascular Community Trial Study Group.,R A Kloner; J R Sowers; G F DiBona; M Gaffney; M Wein,"This community-based study assessed whether there were age, sex, or racial differences in response to amlodipine 5 to 10 mg once daily in patients with mild to moderate essential hypertension. This prospective, open-label trial had a 2-week placebo period, a 4-week upward drug titration/efficacy period, and a 12-week drug maintenance period. There were 1,084 evaluable patients (mean age 55.5 years; 65% men and 35% women; 79% white and 21% black; 75% <65 and 25% > or = 65 years old). At the end of the titration/efficacy phase, the mean +/- SD blood pressure (BP) decreased by -16.3 +/- 12.3/-12.5 +/- 5.9 mm Hg, (p < or = 0.0001). Amlodipine produced a goal BP response (sitting diastolic BP < or = 90 mm Hg, or a 10 mm Hg decrease) in 86.0% of patients overall. The BP response was greater in women (91.4%) than in men (83.0%, p < or = 0.001), and greater in those > or = 65 years old (91.5%) than in those < 65 years old (84.1%, p < or = 0.01); however, it was similar between whites and blacks (86.0% vs 85.9%, respectively, p = NS). The sex difference in BP response could not be fully explained by differences in age, weight, dose (mg/kg), race, baseline BP, or compliance, and there were no differences among women based on use of hormone replacement therapy. Amlodipine was well tolerated; mild to moderate edema was the most common adverse effect. Thus, amlodipine was effective and safe as once-a-day monotherapy in the treatment of mild to moderate hypertension in a community-based population. Women had a greater BP response to amlodipine.",1996.0,0,0
870,8652903,Gingival overgrowth in renal transplant patients administered cyclosporin A in mixture or in capsule form. A longitudinal study.,B Wondimu; J Sandberg; T Modéer,"Cyclosporin A (CsA)-induced gingival overgrowth was longitudinally studied in 45 adult renal transplant patients randomly assigned to be administered CsA orally in mixture or in capsule form. After 1 year of CsA therapy, 37% of the mixture and 43% of the capsule patients exhibited gingival overgrowth. In mixture patients gingival overgrowth was present, already after 1 month of CsA therapy and, after 12 months, mixture patients exhibited an increased number of sites with gingival overgrowth in the regions of the upper front and lower molars compared to capsule patients. In addition, the relative increase in gingival width of the interdental papillae of the maxillary central incisors and the mandibular first molars, measured buccolingually on stone casts, was also higher in mixture patients than in capsule patients. In a stepwise multiple logistic regression analysis, the use of nifedipine and the total CsA dose administered during the first 6 posttransplant months were the predictors associated with gingival overgrowth. The study suggests that concomitant administration of nifedipine in renal transplant patients should be avoided and a change from the mixture form of CsA to the capsule form should be considered in order to minimize the development of CsA-induced gingival overgrowth.",1996.0,0,0
871,8665991,Clinical equivalence of two tablet formulations of felodipine. A placebo-controlled study of 24-hour blood pressure control and tolerability.,B P McGrath; R W Watts; D B Elmfeldt,"This study was performed to assess whether a new formulation of felodipine extended release (FER) tablets with a 9 mm diameter is similar to the presently used 11 mm diameter FER formulation with respect to antihypertensive effect and tolerability in patients with essential hypertension. A randomised, double-blind, placebo controlled, three-way cross-over study design was used. Twenty-four patients with a supine diastolic blood pressure (DBP) of 95-115 mmHg after a 4-week placebo run-in period were given FER 5 mg 9 mm tablets, FER 5 mg 11 mm tablets and placebo in randomised order. The tablets were given once daily and each double-blind treatment period lasted for two weeks. Twenty-four hour ambulatory blood pressure monitoring was performed at the end of each treatment period. The primary effect variable was mean DBP over 24 hours. Nineteen patients had 24-hour blood pressure data valid for analysis using an analysis of variance with patient, treatment, period and carry-over as factors. Both formulations of FER 5 mg tablets significantly reduced the mean 24-hour DBP compared to placebo. The 9 and 11 mm tablets resulted in, on average, 4.7 and 3.4 mmHg lower mean 24-hour DBP than placebo. There was, however, no significant difference between the two different FER formulations. Both FER formulations were well tolerated and similar to placebo in this respect. Both FER 5 mg tablet formulations (9 and 11 mm diameter), given once daily, were clinically equivalent with respect to antihypertensive effect and tolerability in patients with mild to moderate essential hypertension.",1995.0,0,0
872,8674257,Stress-induced hemodynamic and hemostatic changes in patients with systemic hypertension: effect of verapamil.,O C Gebara; A H Jimenez; C McKenna; M A Mittleman; P Xu; I Lipinska; J E Muller; G H Tofler,"Stress-induced hemodynamic and hemostatic responses may acutely trigger atherosclerotic plaque disruption and thrombosis leading to myocardial infarction. This study was designed to evaluate the responses to three stressors and to determine if once-daily sustained release verapamil (Verelan) modified these responses. We studied 13 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 4 weeks of therapy, patients were evaluated following assumption of the upright posture, mental stress, and cold pressor test. During placebo, the stressors produced an increase in systolic pressure (144 +/- 2 to 167 +/- 3 mmHg, p < 0.001), heart rate (70 +/- 2 to 77 +/- 2 beats/ min, p < 0.001), and platelet aggregability to adenosine diphosphate (threshold concentration fell from 2.8 +/- 0.4 to 1.9 +/- 0.1 microM, p = 0.05) and epinephrine (3.4 +/- 0.9 to 1.6 +/- 0.6 microM, p < 0.001). Verapamil lowered systolic pressure at baseline (144 +/- 2 to 134 +/- 2 mmHg, p < 0.001), and after stress (167 +/- 3 to 154 +/- 3 mmHg, p < 0.001), but did not alter the absolute increase with stress. During verapamil, platelet reactivity did not increase with stress, and the post-stress response to epinephrine was reduced (higher threshold concentration) compared with placebo (3.9 +/- 1.3 vs. 1.5 +/- 0.3 microM, p = 0.05). Verapamil also reduced the response to collagen (increased lag time) at baseline and after stress (111 +/- 9 vs. 91 +/- 3 s, p < 0.01). We conclude that verapamil blunted potentially harmful stress-induced hemodynamic and hemostatic changes. Further studies are required to determine whether these effects translate into a lower incidence of acute cardiovascular events.",1996.0,0,0
873,8675249,Comparison of nifedipine alone and with diltiazem or verapamil in hypertension.,J J Saseen; B L Carter; T E Brown; W J Elliott; H R Black,"Receptor binding studies suggest that combinations of calcium channel blockers may result in either enhanced or diminished pharmacological effects, but clinical data in hypertension are incomplete. In this study, we compared blood pressure reductions using nifedipine alone, nifedipine plus diltiazem, and nifedipine plus verapamil and determined whether combinations alter nifedipine pharmacokinetics. After determination of baseline blood pressures. 16 subjects with essential hypertension (12 men, 4 women; mean age, 48 years) received 30 mg/d open-label, sustained release nifedipine for 2 weeks. If still hypertensive (n = 16), they were randomized (double-blind) to receive either additional sustained release diltiazem or sustained release verapamil, both 180 mg/d, for 2 weeks and were then crossed-over for the final 2 weeks of the study. All medications were once-daily, extended-release formulations. Blood pressures and nifedipine plasma concentrations were measured during the final day of each treatment. Overall, each combination lowered mean systolic and diastolic pressures more than nifedipine alone. Mean supine diastolic pressures were significantly lower at 8 hours (77.6 versus 84.6 mm Hg, P = .001) and 12 hours (81.5 versus 87.1 mm Hg, P = .04) with nifedipine plus diltiazem than nifedipine plus verapamil. Mean nifedipine concentrations were inversely correlated with mean blood pressures. Mean nifedipine area under the curve values were greater with diltiazem than verapamil (1430 versus 1134 ng.h/mL, P = .026), with each greater than nifedipine alone (957 ng.h/mL). Nifedipine plus diltiazem had a greater antihypertensive effect than nifedipine plus verapamil. Diltiazem caused greater increases in nifedipine plasma concentrations than did verapamil. These data suggest that combined calcium channel blockers result in additive antihypertensive effects, perhaps because of a pharmacokinetic interaction.",1996.0,0,0
874,8677723,[A trial of the use of nifedipine for preventing relapses in affective and schizoaffective psychoses].,L V Snedkova,"Nifedipine was applied for the secondary prophylaxis of affective phasic disorders. 21 patients with both affective and schizoaffective psychoses were treated with nifedipine for 1-3 years (mostly for 2 years) in a dose of 20-60 mg daily (usually 30-40 mg). The clear prophylactic effect of nifedipine was observed in 76.2% of cases. The duration of affective phases reduced by 44.8% while their frequency decreased by 40.4% as compared with the control group. The positive therapeutic effect was more pronounced for manic disorders (the transition of the disturbances to subclinical, ambulant level). The preventive effect of the drug was more clear in affective than in schizoaffective psychoses (91.7% and 55.6%, respectively) as well as it was more expressed in bipolar (84.6%) than in monopolar (62.5%) patients. The low frequency (23.8%) of side-effects occurred to be the positive characteristics of nifedipine treatment especially in long-term therapy.",1996.0,0,0
875,8682000,Pointers from recent multicentre trials using ambulatory monitoring--placing placebo in perspective.,D Mulcahy,,1995.0,0,0
876,8682116,,,,,1,1
877,8682134,Effects of metoprolol vs verapamil in patients with stable angina pectoris. The Angina Prognosis Study in Stockholm (APSIS),N Rehnqvist; P Hjemdahl; E Billing; I Björkander; S V Eriksson; L Forslund; C Held; P Näsman; N H Wallén,"To study long-term treatment effects of metoprolol or verapamil on combined cardiovascular end points and psychological variables in patients with stable angina pectoris. Randomized, double-blind, double-dummy trial. The study included 809 patients under 70 years of age with stable angina pectoris. The mean age of the patients was 59 +/- 7 years and 31% were women. Exclusion criteria were myocardial infarction within the previous 3 years and contraindications to beta-blockers and calcium antagonists. The patients were followed between 6 and 75 months (median 3.4 years and a total of 2887 patient years). The patients were treated with either metoprolol (Seloken ZOC 200 mg o.d.) or verapamil (Isoptin Retard 240 b.i.d.). Acetylsalicylic acid, ACE inhibitors, lipid lowering drugs and long acting nitrates were allowed in the study. Death, non-fatal cardiovascular events including acute myocardial infarction, incapacitating or unstable angina, cerebrovascular or peripheral vascular events. Psychological variables reflecting quality of life i.e. psychosomatic symptoms, sleep disturbances and an evaluation of overall life satisfaction. Combined cardiovascular events did not differ and occurred in 30.8% and 29.3% of metoprolol and verapamil treated patients respectively. Total mortality in metoprolol and verapamil treated patients was 5.4 and 6.2%, respectively. Cardiovascular mortality was 4.7% in both groups. Non-fatal cardiovascular events occurred in 26.1 and 24.3% of metoprolol and verapamil-treated patients, respectively. Psychosomatic symptoms and sleep disturbances were significantly improved in both treatment groups. The magnitudes of change were small and did not differ between treatments. Life satisfaction did not change on either drug. Withdrawals due to side effects occurred in 11.1 and 14.6% respectively. This long term study indicates that both drugs are well tolerated and that no difference was shown on the effect on mortality, cardiovascular end points and measures of quality of life.",1996.0,1,1
878,8682138,"The Total Ischaemic Burden European Trial (TIBET). Effects of atenolol, nifedipine SR and their combination on the exercise test and the total ischaemic burden in 608 patients with stable angina. The TIBET Study Group.",K M Fox; D Mulcahy; I Findlay; I Ford; H J Dargie,"To determine the effects of atenolol, nifedipine and their combination on exercise parameters and ambulatory ischaemic activity in patients with mild chronic stable angina. Multicentre, multinational study involving 608 patients from 69 centres in nine countries. Placebo washout followed by double-blind parallel-group study comparing atenolol 50 mg bd, nifedipine SR 20 mg bd, and their combination. Patients underwent maximal exercise testing using either a bicycle (n = 289) or treadmill (n = 319) and 48 h of ambulatory ST segment monitoring outside the hospital environment at the end of the placebo washout period and after 6 weeks of active therapy. Both medications alone and in combination caused significant improvements in exercise parameters and significant reductions in ischaemic activity during daily activities, when compared with placebo. There were, however, no significant differences between groups, for any of the measured ischaemic parameters although combination therapy resulted in a greater fall in resting systolic and diastolic blood pressure than either treatment alone. In the management of mild chronic stable angina there appears to be little advantage gained from using combination therapy for ischaemia reduction.",1996.0,0,1
879,8682597,"A comparison of nifedipine once daily (Adalat LA), isosorbide mononitrate once daily, and isosorbide dinitrate twice daily in patients with chronic stable angina.",J M Walker; P V Curry; A E Bailey; S E Steare,"The efficacy of nifedipine gastrointestinal therapeutic system (GITS), 60-90 mg o.d., isosorbide dinitrate, 40-60 mg b.d., and isosorbide mononitrate slow-release, 50-100 mg o.d. was assessed in a six week double-blind, parallel-group study in patients with stable angina on chronic beta-blocker treatment. Of 339 patients who entered the study, 229 were eligible for the valid case analysis of efficacy and 335 for the safety analysis. Nifedipine GITS was significantly better than isosorbide dinitrate (P < or = 0.025) in prolonging time to 1 mm ST-segment depression, time to maximum ST-segment depression, time to occurrence of angina and total exercise duration, in addition to reducing the number of angina attacks and glyceryl trinitrate consumption after six weeks therapy. Nifedipine GITS was also significantly better than isosorbide mononitrate (P < or = 0.025) in prolonging time to occurrence of angina and time to 1 mm ST-segment depression after six weeks therapy. The incidence of headache was considerably higher in both the isosorbide dinitrate and isosorbide mononitrate groups (40% and 41%, respectively) than in the nifedipine GITS group (9.5%, P < or = 0.001), and was the main reason for withdrawal from the study (isosorbide dinitrate 18/99, isosorbide mononitrate 17/99, nifedipine GITS 2/95). Peripheral oedema was more common in patients treated with nifedipine GITS (12.5%) compared to nitrates (2% in both groups, P < or = 0.01), but resulted in withdrawal of only one patient (treated with nifedipine GITS). This study suggests that the efficacy and tolerability of nifedipine GITS is superior to long acting nitrates as second-line therapy to beta-blockade in the treatment of chronic stable angina.",1996.0,0,1
880,8686946,[An assessment of the efficacy of Lomir in treating hypertension in patients in the early period after aortocoronary bypass operations].,S V Tskhovrebov; L M Poplavskaia,"The authors assessed the efficacy and safety of intravenous lomir used to treat arterial hypertension in 10 coronary patients early after aortocoronary shunting. The following parameters were monitored: systolic, diastolic, and mean arterial pressure, ECG, pressure in the pulmonary artery, blood gases, and minute volume obtained by thermodilution. Intravenous lomir was found to be a highly effective hypotensive agent in patients in the early periods after aortocoronary shunting, well tolerated by the patients, the infusions being easy to monitor and involving virtually no side effects. Lomir improved the coronary bloodstream, virtually did not influence the heart rate, atrioventricular conduction, and pumping function of the heart.",1996.0,0,0
881,8690823,Effects of dihydropyridine calcium antagonists on albuminuria in patients with diabetes.,K Abbott; A Smith; G L Bakris,"The present study was designated to assess the effects of two different dyhydropyridine calcium antagonists (DHPCAs) on proteinuria in patients with noninsulin-dependent diabetes mellitus (NIDDM). The hypothesis that similar levels of blood pressure reduction with two different DHPCAs produce similar degrees of proteinuria reduction was tested. In a prospective randomized study, 14 patients with NIDDM, hypertension, proteinuria, and renal insufficiency were given either isradipine (n = 7) or nifedipine XL (n = 7) for 6 months. After a 2-week washout period, patients were crossed over to the other drug and observed for an additional 6 months. Drugs were titrated to lower arterial pressure to < 140/90 mmHg. Patients also instructed to follow a low-sodium diet at the initial visit. Blood pressure and 24-hour urine values for creatinine clearance, albuminuria, proteinuria, and sodium were assessed monthly. At the end of the initial and crossover treatment periods, there were no significant reductions in the level of albuminuria from baseline with either drug. Sodium excretion was < 110 mEq/L with each drug tested. The results of this study support the concept that DHPCAs do not reduce proteinuria in patients with type II diabetes. This failure to reduce albuminuria and proteinuria occurred despite adequate blood pressure reduction and an effort at dietary sodium restriction.",1996.0,0,0
882,8699214,Age and severe adverse drug reactions caused by nifedipine and verapamil. Gruppo Italiano di Farmacovigilanza nell' Anziano (GIFA).,M Pahor; A Manto; C Pedone; L Carosella; J M Guralnik; P Carbonin,"The association of age with risk for severe adverse drug reactions (SADRs) was studied in 2371 and 862 hospitalized patients taking nifedipine and verapamil, respectively. Nifedipine caused hypotension (n = 22), tachycardia (n = 3), and acute renal failure (n = 1) (total SADR rate, 1.1%, 26/2371). Verapamil caused hypotension (n = 3), bradycardia (n = 9), and atrioventricular blocks (n = 2) (total SADR rate, 1.6%, 14/862). The mean age of patients with and without SADRs was for nifedipine 77.1 +/- 1.7 and 71.8 +/- 0.8 years, respectively (p < 0.05), and for verapamil 73.4 +/- 2.9 and 73.1 +/- 0.4 years, respectively. Sex, length of stay, comorbidity, polypharmacy, intake of slow-release preparations, daily dosage, and new intake of calcium antagonists were examined as potential confounders of the age-SADR association. After adjusting for potential confounders, age was significantly and independently associated with SADRs caused by nifedipine, but not with SADRs caused by verapamil (OR = 1.69, 95% CI = 1.05-2.72 and OR = 1.06, 95% CI = 0.63-1.68 for 10-year increase, respectively). Although nifedipine and verapamil did not have significantly different rates of SADRs, an age-related gradient was found only for nifedipine.",1996.0,1,1
883,8705151,Comparison of antihypertensive effects of nicardipine with nitroglycerin for perioperative hypertension.,T L Chen; W Z Sun; Y J Cheng; T S Lee; S Y Lin; C J Lin,"To compare the efficacy of intravenous (iv) nicardipine with nitroglycerin for the treatment for patients with perioperative hypertension. Forty patients with perioperative hypertension randomly divided into two groups were treated with intravenous calcium entry blocker, nicardipine, or vasodilator, nitroglycerin. Haemodynamic measurements including mean arterial and pulmonary arterial pressure, central venous and pulmonary capillary wedge pressure, and cardiac output were recorded; peripheral and pulmonary vascular resistance were calculated. Both medications were effective in reducing blood pressure and controlling haemodynamics. During the maintenance by continuous iv infusion, nicardipine controlled hypertension more rapidly than nitroglycerin (nicardipine 10.5 +/- 2.5 min and nitroglycerin 18.7 +/- 2.8 min, p < 0.05) without significant alteration in heart rate. The total frequency of dose adjustments required to achieve therapeutic response was significantly less in the nicardipine-treated group (2.5 +/- 0.3 for nicardipine and 6.2 +/- 1.4 for nitroglycerin, p < 0.05). Incidence of hypotensive episodes during the infusion were observed in both groups [nicardipine 5% (1/20) and nitroglycerin 30% (6/20), p < 0.05]. Intravenous nicardipine is as effective as nitroglycerin in the treatment of perioperative hypertension. Specific advantages have been identified such as stable dose-response effect, less hypotensive and tachycardial effects during the use of iv nicardipine in treatment of hypertensive patients.",1995.0,0,0
884,8706625,[Calcium antagonists and lithium in preventive treatment of manic-depressive disorder].,Y Sarfati; C Spadone; J M Vanelle; H Lôo,"Recent advances in knowledge about calcium's role as an intracellular regulator allow to broaden understanding of possible pathophysiologic mechanisms in affective disorders. An hypothesis emerge that bipolar illness arise from disorders in calcium-regulated functions. Given this hypothesis, some authors propose to describe the common profiles of action of the different mood-stabilizers: all the neural mechanisms that are hypothesized to explain various psychopharmacological treatments of bipolar illness involve functions that are critically controlled by calcium. Moreover, in every instance, a known action of lithium on calcium-dependent processes could account for lithium's prophylactic results. Similarities exist between the action of lithium and calcium antagonists like verapamil and nimodipine. From these considerations the hypothesis emerge that calcium antagonists could be an alternative pharmacological agent in the maintenance treatment of bipolar illness. Calcium antagonists have been found useful in this indication by a number of investigators. Given the safety and relative lack of side effects of calcium channel blocking agents, their potential efficacy in mood disorders, it is concluded that calcium antagonists may be an alternative choice in prophylactic treatment for bipolar illness, especially in patients who cannot be treated with lithium or carbamazepine. There is evidence for using verapamil at 240 to 320 mg a day, in 2 to 4 times. Some studies suggest that the association of lithium with calcium antagonist resulted more effective than lithium alone or calcium antagonist alone in the reduction of episodes of affective disorders. However, concomitant administration of a calcium channel antagonist and lithium present adverse interactions (lithium toxicity, cardiovascular accidents), probably because of synergistic toxic effects. Therefore, authors advise care in monitoring patients receiving the combination of these medications.",1996.0,0,0
885,8707025,[Efficacy and tolerability of felodipine and nifedipine in stable angina refractory to beta-blocker therapy].,G Mazzotta; M Falcidieno; E Ravera; C Vecchio,"Medical therapy of stable angina contemplates beta-blockers as a first line. The combination of dihydropyridines with beta-blocking drugs enhances the effectiveness of both single therapies. Nifedipine, in the usual formulation (AR), is burdened by an unsatisfactory tolerability, and this is the main reason to study new dihydropyridines. To compare efficacy and tolerability of felodipine ER 10 mg o.d. with that of nifedipine AR 20 mg b.d. in patients with stable angina pectoris refractory to beta-blocker therapy. Of 15 initial patients, 14 were entirely evaluable for the study, the design of which was double blind, double dummy, random cross over and placebo controlled. All patients showed reproducible threshold of ischemia at exercise testing. In constancy of beta-blocker therapy, they were given placebos for 2 weeks, then one of the active drugs with a placebo of the other one for 4 weeks, followed by the cross-over period of 4 weeks. Efficacy and tolerability of treatments were evaluated by clinical observation and rest and exercise radionuclide angiography. At the end of each individual study, it was decided blindly if and which of the 2 drugs seemed preferable, considering symptoms, undesired collateral effects and the results of exercise procedures. The efficacy on angina of the 2 active treatments was not different. More patients suffered undesired side effects on nifedipine than on felodipine. Left ventricular ejection fraction (LVEF) at rest was 65.3 +/- 4.3% (s.e.) on placebo, 64.6 +/- 2.6% on felodipine and 67.5 +/- 2.5% on nifedipine (p n.s.). A significant reduction in resting LV function (that is, a decrease of LVEF > or = 5%) was observed in 2 patients on felodipine and 3 on nifedipine, but in both groups other 3 patients showed improvement in LVEF. During exercise, LVEF decreased 6.1 +/- 2.0% on placebo and 3.3 +/- 3.2% on nifedipine, while it increased 1.0 +/- 2.6% on felodipine (p < 0.01 vs. placebo). At the end of the study, felodipine was blindly judged superior to nifedipine in 10 patients, nifedipine was superior in 1 case, in the other 3 there was no clear difference (p < 0.02). In 14 patients with stable angina refractory to beta-blockers, the addition of felodipine or nifedipine has similar antiischemic effects. However, felodipine showed better results in LVEF response to exercise and less side effects, and this leaded to a more frequent blind choice of felodipine versus nifedipine to add to beta-blocker therapy.",1996.0,0,0
886,8712120,Comparison of enalapril versus nifedipine to decrease left ventricular hypertrophy in systemic hypertension (the PRESERVE trial).,R B Devereux; B Dahlof; D Levy; M A Pfeffer,"The PRESERVE (Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement) study is designed to provide a definitive test of the ability of enalapril to achieve greater left ventricular (LV) mass reduction than nifedipine GITs (gastrointestinal treatment system) by a degree that would be prognostically meaningful on a population basis (10 g/m2). To achieve this goal, an ethnically diverse population of 480 men and women with essential hypertension and increased LV mass of screening echocardiography will be enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6 and 12 months' randomized therapy. Blinded readings of echocardiograms at a central laboratory will provide systematic information about treatment effects on LV structure, wall motion, and Doppler blood flow. The study power is at least 90% to test the primary hypotheses that enalapril will induce greater normalization of LV mass and diastolic filling than nifedipine. After the 1-year echocardiographic trial, the study population will be followed 3 more years to test the hypothesis that a reduction in LV mass, independent of blood pressure lowering, is associated with a reduction in the risk of morbid and fatal cardiovascular events.",1996.0,1,1
887,8712135,Trends and determinants of calcium antagonist usage after acute myocardial infarction (the GISSI experience).,G Zuanetti; R Latini; F Avanzini; M G Franzosi; A P Maggioni; F Colombo; E Nicolis; F Mauri,"In the last decade, several clinical trials in patients with, or recovering from, acute myocardial infarction (AMI) have evaluated the role of calcium antagonists in affecting patients' prognosis. Results have been disparate, with evidence of possible harm, no effect, or some benefit, depending on the agent used. We evaluated how the evidence from these trials has influenced the pattern of prescription of calcium antagonists and assessed the important determinants of use of these agents in patients after AMI. We analyzed retrospectively the prescription of calcium antagonists at discharge in all patients recovering from AMI enrolled in 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto-1 [GISSI-1], GISSI-2, and GISSI-3) during the last 10 years. A progressive decrease in prescriptions for calcium antagonists was evident, from 47.2% in GISSI-1 to 35.1% in GISSI-2 to 19.0% in GISSI-3 (p<0.001). The presence of post AMI angina, history of hypertension, and occurrence of reinfarction were associated with a higher usage of calcium antagonists, whereas the use of beta blockers at discharge was a major independent negative determinant. Use of calcium antagonists for secondary prevention after AMI (i.e., without specific clinical indications for their use) decreased by approximately 60% (from 26.1% to 10.3%). The data indicate that the usage of calcium antagonists in GISSI studies has been strongly affected by the results of other large multicenter trials evaluating calcium antagonists. These agents are now prescribed in patients after AMI almost exclusively in the presence of specific indications such as systemic hypertension or angina.",1996.0,0,0
888,8712143,"Comparison of the effects of amlodipine and diltiazem on 24-hour blood pressure, plasma catecholamines, and left ventricular mass.",F H Leenen; A Fourney,"In 30 patients with mild to moderate essential hypertension and high-normal left ventricular (LV) mass, the effects of treatment for 6 months with amlodipine (5 to 10 mg every morning) versus diltiazem-sustained release (SR) (90 to 180 mg twice daily) on 24-hour blood pressure (BP), plasma catecholamines, and echocardiographic estimates of LV mass and function were evaluated. Both amlodipine and diltiazem caused stable, persistent BP reduction over 24 hours with no evidence for a ""peak"" effect. For a similar decrease in diastolic BP, amlodipine caused a significantly larger decrease in systolic BP. Amlodipine decreased BP by lowering total peripheral resistance, whereas diltiazem caused small decreases in both total peripheral resistance and cardiac index. Both calcium antagonists caused modest but significant decreases in supine and standing plasma catecholamines. LV wall thickness and LV mass decreased significantly over the 6 months of follow-up: -6 +/- 2 with diltiazem and -10 +/- 2 g/m2 with amlodipine. In patients taking amlodipine, the decrease in LV mass correlated significantly with the decrease in plasma norepinephrine. In contrast to rapid-acting calcium antagonists, both amlodipine and diltiazem-SR cause smooth BP control and an appropriate decrease in LV mass without activation of the sympathetic nervous system.",1996.0,0,0
889,8720425,Twenty-four-hour antihypertensive efficacy of felodipine 10 mg extended-release: the Italian inter-university study.,G Pannarale; P E Puddu; F Monti; L Irace; M Bentivoglio; F Collauto; A Barsotti; L Corea; G Trevi; P P Campa; A Jacono,"We assessed the 24-h antihypertensive efficacy of an extended-release (ER) 10-mg formulation of the dihydropyridine felodipine in mild-to-moderate essential hypertension [World Health Organization (WHO) stage I-II]. Thirty patients, 23 men and 7 women, aged 37-70 years (mean 53 +/- 9 years) participated in a double-blind, randomized, cross-over study of felodipine 10 mg ER versus placebo. An ambulatory daytime diastolic blood pressure (DBP) >90 mm Hg at the end of a 4-week run-in period was necessary to enter the 10-week treatment phase. Twenty-nine patients completed the treatment phase. Twenty-two underwent a 2-day single-blind placebo follow-up to assess residual drug effects. All patients underwent ambulatory BP monitoring (ABPM) by Spacelabs 90207 recorders. Recorders were programmed to make automatic BP and heart rate (HR) measurements every 15 min throughout the 24 h. Felodipine 10 mg ER significantly (p < 0.01) reduced ambulatory systolic BP (SBP) and DBP values throughout the 24-h, day (7 a.m. to 11 p.m.) and night (11 p.m. to 7 a.m.) periods, but not influencing average ambulatory HR values. Trough-to-peak (T/P) ratios, calculated on the average ambulatory BP values measured in the 7-9 a.m. 2-h interval of the second day of ABPM (before the new drug administration: trough) and in the 10 a.m. to 12 noon 2-h interval of the first day of ABPM (peak BP-lowering effect), were 0.71 and 0.58 for SBP and DBP, respectively. Individual T/P calculations, after post hoc selection of nonresponders, gave superimposable results, the consistency of which was judged on mean, median, and confidence intervals (CI). However, the wide variability of the individual T/P ratios suggests that this method cannot be the only means to evaluate the duration of action of an antihypertensive drug by ABPM. The long-acting BP-lowering drug effect was clearly shown by the ABPM performed in the follow-up when SBP and DBP average values of the 24-h, day, and night periods were still reduced. Felodipine 10 mg ER effectively reduced BP in patients with mild-to-moderate hypertension, showing prolonged duration of its antihypertensive action beyond the time of the next dose.",1996.0,0,0
890,8720766,"Antihypertensive drugs and glucose metabolism: a comparison between a diuretic and felodipine, a new calcium antagonist, when added to a beta-blocker in non-diabetic hypertensive women.",C Bengtsson; L Lapidus,"Felodipine, a vascular selective antihypertensive calcium antagonist, was compared with hydrochlorothiazide, a diuretic, with respect to glucose tolerance. An open crossover study was performed comprising 16 non-diabetic hypertensive women (age range 59-75 years). The women continued to take a beta-blocker as a basal therapy. Each treatment period lasted three months. The blood pressure was similar irrespective of treatment. Blood glucose values were not significantly different during the oral glucose tolerance test. Serum insulin levels after glucose administration were lower when the patients were treated with felodipine than when taking hydrochlorothiazide. A possible explanation for this observation may be an increased insulin release as a consequence of treatment with a diuretic in order to maintain normal blood glucose levels during the glucose tolerance test. Felodipine appears preferable to hydrochlorothiazide as an addition to a beta blocker in hypertensive patients from a glucose metabolism point of view.",1994.0,0,0
891,8722433,Clinical outcome of a mandatory formulary switch for dihydropyridine calcium channel blocker therapy at a Veteran's Administration Medical Center.,G Gustin; W B White; S Taylor; C Daragjati,"Recently, changes in antihypertensive therapies with similar properties have been made based primarily on cost savings for hospital formularies. To assess blood pressure (BP) control and adverse side effects associated with a switch of patients on nifedipine GITS to felodipine at our Veteran's Administration Medical Center (VAMC), we prospectively studied physician records and patient-reported side effects (both from the medical record and patient questionnaires) in 127 hypertensive patients (70 +/- 10 years, 95% men, 88% nonblack, 44% with coronary disease) who underwent the forced switch in therapy. During the period of patient visits/chart review, physicians were unaware that the study was being conducted. A minimum of 2 months and two visits on each therapy was required for patient inclusion. The mean doses of nifedipine GITS and felodipine used were 55 +/- 24 mg/day and 8 +/- 2.6 mg/day, respectively. The use of supplemental antihypertensive agents was similar in both calcium channel blocker groups. Systolic BPs and heart rates were similar in patients taking the two drugs, and the diastolic BP was modestly lower in patients taking felodipine (78 +/- 10 mm Hg for felodipine and 80 +/- 10 mm Hg for nifedipine, P < .05). There were no differences in the incidence of side effects (both patient-reported and provider-reported) for the two antihypertensive therapies. These data demonstrate that in an hypertensive population followed in a VAMC, mandatory switching of stable dihydropyridine calcium channel blocker therapy did not result in any significant changes in short-term (2 to 3 months) BP control nor were adverse side effects different based on both physician- and patient- reported sources of information.",1996.0,0,1
892,8722437,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
893,8727625,"To treat or not to treat (out-of-hospital) paroxysmal supraventricular tachycardia, that is the question.",M Gausche,,1996.0,0,0
894,8727628,Treatment of out-of-hospital supraventricular tachycardia: adenosine vs verapamil.,W J Brady; D J DeBehnke; L L Wickman; G Lindbeck,"To compare the use of adenosine and the use of verapamil as out-of-hospital therapy for supraventricular tachycardia (SVT). A period of prospective adenosine use (March 1993 to February 1994) was compared with a historical control period of verapamil use (March 1990 to February 1991) for SVT. Data were obtained for SVT patients treated in a metropolitan, fire-department-based paramedic system serving a population of approximately 1 million persons. Standard drug protocols were used and patient outcomes (i.e., conversion rates, complications, and recurrences) were monitored. During the adenosine treatment period, 105 patients had SVT; 87 (83%) received adenosine, of whom 60 (69%) converted to a sinus rhythm (SR). Vagal maneuvers (VM) resulted in restoration of SR in 8 patients (7.6%). Some patients received adenosine for non-SVT rhythms: 7 sinus tachycardia, 18 atrial fibrilation, 7 wide-complex tachycardia (WCT), and 2 ventricular tachycardia; no non-SVT rhythm converted to SR and none of these patients experienced an adverse effect. Twenty-five patients were hemodynamically unstable (systolic blood pressure < 90 mm Hg), with 20 receiving drug and 13 converting to SR; 8 patients required electrical cardioversion. Four patients experienced adverse effects related to adenosine (chest pain dyspnea, prolonged bradycardia, and ventricular tachycardia). In the verapamil period, 106 patients had SVT: 52 (49%) received verapamil (p < 0.001, compared with the adenosine period), of whom 43 (88%) converted to SR (p = 0.11). Two patients received verapamil for WCT; neither converted to SR and both experienced cardiovascular collapse. VM resulted in restoration of SR in 12 patients (11.0%) (p = 0.52). Sixteen patients were hemodynamically unstable, with 5 receiving drug (p = 0.005) and 5 converting to SR; 9 patients required electrical cardioversion (p = 0.48). Four patients experienced adverse effects related to verapamil (hypotension ventricular tachycardia, ventricular fibrillation). Recurrence of SVT was noted in 2 adenosine patients and 2 verapamil patients in the out-of-hospital setting and in 23 adenosine patients and 15 verapamil patients after ED arrival, necessitating additional therapy (p = 0.48 and 0.88, for recurrence rates and types of additional therapies, respectively). Hospital diagnoses, outcomes, and ED dispositions were similar for the 2 groups. Adenosine and verapamil were equally successful in converting out-of-hospital SVT in patients with similar etiologies responsible for the SVT. Recurrence of SVT occurred at similar rates for the 2 medications. Rhythm misidentification remains a common issue in out-of-hospital cardiac care in this emergency medical services system.",2001.0,0,0
895,8728305,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
896,8733032,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.",1996.0,1,1
897,8733038,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
898,8733039,A study of the efficacy of felodipine given once or twice daily in the management of elderly hypertensive patients.,T Morgan; O Morgan; A Anderson,"The use of medication given once daily in clinical practice may lead to inadequate control of blood pressure (BP) over 24 h because medication is frequently titrated at the time of peak effect. Twenty-three patients aged 65-84 completed a study in which they received placebo, felodipine 2.5 mg once daily, felodipine 2.5 mg 12-hourly, and felodipine 5 mg once daily in a randomized, double-blind crossover design. BP response was assessed in the clinic 24 h after medication and by 24 h ambulatory monitoring. The trough/peak ratio was defined as the fall in BP in the 23rd and 24th hour post dose divided by the fall in BP in the 3rd and 4th hour post dose. BP fell with all three regimes and the clinic BPs did not differ from each other but were lower than placebo. Peak BP responses from the ambulatory BP monitor recording were similar with each dose but a greater percentage of the effect was maintained prior to the morning dose with 2.5 mg 12 hourly and 5 mg once daily. Felodipine 2.5 mg once daily reduces BP and in some people this effect persists for 24 h. However if this dose is used BP should be measured prior to the dose of the drug to ensure that 24 h control is maintained. Felodipine 5 mg once daily and felodipine 2.5 mg b.d. were equally effective at maintaining control and there was no significant advantage in using the twice daily regime. If felodipine 5 mg once daily or higher doses are used BP can be titrated post dose with the knowledge that more than 75% of the effect will still be present prior to the next dose of the drug. Thus once daily felodipine extended release (ER) 5 mg or more can be used effectively to maintain BP control over 24 h in clinical practice. In some elderly patients felodipine ER 2.5 mg once daily is an adequate regime.",1996.0,0,0
899,8733040,Decreased blood viscosity and serum levels of erythropoietin after anti-hypertensive treatment with amlodipine or metoprolol: results of a cross-over study.,T Linde; B Sandhagen; A Hägg; C Mörlin; B G Danielson,"The increased viscosity of blood of hypertensive patients can be assumed to be a risk factor for the development of cardiovascular diseases. The aim of the present study was to elucidate whether anti-hypertensive treatment has any impact on blood rheology. Twenty patients with previously untreated hypertension who consecutively attended our outpatient hypertension clinic were included in this prospective, open, cross-over study. The patients were randomly selected to treatment with amlodipine or metoprolol. The anti-hypertensive therapy was switched after 4 months. Haemorheological and haemodynamic variables were measured with rotational viscometry and impedance cardiography, respectively. Fifteen and 16 patients could be evaluated after amlodipine or metoprolol treatment respectively. The mean blood pressure (BP) decreased from 159 +/- 22/105 +/- 7 to 139 +/- 21/91 +/- 6 mm Hg on amlodipine and from 162 +/- 22/104 +/- 5 to 145 +/- 24/90 +/- 8 mm Hg on metoprolol therapy. After amlodipine treatment, the total peripheral resistance index decreased whereas metoprolol treatment was accompanied by a decrease in the cardiac index. Decreases in whole blood viscosity, haematocrit and serum erythropoietin were found after amlodipine as well as metoprolol treatment. After amlodipine the plasma viscosity decreased and the erythrocyte deformability increased in the majority of patients. Plasma fibrinogen decreased after metoprolol treatment. Despite the differences in haemodynamic mechanisms underlying the decrease in BP, amlodipine and metoprolol exert beneficial effects on blood viscosity. Haemodilution and a decrease in serum erythropoietin may be factors underlying this decrease in blood viscosity.",1996.0,0,0
900,8733072,Calcium antagonism in perspective: new data on diltiazem in unstable angina.,W H van Gilst; K I Lie,,1996.0,0,1
901,8734139,"[Evaluation of amlodipine in stable effort angina. Comparison with diltiazem in terms of efficacy, tolerability and maintenance of the anti-ischemic action 24 hours after the last dose].",X Marchand; T Tibi; C Bernaud; P Morand,"83 patients were enrolled in a multicentre, randomized, open study to assess the efficacy of amlodipine in stable effort angina. Preselected patients were submitted to a one-week placebo wash-out period during which only nitrates or molsidomine were authorized. Patients were then randomized to receive either 5 mg of amlodipine as a morning dose, or 180 mg of diltiazem in three divided doses. After two weeks, the dosage was able to be increased (according to clinical efficacy) to 10 mg of amlodipine as a single dose or 240 mg of diltiazem in four divided doses. The antianginal efficacy of these two treatments was essentially evaluated in terms of the results of stress tests (ST) conducted at the end of the second week and fourth week of active treatment: and 24 hours after the last dose of the drug. The results of 63 patients who scrupulously complied with the protocol showed that amlodipine and diltiazem corrected or improved the ST parameters (time to onset and amplitude of ST depression, duration of ST, work performed). The anti-ischaemic action of amlodipine was maintained for at least 24 hours after the last dose and therefore provides better security (by covering the entire 24-hour period) and better compliance (by tolerating a dose omission of several hours).",1996.0,0,0
902,8737216,Anti-ischaemic efficacy of L-propionylcarnitine--a promising novel metabolic approach to ischaemia?,G L Bartels; W J Remme; K J Holwerda; D A Kruijssen,"L-propionylcarnitine, a naturally occurring derivative of L-carnitine, essential for mitochondrial fatty acid transport and high-energy phosphate exchange, acutely reduces myocardial ischaemia and improves ischaemia-induced cardiac dysfunction following intravenous administration. This randomized, crossover study was designed to compare the long-term anti-ischaemic effects of oral L-propionylcarnitine with diltiazem in patients with stable, exercise-induced angina. After a 2-week washout phase of anti-anginal medication and a 2-week single-blind placebo period, 46 patients were included in the study, 23 of whom received 1500 mg L-propionylcarnitine daily for 6 weeks, and 23 diltiazem (180 mg daily for 3 weeks, followed by 360 mg daily for 3 weeks), crossing over to the other treatment after a 1-week washout period. Three patients on L-propionylcarnitine and two on diltiazem discontinued. Both treatments resulted in comparable exercise duration (582 +/- 35 s and 588 +/- 33 s, mean +/- SEM), time to 0.1 mV ST depression (436 +/- 38 s and 465 +/- 36 s), and increase in time to 0.1 mV ST depression from baseline (20% and 28%), L-propionylcarnitine and diltiazem, respectively. Diltiazem decreased the rate-pressure product at rest and exercise, L-propionylcarnitine did not. Both compounds significantly reduced ST depression at maximal exercise [23% (L-propionylcarnitine) vs 35% (diltiazem), P < 0.05 diltiazem vs L-propionylcarnitine]. Diltiazem increased the time to onset of angina by 22%. In contrast, no significant changes occurred with L-propionylcarnitine. During the study, anginal attacks were reduced by 70% and 57%, and nitroglycerin consumption decreased by 57% and 70%, L-propionylcarnitine and diltiazem, respectively. Thus, both L-propionylcarnitine and (high-dose) diltiazem result in anti-ischaemic effects and decrease anginal attacks in daily life. Although the effect of diltiazem on exercise-induced ischaemia appears more pronounced than that of L-propionylcarnitine, this novel metabolic approach to ischaemia warrants further development.",1996.0,0,1
903,8739813,Comparison between a bid and a tid regimen: improved compliance with no improved antihypertensive effect. The EOL Research Group.,J P Boissel; O Meillard; E Perrin-Fayolle; T Ducruet; Y Alamercery; P Sassano; R Benghozi,"To compare compliance with an antihypertensive treatment administered either twice daily or three times daily. The two formulations of the antihypertensive treatment used (nicardipine) ""regular tablets"" (t.d.) and ""slow release tablets"" (b.d.) are bioequivalent at the daily dosage used in the study. Open, controlled, parallel designed study with centralised, randomised allocation to the treatment groups: TID group: A nicardipine 20 mg tablet, three times daily for 3 months. BID group: A capsule of slow release (SR) nicardipine, 50 mg twice daily for 3 months. 7274 hypertensive patients were investigated by 2.651 general practitioners. Compliance with the nicardipine was assessed by means of standardised interviews with the patients and by a questionnaire for the investigators. Compliance was slightly higher in the BID than in the TID group; 71.2% and 24.5% of patients in the first group declared their compliance was 100% and 80% compared to 82.3% and 15% in the second group. A statistically significant relationship was shown between compliance with nicardipine and the decrease in blood pressure after three months of therapy. However, no significant difference was noticed between the two groups of patients in the absolute decrease in blood pressure after the treatment period: 25.7/14.7 mm Hg in the TID group compared with 25.9/15.0 mm Hg in the BID group. A difference in compliance between the bioequivalent BID and TID formulations of the same active agent was shown in hypertensive patients. However, the difference was not large enough to lead to a difference either in the number of controlled patients or in the decrease in blood pressure. Reducing the number of daily doses does not automatically lead to greater efficacy of treatment.",1996.0,0,0
904,8742912,Cardiac function improvement 24 hours after isradipine SRO in patients with chronic stable angina: a double-blind randomized study.,M Doat; J P Hacot; D Pavin; A Righetti,"We recently showed that Isradipine, a calcium antagonist from the dihydropyridine group, reduces ischemia and improves ventricular function at rest and during exercise, 2 hours after a single oral dose, in patients with chronic stable angina. In the present study, we evaluated the effects of long acting slow release oral (SRO) Isradipine (5 mg) compared to a placebo in 30 coronary patients with stable chronic angina, randomized in a double blind-fashion. The following parameters were obtained at rest and during submaximal exercise: left and right ventricular (LV, RV) ejection fractions (EF; %) and peak filling rate (PFR; EDV/s), assessed by gated radionuclide angiography, clinical symptoms, electrocardiograms (ECG, ST segment depression; mm), systolic and diastolic blood pressure (SBP and DBP; mm Hg). Patients were then given two oral doses of either Isradipine or placebo (one a day). The same parameters were reassessed, at rest and during n equivalent exercise, 48 hours later (24 hours after the last administration of the drug). The results after Isradipine (n = 14) showed, at rest, a significant increase in LVEF and Pfr (51 +/- 9 to 54 +/- 8 and 1.97 +/- 0.44 to 2.36 +/- 0.71, respectively) and a decrease in DBP (93 +/- 11 to 87 +/- 13); and during exercise, a significant increase in LVEF (51 +/- 11 tot 55 +/- 13) and a decrease in ST segment depression (2.3 +/- 1.9 tot 1.9 +/- 1.6). No significant change was observed after placebo in the other 16 patients. We conclude that even 24 hours after an oral administration, Isradipine SRO maintains its beneficial effects both, at rest on LV systolic and diastolic function and pressure, and during exercise on ECG signs of ischemia with improvement in LV ejection fraction.",1996.0,0,0
905,8749878,Comparative study of efficacy and safety of low-dose diltiazem or betaxolol in combination with digoxin to control ventricular rate in chronic atrial fibrillation: randomized crossover study.,K K Koh; J H Song; K S Kwon; H B Park; S H Baik; Y S Park; H H In; T H Moon; G S Park; S K Cho,"The combination therapy of low-dose diltiazem or bexatolol with digoxin can be a useful adjunct for achieving heart rate control with minimal side effects. But there has not been a study including patients with impaired left ventricular function and evaluating whether the beneficial effects of medication will be maintained during a follow-up period. The purpose of this study was three-fold: (1) to compare the efficacy of digoxin with low-dose diltiazem and digoxin with low-dose betaxolol on randomized crossover study; (2) to evaluate whether the beneficial effects of medication will be maintained after 7 months; (3) to evaluate the safety of the combination therapy in patients with impaired left ventricular function. We did a prospective randomized crossover study in 35 patients with chronic atrial fibrillation (AF) including 15 patients with left ventricular dysfunction. After enrollment, each patient was evaluated for heart rate, blood pressure, rate-pressure products, maximal exercise tolerance at rest and during symptom-limited treadmill test before medication, at 4 weeks after medication of digoxin (0.125-0.5 mg daily) with diltiazem (90 mg twice daily), and at 4 weeks after digoxin with betaxolol (20 mg once daily). We performed 24-h ambulatory electrocardiogram (ECG) in 15 patients at the end of each phase of treatment. We repeated symptom-limited treadmill test like above method in 15 patients at 7 months of medication. (1) Ventricular rates were significantly reduced in digoxin with low-dose betaxolol therapy at rest and during exercise (67 +/- 3, 135 +/- 5 (mean +/- S.E.M.) beats/min, respectively) in comparison to digoxin with low-dose diltiazem therapy (80 +/- 7, 154 +/- 5) (P < 0.05). (2) Rate-pressure products were significantly less in digoxin with low-dose betaxolol at rest and during exercise (85 +/- 4, 213 +/- 12 x 10(2) mmHg/min) than in digoxin with low-dose diltiazem therapy (105 +/- 6, 269 +/- 12) (P < 0.05). (3) Exercise capacity was significantly improved in digoxin with low-dose betaxolol (9.3 +/- 0.5 METS) or digoxin with low-dose diltiazem (9.7 +/- 0.5) in comparison to control state (8.3 +/- 0.5) (P < 0.05). (4) At 7 months evaluation, there was no significant difference between at 4 weeks and at 7 months. (5) Results on 24-h ambulatory ECG showed the same findings as on treadmill test. (6) Although side effects occurred more frequently in digoxin with low-dose betaxolol therapy, they were minimal and no patient had to withdraw medication. Worsening of left ventricular dysfunction was not observed. Our study suggested that (1) combination therapy of low-dose betaxolol with digoxin was more superior to low-dose diltiazem with digoxin in controlling ventricular rate and reducing rate-pressure products; (2) the effects controlling ventricular rate, reducing rate-pressure products and improving exercise capacity have been well maintained even after 7 months of medication with each combination therapy.",1995.0,1,1
906,8751017,Antianginal effect of conventional and controlled release diltiazem in stable angina pectoris.,K Boman; H Saetre; L G Karlsson; B Ritter; R Marsell; H Wingman; O Lövheim; E W Michaeli; P Löfdahl; S O Olsson,"Two preparations of diltiazem, controlled release (CR) given twice a day (b.i.d.) and plain given 4 times a day (q.i.d.), were compared in a multicentre, double-blind, crossover study in 41 patients with stable angina pectoris. Therapeutic efficacy was assessed with maximal exercise tests, patient recordings on nitroglycerine consumption and angina attacks. No significant differences between the CR and plain tablets were seen in any of the efficacy variables. Maximal workload significantly increased from 127 W on placebo to 146 W on CR tablets and to 147 W on plain tablets. Anginal attacks/week significantly decreased from 11.7 on placebo to 4.9 on CR tablets and to 5.0 on plain tablets. Consumption of nitroglycerine tablets/week significantly decreased from 6.3 on placebo to 2.6 and to 3.4 on CR and plain-tablets, respectively. The number or the seriousness of the adverse events did not differ between the groups. The results imply that diltiazem CR b.i.d. is equally potent and safe as conventional diltiazem q.i.d. in the control of stable angina pectoris.",1995.0,0,1
907,8751029,"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.",1995.0,0,0
908,8752790,Prognostic significance of transient ischemic episodes: response to treatment shows improved prognosis. Results of the Total Ischemic Burden Bisoprolol Study (TIBBs) follow-up.,T Von Arnim,"The Total Ischemic Burden Bisoprolol Study (TIBBS) follow-up examined cardiac event rates in relation to transient ischemia and its treatment. It is unclear whether transient ischemia on the ambulatory electrocardiogram has prognostic implications in stable angina and whether medical treatment can improve the prognosis. The TIBBS trial was an 8-week, randomized, controlled comparison of the effects of bisoprolol and nifedipine on transient ischemic episodes in patients with stable angina pectoris. Of the 545 patients screened, 520 (95.4%) could be followed up. Rates of cardiac and noncardiac death, nonfatal acute myocardial infarction, hospital admission for unstable angina and need for coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty were recorded. A total of 145 events occurred in 120 (23.1%) of 520 patients. Patients with more than six episodes had an event rate of 32.5% compared with 25.0% for patients with two to six episodes and 13.2% for patients with less than two episodes (p < 0.001). Hard events (death, acute myocardial infarction, hospital admission for unstable angina pectoris) were more frequent in patients with two or more ischemic episodes (12.2% vs. 4.7%, p = 0.0049). Patients with a 100% response rate of transient ischemic episodes during the TIBBS trial had a 17.5% event rate at 1 year compared with 32.3% for non-100% responders (p = 0.008). Patients receiving bisoprolol during the TIBBS tria had a lower event rate (22.1%) at 1 year than patients randomized to nifedipine (33.1%, p = 0.033). In patients with stable angina pectoris, frequent episodes of transient ischemia are a marker for an increased event rate. A 100% response to medical treatment reduces the event rate. The greater reduction of ischemia with bisoprolol than nifedipine during the TIBBS trial translated into an improved outcome at 1 year.",1996.0,0,1
909,8755005,The nifedipine scare in hypertension: fact or fiction.,D S Gambhir,,1996.0,0,0
910,8757150,Calcium-channel blockade and incidence of cancer in aged populations.,M Pahor; J M Guralnik; L Ferrucci; M C Corti; M E Salive; J R Cerhan; R B Wallace; R J Havlik,"Calcium-channel blockers can alter apoptosis, a mechanism for destruction of cancer cells. We examined whether the long-term use of calcium-channel blockers is associated with an increased risk of cancer. Between 1988 and 1992 we carried out a prospective cohort study of 5052 people aged 71 years or more and who lived in three regions of Massachusetts, Iowa, and Connecticut USA. Those taking calcium-channel blockers (n = 451) were compared with all other participants (n = 4601). The incidence of cancer was assessed by survey of hospital discharge diagnoses and causes of death. These outcomes were validated by the cancer registry in the one region where it was available. Demographic variables, disability, cigarette smoking, alcohol consumption, blood pressure, body-mass index, use of other drugs, hospital admissions for other causes, and comorbidity were all assessed as possible confounding factors. The hazard ratio for cancer associated with calcium-channel blockers (1549 person-years, 47 events) compared with those not taking calcium-channel blockers (17225 person-years, 373 events) was 1.72 (95% CI 1.27-2.34, p = 0.0005), after adjustment for confounding factors. A significant dose-response gradient was found. Hazard ratios associated with verapamil, diltiazem, and nifedipine did not differ significantly from each other. The results remained unchanged in community-specific analyses. The association between calcium-channel blockers and cancer was found with most of the common cancers. Calcium-channel blockers were associated with a general increased risk of cancer in the study populations, which suggested a common mechanism. These observational findings should be confirmed by other studies.",1996.0,1,1
911,8757160,Do calcium antagonists cause cancer?,N M Kaplan,,1996.0,0,0
912,8757225,The multiple drug allergy syndrome: a matched-control retrospective study in patients allergic to penicillin.,L Khoury; R Warrington,,1996.0,0,0
913,8759075,Diltiazem improves cardiac function and exercise capacity in patients with idiopathic dilated cardiomyopathy. Results of the Diltiazem in Dilated Cardiomyopathy Trial.,H R Figulla; F Gietzen; U Zeymer; M Raiber; J Hegselmann; R Soballa; R Hilgers,"Evidence is arising that calcium antagonists in idiopathic dilated cardiomyopathy (IDC) may have beneficial effects on virus-induced cardiopathology, alcohol toxicity, micro-circulatory disorders, and impaired calcium cycling, all possibly involved in the pathogenesis of the disease. Thus, the effect of adjunct diltiazem (60 to 90 mg TID) on standard treatment was investigated. The Diltiazem in Dilated Cardiomyopathy (DiDi) trial was a randomized, double-blind, placebo-controlled, multicenter trial of 186 patients (92 receiving diltiazem, 94 receiving placebo) with IDC diagnosed by coronary angiography, catheterization of the left side of the heart, and a left ventricular ejection fraction of < 0.50 (mean, 0.34 +/- 0.11). The effect of adjunct diltiazem treatment on transplant listing-free survival, hemodynamics, exercise capacity, and subjective status was investigated. During the 24-month study period, 33 patients dropped out of the study; 153 patients finished the study protocol. Twenty-seven patients died or had a listing for heart transplantation: 16 in the placebo group and 11 in the diltiazem group. The transplant listing-free survival rate was 85% for diltiazem and 80% for placebo recipients (P = .444). After 24 months, only diltiazem significantly increased cardiac index at rest (P = .01) and under a workload (P = .02), systolic and diastolic pressures (P = .003 and P = .004), stroke volume index (P = .003), and stroke work index (P = .000) and decreased both pulmonary artery pressure under workload (P = .007) and heart rate (P = .001). Diltiazem also increased exercise capacity (P = .002) and subjective well-being (P = .01). Adverse reactions were minor and evenly distributed in both groups, except for an increase in the PQ interval in the diltiazem group. In patients with IDC, the adjunct therapy of diltiazem improves cardiac function, exercise capacity, and subjective status without deleterious effects on transplant listing-free survival.",1996.0,1,1
914,8762211,Trough:peak ratio of nifedipine gastrointestinal therapeutic system and nifedipine retard in essential hypertensive patients: an Italian multicentre study.,A Salvetti; A Virdis; S Taddei; S Ambrosoli; A Caiazza; E Gandolfi; C del Prato; G Saba; C nello Ceccarelli; R Buoninconti; G Spadari; M O Kilama,"To evaluate the antihypertensive effect of nifedipine gastrointestinal therapeutic system and retard in terms of trough:peak ratio efficacy. According to a double-blind, randomized, crossover design, 58 patients with mild-to-moderate essential hypertension, after 1 month placebo washout, received 30 mg/day nifedipine gastrointestinal therapeutic system, 20 mg nifedipine retard twice a day and the corresponding placebos for 1 month. At the end of each treatment period, blood pressure was measured by using a mercury sphygmomanometer at trough and 1, 2, 3 and 4 h after the last dosing. The peak effect was identified as the maximum decrement induced by the three randomized treatments with respect to the value at the end of the placebo washout period during the 4 h interval. The trough:peak ratios of systolic and diastolic blood pressure were calculated as group ratios and individual ratios from decrements induced by nifedipine gastrointestinal therapeutic system and retard, corrected for those induced by randomized placebo. Patients were defined as responders to each randomized treatment if their diastolic blood pressure at trough time was reduced by at least 10 mmHg relative to that at the corresponding time at the end of placebo washout. Nifedipine gastrointestinal therapeutic system and retard significantly reduced blood pressure to a similar extent both at trough and at peak. Systolic and diastolic group trough:peak ratios in responders to nifedipine gastrointestinal therapeutic system (n = 41) were 0.80 and 0.88, respectively, and those in responders to nifedipine retard (n = 30) 0.84 and 0.93, respectively. The percentage of patients with trough:peak ratios > 0.50 was > 80% (systolic trough:peak ratios) and above 90% (diastolic trough: peak ratios) for both nifedipine formulations. Our data show that 30 mg/day nifedipine gastrointestinal therapeutic system and 20 mg nifedipine retard twice a day have a favourable trough:peak ratios efficacy when given as monotherapy to essential hypertensive patients.",1996.0,0,0
915,8762212,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
916,8762218,[Double blind randomized comparative study of two antihypertensive combinations. Enalapril-hydrochlorothiazide versus enalapril-nifedipine in 240 hypertensive patients resistant to monotherapy].,Y Frances; V Lafay; O Madona; C Chastang; T Souchet; F Chazelle,"The combination of two antihypertensive drugs is recommended when mild to moderate hypertension is not controlled by sequential monotherapy. The aim of our study was to compare the efficacy and the safety of the combination enalapril 20 mg-hydrochlorothiazide 12.5 mg to that of enalapril 20 mg-nifedipine SL 20 mg x 2. Two hundred and forty four hypertensive patients not controlled (DPB > 95 mmHg) by a single dose of enalapril 20 mg/24 h, received for 4 weeks, one of these two combined therapies in a randomized double-blind trial. The efficacy was of same amplitude in the two groups (DBP: -10.8 mmHg enalapril-hydrochlorothiazide vs-10.3 mmHg enalapril-nifedipine). The side effects were less frequent in the enalapril-hydrochlorothiazide group (14 per cent vs 24 per cent, p = 0.04).",1996.0,0,0
917,8762219,"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
918,8767350,[Antihypertensive effect and adverse effects of isradipine in patients with sever hypertension. Results of an open multicenter study].,K J Burger; R Dehner,"Antihypertensive Efficacy and Tolerability of Isradipine in Patients with Severe Hypertension/Results of an open multicenter study. In this open multicentre study 55 patients (mean age 51.2 years) with severe hypertension (diastolic blood pressure > 115 mmHg) were treated for seven weeks with the calcium antagonist of the dihydropyridine type isradipine (CAS 75695-93-1, Lomir). If necessary, metoprolol or enalapril were added to the regimen. Before inclusion into the active treatment phase, responsiveness of the patients to a single administration of isradipine (5 mg) was compared with placebo. Preexisting antihypertensive therapy (18 patients) was to be maintained during the study period. Blood pressure was recorded with an automatic device. During the 7-week period blood pressure decreased from 173.7/124.8 mmHg to 143.2/97.8 mmHg. Both the group with isradipine monotherapy (n = 32) and the combination group (n = 11) showed a significant reduction in systolic and diastolic blood pressure. Diastolic blood pressure response, defined as a decline of more than 15 mmHg, was noted in 87.5% (monotherapy) and 72.7% (combination group) of patients. On the whole, blood pressure was normalized in 27.9% of the participants. Nineteen patients experienced 43 adverse events, most of which were rated mild to moderate. Therapy was withdrawn in only one patient (due to ankle edema). The most frequent adverse event was headache (20.9%).",1996.0,0,0
919,8767776,[Effectiveness of depot diltiazem in stable effort angina: a double-blind study compared with placebo].,N Baldi; U Guiducci; R Piccitto,"The antianginal efficacy of slow-release (SR) Diltiazem and change in ergometric parameters during treatment were evaluated in patients with stable effort angina. Forty eight patients with documented ischemic cardiopathy were studied. The study design was double blind randomised cross over versus placebo. After a 7 days run-in period of pharmacological washout, patients were randomised to treatment with diltiazem SR (120 mgs bid) or placebo for 1 week, followed by crossover of treatments. No concomitant antianginal therapy, except sublingual nitro-glycerine was allowed during the trial. Exercise tests were performed during the run-in period and at the end of each week of treatment. After diltiazem administration, exercise duration increased significantly in comparison with placebo (645.6 +/- 196.31 vs 563.9 +/- 244.52 s, p < 0.01). Similarly, time to onset of angina and time to ischemic threshold increased in comparison to placebo (603.78 +/- 198.50 vs 459.69 +/- 239.40 s, p < 0.01 and 576.06 +/- 208.88 vs 463.16 +/- 246.12 s, p < 0.01 respectively). No significant changes in heart rate, blood pressure and double product at ischemic threshold and peak exercise were detected. SR-diltiazem is effective and well tolerated in the treatment of patients with stable angina.",1996.0,0,0
920,8769587,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.",1996.0,0,1
921,8773038,Nifedipine in migraine and tension headache: a randomised double blind crossover study.,R Shukla; R K Garg; D Nag; R C Ahuja,Nifedipine was evaluated in the prophylaxis of 28 patients each of migraine and tension headache using a double blind cross over design with random allocation to drug or placebo group. The duration of the trial was 3 months with a 2 week run-in period and 2 week wash-oat period separating two treatment periods of 4 weeks each. A satisfactory response was obtained in 71.4% of migraineurs (p < 0.001) and 28.6% of patients with tension headache (p = N.S). Minor side effects were observed in 5 patients. Nifedipine is a useful agent for the management of migraine as it reduces frequency and severity of pain but the drug cannot be recommended for tension headache.,1995.0,0,0
922,8773944,Randomised controlled trial of methyldopa and isradipine in preeclampsia--effects on uteroplacental and fetal hemodynamics.,S Montan; C Anandakumar; S Arulkumaran; I Ingemarsson; S Ratnam,"This is a prospective randomised controlled study in 21 women admitted with preeclampsia in the third trimester. The mean arterial blood pressure decreased by 11.1 mmHg (95% confidence interval -14.9 to -7.3 mmHg) in the methyldopa group, and by 9.3 mmHG (95% confidence interval-14.4 to -4.2 mmHG) in the isradipine group. The maternal heart rate decreased by 6.9 beats per min (95% confidence interval -11.6 to -2.2 bpm) during methyldopa treatment, and by 2.5 beats per min (95% confidence interval -9.2 to 4.3) during isradipine treatment. Pulsatility index in maternal and fetal vessels was not affected by either of the two drugs. The birth weight and placental weight and neonatal outcome were similar and uneventful. The hypotensive effect was similar for methyldopa and isradipine. Except reduced maternal heart rate on methyldopa, fetal and uteroplacental hemodynamics were not altered during treatment of preeclampsia with methyldopa or isradipine.",1996.0,0,0
923,8775337,"Long-term prevention of atrial fibrillation after coronary artery bypass surgery: comparison of quinidine, verapamil, and amiodarone in maintaining sinus rhythm.",A T Yilmaz; U Demírkiliç; M Arslan; E Kurulay; E Ozal; H Tatar; O Oztürk,"To evaluate the necessity and efficacy of quinidine fumarate, verapimil, or amiodarone prophylaxis for sinus rhythm maintenance in patients who experienced atrial fibrillation after coronary artery bypass surgery. Between 1992 and 1995, this prospective, randomized, placebo-controlled study examined 120 patients in whom atrial fibrillation occurred and was restored to sinus rhythm by pharmacological therapy or direct current cardioversion in the immediately postoperative period after coronary artery by-pass surgery. There were no significant differences in perioperative characteristics among the patients, who were randomly separated into four groups in the course of discharge. In group 1 (n = 30), patients did not receive antiarrhythmic drugs. Quinidine fumarate was given in group 2 (n = 30), verapimil in group 3 (n = 30), and amiodarone in group 4 (n = 30). Patients were monitored six times over a 90-day postoperative period by 24-hour Holter monitoring and routine examination. The recurrent atrial fibrillation usually developed within 15 days of discharge. Atrial fibrillation occurred in one patient (3.33%) in group 1, and two each (6.66%) in groups 2, 3, and 4. Atrial fibrillation was asymptomatic and occurred with slow ventricular response in groups 3 and 4. Side effects occurred in 5 patients (16.6%) given quinidine, 1 patient given amiodarone, but in no patient given verapimil. There were no significant differences in the maintenance of sinus rhythm among the four groups, so we suggest that long-term prevention of atrial fibrillation in patients with coronary artery bypass grafting was not necessary at the postdischarge period.",1996.0,1,1
924,8776276,"Acute hemodynamic and long-term clinical effects of isradipine in patients with coronary artery disease and chronic heart failure. A double-blind, placebo-controlled study.",E W van den Toren; D J van Veldhuisen; A van Bruggen; S A van den Broek; W H van Gilst; K I Lie,"To assess the acute hemodynamic and long-term clinical effects of isradipine, a calcium antagonist of the dihydropyridine class, we performed a double-blind, placebo-controlled parallel study in 19 patients with coronary artery disease (CAD) and stable chronic heart failure (CHF). Their mean age was 56 +/- 5 years, and left ventricular ejection fraction (LVEF) was 0.18 +/- 0.05. Patients were treated with diuretics and digoxin only. All were clinically stable and in sinus rhythm. The acute hemodynamic study showed that (intravenous) isradipine increased cardiac index (+36%) and stroke volume index (+30%) (both P < 0.001), while systemic vascular resistance (-33%) and mean arterial pressure (-10%) decreased (both P < 0.005). Filling pressures and heart rate were not affected. Of the 19 patients, 17 completed the 12 week study; 2 patients on placebo (1 death, 1 side-effects) but no patient on isradipine (5 mg 3 times daily) dropped out. After 12 weeks, peak oxygen consumption (VO2), LVEF, echocardiographic indices, and other clinical parameters were unaffected by treatment. Repeat invasive hemodynamic measurements showed that the initial improvement by isradipine was not present anymore. In conclusion, despite a beneficial acute hemodynamic effect, isradipine has no favorable clinical influence during prolonged treatment in patients with mild to moderate CHF.",1996.0,1,1
925,8783785,Comparison of nifedipine GITS and hydrochlorothiazide in the management of elderly patients with stage I-III diastolic hypertension.,H M Dey; R Soufer; P Hoffer; F J Wackers; H R Black,"A randomized, double blind, parallel study was performed to compare the effects of nifedipine gastrointestinal therapeutic system (GITS) to hydrochlorothiazide (HCTZ) in the management of the elderly hypertensive. Eighteen patients, mean age 65 +/- 5 years, with Stage I-III diastolic hypertension (sitting diastolic BP between 90 and 115 mm HG) were included in each treatment group. Following a 2 to 8 week placebo washout phase, patients received either nifedipine GITS or HCTZ and were titrated over 5 weeks to achieve a goal diastolic blood pressure less than 90 mm Hg. Patients were then continued on medication during an 8 week maintenance phase. Treatment effect on systolic and diastolic blood pressure was assessed. Serum electrolytes, lipids, blood urea nitrogen, and creatinine were measured before and after treatment. Posttreatment changes in renal and cardiovascular function, as well as left ventricular mass were evaluated. The results showed significant reductions in systolic and diastolic blood pressure with both drugs; no treatment difference was found, although goal blood pressure was achieved more rapidly with nifedipine GITS (28 v 34 days, P < .05). BUN was significantly increased only after diuretic therapy (P < .01) and serum potassium fell to a greater degree with HCTZ (0.3 mEq/L v 0.1 mEq/L) than with nifedipine GITS. No statistically significant changes in left ventricular mass, ejection fraction, glomerular filtration rate, or renal blood flow were seen after therapy with either drug. However, the time peak LV diastolic filling rate decreased with nifedipine GITS (197 to 164 msec) and increased with HCTZ (172 to 198 msec). This treatment difference approached statistical significance (P = .07). Adverse side effects of treatment were reported by 50% of nifedipine GITS patients and 28% of patients treated with HCTZ. This treatment difference was not statistically significant. We conclude that both nifedipine GITS and HCTZ monotherapy provide significant blood pressure reduction in older hypertensives with Stage I-III diastolic hypertension. Both drugs are well tolerated with no significant adverse effect on renal or cardiovascular function after short term therapy.",1996.0,0,0
926,8785466,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
927,8799682,New antiherpesvirus agents. Their targets and therapeutic potential.,F A Alrabiah; S L Sacks,"Of the large number of agents under development for the treatment of herpes virus infections [herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV)], only ten have apparently reached clinical development. Aciclovir was approved for the treatment of HSV infections over 10 years ago, and it remains an important and reliable antiviral agent. Recent approvals in some countries of valaciclovir for VZV infection and famciclovir for both HSV and VZV infections demonstrate the rapidity of change in this field. Intravenous ganciclovir and foscarnet are approved for the treatment of CMV infection in the immunocompromised patient. Five of the antiherpetic drugs under current clinical development are nucleoside analogues or their prodrugs; another is a phosphorylated nucleoside (nucleotide). Four of the nucleoside agents-penciclovir, famciclovir, valaciclovir and lobucavir-are being developed for the management of HSV and VZV infections. Valaciclovir is also being developed for the prevention of CMV infections and famciclovir and lobucavir for the treatment of hepatitis B virus infection. Oral ganciclovir, lobucavir, ISIS 2922 and cidofovir are being developed for the suppression of CMV infections in immunocompromised patients. Sorivudine has been studied in VZV infections. n-Docosanol is under development for HSV infections, and cidofovir is being developed for both HSV and CMV infections, as well as for treatment of other viral diseases. Traditionally, the adverse effects associated with anti-CMV compounds have been more difficult to manage and are acceptable clinically only because of the severity of the underlying infection and lack of safer therapeutic alternatives. In general, toxicity issues continue to be problematic in the anti-CMV arena, although newer agents have improved the situation to some extent. In contrast, the safety of anti-HSV compounds has traditionally been excellent, establishing a safety standard that must be met by newer agents entering the field.",1996.0,0,0
928,8813041,Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.,M Packer; C M O'Connor; J K Ghali; M L Pressler; P E Carson; R N Belkin; A B Miller; G W Neuberg; D Frid; J H Wertheimer; A B Cropp; D L DeMets,"Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.",1996.0,1,1
929,8817135,Efficacy and safety of low-dose propranolol versus diltiazem in the prophylaxis of supraventricular tachyarrhythmia after coronary artery bypass grafting.,J Babin-Ebell; P R Keith; O Elert,"Supraventricular tachyarrhythmias (SVT) complicate postoperative management after coronary bypass surgery in about 30% of all patients. Though a prophylactic treatment both with beta-adrenergic blocking agents and the calcium antagonist diltiazem has been used for the prevention of post-operative SVT, no study yet has performed a prospective comparison of the efficacy of these therapies. To investigate the prophylactic effect of either a calcium antagonist (diltiazem, 0.1 mg/kg per h i.v.) or a beta-adrenergic blocking agent (propranolol, 10 mg every 6 h postoperatively), we randomized prospectively 103 consecutive patients into three groups, the third one serving as a control group. Anti-arrhythmic medication was started with the procedure and was continued until the 3rd postoperative day. Preoperative conditions were the same for the three groups concerning age, extent of coronary heart disease, ventricular function and heart-related medication. There were no differences in intraoperative parameters or postoperative enzyme patterns. Diltiazem was ineffective in preventing SVT, the incidence being exactly the same as in the control group (35%). Propranolol reduced the occurrence of SVT significantly (7%, P < 0.05). Furthermore, patients treated with diltiazem needed positive inotropic support more often in the first hours after surgery than patients of the control group (30% vs 5%, P < 0.01). The perioperative administration of low-dose propranolol is considered a safe and effective drug prophylaxis to avoid the occurrence of SVT after bypass surgery.",1996.0,0,0
930,8817399,Calcium channel blockers in the dock: innocent or guilty?,J A Mackay; P S Sever,"Several studies have recently been published which have raised doubts over the long-term safety of calcium channel blockers (CCB). These have included retrospective case control studies in hypertension and meta-analyses of small scale studies in unstable angina and myocardial infarction (MI). Most of the reports were primarily concerned with the use of the short acting dihydropyridine nifedipine. Despite wide media coverage of these reports, the results are by no means irrefutable and, because of the nature of the studies themselves, are open to several criticisms. Calcium channel blockers are currently being evaluated in large-scale, prospective, randomised controlled studies, but results are unlikely to be available within the next few years. Meanwhile, the consensus view seems to be that short acting dihydropyridines should in general be avoided and have no place in the management of unstable angina and post MI. In the setting of stable angina, long acting dihydropyridines should generally be used in conjunction with a beta-blocker. In hypertensive patients, long acting dihydropyridines may be used as alternative antihypertensive agents in patients in whom the first line agents (diuretics and beta-blockers) are poorly tolerated, contra-indicated or ineffective.",1996.0,0,0
931,8817407,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
932,8818583,Calcium antagonists in the elderly. A risk-benefit analysis.,J B Schwartz,"Calcium antagonists are effective in lowering blood pressure, relieving anginal symptoms and improving exercise tolerance in older and younger patients with coronary artery disease. Verapamil and diltiazem are effective in slowing ventricular response rates to supraventricular arrhythmias in both older and younger patients. Although they belong to at least 3 distinct chemical classes, a moderate decrease in the clearance of all calcium antagonists occurs with aging. Most clinical trials of these drugs have used the same dosages in older and younger patients, confounding analyses of sensitivity in older compared with younger patients. Greater reductions in blood pressure usually occur in older compared with younger patients receiving the same dosages of calcium antagonists; similarly, the dosage required to reduce blood pressure to a certain level is usually lower in older compared with younger patients. Drug acquisition costs are generally higher for calcium antagonists than for beta-blockers or diuretics. Compared with younger patients, greater heart rate suppression may be seen in older patients treated with verapamil and diltiazem; conversely, heart rate increases are usually seen with dihydropyridines. Calcium antagonists have not been shown to provide long-term benefits or decreased morbidity or mortality in elderly patients with hypertension. Verapamil, but not dihydropyridines, decreases mortality after myocardial infarction in patients without congestive heart failure. Calcium antagonists have not been shown to be beneficial in the treatment of acute stroke. Adverse effects, such as a postural hypotension, may be more frequent in elderly compared with younger patients. In addition, the elderly are at greater risk for drug interactions with calcium antagonists due to the higher likelihood that they are receiving other drugs.",1996.0,0,0
933,8829017,,,,,0,1
934,8829020,Nisoldipine versus isosorbide dinitrate in coronary heart disease: results of a double-masked study.,B Heublein; I Amende; P M Blanke; A R Baunack-Frost; H W Breuer,"The efficacy and tolerability of a twice-daily dose of 5 mg of nisoldipine versus 40 mg of sustained-release isosorbide dinitrate (ISDN) were compared in a randomized, double-masked study in 91 patients. During the 21-day treatment period, the mean time taken during bicycle ergometry to the appearance of an ST segment depression of at least 0.1 mV compared with the resting value increased from 287 +/- 129 seconds to 391 +/- 150 seconds in the nisoldipine group and from 254 +/- 140 seconds to 350 +/- 191 seconds in the ISDN group. The mean value at the end of treatment calculated by using analysis of covariance was 383 seconds in both groups. The difference between the two treatment groups was not statistically significant. The mean ST segment depression at individually maximal workload decreased from 0.19 +/- 0.07 mV to 0.12 +/- 0.08 mV in the nisoldipine group and from 0.18 +/- 0.07 mV to 0.14 +/- 0.08 mV in the ISDN group. The mean total duration of exercise increased from 420 +/- 161 seconds to 497 +/- 140 seconds in the nisoldipine group and from 425 +/- 167 seconds to 456 +/- 168 seconds in the ISDN group. In the nisoldipine group, 9 patients reported 12 adverse events that were considered to be possibly or probably related to the test medication; in the ISDN group, 13 patients reported 26 adverse events. Although the anti-ischemic effect of the two treatments was comparable, nisoldipine was descriptively superior to ISDN in terms of tolerability.",1996.0,0,0
935,8831181,Treatment of hypertension associated with stable angina pectoris: favourable interaction between new metoprolol formulation (OROS) and nifedipine.,S Di Somma; M de Divitiis; F Bertocchi; A Carotenuto; G Cudemo; M Petitto; M Napodano; O de Divitiis,"This was a double-blind, within-patient, crossover study to evaluate the effects of a new formulation of metoprolol on blood pressure (BP) and myocardial ischemia. Twenty outpatients with mild to moderate essential arterial hypertension, chronic stable angina pectoris and positive exercise test, after a 2-week baseline placebo period, were randomized to receive long-acting metoprolol (OROS) 14/190 mg o.d., nifedipine SR 20 mg b.i.d. or their combination in a sequence of a 3 x 3 Latin square design. Two patients withdrew from the study (1 for adverse event during metoprolol and 1 for rise of BP during nifedipine). Nifedipine, metoprolol and their combination significantly reduced the weekly number of angina attacks and nitroglycerin consumption with respect to baseline. The total number of ischemic events (at 24-hour ECG monitoring) significantly decreased after each treatment with respect to baseline. Twenty-four hours mean systolic and diastolic BP were reduced by both nifedipine alone and metoprolol alone; the combination of the two drugs led to a further decrease in both systolic and diastolic BP. The duration of silent ischemic episodes was significantly reduced by nifedipine and combination but not by metoprolol. On the other hand 24 hours symptomatic attacks/patient were significantly reduced by beta-blocker and combination, but not by nifedipine. Metoprolol alone and administered with nifedipine caused a decrease, with respect to placebo baseline, in 24-hour mean heart rate (HR) and reduced the increase of HR and systolic BP at the onset of ST depression during symptomatic ischemic episodes. The effort time and time to ST = -1 mm at treadmill were significantly increased by treatment with nifedipine alone, with metoprolol alone and with their combination, but the combination was more effective than the individual therapies. ST depression at peak exercise was significantly reduced by each treatment. The slopes of correlations between the ST-segment variation and systolic BP, HR and rate-pressure product during exercise, significantly decreased after all treatments with respect to placebo baseline, more with the combination therapy than with nifedipine alone and metoprolol alone. In conclusion, based on our results the favourable interaction of metoprolol OROS and nifedipine given concomitantly, is likely to be due to a better control, respect to each individual therapy, of the pathogenetic mechanism of myocardia ischemia: BP and HR increases during exercise and during symptomatic ischemic episodes are controlled by the beta-blocker and coronary vasoconstriction during silent ischemia is prevented by the calcium-antagonist.",1996.0,0,0
936,8833599,Possible roles of medullasin in nifedipine-induced human gingival overgrowth.,K Kunimatsu; Y Ozaki; Y Aoki; I Kato,"In order to clarify a possible pathophysiological role of medullasin, a neutrophil elastase-like proteinase, in nifedipine (NF)-induced gingival overgrowth, the distributions of medullasin-positive cells immunostained in specimens from patients with NF-induced gingival overgrowth and chronic marginal gingivitis were compared in three different biopsy areas. Twenty gingival biopsies were obtained from five patients with gingival overgrowth and 20 biopsies from another five patients with chronic marginal gingivitis. In the marginal gingivitis group, the mean percentage of positive cells in the vicinity of pocket epithelium (zone I) was significantly higher than in the areas of connective tissue of the mid-portion (zone II) and adjacent to oral epithelium ( zone III) (p < 0.05). In the gingival overgrowth group, on the contrary, the positive cells significantly increased in zone II as compared with zones I and III (p < 0.05). Further, medullasin-positive cells of zones II and III in the overgrowth group had infiltrated more extensively than those in the gingivitis group (p < 0.001), indicating the participation of this enzyme in the mechanism of NF-induced gingival overgrowth. These observations suggest that medullasin may play a part in NF-induced overgrowth both in host defence and in immunoregulation, possibly cytotoxically.",1996.0,0,0
937,8838433,Persistence of anti-hypertensive effect after 'missed doses' of calcium antagonist with long (amlodipine) vs short (diltiazem) elimination half-life.,F H Leenen; A Fourney; G Notman; J Tanner,"1. Calcium antagonists with long vs short elimination half-life may show marked differences in their antihypertensive effect during short interruptions of therapy by missed doses. 2. In the present study we evaluated the blood pressure lowering effect of amlodipine vs diltiazem both on active maintenance treatment and after active treatment was interrupted for 2 days by placebo using a double-blind randomized design. After a single blind placebo run-in period, hypertensive patients were randomized to amlodipine 5 mg once daily or diltiazem 90 mg twice daily. After 4-6 weeks, doses were increased to 10 mg once daily or 180 mg twice daily, if necessary for control of diastolic blood pressure. During week 9 or 10 on active treatment blisterpacks contained 2 days of placebo. Twenty-four hour blood pressure monitoring was performed at the end of run-in period and during week 9 and 10 on active vs interrupted therapy. 3. Active therapy by amlodipine (n = 20) lowered day systolic blood pressure by 17 +/- 2 mmHg and diastolic blood pressure by 12 +/- 2 mmHg and did not change heart rate. In second day of interrupted therapy most of these responses were still present. Diltiazem (n = 14) lowered day systolic blood pressure by 13 +/- 2 mmHg, diastolic blood pressure by 11 +/- 2 mmHg and heart rate by 10 +/- 2 beats min-1. Most of these responses had disappeared during the second day of interrupted therapy. 4. We conclude that amlodipine and diltiazem are fairly similar in lowering blood pressure from an efficacy point of view. However, during short periods of noncompliance blood pressure control will persist markedly better with the agent with a long vs the one with a short elimination half-life.",1996.0,0,0
938,8841897,Evaluation of gingival and periodontal conditions following causal periodontal treatment in patients treated with nifedipine and diltiazem.,P Bullon; G Machuca; A Martinez-Sahuquillo; J V Rios; E Velasco; J Rojas; J R Lacalle,"It is established that phenytoin, cyclosporin and some calcium antagonists produce gingival overgrowth, but it is not known how this condition may respond to causal periodontal treatment. In order to find out, a longitudinal study was carried out, over a year, comparing a group of patients who were given nifedipine (NG, n = 18) and another group who were given diltiazem (DG, n = 13) with 2 others: one comprised cardiopathic patients who took no calcium antagonists (CG, n = 12) and the other contained patients who were medically healthy, with moderate periodontitis (HG, n = 12). On their basal visit, they were examined and instructed in oral hygiene, and then given causal periodontal treatment, being seen again at 4 and 8 months, when hygiene instructions were reinforced. They were seen for the last time at 12 months, when they were again examined. Groups NG and DG, on their basal visit, showed larger gum size than groups HG and CG, which was statistically significant; on their final visit, these differences remained only at the interproximal level. The number of patients with gingival overgrowth-taking the average of group HG as a minimal value-was much higher in groups CG (92%), DG (100%) and NG (89%) on the basal visit; on the final visit, the differences remained only in groups DG (85%) and NG (83%). The probing pocket depth reduction was much greater in groups HG and CG than in DG and NG, basically due to a greater gaining on clinical attachment level. The % of sites in which the pocket depth improved by more than 2 mm was 39.8% in HG, 54.5% in CG, 23.7% in DG and 28.7% in NG. The % of sites where the attachment gain by more than 2 mm was 46.2% in HG, 55.5% in CG, 22.8% in DG and 21.4% in NG. The amount of plaque and bleeding on probing, which was similar in all groups on the basal visit, decreased throughout the study, especially between the basal and 2nd visit in groups HG and CG. We have demonstrated that patients that take nifedipine and diltiazem show a larger gum size and their response to causal periodontal treatment is poorer than in the healthy and the cardiac groups.",1996.0,0,1
939,8847861,The Diltiazem Different Doses Study--a dose-response study of once-daily diltiazem therapy for hypertension.,P Nilsson; L H Lindholm; T Hedner,"The objective was to evaluate the dose-related efficacy/tolerance profile of 240, 300, 360, and 420 mg diltiazem slow-release, once-daily (OD) doses, with emphasis on the 300 mg dose. The study was randomized and double-blinded with a 36-week parallel, two-branched, cross-over design after a single-blind, run-in period of 4 weeks on placebo and 6 weeks on 300 mg diltiazem OD. Each branch included six 6-week active treatment periods with 180, 240, and 300 mg tablets, one or two tablets OD. Participants were men and postmenopausal women, aged 40-70 years, with uncomplicated primary hypertension (WHO stages I and II) and a supine diastolic blood pressure of 95-115 mm Hg in the absence of antihypertensive medication. A total of 138 patients from various clinics participated in the study. All were included in the intention to treat analysis, and 117 patients were included in the per protocol analysis. Criteria for evaluation were blood pressure, heart rate, and response rate, as well as plasma diltiazem and metabolite M1 concentration before morning dose. Well-being of the patients and adverse events were recorded. Electrocardiogram and standard laboratory tests were obtained. Analysis of variance was used for statistical calculations. Supine blood pressures and response rates in the per protocol analysis were 161.2/97.0 for placebo (29.1%), 155.2/ 92.8 for 240 mg (54.7%), 153.8/91.6 for 300 mg (55.6%), 155.5/92.0 for 360 mg (59.0%), and 152.0/90.5 for 420 mg (63.2%) of diltiazem OD. The intention to treat analysis was very similar to the per protocol analysis. There was a small but statistically significant decrease in heart rate for all doses of diltiazem OD compared to placebo. A linear relationship existed between the dose and the plasma concentration of both diltiazem and metabolite M1, as well as a dose-response relationship. Diltiazem OD in the dose range 240-420 mg was generally well tolerated and not differently perceived from the placebo treatment except for ankle edema (2-6%). The study shows that OD diltiazem is significantly superior to placebo for mild to moderate hypertension and that the effect is large enough to be clinically valuable. It also shows that there is a linear dose-response relationship for diltiazem between 240 and 420 mg.",1996.0,0,0
940,8852523,Bezoars: implicated drugs and avoidance strategies.,K C Thompson; J P Iredale,"A wide variety of drugs or combinations of drugs have the potential to form bezoars. In the majority of patients presenting with bezoars there is a clear predisposing factor. This article highlights those drugs or groups of drugs which have been implicated in bezoar formation. Although bezoars are rare, it is important that the clinician is aware of the possibility of their development, particularly in susceptible individuals. This is because bezoars often develop in the elderly and in those with serious coexistent disease. They may be difficult to diagnose and recourse to laparotomy is frequently required to treat them. As a result, they are associated with a significant morbidity and mortality.",1996.0,0,0
941,8856491,,,,,0,0
942,8860064,Comparison of once daily and twice daily nisoldipine as monotherapy in essential hypertension.,G K Davidsson; J S Edwards; C Davidson,"Twenty-four patients completed a dose ranging study of the effect of nisoldipine as monotherapy in the treatment of hypertension. This randomized double-blind study consisted of two crossover phases in each of which once and twice daily treatment were compared. In the first treatment phase the total daily dose of nisoldipine was 10 mg, which increased to 20 mg during the second phase. Trough blood pressure measurements were made 12/24 h postdose. During the first phase the blood pressure values following treatment with nisoldipine 5 mg twice daily were significantly lower than with 10 mg once daily. However, when the daily dose was increased to 20 mg there was no significant difference between the two treatment regimens. There was also no significant difference between nisoldipine 5 mg twice daily and 10 mg twice daily but the results for 20 mg once daily were significantly lower than for 10 mg once daily. Four patients withdrew from the study because of adverse events, one while on placebo and three while on nisoldipine therapy. Between 33 percent and 47 percent of patients reported adverse events during nisoldipine treatment but the majority of adverse events reported were mild and did not require treatment withdrawal. Nisoldipine twice daily appeared to be more effective and better tolerated than once daily treatment for 24-h blood pressure control.",1996.0,0,0
943,8861548,Verapamil: a review of its pharmacological properties and therapeutic use in coronary artery disease.,R N Brogden; P Benfield,"Verapamil has well proven efficacy in the treatment of patients with hypertension, and early studies indicated its efficacy in the treatment of coronary artery disease. The efficacy of verapamil relative to placebo in patients with stable angina pectoris is confirmed, and the drug is at least as effective as nifedipine, propranolol or metoprolol and of similar efficacy to bepridil and nicardipine when administered as a conventional or sustained release formulation. Verapamil is the first calcium antagonist to be shown in a double-blind study to significantly reduce mortality and reinfarction rate after acute myocardial infarction in patients without heart failure. In these patients, the reduction in mortality achieved with verapamil was similar to that reported with beta-adrenoceptor antagonists, suggesting that verapamil may be a suitable alternative to beta-blockers as secondary prevention in patients intolerant of these drugs. Recurrence of stenosis in patients who successfully undergo percutaneous transluminal coronary angioplasty (PTCA) limits the usefulness of the procedure. Verapamil has recently been shown to significantly reduce the rate of restenosis in patients with stable angina at risk of recurrence, although these initial results require confirmation. Verapamil, therefore, is effective in the treatment of patients with stable angina pectoris, appears to be an alternative to beta-blockers in selected patients as late start secondary prevention after acute myocardial infarction and has a potential role in preventing recurrent stenosis after PTCA, if initial results are confirmed.",1996.0,0,0
944,8867566,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.",1996.0,1,1
945,8869861,Long-term survival after myocardial infarction: relationship with thrombolysis and discharge medication. Results of the Augsburg Myocardial Infarction Follow-up Study 1985 to 1993.,W Koenig; H Löwel; M Lewis; A Hörmann,"A large number of randomized clinical trials have shown that thrombolysis, long-term treatment with beta-blockers, antiplatelet drugs, and angiotensin converting enzyme inhibitors improve survival after acute myocardial infarction (AMI). However, for calcium channel blockers (nifedipine, diltiazem, and verapamil) there was either no benefit, or positive effects have been reported in subgroups only. Recent studies have raised concern about the safety of this drug class, especially in patients with coronary heart disease. We studied the long-term survival, for a median follow-up time of 4.4 years, of 1197 non-diabetic patients in the population-based AMI registry in Augsburg, Germany, aged 25-74 years, who had survived a first Q wave acute myocardial infarction for at least 28 days. The impact of thrombolysis and prescribed medication at discharge (beta-blockers, antiplatelet drugs, and calcium channel blockers) on long-term survival was analysed using the Cox-Proportional-Hazard model, controlling for age, sex, and concomitant cardiac drug use. Thrombolysis (risk ratio, RR, 0.72; 95% confidence interval, CI, 0.48-1.08), long-term beta-blockade (RR 0.52; 95% CI 0.36-0.74) and antiplatelet drug use (RR 0.69; 95% CI 0.50-0.94) were associated with considerable reductions in total mortality. The use of calcium channel blockers was not associated with a reduction in total mortality (RR 1.23; 95% CI 0.89-1.69). Separate analyses for nifedipine (RR 1.00; 95% CI 0.68-1.48), and diltiazem (RR 1.55; 95% CI 1.04-2.32) showed an increased risk of death associated with the latter. Using patients on beta-blockers only (RR 1.00) as a reference, the prescription of these calcium channel blockers was consistently associated with an increased total mortality (nifedipine, without beta-blockers RR 1.20; 95% CI 1.12-3.57, diltiazem, without beta-blockers RR 2.87; 95% CI 1.75-4.70). These results from an observational study demonstrate a benefit of thrombolysis, beta-adrenergic blockade and antiplatelet drug use on long-term survival in acute myocardial infarction patients. Calcium channel blocker use appears to be associated with an increased risk of death. These data support the need for controlled trials to address this issue specifically.",1996.0,0,1
946,8869897,Ultraviolet-A1 (340-400 nm) irradiation therapy in systemic lupus erythematosus.,H McGrath; P Martínez-Osuna; F A Lee,"Ultraviolet-A1 (UV-A1) wavelengths have been found effective in mitigating signs and symptoms of disease activity in systemic lupus erythematosus (SLE) but studies have been uncontrolled. To rigorously assess the effectiveness and safety of daily low-dose UV-A1 irradiation as a therapeutic agent in this disorder we enrolled 26 women with SLE in an 18-week two-phase study. During the initial six-week prospective, double-blind, placebo-controlled phase, the patients were divided into two groups; Group A was exposed to 60kJ/m2 of UV-A1 (340-400 nm) irradiation within a sunbed five days a week for three weeks and Group B was exposed for an equal amount of time to visible light of greater than > 430 nm (placebo). Each group was then crossed over for exposure to the other source for three weeks. During the second phase-2 weeks-patients and physicians were unblinded and patients were irradiated with progressively decreasing levels of UV-A1 only. Twenty-five patients completed the six-week placebo-controlled phase of the study and eighteen patients participated for the entire 18 weeks. In Group A the systemic lupus activity measure (SLAM) score improved significantly after three weeks of five-day-a-week UV-A1 irradiation (P < 0.05), regressing to baseline during the three weeks of placebo irradiation. Improvement recurred and progressed with six weeks of three-day-a-week UV-A1 irradiation (P < 0.05). Group B patients responded negligibly to the three weeks of visible light, more sharply to UV-A1, and as with Group A, maximally to the six weeks of three-day-a-week UV-A1 (P < 0.01). With twice- and then once-weekly UV-A1 irradiation the SLAM scores worsened slightly. All patients decreased their drug use. Anti-double-stranded DNA antibodies (anti-dsDNA) decreased significantly (P < 0.05) and anti-nuclear antibodies non-significantly. Side effects were negligible. Visible light had no significant effect. In conclusion, low-dose UV-A1 irradiation effectively, comfortably, and without apparent toxicity diminished signs and symptoms of disease activity in SLE.",1996.0,0,0
947,8877673,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
948,8879341,"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.",1996.0,1,1
949,8879890,"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.",1996.0,0,1
950,8880557,,,,,0,0
951,8881845,"Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial.",P K Rønnevik; B Silke; O Ostergaard,"The additional efficacy, duration of action and tolerability of felodipine were evaluated in patients with stable angina pectoris and a positive stress test who were already receiving therapy with a beta-adrenergic blocker. One hundred and twenty-eight patients were randomized to double-blind treatment with 5-10 mg felodipine once daily or matching placebo, and were evaluated by serial exercise testing during 12 weeks of treatment. Felodipine at 4 h significantly increased exercise duration assessed after 4 weeks of treatment (increase 34 +/- 65 s vs 18 +/- 71 s in placebo-treated patients; 95% confidence interval 1.01-1.11; P = 0.01), and after 12 weeks of treatment (increase 39 +/- 103 s vs 3 +/- 72 s; 95% confidence interval 1.01-1.16; P = 0.02). The time until onset of exercise-induced anginal pain and time until 1 mm ST depression assessed after 4 weeks of treatment also increased significantly with felodipine compared to placebo. No statistically significant changes in exercise test parameters evaluated 24 h after medication were observed. The addition of felodipine once daily demonstrated a sustained improvement in exercise duration in patients symptomatic despite treatment with a beta-blocker evaluated 4 h after drug intake. At 24 h post dose, no statistically significant effect was observed. Felodipine is well tolerated with a low incidence of side-effects and no adverse effect on quality of life.",1995.0,1,1
952,8881946,"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
953,8884161,A comparative review of the adverse effects of calcium antagonists.,H T Dougall; J McLay,"A large number of drugs within the 3 currently classes of calcium antagonists are in common medical use for the treatment of hypertension and ischaemic heart disease. The reported adverse effect profile for each of these drugs varies, but tends to hold true to drug class and are typified by the adverse reactions reported for nifedipine and amlodipine (dihydropyridines), diltiazem (benzothiazepines) and verapamil (phenylalkylamines). Minor adverse effects such as flushing, headache, ankle oedema, palpitations and constipation are not uncommon and frequently require the cessation of treatment. Of greater concern affecting the wide and common first-line use of calcium antagonists is the as-yet unresolved issue of a reportedly greater risk of myocardial infarction and death following the use of short-acting nifedipine in patients with a history of hypertension, myocardial infarction or angina. Until this issue is fully resolved, it would seem prudent to limit the use of this agent in 'at-risk' patients and to await the results of further prospective studies before a final conclusion can be made.",1996.0,0,0
954,8888089,Comparison of two formulations of nifedipine during 24-hour ambulatory blood pressure monitoring.,M C Granberry; S F Gardner; E F Schneider; I R Carter,"To determine if one commercial extended-release formulation of nifedipine (Adalat CC) is as effective as another (procardia XL) in controlling blood pressure over 24 hours. Open-label, randomized, crossover study. University-affiliated family medicine clinic. Fifteen patients with stage 1-4 primary hypertension. Procardia XL or Adalat CC once/day was titrated to achieve blood pressure control. The effective dose was continued for 4 weeks, washed out for 1 week, and reinstituted with other study drug. Twenty-four-hour ambulatory blood pressure was recorded the conclusion of each treatment phase. Treatment phases were compared for mean 24-hour blood pressure, mean daytime (6:00 A.M.-10:00 P.M.) and mean nighttime blood pressure, and mean blood pressure load (percentage of blood pressure measurements > 140/90 mm Hg daytime and > 120/80 mm Hg nighttime). Thirteen patients completed the study. No statistically significant difference was seen in mean 24-hour blood pressure (138/86 mm Hg for Procardia XL vs 137/85 mm Hg for Adalat CC), daytime or nighttime blood pressure, or blood pressure load. Two patients experienced clinically significant adverse effects while taking Adalat CC. In these patients with primary hypertension, Adalat CC was as effective as Procardia XL at controlling blood pressure for 24 hours. Blood pressure, heart rate, and adverse effects should be monitored 2-4 weeks after any exchange of Adalat CC for Procardia XL.",1996.0,0,0
955,8889897,Chronopharmacologic considerations when treating the patient with hypertension: a review.,R J Straka; S R Benson,Recognition of the existence of circadian variation in exacerbation of cardiovascular disease may have relevance to clinical use of cardioactive agents. Physiologic rational for the chronobiology of cardiac disease exists and can provide a basis on which to examine the efficacy of agents to manage cardiac disease. The use of 24-hour ambulatory blood pressure monitoring (ABPM) devices have advanced our ability to describe the interplay of chronobiologic rhythms and pharmacodynamic response to antihypertensive medications. This review summarizes the studies evaluating the use of various antihypertensive medications in the context of using 24-hour blood pressure monitoring devices. The studies are described in an attempt to increase awareness of chronobiology and potential implications of designing chronotherapeutic regimens.,1996.0,0,0
956,8906524,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
957,8916562,Prescribing practices for the management of headache in Newfoundland and Labrador.,S Furlong; W Pryse-Phillips; M Crowley; C J Turner,"To assess the impact of sumatriptan in clinical practice, we undertook a retrospective analysis of the government of Newfoundland and Labrador's prescription drug program data base for 35 consecutive patients prescribed sumatriptan. The number of doses of all drugs prescribed ranged from 121 to 18,874 on from 4 to 357 prescriptions per patient over 1 to 19 months. The mean number of doses of analgesic drugs prescribed before sumatriptan therapy was 56 per month and after initiation of sumatriptan was 46 per month. The prescribing of multiple analgesics was common; 79% received three or more different analgesics. Twenty-two (63%) patients were prescribed medications indicated for the prophylaxis of migraine concomitantly with drugs indicated for symptomatic treatment. Twenty-four (69%) patients were prescribed medication capable of inducing migraine. We conclude that sumatriptan did not have a major impact on the outcomes of these patients judged by their use of analgesics. The simplest explanation is that many of the patients were suffering from analgesic-induced headache rather than migraine. In addition, we conclude that there were deficiencies in prescribing practices including numbers, quantities, and choice of analgesics; the use of analgesics concomitantly with drugs indicated for migraine prophylaxis; and the use of drugs capable of inducing migraine. Further research is required to validate these findings.",1996.0,0,0
958,8919632,Clinical evaluation of serum amlodipine level in patients with angina pectoris.,K Watanabe; Y Ochiai; T Washizuka; T Inomata; Y Miyakita; M Shiba; T Izumi; A Shibata; Y L Qu; T Nagatomo,"Serum amlodipine levels were determined in 18 patients with vasospastic angina. Patients were divided into two groups: Group A (n = 9) received amlodipine 5 mg by single daily administration, and Group B (n = 9) received 10 mg given by single daily administration for the first 3 days, then 5 mg from the 4th day on. The serum amlodipine concentration in Group A took 7 days to reach a steady state of around 8 ng/ml. The level in Group B was 8.9 ng/ml at 3 days. From these results, the optimal dosage of amlodipine in the treatment of angina pectoris is 10 mg for the initial 3 days followed by 5 mg thereafter.",1996.0,0,0
959,8924054,Calcium channel blocker debate: true lies?,J Leor; A Battler,,1996.0,0,0
960,8927880,[Comparative antihypertensive action of 20 mg delayed-action nifedipine with either 25 or 50 mg atenolol. A study on the treatment of patients with mild to moderately severe arterial hypertension].,K Kraft; S Schiessl; H Vetter,"In the present double-blind, randomized, placebo-controlled study 36 untreated patients (57.8 +/- 8.4 years) with mild to moderate hypertension were included. After a 14 days' placebo period they were treated with a combination of 20 mg retarded nifedipine and 25 or 50 mg atenolol for six weeks each. Group A started with 25 mg, group B with 50 mg atenolol. Casual sitting blood pressure was measured automatically every second week, routine laboratory parameters and side effects were evaluated at the end of placebo and the verum periods. The blood pressure of the two groups was comparable during placebo and was reduced by 31.6/14.7 mmHg in group A or 29.9/15.8 mmHg in group B (p < 0.001 vs. placebo) after six weeks. In the second treatment period with verum, blood pressure was not further reduced. Both combinations were equally efficient also in the female and the elder subgroups (> 60 years) who were characterized by higher systolic blood pressure. The response rates were 83% and 86% for the combination with 25 and 50 mg atenolol respectively. Heart rate was significantly reduced in all groups during 50 mg atenolol. Laboratory parameters were not altered by treatment. Frequency and severeness of side effects were equal in both groups. It is concluded that in patients with mild to moderate uncomplicated hypertension the combination of 20 mg retarded nifedipine with 25 mg atenolol is equally efficient to the combination with 50 mg atenolol.",1996.0,0,0
961,8933239,Comparison of the therapeutic effects of the beta-blocking agent bisoprolol and the calcium-blocking agent diltiazem in patients with heart failure due to dilated cardiomyopathy.,M Suwa; T Ito; Y Otake; A Moriguchi; Y Hirota; K Kawamura,"Beta-blocking agents reduce mortality and improve symptoms in patients with dilated cardiomyopathy (DCM). There have been reports that diltiazem, a calcium-blocking agent, is also effective in such patients. We prospectively compared the effects of the beta-blocking agent bisoprolol with those of the calcium-blocking agent diltiazem in 18 patients (11 males and 7 females, age 14 to 68) with DCM. The 18 patients, (10 in New York Heart Association functional class III and 8 in class IV) were randomly assigned to 2 groups. Bisoprolol was administered as the first drug in 10 patients and diltiazem was administered in 8. Cross-over to bisoprolol was also performed in 3 patients. At the end of the study, among the 13 patients who had been given bisoprolol, 9 showed a good response (efficacy rate: 69%). In contrast, only 3 of the 8 patients who received diltiazem showed a good response (efficacy rate: 37.5%). Among the patients in NYHA class III, all 7 (100%) who were treated with bisoprolol responded but only 2 of the 4 (50%) treated with diltiazem responded (p < 0.05). Among the patients in class IV, 2 of 6 (33%) responded to bisoprolol and 1 of 4 (25%) responded to diltiazem (not significant). These results suggest that diltiazem, like bisoprolol, has a beneficial effect in patients with DCM, with a greater effect in class III patients. However, we conclude that diltiazem should usually be used as a second choice to improve heart failure in DCM, and as the first medication only in those with contraindications to beta-blocking agents.",1996.0,1,1
962,8935693,[Multicenter comparative study of felodipine-ER and nifedipine-OROS in the treatment of mild-to-moderate arterial hypertension].,M Batlouni; R Leite Luna; I Castro; A Silveira Sbissa; D Armaganijan; H de C Chaves Junior; F Nobre; C Pereira da Cunha,"To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3%) patients in the felodipine group and in 38/51 (74.5%) in the nifedipine group (NS). Side effects, occured in approximately 15% of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.",1996.0,0,0
963,8948688,,,,,0,0
964,8949385,[Short and long-term clinical tolerance of hypertensive treatment during the HOT study (Hypertension Optimal Treatment)].,J M Mallion; N G Pehrsson; C Raveau-Landon; S Boutelant; J Ménard,"International, prospective, randomized HOT study aims to determine the optimal BP level under treatment in order to reduce at the most the cardiovascular morbidity/mortality. Defined by randomization, the level to obtain is DBP < or = 80, 85, 90 mmHg. The treatment is started by felodipine 5 mg/day then, if necessary, a bitherapy is prescribed and then, if necessary, a tritherapy. 19,193 patients have been included (BP at randomization 170 +/- 15/105 +/- 4 mmHg). After 1 year treatment, it is possible to search for the influence on the clinical tolerance of sex, age, BP goal, geographic area, time and treatment. The percentage of patients with side effects by BP goals and by treatment type are, during the time and in different geographic areas, the following (NE/Northern Europe = Norway, Switzerland, Belgium, Hungary, Sweden, Denmark, Finland, The Netherlands, UK, Germany, Austria; SE/Southern Europe = Italy, Spain, Greece): [table: see text] The target BP and age don't nearly influence the clinical tolerance. The side effects reported by the physicians are more numerous at the treatment start than at longeur terme. That is due to the therapeutic modifications of the physicians or to a better acceptation of the drugs by the patients or to a real disappearance of the side effects. Reported side effects are more frequent in Southern Europe, France than Northern Europe and more frequent among women that men. The incidence of side effects is proportional to the number of prescribed drugs. Time and the number of antihypertensive drugs appear as the most important factors.",1996.0,0,0
965,8953207,Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life.,J W van Ree; G A van der Pol,"To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. Randomised, double-blind placebo controlled 6 weeks parallel study. From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.",1996.0,1,1
966,8959570,The effect of verapamil on the prevalence and severity of cyclosporine-induced gingival overgrowth in renal allograft recipients.,I Cebeci; A Kantarci; E Firatli; M Carin; O Tuncer,"Cyclosporine A (CsA) and verapamil are two agents used in renal transplantation, both of which are suspected of inducing gingival overgrowth. This study was conducted to investigate the effect of verapamil on the severity and prevalence of CsA-induced gingival overgrowth. Fifty-one (51) renal transplant recipients (total group) of whom 22 were using only CsA (Group A) and 29 of whom were prescribed CsA + verapamil (Group B) were evaluated for various periodontal and pharmacological parameters. No statistically significant differences were found in age, sex, plaque index, gingival index, calculus index, probing depth, CsA oral dose, CsA whole blood level, duration of CsA therapy, azathioprine dose, and prednisolone dose. Although the prevalence of the gingival overgrowth was more pronounced in CsA + verapamil group compared to CsA group (51.72% vs. 40.91%), the difference was not statistically significant. Similarly, the severity of gingival overgrowth, although more manifest in CsA + verapamil group than CsA patients (34.24% vs. 28.91%), was not significantly different. Gingival overgrowth scores in the main group, CsA, and CsA + verapamil groups were found to be positively correlated to periodontal probing depths (r = 0.60, r = 0.70, r = 0.52, respectively) and the gingival index (r = 0.60, r = 0.70, r = 0.54, respectively). CsA oral dose, whole blood level, and duration of CsA therapy were not found to be correlated with the gingival overgrowth in either group. Likewise, the dose of verapamil and the duration of verapamil therapy were not correlated with the gingival overgrowth in Group B. This study indicates that verapamil, when prescribed as the calcium channel blocker in renal transplant patients, has no augmenting effect on the severity and the prevalence of CsA-induced gingival overgrowth.",1996.0,0,0
967,8960842,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
968,8960857,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.",1996.0,1,1
969,8967905,"[The effects of treatment with trapidil compared to nifedipine on physical, emotional and cognitive exercise tolerance in patients with coronary heart disease].",I Assmann; S Lehrl; G Burkard; W Strösser,"The present study was carried out to investigate exercise test results and the outcome of the quality of life after administration of trapidil (CAS 15421-84-8, Rocornal) or nifedipine (CAS 21829-25-4) to patients with coronary heart disease. The characteristics of the life quality in combination with the results of exercise test are considered of great importance for selecting medical treatment in patients with chronic stable angina pectoris. However, little information is available on how this first evaluation may be used to select the best pharmacological approach in individual patients. In this prospective multicentre study, 144 patients with stable angina were enrolled in 6 centres. Due to protocol violations and drop-outs 116 patients were evaluated for tolerability; 101 patients were evaluated for efficacy. After baseline evaluation, consisting of an exercise test and a questioning investigating patients' anginal symptoms and several psychometric testings, the patients were randomly allocated to double-blind treatment for 12 weeks with either trapidil, 200 mg t.i.d. or nifedipine, 10 mg t.i.d. according to a parallel group design. After 6 and 12 weeks exercise tests and psychometric testings were repeated. Both trapidil and nifedipine prolonged exercise tolerance (trapidil 39.2% vs. nifedipine 33.3%) or increased the total exercise over baseline levels (trapidil 57.8% vs. nifedipine 61.2%). Using Mann-Whitney U-test the SB-S-rating scale and the physician's assessment revealed a comparable improvement of life quality (trapidil 69.4% vs. nifedipine 80.0%) under both treatments. In addition patient questioning showed a significant reduction in angina attacks and in nitroglycerin consumption. None of the characteristics of anginal symptoms or exercise test gave evidence for a significant difference between nifedipine and trapidil. Both drugs demonstrated similar safety profiles (adverse events (AEs) 12.7% for trapidil and 11.1% for nifedipine); four patients of the trapidil group and one of the nifedipine group discontinued the clinical trial because of AEs. The results of a baseline exercise test and rating questionnaires may offer useful information for selecting medical treatment in stable angina pectoris.",1996.0,0,0
970,8969572,Novel delivery system for verapamil designed to achieve maximal blood pressure control during the early morning.,J M Neutel; M Alderman; R J Anders; M A Weber,"Because the risk of cardiovascular events appears to be greatest in the early morning, this period is a time during which adequate blood pressure (BP) control appears to be most desirable. In this study, a controlled-onset extended-release system (COER-24) that delivers verapamil in a manner designed to achieve maximal levels of drug during the early morning surge in BP was compared with placebo. Ninety-five patients with mild to moderate hypertension were studied. Of this group, 49 patients (mean age 57.6 +/- 1.4 years; 35 men and 14 women) were randomized to take verapamil COER-24 240 mg at 10 PM, and 46 subjects (mean age 55.8 +/- 1.5 years; 29 men and 17 women) were randomized to take placebo. Ambulatory BP monitoring was performed after a 4-week initial placebo period and was repeated after 4 weeks of treatment with verapamil or placebo. Verapamil COER-24 resulted in significant (p < 0.001) decreases in mean whole-day systolic and diastolic BP (-8.2/-6.3 mm Hg; baseline 152/93.0 mm Hg) when compared with placebo (+0.3/-0.9 mm Hg; baseline 150.3/93.2 mm Hg). From 6 AM to noon, verapamil COER-24 resulted in a change in systolic and diastolic BP of -11.6/-9.0 mm Hg, which was significantly (p < 0.001) greater than the change that occurred with placebo (-0.5/-1.0 mm Hg) during the same period. In the last 4 hours of the dosing interval (6 PM to 10 PM), verapamil COER-24 caused significantly greater (p < 0.001) decreases in BP (-7.4/-4.8 mm Hg) than did placebo (+2.7/+1.0 mm Hg). These data demonstrate that the COER-24 system, when administered in the late evening, achieves maximal BP reduction during the early morning hours. Moreover, BP reductions were sustained throughout the 24-hour period.",1996.0,0,0
971,8973753,Effects of bunazosin and atenolol on serum lipids and apolipoproteins in a randomised trial.,G Schmitz; K O Stumpe; W Herrmann; G Weidinger,"The effects of bunazosin and atenolol on serum lipids and lipoproteins after 6 months of treatment were compared in this multicentric, double-blind, randomised trial. A total of 174 patients with mild to moderate essential hypertension from 15 hospitals in Germany and Poland was included in the study. Eighty-seven were treated with the alpha-receptor blocker bunazosin and the same number with the beta-blocker atenolol. Systolic and diastolic blood pressure decreased significantly in both groups, whereas only atenolol decreased pulse rate. In the bunazosin group HDL-cholesterol was significantly increased after 6 months of treatment, whereas all other analysed parameters remained unchanged. In the atenolol group total cholesterol, LDL-cholesterol, total triglycerides, apolipoprotein E, VLDL-cholesterol and VLDL-triglycerides were significantly increased after 6 months of therapy. There was a significant difference between bunazosin and atenolol for total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, VLDL-triglycerides and apolipoprotein B levels. As a consequence, there was a significant difference in the atherogenic index of both groups. We conclude that bunazosin is favorable in the treatment of high blood pressure, because the coronary risk is not negatively influenced as shown for atenolol.",1996.0,0,0
972,8977754,Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men.,J H Romeo; R Dombrowski; Y S Kwak; S Fuehrer; D C Aron,"Verapamil has been associated with hyperprolactinaemia, but there have been no population-based studies. Our objective was to determine the prevalence and degree of hyperprolactinaemia associated with verapamil in the clinical setting. Observation with cross-sectional and longitudinal components in the setting of an urban teaching hospital and its satellite out-patient clinics. Male out-patients excluding those taking other drugs known to raise PRL, renal failure and known primary hypothyroidism (1265 eligible subjects). Control subjects were drawn from eligible out-patients not taking verapamil. Serum PRL levels, frequency of persistent hyperprolactinaemia and total testosterone levels. Prolactin levels were obtained in 449 subjects on verapamil (35.5% response rate) and 166 controls. The proportions of individuals with hyperprolactinaemia (PRL > 460 mU/l) were 0.085 and 0.030 in the verapamil and control groups, respectively (P = 0.012, X2-test). The mean (+/- SD) serum PRL levels were 267 +/- 205 and 203 +/- 118 mU/l in the verapamil and control groups, respectively (P < 0.001, independent t-test). Of the 38 patients with previously determined elevated PRL levels, follow-up data were obtained in 25 (65.8%); one was found to have a pituitary adenoma and was excluded from the analysis. Fifteen of the 24 were still on verapamil (Group 1) and 14 (93.3%) continued to be hyperprolactinaemic. In 9 patients verapamil had been discontinued (Group 2) and all had normal PRL levels. Continued verapamil use was associated with persistent hyperprolactinaemia (odds ratio > 120, P < 0.00001). The mean +/- SD serum testosterone levels at follow-up were significantly lower in Group 1 (6.16 +/- 2.52 nmol/l) than in Group 2 (9.42 +/- 3.92 nmol/l, P = 0.029, independent t-test). The prevalence of hyperprolactinaemia associated with verapamil use in this study of male out-patients was 8.5% (95% CI 5.9-11.1%). The persistence of hyperprolactinaemia when verapamil was continued (Group 1) and the return to normal PRL levels when verapamil was discontinued (Group 2) confirm verapamil's causal role in the development of hyperprolactinaemia. While low testosterone levels were common in both groups, testosterone levels were lower in patients on verapamil. Our data suggest that screening for hyperprolactinaemia should be considered in male patients taking verapamil.",1996.0,0,1
973,8998091,Effectiveness of verapamil-quinidine versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation.,G D Innes; L Vertesi; E C Dillon; C Metcalfe,"To determine the relative effectiveness of a verapamil-quinidine sequential combination versus digoxin-quinidine in the emergency department treatment of paroxysmal atrial fibrillation (PAF). This prospective, double-blind, randomized, controlled trial involved patients, aged 18 to 75 years, with new-onset (< 48 hours) atrial fibrillation who presented to a community-based urban hospital with an annual ED census of 65,000. Exclusion criteria included ventricular response rate lower than 100 or higher than 200 beats/minute, allergy to study drugs, hypotension with evidence of end-organ hypoperfusion, and conduction abnormalities. Consenting patients were randomly assigned to receive rapid digitalization (1.0 mg over 2 hours) or i.v. verapamil (sequential 5-mg boluses up to 20 mg). After ventricular rate was controlled (< 100 beats/minute), oral quinidine (200 mg) was initiated and repeated every 2 hours until conversion to normal sinus rhythm (NSR) occurred, until 1 g of quinidine was administered, or until adverse effects supervened. Heart rate, blood pressure, cardiac rhythm, time to conversion, and adverse effects were documented. Forty-four patients received the study drugs. Three were withdrawn, leaving 19 in the verapamil-quinidine (VER-Q) group and 22 in the digoxin-quinidine (DIG-Q) group. Sixteen patients (84%) in the VER-Q group and 10 (45%) in the DIG-Q group converted to NSR within 6 hours (P < .02). Mean time to conversion (+/-SD) was 185 +/- 146 minutes for VER-Q and 368 +/- 386 minutes for DIG-Q patients (P = NS). Twelve VER-Q patients (63%) and 6 DIG-Q patients (27%) were discharged from the ED (P < .05). Minor adverse effects were more common in the VER-Q group. No mortality or significant morbidity occurred. The sequential combination of verapamil and quinidine, in the doses studied, is an effective treatment for PAF and is superior to digoxin-quinidine. Digoxin should no longer be considered the treatment of choice for uncomplicated PAF.",1997.0,0,0
974,8998248,Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension.,Y Lacourcière; L Poirier; J Lefebvre; F Archambault; J Cléroux; G Boileau,"Recent studies and authorities have advocated the use of low-dose thiazide diuretics as first-line treatment agents in elderly hypertensives. However, these recommendations were based solely on blood pressure (BP) measured in the clinic. The objective of the present 32-week double-blind study was to compare the effects of hydrochlorothiazide (HCTZ) and amlodipine (AML) in elderly patients with confirmed ambulatory hypertension. After a 4-week placebo washout period, 42 (25 men, 17 women) patients (mean age, 69 years) with clinic sitting diastolic BP of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were randomized double-blind to receive AML 5 to 10 mg (n = 21) or HCTZ 12.5 to 25 mg (n = 21) once daily. After 8 weeks of monotherapy, patients in whom clinic diastolic BP remained > or = 90 mm Hg were given combination therapy with the other agent. Amlodipine monotherapy induced significant reductions in clinic, mean 24-h, daytime and sleep systolic/diastolic BPs whereas only clinic BP decreased significantly in patients treated with HCTZ monotherapy. Moreover, 19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP control. At the end of the 32-week treatment period, combination therapy in the HCTZ group resulted in statistically significant reductions in clinic as well as in 24-h, daytime and sleep ambulatory BPs that were similar to those observed in the AML monotherapy group. In conclusion, the administration of AML monotherapy induced significant reductions in both clinic and ambulatory BPs in elderly patients whereas only clinic BP was significantly decreased by HCTZ monotherapy. Moreover, the addition of AML to HCTZ in patients inadequately controlled by monotherapy has permitted statistically significant decrements in clinic as well as in ambulatory BP. Consequently, the results of the present study suggest that the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP control in the elderly despite official recommendations.",1995.0,0,0
975,8998256,Treatment of non-insulin-dependent diabetic hypertensive patients with Ca2+ channel blockers is associated with increased platelet sensitivity to insulin.,R M Touyz; E L Schiffrin,"Insulin influences platelet function by reducing platelet responsiveness to vasoactive agonists. In hypertension these insulin-related inhibitory effects are blunted. The aim of this study was to determine whether platelet sensitivity to insulin is affected after 12 weeks of antihypertensive treatment with calcium channel blockers. Eleven patients with essential hypertension and non-insulin-dependent diabetes were treated with either isradipine or diltiazem. Platelet free calcium concentration was measured spectrofluorometrically in nonstimulated and in angiotensin II (1 nmol/L)-stimulated platelets that had been pre-exposed to insulin (70 microU/mL). Platelets were studied before therapy and after 12 weeks of treatment. Systolic blood pressure and mean arterial pressure decreased significantly during treatment. Both calcium channel blockers equally decreased fasting serum insulin levels (from 138 +/- 2.7 pmol/L before therapy to 106 +/- 9.9 pmol/L after therapy). Results with both calcium channel antagonists were similar and have been pooled. In the pretreatment phase, insulin pre-incubation had no effect on angiotensin II-stimulated intracellular free calcium and responses to angiotensin II were similar in the absence (265 +/- 10.5 nmol/L) and presence of insulin (233 +/- 12.1 nmol/L). After treatment with calcium channel blockers, insulin significantly (P < .001) reduced angiotensin II-induced rise of intracellular free calcium from 214 +/- 7.7 nmol/L (absence of insulin) to 153 +/- 9.3 nmol/L (presence of insulin). Whether these effects are due specifically to calcium channel blockers or whether they are the result of lowering of blood pressure remains unclear. Serum insulin levels were positively correlated with angiotensin II-stimulated increase in intracellular free calcium in platelets pre-exposed to insulin, (r = 0.46; P < .05) suggesting that with increasing levels of insulin resistance, the inhibitory effects of insulin are reduced. This study shows that treatment of non-insulin-dependent diabetic hypertensive patients with these calcium channel blockers reduces hyperinsulinemia and increases sensitivity of platelets to the inhibitory effect of insulin on angiotensin II-stimulated calcium responses.",1995.0,0,0
976,9001838,"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
977,9004108,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
978,9008250,Blood pressure and metabolic responses to moderate sodium restriction in isradipine-treated hypertensive patients.,D A McCarron; A B Weder; B M Egan; G G Krishna; C D Morris; M Cohen; S Oparil,"This multicenter, randomized, controlled clinical trial assessed the influence of sodium chloride intake on the antihypertensive effect of the calcium channel blocker isradipine. Participants with uncomplicated hypertension controlled by isradipine entered a 4-week sodium-restricted (60 to 80 mmol/24 h) period. Participants with urinary sodium levels < 120 mmol/24 h (n = 99) were randomized to placebo or sodium chloride (100 mmol/24 h) for 4 weeks, and then crossed over to the alternative treatment for an additional 4 weeks. Mean baseline systolic blood pressure was 151.9 +/- 16.7 mm Hg (mean +/- SD). During open-label isradipine treatment, systolic blood pressures for ad libitum sodium chloride and restriction were 134.1 +/- 11.1 and 132.1 +/- 12.2 mm Hg respectively; for double-blind sodium chloride restriction and supplementation: 133.6 +/- 12.6 and 138.5 +/- 12.8 mm Hg (P < .01). Urinary sodium excretion values for open-label isradipine ad libitum versus restricted were 140.6 +/- 61.9 versus 76.9 +/- 32.4 mmol/24 h; for double-blind restricted versus supplemented, sodium excretion was 120.5 +/- 68.9 v 175.9 +/- 68.7 mmol/24 h (P < or = .0001). Changes in urinary sodium excretion were not predictive of variations in blood pressure. Urinary sodium excretion during sodium restriction correlated directly with HDL-cholesterol (P < .02) and inversely with total cholesterol:HDL-cholesterol (P = .02), despite decreased total and saturated fat intake (P < .01). Sodium restriction was associated with significant reductions (P < .01) in virtually all macronutrients and electrolytes, and thus had an adverse impact on overall nutrition. The antihypertensive action of isradipine was not enhanced by dietary sodium chloride restriction, and the lipoprotein profile was least favorable with sodium chloride restriction.",1997.0,0,0
979,9013266,Nifedipine gastrointestinal therapeutic system versus atenolol in stable angina pectoris. The Netherlands Working Group on Cardiovascular Research (WCN).,R J de Vries; A F van den Heuvel; D J Lok; R J Claessens; P J Bernink; W H Pasteuning; J H Kingma; P H Dunselman,"The gastrointestinal therapeutic system formulation of nifedipine enables a once-daily dosing resulting in predictable, relatively constant plasma concentrations. To evaluate the efficacy and safety of this formulation and to compare this with the beta-blocker atenolol, we conducted a double-blind, randomised, multi-centre study in 129 male patients with documented exercise induced angina pectoris. After 4 weeks' treatment, nifedipine (60 mg), improved time to onset of 0.1 mV ST-segment depression from 536 s by 72 +/- 117s, time to onset of pain from 619 s by 56 +/- 120 s, and total exercise time from 685 s by 40 +/- 88 s. Atenolol 100 mg, had a comparable effect, time to onset of 0.1 mV ST-segment depression improved from 496 s by 53 +/- 129 s, time to onset of pain from 572 s by 57 +/- 118 s, and total exercise time from 653 s by 33 +/- 99 s. Between group analysis revealed no statistically significant differences for these exercise parameters. Atenolol, but not nifedipine, significantly reduced heart rate and systolic blood pressure at rest and during exercise (P < 0.001 between groups), indicating different modes of action of the drugs. With regard to safety, both drugs were generally well tolerated. There were significantly (P = 0.01) more vasodilation related side effects with nifedipine. These data demonstrate that gastrointestinal therapeutic system formulation of nifedipine and atenolol as once-daily monotherapy are equally effective and safe, but with different effects on exercise parameters.",1996.0,0,1
980,9017770,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
981,9017781,Pharmacologic conversion of atrial fibrillation and atrial flutter to normal sinus rhythm: the role of ibutilide.,M S Katcher; N A Estes,,2001.0,0,1
982,9037327,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
983,9038037,"Calcium antagonists, a useful additional therapy in treatment resistant hypertension: comparison of felodipine ER and nifedipine Retard by 24-h ambulatory blood pressure monitoring.",A Dees; T Kremer Hovinga; J G Breed; V M Verstappen; S M Puister; L Meems,"To compare the efficacy and tolerability of felodipine extended release (ER) 2.5 mg (F2.5) and 5 mg (F5) once daily with nifedipine Retard 10 mg (N20) and 20 mg (N40) twice daily as additional therapy in patients who remained hypertensive despite treatment with an ACE-inhibitor, beta-blocker or diuretic. In a multicentre, double-blind parallel study, 61 men and 54 women, aged 35-75, with a supine diastolic blood pressure between 95 and 115 mmHg were randomised to treatment with F2.5, F5, N20 or N40 for 8 weeks, with optional doubling of the dose after 4 weeks. Blood pressure was measured at the office after 0, 4 and 8 weeks and by 24-h ambulatory monitoring (ABPM) after 0 and 4 weeks. Spontaneously reported adverse events and a subjective symptom assessment questionnaire were used for side-effect profiling. Mean office systolic/diastolic blood pressure was clinically relevantly reduced in all treatment groups after 4 weeks by 8/7, 12/9, 11/9 and 18/11 mmHg for F2.5, F5, N20 and N40, respectively, and after 8 weeks (F2.5-5: 17/11 mmHg: F5-10: 18/14 mmHg; N20-40: 19/14 mmHg; N40-80: 25/14 mmHg) with no statistically significant differences between these groups. The lowest dose of felodipine (F2.5) was the least effective. After 4 weeks the ABPM showed consistent 24-h reductions in blood pressure (4/2; 8/5; 7/5; 10/6 mmHg, respectively) over 24 h for the felodipine ER 5 mg group only and for both nifedipine groups. No statistically significant difference between these groups was found. An office responder does not appear to be identical to an ambulatory one and vice versa. The adverse events, mostly oedema, flushing and headache, were dose-related. Both felodipine ER and nifedipine Retard are effective ""add-on' drugs in patients with monotherapy-resistant hypertension. The blood-pressure-lowering effect is dose-dependent and tolerability is inversely related to efficacy. The results emphasize the benefits of combining two agents with low doses.",1997.0,0,0
984,9039073,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
985,9039480,Quinine-induced hearing loss in the guinea pig is not affected by the Ca2+ channel antagonist verapamil.,W Jäger; E Idrizbegovic; K K Karlsson; G Alván,"It is well documented that quinine induces reversible hearing loss and tinnitus. The purpose in this study was to induce a quinine hearing loss and to investigate if verapamil, a Ca2+ channel antagonist of L-type might affect the response. Pigmented guinea pigs (n = 24) were anaesthetized by atropine. Hypnorm and midazolam but permitting spontaneous respiration. An electrode of platinum was placed on the round window and short (10 msec) tone pulses at 8 kHz were presented to the external ear. A typical deflection of the N1-wave was determined as the hearing threshold. Quinine hydrochloride 40 mg/kg and verapamil 1 mg/kg were given intravenously. Quinine induced a significant and reversible hearing loss (mean 16 dB). This hearing loss was not at all affected by verapamil given before or after quinine. Verapamil often caused acute cardiac arrest and particularly the combination verapamil followed by quinine-induced death to the animal. We conclude that verapamil and quinine had no in vivo interaction with regard to the hearing ability.",1997.0,0,0
986,9040648,Safety of calcium-channel blockers.,,,1997.0,0,0
987,9042095,"Haemostatic markers, inflammatory parameters and lipids in male and female patients in the Angina Prognosis Study in Stockholm (APSIS). A comparison with healthy controls.",C Held; P Hjemdahl; N Rehnqvist; N H Wallén; L Forslund; I Björkander; B Angelin; B Wiman,"To investigate haemostatic markers (especially fibrinolysis), inflammatory parameters and lipids in patients with stable angina pectoris. Special attention was paid to differences between male and female patients, and to the reactivity to exercise or the diurnal variation of certain parameters. Eight hundred and nine patients (31% females) and a matched healthy control group (n = 50). The patients had signs of disturbed fibrinolysis, with elevated plasma levels of tissue plasminogen activator (tPA) antigen and plasminogen activator inhibitor (PAI-1) activity at rest, and attenuated responses of tPA antigen and activity to exercise. Elevated levels of fibrinogen, white blood cell counts and orosomucoid were found, suggesting increased inflammatory activity, as well as a more disturbed lipid profile (higher triglycerides and lower HDL cholesterol levels) than among controls. Female patients had higher HDL cholesterol and lower triglyceride levels than male patients, but higher platelet counts and signs of enhanced platelet activity (beta-thromboglobulin excretion). In addition, female patients had lower white blood cell counts, suggesting lesser inflammatory activity. Patients with stable angina pectoris have signs of markedly disturbed fibrinolysis both at rest and in response to exercise, as well as signs of enhanced inflammatory activity and dyslipidemia. The observed sex differences suggest that male patients with stable angina pectoris may have a more lipid-related disease, whereas it may be more dependent on platelet function in females.",1997.0,0,0
988,9049513,Doppler flow and echocardiography in functional cardiac insufficiency: assessment of nisoldipine therapy. Results of the DEFIANT-II Study. The DEFIANT-II Research Group.,,"A multicentre, double-blind, placebo-controlled trial was conducted in 542 patients, randomized 7-10 days after myocardial infarction, to study the effect of nisoldipine coat-core (nisoldipine-CC) on exercise after 6 months. Secondary endpoints included exercise-induced ischaemia, left ventricular function measured by Doppler echocardiography, adverse cardiac events and clinical outcome. Patients had reduced left ventricular ejection fraction between 25 and 50%, but no heart failure. Exercise time was not different in the two groups. Nisoldipine-CC prolonged time to 1 mm ST deviation (P = 0.03). There was an effect of nisoldipine-CC of +3.6 cm.s-1 on early peak velocity (P = 0.01) and of -6.2 ms on isovolumic relaxation time (P = 0.005), but no effects on left ventricular volumes or ejection fraction. There was a trend towards reduced mortality (one death in the nisoldipine-CC group vs seven in the placebo group. P < 0.07) and the combined end-point of mortality and cardiac events (P = 0.09). Peripheral oedema occurred in 49 patients assigned to nisoldipine-CC and two assigned to placebo (P < 0.001). There were no differences in non-cardiac events. Nisoldipine-CC did not improve exercise time but increased time to 1 mm ST deviation, and improved diastolic left ventricular function. It is safe and well tolerated in post-infarction patients with impaired left ventricular function.",1997.0,0,0
989,9049531,The unnecessary controversy or lack of knowledge?,J Fischer-Hansen,,1997.0,0,0
990,9052345,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
991,9052890,Effect of calcium channel or beta-blockade on the progression of diabetic nephropathy in African Americans.,G L Bakris; A Mangrum; J B Copley; N Vicknair; R Sadler,"beta-Blockers are known to slow the progression of diabetic nephropathy by lowering arterial pressure. Moreover, in individuals with diabetic nephropathy, antihypertensive agents that provide sustained reductions in proteinuria slow the rate of decline in renal function compared with agents without this antiproteinuric effect. To examine whether differential effects on proteinuria affect the progression of diabetic nephropathy, we conducted a randomized study that compared the effects of a heart rate-lowering calcium channel blocker, sustained-release verapamil, with those of a beta-blocker, atenolol, on the progression of diabetic renal disease. The primary end point of the study was a change in creatinine clearance slope. Thirty-four African Americans with the following inclusion criteria were randomized to one of the two groups: serum creatinine greater than 1.4 mg/dL, proteinuria greater than 1500 mg/d, longer than a 5-year history of both non-insulin-dependent diabetes mellitus and hypertension, and exclusion of other renal diseases. Goal blood pressure was less than 140/90 mm Hg. All subjects received loop diuretics as second line agents to help achieve the blood pressure goal. Twenty-four-hour urinary protein and sodium excretions as well as creatinine clearance were measured at 6-month intervals. Blood pressure was measured every 3 months. After a mean follow-up of 54+/-6 months, the calcium channel blocker group demonstrated both a slower rate of decline in creatinine clearance (-1.7+/-0.9 versus -3.7+/-1.4 mL/min per year per 1.73 m2, P<.01) and a greater reduction in proteinuria compared with the atenolol group. Additionally, a greater proportion of the atenolol group had a 50% or more increase in serum creatinine compared with the verapamil group (32+/-9% versus 16+/-7%, P<.05). These between-group differences could not be explained by differences in blood pressure control. These data support the concept that antihypertensive agents that persistently maintain reductions in both arterial pressure and proteinuria slow the progression of diabetic renal disease in African Americans to a greater extent than those agents without these effects.",1997.0,0,0
992,9052891,Calcium channel blockers blunt postural cutaneous vasoconstriction in hypertensive patients.,M L Iabichella; G Dell'Omo; E Melillo; R Pedrinelli,"The aim of this work was to test whether calcium channel blockers interfere with skin vasoconstrictor reflexes that minimize postural increases in capillary pressure and avoid fluid extravasation and eventually subcutaneous edema. Studies were conducted in 23 untreated mild to moderate essential hypertensives; drugs, either calcium channel blockers or not, were given for 2 weeks according to a crossover, sequence-randomized design. Skin blood flow was measured by laser Doppler flowmetry in two skin areas: (1) the dorsum of the foot, where arteriovenous anastomoses are poorly represented, and (2) the plantar surface of the great toe, where those anastomoses are predominant. Determinations were obtained both with the foot at heart level and with it placed passively 50 cm below the heart level; percent flow changes from the horizontal to the dependent position were the measure of postural vasoconstriction. Two dihydropyridine derivatives, amlodipine (10 mg UID) and nifedipine (60 mg UID), and verapamil (240 mg BID), a chemically unrelated compound, diminished to similar extents the postural fall in skin blood flow at the dorsum of the foot. Blockade of alpha1-adrenergic and AT-1 subtype angiotensin II receptors by doxazosin (4 mg UID) and losartan (50 mg UID), respectively, exerted no effect. Postural skin blood flow responses at the plantar surface of the great toe were unmodified during the pharmacological trials. Thus, calcium channel blockers of different chemical origins antagonized postural skin vasoconstriction at the dorsum of the foot. The data indicate altered postural capillary blood flow regulation, since arteriovenous anastomoses are anatomically absent at this site; the effect was independent of either alpha1-adrenoceptor or angiotensin II receptor antagonism. Interference with skin postural vasoconstrictor mechanisms may result in net filtration of fluid to the extravascular compartment. This mechanism might explain the as yet unknown pathogenesis of ankle edema during treatment with calcium antagonists.",1997.0,0,0
993,9056681,Efficacy and tolerability of nisoldipine coat-core formulation in the treatment of essential hypertension: The South African Multicenter ANCHOR Study. Ambulatory Nisoldipine Coat-Core Hypertension Outpatient Response (ANCHOR) Investigators.,L H Opie; F O Müller; D P Myburgh; C Rosendorff; P Sareli; Y K Seedat; D J Weich; H G Luus,"A double-blind, placebo-controlled, multicenter trial was undertaken to assess the antihypertensive efficacy and tolerability of a controlled-release (Coat-Core [CC] tablet) formulation of the second-generation dihydropyridine calcium channel antagonist, nisoldipine. Of the 208 patients with mild-to-moderate essential hypertension, two were excluded from the main efficacy analysis, and the rest randomized into one of four treatment groups, to receive either placebo, or nisoldipine CC at doses of 10, 20, or 30 mg once daily for 6 weeks, following a 4-week placebo run-in period. Blood pressure measurements (supine, standing, diastolic, and systolic) were taken at trough plasma levels, 24 h after previous dosing at 2-week intervals throughout the study. Adverse events and laboratory parameters (plasma lipid and glucose levels, and thyroid function) were monitored. All three doses of nisoldipine CC lowered blood pressure, as compared with placebo, 24 h after dosing. At endpoint (after 6 weeks) mean changes in supine blood pressure from baseline were (systolic/diastolic) 0.9/-2.3, -8.0/-5.5, -16.9/-9.0, and -15.0/-10.3 mm Hg for the groups assigned to placebo and nisoldipine CC 10, 20, and 30 mg, respectively. The response rates were 35%, 47%, and 63% for nisoldipine CC 10, 20, and 30 mg, respectively. Twenty-four-hour ambulatory blood pressure monitoring showed that nisoldipine CC effectively controlled blood pressure throughout the dosing interval. No change in heart rate was seen for all three doses of nisoldipine CC over the 24-h dosing interval. Nisoldipine CC was at least as effective in black patients as in whites. Generally adverse events were not increased, except for peripheral edema, with rates of 7% in placebo, and 6%, 9%, and 19%, respectively, in those receiving nisoldipine CC 10, 20, or 30 mg daily. There were no clinically significant changes in blood lipids, blood glucose, or thyroid function. In conclusion, once-daily nisoldipine CC at doses of 10 to 30 mg was an effective and well tolerated antihypertensive agent, providing 24-h control of blood pressure without any increase in heart rate.",1997.0,0,0
994,9057957,Antihypertensive and anti-albuminuric effects of losartan potassium and felodipine in Chinese elderly hypertensive patients with or without non-insulin-dependent diabetes mellitus.,J C Chan; J A Critchley; B Tomlinson; T Y Chan; C S Cockram,"After a 4-week placebo baseline period, 29 Chinese elderly hypertensive patients were randomized, double-blind, to 12 weeks of treatment with either losartan potassium (n = 19), an angiotensin II antagonist at the AT1 receptor, or felodipine (n = 10), a calcium channel blocking agent. Of these 29 patients 12 had coexisting non-insulin-dependent diabetes mellitus. At week 12, the mean reductions (95% confidence intervals) in mean arterial pressure were similar in both groups: losartan -18 (range -22 to -14) mm Hg; felodipine -19 (range -25 to -11) mm Hg. In the whole group, the 24-hour urinary albumin excretion was reduced by 27% with losartan as compared with no change in the felodipine-treated group (p = 0.03; analysis of variance). In the diabetic group, losartan treatment reduced the urinary albumin excretion by 24% as compared with 11% in the felodipine-treated group. In the non-diabetic patients, the urinary albumin excretion fell by 29% in the losartan-treated group, but increased by 14% in the felodipine-treated group (p < 0.001; repeated-measures analysis of variance). Plasma sodium increased to a similar extent in both groups. The fasting plasma triglyceride level declined by 25% (p < 0.001 within group) with losartan, but was not significantly reduced in the felodipine-treated group. For comparable reductions in blood pressure, a greater reduction in albuminuria was seen with losartan than with felodipine treatment in Chinese hypertensive patients with or without non-insulin-dependent diabetes mellitus. Long-term studies are required to examine whether these antiproteinuric effects of losartan can be translated to renoprotection.",1997.0,0,0
995,9061722,Analysis of the risks associated with calcium channel blockade: implications for the obstetrician-gynecologist.,W B Davis; S R Wells; J A Kuller; J M Thorp,"Calcium channel antagonists are widely prescribed in obstetrics and gynecology for blood pressure control and tocolysis. Concerns have recently arisen regarding the safety of these agents. Several studies found that short-acting forms of calcium channel blockers were associated with increased cardiovascular mortality, malignancy, and gastrointestinal bleeding. A recent meta-analysis found a significant increase in the risk of mortality in patients treated with a short-acting form of nifedipine. Another subgroup analysis of an observational study of older hypertensive patients found a significantly increased risk of cancer and gastrointestinal hemorrhage in patients prescribed calcium channel blockers. Both in vitro and small human in vitro series have reported a potential for cardiac toxicity in pregnant women treated concomitantly with calcium channel blockers and magnesium sulfate. Until additional data are available, we suggest that when calcium channel blockers are used in obstetrics and gynecology, the long-acting variety be prescribed. Concurrent use of calcium channel blockers and magnesium sulfate should be undertaken cautiously because of the potential for synergistic depression of cardiac function.",2001.0,0,0
996,9067125,Pharmacoepidemiology of ACE inhibitor--induced cough.,B Tomlinson; R P Young; J C Chan; T Y Chan; J A Critchley,,1997.0,0,0
997,9070551,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.",1997.0,1,1
998,9080918,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.",2001.0,1,1
999,9082044,Site-specific variations in metabolism by human fibroblasts exposed to nifedipine in vitro.,J S Henderson; J C Flynn; M A Tucci; A K Tsao; E J Zebrowski; O Odlum; R B Johnson,"Nifedipine induces overgrowth of gingival tissues in some patients. However, other collagenous tissues in their body do not overgrow. The purpose of this study was to compare effects of serial dilutions of nifedipine on the in vitro metabolism of fibroblasts derived from normal gingiva, nifedipine-induced hyperplastic gingiva, knee capsular ligament, and dermis. The data suggested that nifedipine affects the metabolism of fibroblasts derived not only from gingiva, but also from other collective connective tissues. Thus, nifedipine-responder cells are present in tissues other than gingiva. There was an inverse relationship between in vivo tissue levels of IL-1-beta and in vitro responsiveness to nifedipine of fibroblasts derived from that tissue. Nifedipine-induced overgrowth of connective tissues, other than gingiva, probably does not occur either because of the relatively slow rate of collagenous protein synthesis by resident fibroblasts or because of alterations in collagen deposition/resorption within susceptible tissues produced by nifedipine on collagenase synthesis.",1997.0,0,0
1000,9104926,Overview of the safety of felodipine based on clinical trials in patients with hypertension.,L Welin; L Elvelin; A Niklasson; G Olsson; D Elmfeldt,All clinical studies of at least 1 week's duration with felodipine in patients with hypertension were included in a safety analysis. The major finding was that felodipine does not increase mortality or the incidence of major cardiovascular events and that the data indicate a favorable effect.,1997.0,0,1
1001,9112363,"Isradipine for the prevention of cyclosporine-induced hypertension in allogeneic bone marrow transplant recipients: a randomized, double-blind study.",M Bursztyn; O Zelig; R Or; A Nagler,"Hypertension and nephrotoxicity frequently occur in patients who receive cyclosporine therapy after bone marrow transplantation (BMT). Isradipine, a calcium channel entry blocker, has been used successfully in cyclosporine-induced hypertension. Thirty leukemic patients who received cyclosporine after BMT were randomized to receive isradipine (0.005 mg/kg) from 72 hr before commencement of cyclosporine therapy until day 100 after BMT or placebo. The placebo and isradipine groups were well matched. No differences were found between the isradipine and placebo groups in the level of blood pressure, renal function, marrow engraftment, or mortality. Hypertension incidence was surprisingly low (30% a week after hospital discharge and 10% by day 100 after BMT), and did not differ between the groups. Isradipine does not harm immunohematopoietic reconstitution after BMT; therefore, it may be used in this setting, although the previously reported incidence of hypertension has been exaggerated.",1997.0,0,0
1002,9133513,Asymptomatic Cardiac Ischemia Pilot (ACIP) study two-year follow-up: outcomes of patients randomized to initial strategies of medical therapy versus revascularization.,R F Davies; A D Goldberg; S Forman; C J Pepine; G L Knatterud; N Geller; G Sopko; C Pratt; J Deanfield; C R Conti,"Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization. The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia-guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison. A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.",1997.0,0,0
1003,9146330,Effects of diltiazem versus digoxin on dysrhythmias and cardiac function after pneumonectomy.,D Amar; N Roistacher; M E Burt; V W Rusch; M S Bains; D H Leung; R J Downey; R J Ginsberg,"This prospective study was designed to determine whether diltiazem is superior to digoxin for the prophylaxis of supraventricular dysrhythmias (SVD) after pneumonectomy or extrapleural pneumonectomy (EPP) and to assess the influence of these drugs on perioperative cardiac function. Seventy consecutive patients without previous SVD were randomly allocated immediately after pneumonectomy or EPP to receive diltiazem (n = 35) or digoxin (n = 35). Diltiazem-treated patients received a slow intravenous loading dose of 20 mg, followed by 10 mg intravenously every 4 hours for 24 to 36 hours, then 180 to 240 mg orally daily for 1 month. Digoxin-treated patients received a 1-mg intravenous loading in the first 24 to 36 hours, then 0.125 to 0.25 mg orally daily for 1 month. A concurrent prospective cohort of 40 patients without previous SVD, who did not participate in the study and underwent pneumonectomy or EPP without prophylaxis, served as a comparison group for SVD occurrence. Serial Doppler echocardiograms were performed to assess cardiac function and all patients were continuously monitored with Holter recorders for 3 days. Data were analyzed by intent-to-treat. In patients undergoing standard or intrapericardial pneumonectomy, diltiazem prevented the overall incidence of postoperative SVD when compared with digoxin, 0 of 21 patients versus 8 of 25 patients, respectively, p < 0.005. When EPP patients were included in the analysis, diltiazem decreased the incidence of all SVD from 11 of 35 patients (31%) to 5 of 35 patients (14%) when compared with digoxin, p = 0.09. Digoxin-treated patients had a similar incidence of all SVD (31%) as concurrent controls (11 of 40 patients [28%]). The two treated groups did not differ in right or left atrial size, left ventricular ejection fraction, or right heart pressure. When all patients were combined, those in whom SVD developed were significantly older (65 +/- 12 years versus 55 +/- 11 years, p = 0.004) and had a longer median hospital stay (9 versus 6 days, p = 0.03), when compared with those in whom SVD did not develop, respectively. The subset of patients undergoing EPP had a greater incidence of atrial fibrillation and electrocardiographic changes suggestive of postoperative pericarditis than all other pneumonectomy patients. Diltiazem was both safe and more effective than digoxin in reducing the overall incidence of SVD after standard or intrapericardial pneumonectomy. Digoxin therapy had no effect on the incidence of postoperative SVD and is not recommended for prophylaxis of SVD. Dysrhythmias after pneumonectomy or EPP occur in older patients and are associated with a greater length of hospital stay.",1997.0,0,1
1004,9149671,Cancer risk in users of calcium channel blockers.,J H Olsen; H T Sørensen; S Friis; J K McLaughlin; F H Steffensen; G L Nielsen; M Andersen; J F Fraumeni; J Olsen,"Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+ in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17911 patients who received at least one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned.",2001.0,1,1
1005,9156363,Felodipine and amlodipine in stable angina pectoris: results of a randomized double-blind crossover trial.,W Koenig; M Höher,"A randomized, double-blind, crossover study tested the antiischemic and antianginal efficacy of felodipine, extended-release 5-10 mg, versus amlodipine, 5-10 mg once daily. Fifty-two patients with documented exercise-induced angina pectoris and myocardial ischemia during 24-h electrocardiographic monitoring were included in the study. Forty-seven patients completed the 8-week treatment period, whereas five patients withdrew from the study. The mean number of ischemic episodes/24 h was reduced from 19.9 at baseline to 2.3 during amlodipine and to 2.4 during felodipine; the total duration of ischemic episodes decreased from 69.8 min/24 h to 15.2 min and 15.5 min during amlodipine and felodipine, respectively (for both variables, p = 0.83 and p = 0.53 between treatments, and for both treatments, p < 0.001 compared with baseline). Eighteen (38%) patients receiving amlodipine and 19 (40%) patients receiving felodipine showed no ST-segment depression during treatment. Maximal ST-depression was reduced from an average of 2.1 mm to 1.1 and 1.2 mm on amlodipine and felodipine, respectively (p = 0.68 between treatments and p < 0.001 compared with baseline). Mean heart rate remained unchanged compared with baseline. Anginal attacks were reduced from 16.4/week at baseline to 4.7/week with amlodipine and to 4.3/week with felodipine (p = 0.26 between treatments, and p < 0.001 vs. baseline). Accordingly, nitrate consumption was reduced from 14.7 capsules per week to 4.0 and 3.8 with amlodipine and felodipine, respectively (p = 0.40 between treatments, and p < 0.001 compared with baseline). Adverse reactions were infrequent and distributed similarly between the two treatments. It is concluded that both drugs effectively reduced ischemic episodes and anginal attacks and were well tolerated in patients with stable angina pectoris. There was no evidence that the two regimens were different in their antiischemic and antianginal properties.",1997.0,0,1
1006,9160758,"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
1007,9160765,"The effects of isradipine and spirapril as monotherapy and combined therapy on blood pressure, renal hemodynamics, natriuresis, and urinary kallikrein in hypertensive nephropathy.",E R Maccariello; V Genelhu de Abreu Fagundes; E A Francischetti,"In this cross-over, double-blind study, 12 essential hypertensive patients (stage I, II, and III) with glomerular filtration rate (GFR) between 50 to 80 mL/min/1.73 m2, were submitted to 4 weeks of placebo followed by 12 weeks with isradipine SRO (IS) 5 mg, spirapril (SP) 6 mg, and isradipine plus spirapril (IS + SP). The study evaluated the effects of these drugs on GFR ((99m)Tc DTPA), effective renal plasma flow (ERPF) ((131)I-orthoiodohippurate), urinary sodium excretion (UNaV), urinary kallikrein excretion (UKal), urinary albumin excretion (UAE), and plasma renin activity (PRA). The three protocols significantly reduced mean blood pressure (128 v 107 mm Hg; 126 v 112 mm Hg; 129 v 104 mm Hg with IS, SP and IS + SP, respectively). ERPF and GFR did not change. UNaV increased significantly after IS (0.17 v 0.22 mEq/min) and IS + SP (0.18 v 0.24 mEq/min). UKal increased significantly after IS (58.6%) and IS + SP (53.6%). UAE decreased significantly only after SP. PRA increased significantly after IS (1.31 v 2.84 ng/mL/h), SP (1.10 v 2.15 ng/mL/h), and after IS + SP (1.23 v 3.21 ng/mL/min). In conclusion, IS, SP and IS + SP were effective in reducing blood pressure while keeping renal function stable. Only SP significantly decreased UAE. Enhanced UKal may have played a role in natriuresis observed after IS and IS + SP.",1997.0,0,0
1008,9160770,Calcium channel blockers for hypertension: dissecting the evidence for adverse effects.,L H Opie,"Safety in the drug treatment of hypertension can only be seen in relation to efficacy, which has now come to mean not just blood pressure (BP) reduction but improvements in hard end points including mortality. Information on safety can come from a variety of sources, in an ascending hierarchy, which is as follows: case-control studies, cohort studies, randomized control trials (RCTs), and metaanalyses based on good RCTs. Only in the case of metaanalyses are definite criteria for acceptability established, but evaluation of case-control and cohort studies remains subjective. Despite these reserves about the data sources, it is proposed that the case-control study pointing to the risk of acute myocardial infarction during therapy with short-acting calcium channel blockers (CCBs) can be balanced out by another better more recent study, and by a large cohort study from Israel. In a very elderly population, a well-designed cohort study strongly suggests that short-acting nifedipine can be linked to increased mortality and that the specific links may be with a high dose and when the initial BP is less than 160/90 mm Hg. However, initial BP was only available in an unspecified number of patients. The risk of using short-acting verapamil was no more than that of beta-blockade. These differences can be attributed at least in part to the low catecholamine profile of verapamil and the marked rapid adrenergic activation with short-acting nifedipine, which could also explain the adverse effects found when this agent is given to patients with acute coronary syndromes. During the chronic use of long-acting dihydropyridine (DHP) CCBs, most evidence suggests that there is little or no catecholamine activation, or in the case of amlodipine, even a decrease in plasma catecholamine levels. These differences may explain why the expected regression of left ventricular hypertrophy is obtained with long- but not short-acting DHPs. At present the results of several large randomized controlled trials with long-acting CCBs are awaited. In the meantime, when the decision has been made to use a CCB, the preferential choice is for the use of a non-DHP for hypertension with clinical ischemia or for postinfarct hypertension, for a long-acting CCB for the control of left ventricular hypertrophy, and for the DHP amlodipine when there is associated depression of myocardial function.",1997.0,0,1
1009,9161650,,,,,0,1
1010,9164003,[Example of a phase IV trial involving several physicians and aiming at answering a scientific question: EOL].,J P Boissel; O Meillard; E Perrin-Fayolle; T Ducruet; Y Alamercery; P Sassano; R Benghozi,"The aim of this trial was to test the hypothesis that a reduced number of doses improves compliance in current medical practice. Compliance with twice a day dosage was compared with compliance with three doses a day. Two bioequivalent presentations of nicardipine were used, the regular presentation (t.i.d.) and the slow-release (b.i.d.). The trial was controlled, randomized, open, in two parallel groups: (1)'t.i.d.' group: one tablet of regular nicardipine, 20 mg, three times a day, three months; (2) 'b.i.d.' group: one capsule of slow-release nicardipine, twice a day, three months. 2651 general practitioners randomized 7274 hypertensive patients. The primary criterion was documented in 93.7 per cent of the cases at the end of the trial. The remaining 6.3 per cent comprised treatment withdrawal (2.8 per cent) and patients lost to follow-up (3.5 per cent). The primary criterion study was compliance, assessed by a self-questionnaire filled in by the patient and a standardised interview by the physician. Compliance was slightly better in the b.i.d. group than in the t.i.d. group (p < 0.001). Remaining pill count was also used but it was a failure. A random sample of investigators made on-site visits. Discordant data were infrequent and were limited to dates of visits. Difficulties with on-site visits were mostly due to a rather frequent lack of source records.",1996.0,0,0
1011,9164897,Effect of sustained-release Verapamil on the morning systemic arterial pressure surge during daily activity in patients with systemic hypertension.,G A Rosito; O C Gebara; C A McKenna; H S Solomon; J E Muller; G H Tofler,"In a placebo-controlled study of 13 subjects with systemic hypertension, sustained-release verapamil reduced the morning surge in systolic pressure by 10.2 mm Hg (p = 0.04), diastolic pressure by 11.1 mm Hg (p = 0.008), and heart rate by 3.3 beats/min (p = 0.17). Blunting of the morning hemodynamic surge may be a mechanism by which verapamil could reduce the risk of plaque disruption and acute coronary events in the morning.",1997.0,0,0
1012,9165176,Effects of aerobic training on exaggerated blood pressure response to exercise in African-Americans with severe systemic hypertension treated with indapamide +/- verapamil +/- enalapril.,P F Kokkinos; P Narayan; R D Fletcher; D Tsagadopoulos; V Papademetriou,"Hypertensive patients are likely to have an exaggerated blood pressure (BP) response during physical exertion. When moderate aerobic exercise was added to medical antihypertensive therapy in patients with severe hypertension, excessive elevations in BP during physical exertion were attenuated even with a modest reduction in BP at rest.",1997.0,0,0
1013,9170398,Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Secondary Prevention Group.,K Ishikawa; S Nakai; T Takenaka; K Kanamasa; J Hama; I Ogawa; T Yamamoto; M Oyaizu; A Kimura; K Yamamoto; H Yabushita; R Katori,"The administration of calcium antagonists to patients with healed myocardial infarction is a controversial treatment. This study was conducted to elucidate the effect of short-acting nifedipine and diltiazem on cardiac events in patients with healed myocardial infarction. A controlled clinical open trial of 1115 patients with healed myocardial infarction was carried out between 1986 and 1994. The patients included 595 who received no calcium antagonist, 341 who received short-acting nifedipine 30 mg/d, and 179 who received short-acting diltiazem 90 mg/d. The primary end points were cardiac events, which were defined as fatal or nonfatal recurrent myocardial infarction; death from congestive heart failure; sudden death; and hospitalization because of worsening angina, congestive heart failure, or premature ventricular contractions. Cardiac events occurred in 51 patients (8.6%) in the no-calcium-antagonist group and 54 (10.4%) in the calcium-antagonist group (odds ratio, 1.24; 95% CI, 0.83 to 1.85), demonstrating that the calcium antagonists did not reduce the incidence of cardiac events. Subgroup analysis revealed no beneficial effects of these drugs for reducing cardiac events in patients with such complications as hypertension or angina pectoris. This study showed that use of short-acting nifedipine and diltiazem in this postmyocardial infarction population was associated with a 24% higher cardiac event rate, but this strong adverse trend did not reach statistical significance.",1997.0,0,0
1014,9170400,Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm.,C Held; P Hjemdahl; N Rehnqvist; N H Wallén; I Björkander; S V Eriksson; L Forslund; B Wiman,"Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double-blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow-up time of 3.2 years (2132 patient-years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI-1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA-ag at rest (P < .05), high PAI-1 activity (P < .05), and low TPA-ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA-ag independently predicted CV death or MI. In addition, PAI-1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA-ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). Plasma TPA-ag levels at rest, and among male patients PAI-1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.",1997.0,0,0
1015,9174677,Carvedilol versus verapamil in chronic stable angina: a multicentre trial.,U Hauf-Zachariou; R A Blackwood; K A Gunawardena; J G O'Donnell; S Garnham; E Pfarr,"In a multicentre, double-blind, parallel group study, the anti-anginal and the anti-ischaemic efficacy of 12 weeks of therapy with the vasodilating beta-adrenoceptor-blocker carvedilol 25 mg b.i.d. was compared with verapamil 120 mg t.i.d. During a 2-week placebo run-in period, patients were required to have two treadmill exercise tests (modified Bruce Protocol) differing by not more than 15% with regard to total exercise time (TET). Of 313 patients enrolled, 248 were randomized and 212 completed the study according to the protocol. The primary variable TET was analysed using the Cox Proportional Hazards Model to take into account censored values due to the patient stopping the exercise test for reasons other than angina. Forty-three per cent of patients allocated to carvedilol and 36% to verapamil did not stop with angina at the final visit. There was no difference in the TET between the groups, the risk ratio being 1.14 in favour of carvedilol (90% CI 0.85-1.52). TET increased from 378 s at baseline to 436 s at the final visit in the carvedilol group and from 386 to 438 s in the verapamil group. Results for time to angina and time to 1 mm ST-segment depression were similar. Compared to verapamil, carvedilol significantly reduced HR, systolic BP and rate pressure product at peak exercise. Analysis of 48 h Holter monitor data showed a greater reduction of HR and PVCs with carvedilol. Lown grading improved in both groups. Adverse events were reported by 48% (3.2% serious adverse events) of patients taking carvedilol and 58% (5.7% serious adverse events) taking verapamil. Carvedilol is at least as effective as verapamil in the management of chronic stable angina and demonstrated a favourable adverse event profile.",1997.0,1,1
1016,9180665,Blood pressure reduction and tolerability of felodipine ER in older and younger hypertensive patients. The Felodipine ER in the Elderly versus Young Working Group.,T C Fagan,"To evaluate and compare blood pressure reduction and tolerability of felodipine ER (extended-release), in younger and older patients. A multicenter, double-blind, placebo-controlled, parallel group study. Nineteen study sites; approximately half of the sites were at academic medical centers and half were in private primary care practices. Patients were non-hospitalized and free-living. There were 243 younger (< or = 61 years) and older (> or = 64 years) patients, age range 26 to 83, with sitting diastolic blood pressure (SDBP) of 95-115 mm Hg (higher stage 1 to lower stage 3) on placebo. Patients volunteered for the study. After a 2 to 4 week, single-blind, placebo baseline period, patients with SDBP of 95-115 mm Hg were randomized to treatment with felodipine ER 2.5 mg qd or placebo at a ratio of 3:1, felodipine:placebo. The dose of felodipine ER was increased to 5 mg qd after 3 weeks and to 10 mg qd after 6 weeks if the SDBP was greater than 90 mm Hg. The main outcome measure was change in SDBP. Secondary Outcome measures were change in sitting systolic blood pressure (SSBP) and percent of responders, defined as SDBP less than 90 mm Hg or a > or = 10 mm Hg reduction. Other measurements included heart rate, weight, routine laboratory values, and self-reported adverse events. By Week 9, felodipine ER reduced blood pressure in the older subjects (n = 77) by 13/12 mm Hg; in the younger patients, (n = 102), the reduction was 12/8 mm Hg. All reductions were significantly different from placebo (P < or = .003). The reduction in diastolic, but not systolic, blood pressure was significantly greater in the older than in the younger patients (P = .004 and P = .188, respectively). The percentage of patients reporting a clinical adverse experience was similar for felodipine ER and placebo treatment groups. The incidence of side effects was similar between old and young patients. Discontinuation occurred in 9% of the felodipine-treated patients and 19% of the placebo-treated patients. Older patients required lower doses of felodipine ER to achieve equivalent blood pressure control. Felodipine ER is effective in lowering blood pressure and is well tolerated in both young and old people.",1997.0,0,0
1017,9181251,"Effects of calcium antagonists on the risks of coronary heart disease, cancer and bleeding. Ad hoc subcommittee of the Liaison Committee of the World Health Organisation and the International Society of Hypertension.",,,1997.0,0,1
1018,9185031,Lack of effect of a diuretic added to diltiazem.,G A MacGregor; F P Cappuccio,,1997.0,0,0
1019,9187185,A comparison of two long-acting vasoselective calcium antagonists in pulmonary hypertension secondary to COPD.,D Sajkov; T Wang; P A Frith; A J Bune; J A Alpers; R D McEvoy,"STUDY OBJECTIVES AND PATIENTS: Pulmonary hypertension (PH) is common in COPD and may predict mortality in this disorder. We have compared the pulmonary vasodilator effects, dose-response characteristics, and tolerability of two calcium channel blockers, amlodipine and extended-release (ER) felodipine, in 10 patients (seven men, age 68+/-4.8 [SD] years) with clinically stable COPD and PH. Drugs were given in equal single daily oral doses (2.5, 5, and 10 mg), increasing weekly for 3 weeks, in a randomized investigator-blinded crossover manner with a 1-week wash-out period between the two treatments. Doppler measurements of pulmonary hemodynamics were made on the seventh day of treatment at each drug dose. Lung function, arterial blood gases, and adverse events were also monitored weekly. A dose-dependent decline of pulmonary artery pressure (PAP) was observed with each drug. A dose of 2.5 mg produced a significant decrease in PAP compared with baseline (20% amlodipine, 17% felodipine ER). Additional decreases in PAP were observed at 5 mg and 10 mg that were similar for both drugs, but did not reach statistical significance compared with 2.5 mg. There was a dose-related decrease in pulmonary vascular resistance and increase in oxygen delivery with amlodipine and felodipine ER. Lung function and blood gas values were stable throughout. Side effects (headache and ankle edema) were less frequent during amlodipine treatment (p<0.05). Both amlodipine and felodipine ER, given as a single daily oral dose of > or = 2.5 mg, are effective pulmonary vasodilators in COPD patients with PH. Their dose-response characteristics are similar, but amlodipine treatment was associated with fewer side effects.",1997.0,0,0
1020,9192235,Determining the optimum dose for the intravenous administration of nicardipine in the treatment of acute heart failure--a multicenter study. The Nicardipine Heart Failure Study Group.,Y Hirota; C Kawai; R Hori; K Okumura; M Kinoshita; T Kumada; H Ogawa; K Kawamura; R Kusukawa,"Nicardipine is a potent arteriolar vasodilator with a negligible negative inotropic effect. Although intravenous administration of this drug has been reported to be effective in the treatment of heart failure, the optimal dose by this route is not clear. This study was designed to determine the optimum dose for the intravenous infusion of nicardipine in the treatment of heart failure. In Trial 1, nicardipine was administered intravenously at a dose of 0.5 microgram/kg per min to 14 patients with acute heart failure. The dose was increased to 1.0 microgram/kg per min in 13 cases with marked improvement at 2 h. In Trial 2, nicardipine was administered in a double-blind manner to 53 patients at 3 different rates of infusion for 2 h: 1.0 (Group 1, n = 19), 2.0 (Group 2, n = 15), and 3.0 (Group 3, n = 19) micrograms/kg per min. Neither heart rate nor mean right atrial pressure changed in any of the 3 groups. Favorable hemodynamic effects were evident in all groups beginning 30 min after the start of infusion, with an increase in cardiac index (control vs 2 h after infusion, L/min per m2) (Group 1: 2.2 +/- 0.4 vs 3.1 +/- 0.8, Group 2: 2.2 +/- 0.4 vs 2.9 +/- 0.5, Group 3: 2.3 +/- 0.3 vs 3.1 +/- 0.7, all p < 0.01 compared to the control) and a decrease in diastolic pulmonary artery pressure (Group 1: 26 +/- 10 vs 19 +/- 7, Group 2: 27 +/- 10 vs 20 +/- 8, Group 3: 26 +/- 7 vs 18 +/- 5 mmHg, all p < 0.01). The decrease in systolic pressure was greatest in Group 3 (Group 1: 141 +/- 31 vs 119 +/- 18, Group 2: 149 +/- 25 vs 118 +/- 17, Group 3; 147 +/- 27 vs 107 +/- 14 mmHg, all p < 0.01 compared to control, and p < 0.05 between Groups 1 and 3). The intravenous drip infusion of nicardipine is effective in the treatment of heart failure by inducing an increase in cardiac output and a decrease in pulmonary artery wedge pressure. The optimal dose in this study was 1.0 microgram/kg per min.",1997.0,0,0
1021,9194510,Short-term antihypertensive medication does not exacerbate sleep-disordered breathing in newly diagnosed hypertensive patients.,P R Bartel; M Loock; P Becker; E Robinson; C van der Meyden; S Rossouw,"It has been speculated for some time that various antihypertensive medications may have a deleterious effect on respiration during sleep and thereby enhance the apparent association between hypertension and sleep apnea/hypopnea (SAH). However, there are few data to support this contention. The present study used a double-blind, randomized, cross-over design to contrast the effects of 6 weeks treatment with alpha-methyldopa and the combination of hydrochlorothiazide and amiloride with that of amlodipine and the combined diuretics in a group of 24 newly diagnosed patients with primary hypertension. All-night polysomnography was performed before the initiation of therapy (baseline) and at the end of the two treatment periods. Respiratory variables failed to reveal any significant differences between the treatments and baseline, or between the two different treatment regimens. The two treatment regimens achieved similar reductions in blood pressure. The prevalence of SAH was 25% before treatment, which is comparable to a prevalence of 20% in a similar group drawn from the same population but receiving various antihypertensive medications. The findings of this study are in agreement with previous reports using other classes of antihypertensive drugs that also failed to detect any tendency for increases in nocturnal respiratory disturbance indices over assessment periods of 8 weeks or shorter.",1997.0,0,0
1022,9197430,"Effect of gallopamil on myocardial microperfusion in patients with stable effort angina: a randomized, cross-over, double-blind, placebo-controlled trial.",D Acanfora; D F Vitale; C Rengo; G L Iannuzzi; G Furgi; C Picone; M Rossi; L Trojano; F Rengo,"We evaluated the efficacy and safety of daily administration of gallopamil 150 mg/day and its effects on myocardial perfusion in a medium-term, randomized, double-blind, cross-over, placebo-controlled trial. We studied 19 patients (17 males and 2 females; mean age 57 +/- 6.8 years) with stable effort angina, angiographically documented coronary artery disease and reversible perfusion defects during exercise thallium-201 myocardial scintigraphy of at least one segment of the left ventricle. After 2 weeks of a single-blind placebo run-in period, during which each patient underwent at least 2 exercise tests and a 48-hour Holter ECG recording, all patients were treated with either placebo or gallopamil 50 mg t.i.d. for 28 days. At the end of this period, patients crossed over to the alternate regimen. This phase was double blind. After treatment with placebo or gallopamil, patients underwent exercise tests, 24-hour Holter ECG recording and thallium-201 myocardial scintigraphy. Weekly angina frequency and trinitroglycerin (TNT) consumption and safety were also evaluated. No patients dropped out of the study because of major side effects. The number of total ischemic and symptomatic events recorded at 24-hour ECG monitoring, weekly angina frequency and TNT consumption were significantly reduced during gallopamil treatment. After gallopamil administration, exercise duration significantly increased (run-in: 419 +/- 116 s, placebo: 420 +/- 118 s, gallopamil: 511 +/- 144 s; p < 0.05), and ST segment depression was significantly reduced (run-in: -1.3 +/- 0.3 mm, placebo: -1.3 +/- 0.3 mm, gallopamil: -0.94 +/- 0.68 mm; p < 0.01), while heart rate, systolic blood pressure and rate-pressure product were unchanged at rest, at submaximal and at peak exercise. Qualitative and quantitative evaluation of myocardial perfusion and the myocardial uptake percentage of thallium-201 in ischemic zones were significantly improved by gallopamil treatment. These findings demonstrate that gallopamil can improve myocardial perfusion and reduce myocardial oxygen consumption.",1997.0,0,0
1023,9204099,A retrospective study of poisoning in Tehran.,M Abdollahi; N Jalali; O Sabzevari; R Hoseini; T Ghanea,"To examine the causes and mortality of poisoning in Tehran. The 7000 poisoning cases referred to Loghman-Hakim Hospital in Tehran over six months in 1994 were evaluated retrospectively. The overall female to male ratio was 1.8:1. Most poisonings occurred in the age range 2-6 y for children and 21-40 y for adults. Oral ingestion was the most common route of intoxication. In children, boys had a higher frequency of poisonings than girls. Most cases of children were referred to the hospital between 8 am and 8 pm. In adults referred to the hospital, there was little diurnal variation in poisoning presentations. In adults, drugs were the most common cause of intoxication (60.2%). Of these, benzodiazepines (24.5%) were the most frequent, followed by antidepressants (20.5%) and analgesics (18%). Pesticide and opiate intoxications were also commonly observed. In children, after drugs (32.1%), hydrocarbons were the most frequent cause of poisoning (19.2%). Pesticide poisonings were most often fatal (19.2%), followed by barbiturates (18.6%) and opiates (16.2%). Organophosphate insecticides were responsible for 57% of total pesticide poisoning cases. Of the deaths, 87.5% were attributed to suicide. The majority of poisoning cases in adults occur intentionally and in children accidentally.",1997.0,0,0
1024,9205015,Coronary vasodilatory capacity and flow reserve in normal myocardium supplied by bypass grafts late after surgery.,R Campisi; J Czernin; H L Karpman; H R Schelbert,"Coronary artery bypass surgery is used widely for treating myocardial ischemia. However, blood flow and flow reserve of normally perfused myocardium subtended by bypass grafts have not been evaluated late after surgery. Also, it is unknown whether pharmacologic vasodilation evokes comparable myocardial flow responses in arterial and venous conduits. Myocardial blood flow was quantified at rest and during dipyridamole hyperemia using N-13 ammonia and positron emission tomography (PET) in 15 patients 9 +/- 3 years after bypass surgery and in 10 healthy volunteers. Blood flow was analyzed in 26 territories subtended by bypass grafts with normal wall motion and normal perfusion. Myocardial blood flow at rest did not differ between patients and controls (0.65 +/- 0.14 vs 0.68 +/- 0.16 ml/ g/min) and was similar in normal myocardium subtended by saphenous vein (n = 16) and internal mammary artery grafts (n = 10; 0.64 +/- 0.13 vs 0.66 +/- 0.15 ml/g/min). However, the hyperemic response in normal myocardium supplied by bypass grafts was less than that in controls (1.61 +/- 0.33 vs 2.04 +/- 0.30 ml/g/min, p <0.005). No differences between territories supplied by venous and arterial conduits were observed (1.61 +/- 0.35 vs 1.63 +/- 0.32 ml/g/min). Normal myocardium subtended by bypass grafts exhibited a lower flow reserve than that in controls (2.54 +/- 0.51 vs 3.16 +/- 0.85, p <0.02). Myocardial flow reserve was almost identical in regions supplied by venous and arterial grafts (2.55 +/- 0.48 vs 2.52 +/- 0.58). The similar reduction in vasodilatory capacity together with the normal PET polar map findings during dipyridamole argue against flow limiting stenoses in both venous and arterial bypass conduits late after revascularization. Rather, nonobstructive proliferative fibrointimal changes of the bypass conduits or atherosclerosis of the native resistance vessels might account for this finding.",1997.0,0,0
1025,9205931,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.",1997.0,0,1
1026,9207618,Role of cytokines in the mechanism of action of amlodipine: the PRAISE Heart Failure Trial. Prospective Randomized Amlodipine Survival Evaluation.,E R Mohler; L C Sorensen; J K Ghali; D D Schocken; P W Willis; J A Bowers; A B Cropp; M L Pressler,"We sought to determine whether the beneficial effects of amlodipine in heart failure may be mediated by a reduction in tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels. We postulated that TNF-alpha and IL-6 levels may also have predictive value in patients with congestive heart failure (CHF). The molecular mechanism for progression of CHF may involve cytokine overexpression. The effect of amlodipine on cytokine levels in patients with CHF is unknown. In the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) trial, we used enzyme-linked immunosorbent assay to measure plasma levels of TNF-alpha in 92 patients and IL-6 in 62 patients in New York Heart Association functional classes III and IV randomized to receive amlodipine (10 mg/day) or placebo. Blood samples were obtained for cytokine measurement at baseline and at 8 and 26 weeks after enrollment. The baseline amlodipine and placebo groups did not differ in demographics and cytokine levels. Mean (+/- SD) plasma levels of TNF-alpha were 5.69 +/- 0.32 pg/ml, and those of IL-6 were 9.23 +/- 1.26 pg/ml at baseline. These levels were elevated 6 and 10 times, respectively, compared with those of normal subjects (p < 0.001). Levels of TNF-alpha did not change significantly over the 26-week period (p = 0.69). However, IL-6 levels were significantly lower at 26 weeks in patients treated with amlodipine versus placebo (p = 0.007 by the Wilcoxon signed-rank test). An adverse event-CHF or death-occurred more commonly in patients with higher IL-6 levels. Amlodipine lowers plasma IL-6 levels in patients with CHF. The beneficial effect of amlodipine in CHF may be due to a reduction of cytokines such as IL-6.",2001.0,0,1
1027,9208360,"Postabsorption concentration peaks with brand-name and generic verapamil: a double-blind, crossover study in elderly hypertensive patients.",J J Saseen; J A Porter; D J Barnette; J L Bauman; E J Zajac; B L Carter,"The pharmacokinetic actions, bioequivalence, and cardiovascular effects of two verapamil products were studied in a randomized, double-blind, crossover study in eight elderly hypertensive patients (median age, 69.5 years; range, 60-79 years) given brand-name or generic immediate-release verapamil in 120-mg twice-daily doses for 14 days. Blood pressures, heart rates, P-R intervals; and serum concentrations of R-/S-verapamil and norverapamil were measured multiple times in patients during the last day of each therapy. Median blood pressure decreased more with generic verapamil than with the brand-name drug, with the largest difference occurring at 0.5 hours (137/74 mmHg versus 144.5/80.5 mmHg; P = 0.05 and 0.091, respectively). Pharmacokinetic parameters were not different for the two products (P < 0.01). However, the generic product, compared with the brand-name drug, had mean area under the concentration-time curve (time 0 to 12 hours) ratios (90% CI) of 1.09 (0.78-1.52), 1.16 (0.87-1.55) and 1.11 (0.81-1.52) for R-, S-, and total verapamil. Seventy concentration peaks (31 with the brand-name drug, 39 with the generic drug) appeared between 8 and 24 hours. Median percentages of increase of these peaks, compared with those of previous concentrations, were 48.3% and 36.3% for brand-name and generic drugs, respectively. Fifty of the 70 peaks (71%) were associated with a stereospecific concentration peak of norverapamil and, temporally, with meals. Our findings suggest that whereas the two verapamil products may not be bioequivalent by Food and Drug Administration criteria, the observed differences in effects were not clinically significant in this elderly population. Multiple concentration peaks after absorption were observed in all patients with both verapamil products and were perhaps related to enterohepatic recirculation.",2001.0,0,0
1028,9209948,"Comments on 'A comparison of nifedipine once daily (Adalat LA), isosorbide mononitrate once daily and isosorbide dinitrate twice daily in patients with stable angina'.",G Nyberg,,1997.0,0,0
1029,9217563,Calcium antagonists in cardiovascular disease: a necessary controversy but an unnecessary panic.,E Grossman; F H Messerli,,1997.0,0,0
1030,9219047,"Diltiazem, a calcium antagonist, partly attenuates the effects of dextroamphetamine in healthy volunteers.",J E Fabian; P H Silverstone,"Calcium antagonists have previously been shown to be effective in the treatment of mania. In the present study we used dextroamphetamine administered to humans as a model of mania, to determine whether the calcium antagonist diltiazem would prevent dextroamphetamine-induced changes. This may help determine whether diltiazem is likely to be useful in the treatment of mania. Ten healthy volunteers were enrolled in this double-blind, placebo-controlled, balanced crossover study. Subjects received either oral diltiazem (60 mg) and placebo, placebo and dextroamphetamine (20 mg), diltiazem and dextroamphetamine, or placebo alone. Subjective and sleep changes were measured using visual analogue scales. Attentiveness and visual reaction times were measured repeatedly as were diastolic and systolic blood pressure. The results showed that dextroamphetamine alone produced a number of subjective changes, cardiovascular changes and changes in reaction time. Diltiazem significantly attenuated the cardiovascular changes, but not the subjective or reaction time changes. It is hypothesized that these findings may represent effects of diltiazem on noradrenergic neurotransmission. The results are tentatively supportive of suggestions that diltiazem may be clinically useful in the treatment of mania, as is another calcium channel antagonist, verapamil.",1997.0,0,0
1031,9220037,Nifedipine gastrointestinal therapeutic system versus nifedipine coat-core: comparison of efficacy via 24-hour ambulatory blood pressure monitoring.,L F Defina; D A Bookstaver; M P Goldfinger; T A Coffey,"To assess the comparable efficacy and adverse effect profile of two extended-release preparations of nifedipine--gastrointestinal therapeutic system (GITS) and coat-core (CC)--in patients with mild-to-moderate hypertension. Single institution, single-blind, prospective study. Dwight David Eisenhower Army Medical Center, Fort Gordon, GA. Ninety-one patients who were taking nifedipine GITS as a sole antihypertensive agent were randomized to receive either GITS or CC. After 3 weeks, 24-hour ambulatory blood pressure monitoring was conducted and an adverse effect questionnaire was administered. The patients were then crossed over to the other treatment arm and monitoring was repeated after 3 weeks. Mean blood pressure, heart rates, and the percentage of readings exceeding 140 mm Hg systolic and 90 mm Hg diastolic were compared for the 24-hour period. Additionally, mean blood pressures at 4-hour intervals after drug administration and heart rate during the first 8 hours of the dosage interval were compared. Ninety-one patients enrolled, 79 completed the study, and 62 patients were included in the efficacy analysis. A statistically significant difference (p = 0.020) was shown only in the last 4-hour systolic blood pressure. However, this difference was small (122 +/- 15 mm Hg with GITS vs. 126 +/- 14 mm Hg with CC). There was no difference in the percentage of readings exceeding 140 mm Hg systolic or 90 mm Hg diastolic. Neither dosage nor treatment order had an effect on the results. Adverse effects were reported with a greater frequency during CC therapy (40 with CC vs. 22 with GITS; p = 0.006), but were generally transient. Discontinuation of the drug was necessary in 3 patients during the CC cycle. GITS and CC demonstrated clinically equivalent antihypertensive efficacy in the study population. The CC produce may have a higher rate of adverse effects, but drug discontinuation was uncommon.",1997.0,0,0
1032,9220060,Selective prescribing in suicidal patients: a little thought can decrease the risk of future morbidity and mortality.,K O Rynn; S E Graf; F P Paloucek,,1997.0,0,0
1033,9220178,The prognostic significance of angina pectoris experienced during the first month following acute myocardial infarction.,C M Jespersen,"Angina pectoris accompanied by transient ST-segment changes during the in-hospital phase of acute myocardial infarction (AMI) is a well established marker of subsequent cardiac death and reinfarction. This study was undertaken to record the prognostic significance of angina pectoris experienced during the first month following discharge from AMI. In all, 803 patients included in the placebo arm of the Danish Verapamil Infarction Trial II were followed up for 18 months in 20 coronary care units in Denmark. The patients were randomized to placebo and were still on study treatment 1 month after discharge. Of these patients, 311 (39%) reported chest pain during the first month following discharge. Patients with angina pectoris had a significantly increased risk of reinfarction [hazard 1.71; 95%-confidence limit (CL): 1.09, 2.69] and increased mortality risk which, however, only reached borderline statistical significance (hazard 1.52; 95%-CL: 0.96, 2.40). When patients were subdivided according to both angina pectoris and heart failure, those with one or both of these risk markers had significantly increased mortality (p 0.03) and reinfarction (p 0.02) rates compared with patients free of both angina pectoris and heart failure. Patients with postinfarction angina pectoris have a significantly increased morbidity risk.",1997.0,0,0
1034,9231814,Safety of nifedipine in patients with hypertension: a meta-analysis.,W B Stason; C H Schmid; D Niedzwiecki; G W Whiting; J F Caubet; D Luo; S D Ross; T C Chalmers,"Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls. We performed a MEDLARS search using the MeSH heading ""hypertension"" and the text word ""nifedipine"" to identify all articles that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjects. The computerized search was supplemented by a manual search of article bibliographies. Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria. Articles were extracted independently by two doctors who were blinded for author, institution, and treatment regimen, using a structured, pretested extraction form. Differences of opinion were resolved by consensus. Fourteen events occurred in 5198 exposures (0.27%) to nifedipine and 24 events in 5402 exposures (0.44%) to other active drug controls. Unadjusted odds ratios for nifedipine versus controls were 0.49 (95% confidence interval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardial infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odds ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all events (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% CI, 0.59-3.32, respectively). The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15; 95% CI, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (P=.02 for definitive events and P=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.",1997.0,1,1
1035,9234828,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
1036,9241299,Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial.,D N Papatsonis; H P Van Geijn; H J Adèr; F M Lange; O P Bleker; G A Dekker,"To compare the efficacy of nifedipine with ritodrine in the management of preterm labor. One hundred eighty-five singleton pregnancies with preterm labor were assigned randomly to either ritodrine intravenously (n = 90) or nifedipine orally (n = 95). The principal outcome assessed was delay of delivery. Ritodrine was discontinued in 12 patients because of severe maternal side effects, and their results were excluded from further analysis. More women in the ritodrine group delivered within 24 hours (22 versus 11, P = .006), within 48 hours (29 versus 21, P = .03), within 1 week (45 versus 36, P = .009), and within 2 weeks (52 versus 43, P = .005) compared with those receiving nifedipine. There were significantly fewer maternal side effects in the nifedipine group. Apgar scores and umbilical artery and vein pHs were similar in both groups. The number of admissions to the neonatal intensive care unit (NICU) in the nifedipine group was significantly lower than in the ritodrine group (68.4 versus 82.1%, P = .04). Nifedipine in comparison with ritodrine in the management of preterm labor is significantly associated with a longer postponement of deliver, fewer maternal side effects, and fewer admissions to the NICU.",1997.0,0,0
1037,9244644,[Effectiveness and tolerability of bisoprolol vs. nifedipine in uremic patients with ischemic cardiopathy in dialysis treatment].,G Cice; A Di Benedetto; E Tagliamonte; L Ferrara; P Sorice; A Iacono,"The effects of bisoprolol on transient myocardial ischemia have been compared with those of nifedipine in patients with coronary artery disease in end-stage renal failure maintained on haemodialysis. We also evaluated the tolerability of both drugs. Sixty patients (42 males, 18 females, mean age 52 +/- 4 years) in renal failure maintained on haemodialysis, with coronary artery disease and more than four significant episodes of transient myocardial ischemia (> or = 1 min) during 48-hour Holter monitoring, were included in the study. All cardiovascular drugs were discontinued > or = 6 days before this 48-hour ambulatory ECG monitoring, with the exception of sublingual nitrates allowed for relief of anginal attacks. Patients were then randomized to receive either bisoprolol or nifedipine for 2 weeks. After a 15-day wash-out period, they were crossed over to receive either bisoprolol or nifedipine for other 2 weeks. Statistical analysis was carried out using the Student's t test. A p value < 0.01 was considered significant. Both bisoprolol and nifedipine reduced number and duration of transient ischemic episodes as well as the total ischemic burden. Reductions were statistically significant for both antianginal drugs. Only bisoprolol was effective in silent ischemia (p < 0.001). It also reduced heart rate (p < 0.001), while nifedipine raised it (p < 0.001). Both drugs reduced systolic and diastolic blood pressure. The circadian variations of transient ischemic episodes showed two peaks in the 24 hours. Both peaks were reduced with bisoprolol. Nifedipine brought a clear overall reduction in the number of episodes but the circadian pattern was unchanged. During the study, 10 patients taking bisoprolol and 12 patients taking nifedipine had drug adverse effects. No one of them had to be withdrawn from treatment. In conclusion, bisoprolol seems to be more useful than nifedipine because its effects, in transient ischemic episodes, are greatly superior to those of nifedipine, and because it is effective also in silent ischemia. Both drugs showed a good tolerability in these patients. Bisoprolol, reducing the two daily peaks of ischemic episodes frequency, has a protective role towards mortality due to coronary artery disease.",1997.0,0,0
1038,9249234,"A randomised, double-blind trial comparing mibefradil and amlodipine: two long-acting calcium antagonists with similar efficacy but different tolerability profiles. Mibefradil International Study Group.",R J Viskoper; P J Bernink; A Schelling; A B Ribeiro; I M Kantola; M R Wilkins; I Kobrin,"To compare the efficacy and tolerability of mibefradil and amlodipine in patients with uncomplicated mild-to-moderate essential hypertension. A double-blind, randomised, parallel group multicentre trial. 239 patients received 50 mg mibefradil or 5 mg amlodipine for 4 weeks, followed by a forced titration to 100 mg mibefradil or 10 mg amlodipine for an additional 8 weeks. Patients then entered a 4-week withdrawal period either on therapy or switched to placebo. Statistically equivalent reductions in trough sitting diastolic blood pressure (SDBP) were observed after 12 weeks of once-daily treatment with 50/100 mg mibefradil (-11.5 +/- 8.2 mm Hg) and 5/10 mg amlodipine (-13.2 +/- 7.9 mm Hg). The number of patients with normalised SDBP (< or = 90 mm Hg) increased 23.3% in the mibefradil group and 19.5% in the amlodipine group (approximately 74% in both groups). Patients on mibefradil or amlodipine during the withdrawal period had significantly larger decreases in SDBP than those on placebo. Patients on mibefradil had a decrease in heart rate of 5.5 bpm. Patients on amlodipine had no change in heart rate; however, cessation of amlodipine was associated with a decrease in heart rate. Mibefradil was as effective as amlodipine in reducing BP; both compounds were effective treatments of hypertension.",1997.0,0,0
1039,9249636,"Regression of nifedipine-induced gingival hyperplasia following switch to a same class calcium channel blocker, isradipine.",P Westbrook; E M Bednarczyk; M Carlson; H Sheehan; N F Bissada,"Patients with nifedipine-induced gingival hyperplasia (GH) often require continued calcium channel blocker therapy. Switches to diltiazem and verapamil have been described; however, these drugs are of a different chemical class and present therapeutic limitations in some patients. The purpose of this study was to evaluate the effect on nifedipine-induced GH of a switch to a dihydropyridine derivative with a low incidence of GH. Fourteen patients with nifedipine-induced GH were given a medical exam and a periodontal exam. The following parameters were assessed: probing depth (PD), gingival margin (GM), gingival thickness (GT), plaque index (PI), and gingival index (GI). Intraoral photographs, study models, and a gingival biopsy for histological examination were taken. Following baseline measures, patients were randomized to continued treatment with nifedipine or an equivalent dose of isradipine in a single-blind fashion. Biweekly periodontal parameters were taken for 8 weeks. At the end of 8 weeks, some patients elected to receive 4 weeks of open label isradipine therapy, with biweekly examination continuing through the open label phase. The isradipine treatment arm showed a mean decrease in PD of 0.59 mm at week 8 (P < 0.05). No other measured parameter (GM, GT, PI, GI) was significantly changed, compared either to baseline or to the alternate treatment arm. Clinically, 60% of patients treated with isradipine exhibited a decrease in hyperplasia, while 66% of patients treated with nifedipine demonstrated an increase in hyperplasia, a significant difference (P < 0.05). When combined with open label data, patients switching therapy to isradipine exhibited an increase in GM (increase in recession) of 0.74 mm from baseline to week 12 (P < 0.05). No patients treated with isradipine exhibited an increase in gingival overgrowth. All patients exhibited adequate control of hypertension. We conclude that in hypertensive patients with nifedipine-induced GH, switching hypertensive therapy to isradipine may result in a regression of GH. When coupled with aggressive oral hygiene treatment, this drug may provide a reasonable option for patients requiring dihydropyridine treatment.",1997.0,0,0
1040,9249639,Prevalence of amlodipine-related gingival hyperplasia.,M G Jorgensen,"Calcium channel blockers are known to contribute to gingival hyperplasia. The vast majority of reports discuss patients taking the drug nifedipine. During the past few years a newer calcium channel blocker, amlodipine, has been used with increasing frequency. To date, six cases have been published indicating that amlodipine may also promote gingival hyperplasia; however, no data have been reported regarding the prevalence of this phenomenon. The purpose of this study was to examine a large group of patients taking amlodipine and determine the prevalence of gingival hyperplasia. One hundred fifty dentate patients who had been taking amlodipine, 5 mg per day for at least 6 months, volunteered to undergo a screening examination for gingival hyperplasia. Mild hyperplasia (< 1/3 clinical crown) was found in five patients-a prevalence of 3.3%. This is significantly less (P < .001) than rates reported for patients taking nifedipine, and not significantly different from rates previously reported in control groups of cardiac patients not taking calcium channel blockers. The results from this group of patients indicated that amlodipine, 5 mg per day, did not induce gingival hyperplasia.",1997.0,0,0
1041,9250554,"Antianginal response to once-daily diltiazem CD in patients receiving concomitant beta-blockers, long-acting nitrates, or both. Diltiazem CD Study Group.",G V Heller; M Sridharan; J Morse; S Glasser; C L Beach,"To determine the safety and efficacy of diltiazem CD 180 mg administered once/day in patients with chronic stable angina inadequately controlled with P-blockers, long-acting nitrates, or both. Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Medical clinics in the private and academic sectors. Of 172 patients, 170 completed the 2-week double-blind treatment period. . Patients received either diltiazem CD 180 mg or placebo once/day in combination with existing antianginal therapy. The time to termination of exercise tolerance testing, 24 hours after the dose increased significantly in the diltiazem CD group (37.2 sec) compared with the placebo group (21.3 sec, p=0.0438). Time to onset of angina during exercise testing also increased (57.6 vs 35.0 sec, respectively, p=0.0324), as did time to moderate angina (37.5 vs 20.6 sec, respectively, p=0.0354). The rates of total angina attacks and of angina attacks on exertion were significantly reduced in the diltiazem CD group versus placebo (p<0.05). Significant reductions in systolic and diastolic blood pressures and heart rate-blood pressure product measured at rest, submaximum exercise, and exercise termination were observed in diltiazem CD-treated patients compared with placebo (p<0.05). The frequency of treatment-related adverse events was identical in the two groups, 15.1%. Diltiazem CD 180 mg once/day is an effective, safe, and beneficial initial dosage when added to existing antianginal therapy.",1997.0,0,1
1042,9250574,Comparison of two formulations of nifedipine during 24-hour ambulatory blood pressure monitoring--a comment.,B D Lucas; D E Hilleman; R L Wurdeman,,2001.0,0,0
1043,9253691,[Effect of barnidipine hydrochloride on the autonomic nervous system: difference between short- and long-acting components of calcium antagonist].,K Soejima; M Akaishi; K Oyamada; H Mitamura; S Ogawa,"Short-acting calcium antagonists have a deleterious effect on the prognosis for patients with myocardial ischemia, possibly caused by overactivation of sympathetic nerves due to vasodilatation, negative inotropism, or coronary steal. However, there is considerable debate about whether long-acting calcium antagonists as well as the short-acting calcium antagonists have the same effect. Barnidipine-HCl is a newly-developed calcium antagonist with 1:2 short- and long-acting particles. This study evaluated the changes of autonomic tone due to barnidipine. Both the short- and long-acting effect of the calcium antagonist was evaluated. Eleven patients with primary hypertension underwent 24-hour ambulatory electrocardiogram and blood pressure monitoring before and after the treatment with barnidipine. Heart rate and blood pressure were compared before and after the medication. Heart rate variability was analyzed with a Marquette 8000/T. High frequency power (HF), as a parameter of vagal tone, and the ratio to low frequency power (LF), as a parameter of sympathetic tone, were obtained. Twenty-four-hour average blood pressure decreased significantly during the day, but nocturnal hypotension was not observed. Heart rate did not increase. HF decreased at the peak of the short- and long-acting components. LF/HF increased at the peak of the short-acting component. Short-acting particles of barnidipine had a deleterious effect on the autonomic tone, that is overactivation of sympathetic tone and suppression of vagal tone. Long-acting particles of barnidipine suppressed the vagal tone. These findings suggest that short-acting calcium antagonists may cause arrhythmia or deterioration of coronary ischemia.",1997.0,0,0
1044,9259871,Intravenous infusions of nifedipine: an alternative for the prevention of hypertension in eye surgery under local anesthesia.,H Nastou; G Sarros; A Nastos; M Saleh,"In order to control critical rises of blood pressure during the peri-operative period in elderly hypertensive patients, the effectiveness of a continuous intravenous infusion of nifedipine was studied. In a double blind study, patients (n = 60) who underwent eye surgery under local anesthesia were divided randomly into three groups. Patients who were found to have 200 > SBP > 160 and 120 > DBP > 90 mmHg as the previous day of surgery, as well as patients who did not receive any anti-hypertensive treatment regimen during the last week before surgery, were selected. Five min before performing local anesthesia, a continuous infusion of nifedipine at two different rates of 0.65 mg/h and 1.25 mg/h, was administered in groups A and B respectively, whereas group C received a placebo. SBP, DBP and HR were recorded every 5 min. for an hour. Statistically significant differences among the profiles of the three groups were found. The control group had a higher SBP/DBP. None of the groups, showed significant changes in HR. In conclusion, the intravenous infusion of nifedipine in a dose 1.25 mg/h, seems to control the hypertensive phases of blood pressure, without dropping to any unduly low level, risking undesirable side effects in elderly hypertensive patients during perioperative period.",1997.0,0,0
1045,9260367,Comparison of clinical efficacy and adverse effects between extended-release felodipine and atenolol in patients with mild and moderate essential hypertension.,M S Chern; F C Lin; D Wu,"Essential hypertension is a risk factor for cardiovascular disease. Atenolol, a cardio-selective beta-blocker, has been shown to be a safe and effective antihypertensive agent. The extended-release form of felodipine (felodipine ER), a vascular-selective dihydropyridine calcium blocker, is extensively used in Caucasians. However, its effectiveness, tolerability and adverse side-effect have not been assessed in Chinese populations. Sitting blood pressure (BP), heart rate, body weight, adverse reaction and serum biochemistry were assessed in 70 patients with mild-moderate essential hypertension treated either with felodipine ER (37 patients), or atenolol (33 patients) for 10 weeks. Each patient was prescribed 5 mg of felodipine ER or 50 mg of atenolol once daily and this daily dosage was doubled to twice daily if necessary. Six patients who received felodipine ER and 3 who received atenolol withdrew from the treatment because of intolerable side effects. Within ten weeks, 81.1% of the patients had responded to a total daily dosage of 5-10 mg of felodipine ER and 81.8% to a daily dose of 50-100 mg of atenolol. By the end of treatment, the mean BP in the felodipine ER group had decreased from 176/104 mmHg at baseline to 145/85 mmHg, while the BP in the atenolol group had dropped from 173/103 mmHg to 145/84 mmHg (NS between the two groups). Heart rate declined in the atenolol group but did not change in patients who received felodipine ER. Overall, patients in the felodipine ER group had a higher rate of adverse reaction (70.3% vs. 39.4%; p < 0.001), and 16.2% of the patients in the felodipine ER group experienced symptoms of hypotension. Equivalent doses of felodipine ER and atenolol are effective first-line monotherapeutic agents for the treatment of mild-moderate essential hypertension.",1997.0,0,0
1046,9262281,A challenge to the concept that the use of calcium channel blockers causes reversible male infertility.,D Katsoff; J H Check,"The objective of this study was retrospectively to evaluate both in-vitro fertilization (IVF) and non-IVF cycles in which the male partner had been taking calcium channel blockers, either to confirm or refute previous data from another centre, suggesting that these drugs cause a severe but reversible subfertility problem in the male. These drugs were found to inhibit expression of mannose-ligand binding receptors, thus preventing spermatozoa from attaching to the zona pellucida; they were postulated to cause failed fertilization based on one case having this defect, in whom a return to normal was achieved after stopping the drug. However, the couple did not undergo a cycle with IVF to see if fertilization now occurred. The data presented here demonstrated fertilization in all patients having IVF who were taking calcium channel blockers. The subsequent pregnancy rate per transfer was 17.4%. Also, five out of 11 (45.4%) non-IVF patients conceived after correction of various female factors. Failure of the other six patients to conceive could be explained by other confounding factors, especially oligoasthenozoospermia. Taking into consideration other data suggesting poor fertilization when this mannose-ligand binding receptor abnormality was demonstrated, we propose the possibility that this defect, when not associated with calcium channel blockers, may be associated with some other cryptic factor that causes poor fertilization. According to our hypothesis, calcium channel blockers might cause the problem in mannose expression but also adversely affect some other factor that is deficient when non-drug related abnormalities in mannose-ligand binding expression are found.",1997.0,0,0
1047,9264478,Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). DANish trial in Acute Myocardial Infarction.,J K Madsen; P Grande; K Saunamäki; P Thayssen; E Kassis; U Eriksen; K Rasmussen; S Haunsø; T T Nielsen; T Haghfelt; P Fritz-Hansen; E Hjelms; P K Paulsen; P Alstrup; H Arendrup; U Niebuhr-Jørgensen; L I Andersen,"The aim of the DANish trial in Acute Myocardial Infarction (DANAMI) study was to compare an invasive strategy of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) with a conservative strategy in patients with inducible myocardial ischemia who received thrombolytic treatment for a first acute myocardial infarction (AMI). Of the 503 patients randomized to an invasive strategy, PTCA was performed in 266 (52.9%) and CABG in 147 (29.2%) from 2 to 10 weeks after the AMI. Of the 505 patients in the conservative treatment group, only 8 (1.6%) had been revascularized 2 months after the AMI. The patients were followed up from 1 to 4.5 years. The primary end points were mortality, reinfarction, and admission with unstable angina. At 2.4 years' follow-up (median), mortality was 3.6% in the invasive treatment group and 4.4% in the conservative treatment group (not significant). Invasive treatment was associated with a lower incidence of AMI (5.6% versus 10.5%; P=.0038) and a lower incidence of admission for unstable angina (17.9% versus 29.5%; P<.00001). The percentages of patients with a primary end point were 15.4% and 29.5% at 1 year, 23.5% and 36.6% at 2 years, and 31.7% versus 44.0% at 4 years (P=<.00001) in the invasive and conservative treatment groups, respectively. At 12 months, stable angina pectoris was present in 21% of patients in the invasive treatment group and 43% in the conservative treatment group. Invasive treatment in post-AMI patients with inducible ischemia results in a reduction in the incidence of reinfarction, fewer admissions due to unstable angina, and lower prevalence of stable angina. We conclude that patients with inducible ischemia before discharge who have received treatment with thrombolytic drugs for their first AMI should be referred to coronary arteriography and revascularized accordingly.",1997.0,0,1
1048,9264493,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.",1997.0,1,1
1049,9266778,Effect of amlodipine on norepinephrine kinetics and baroreflex function in patients with congestive heart failure.,S R Goldsmith,"The use of calcium channel blocking drugs is controversial in heart failure, partly because of concerns about neurohormonal stimulation. Preliminary data suggest that the newer agent amlodipine may be useful in this syndrome. Suppression of sympathetic activity either directly or by sensitized baroreflex function could be contributing factors to the clinical use of this drug. To assess the effect of short-term amlodipine therapy on baseline measures of sympathetic activity and baroreflex function in patients with chronic stable congestive heart failure (CHF). Seven patients with chronic CHF (New York Heart Association functional class II or III, moderate to severe reduction in left ventricular systolic function) were studied. All patients underwent baroreflex testing with head-up tilt, head-down tilt, and head-down tilt with phenylephrine infusion. Heart rate, mean arterial pressure, forearm blood flow and resistance, and plasma norepinephrine (NE) kinetics were assessed at baseline and after each baroreflex perturbation on three occasions: a control test and after 10 days each of placebo and amlodipine therapy. Plasma NE and NE spillover did not significantly increase after amlodipine administration compared with control and placebo tests (488 +/- 119 pg/ml vs 350 +/- 85 and 325 +/- 87 pg/ml). In three subjects, plasma NE levels were essentially unchanged, whereas in four they rose markedly (289 +/- 87 pg/ml at control vs 551 +/- 158 pg/ml). There was no difference in the response of any variable during baroreflex perturbations after amlodipine administration compared with control and placebo tests. One subject who tolerated head-down tilt coupled with phenylephrine administration during the control and placebo tests became markedly short of breath during the same intervention after amlodipine administration. Plasma NE levels in this patient had risen markedly while receiving amlodipine and were not appropriately suppressed during the baroreflex loading maneuver. Short-term therapy with amlodipine does not suppress sympathetic activity or alter efferent responses to baroreflex perturbation in patients with stable chronic CHF. Significant increases in plasma NE and NE spillover and abnormal responses to baroreflex stimulation are possible after administration of this drug. The relevance of these findings to studies in larger number of patients requires further study.",1997.0,0,0
1050,9269944,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
1051,9282610,"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
1052,9284842,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.",1997.0,0,1
1053,9285652,Effect of morning versus evening dosing of diltiazem on myocardial ischemia detected by ambulatory electrocardiographic monitoring in chronic stable angina pectoris. Dilacor XR Ambulatory Ischemia Study Group.,P C Deedwania; P E Pool; U Thadani; J Eff,"Myocardial ischemia occurs frequently during daily life and has a circadian pattern similar to that reported for myocardial infarction and sudden death. Because of the increased risk of myocardial ischemia in the morning hours, it has been suggested that the administration of anti-ischemic medication before bedtime may be more effective than the traditional morning dosing. This randomized, double-blind, placebo-controlled, crossover study evaluated the effects of 480-mg/day diltiazem (given either in the A.M. or the P.M.) on myocardial ischemia using ambulatory electrocardiographic monitoring in 68 patients with chronic stable angina and > or = 2 minutes of ischemia per 48 hours. During treatment with diltiazem, the duration and number of myocardial ischemic episodes were reduced by 45% (94 to 52 minutes, p <0.004) and by 40% (4.5 to 2.7 episodes, p <0.003), respectively. The duration and number of myocardial ischemic episodes during daytime (6 A.M. to 6 P.M.) hours were also reduced by 52% (74 to 36 minutes, p <0.002) and by 48% (3.1 to 1.6 episodes, p <0.001), respectively. There was no significant difference between A.M. and P.M. dosing. Morning ischemia (6 A.M. to noon), considered separately from daytime ischemia, was also significantly reduced by both A.M. and P.M. dosing regimens, with no difference between the regimens. The results of this study showed that both A.M. and P.M. dosing of long-acting diltiazem were equally effective in suppressing episodes of ambulatory myocardial ischemia at all times.",1997.0,0,1
1054,9285660,Effects of controlled-onset extended-release verapamil on nocturnal blood pressure (dippers versus nondippers). COER-Verapamil Study Group.,W B White; D V Mehrotra; H R Black; T D Fakouhi,"Approximately 1 in 4 patients with systemic hypertension have a 24-hour blood pressure (BP) profile characterized by a blunted or absent nocturnal decline in pressure. We evaluated the effects of a chronotherapeutic delivery system of controlled-onset extended-release (COER) verapamil hydrochloride and placebo in 257 hypertensive patients according to their circadian BP pattern in an 8-week prospective, multicenter, randomized, and double-blind clinical trial. Patients were stratified into 193 dippers (>10% decline in BP during the period of 10 P.M. to 5 A.M. compared with the hours of 5 A.M. to 10 P.M.) and 64 nondippers (<10% decline in BP during nighttime). During daytime, placebo-subtracted BP was similarly decreased in dippers and nondippers by COER verapamil. During nighttime, the placebo increased nocturnal BP in dippers (baseline nocturnal BP, 133/78 mm Hg) by 3/3 +/- 2/2 mm Hg and reduced BP by -5/-3 +/- 2/2 mm Hg in nondippers (baseline nocturnal BP, 152/94 mm Hg) (p = NS between groups). After controlling for age, gender, ethnicity, and the regression to the mean observed on placebo for all doses, COER verapamil reduced nocturnal BP more in nondippers than dippers -5.8/-2.4 mm Hg, p <0.0001 for systolic BP and p = 0.09 for diastolic BP). Additionally, a significant dose-related reduction in systolic and diastolic nocturnal BP (r = 0.56, p <0.0001 for systolic BP and r = 0.62, p <0.0001 for diastolic BP) was observed with COER verapamil after controlling for baseline covariates. These data demonstrate that nocturnal BP is decreased by a greater extent in nondipper hypertensives than in dipper hypertensives following treatment with COER verapamil HCL.",1997.0,0,0
1055,9297994,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.",1997.0,0,1
1056,9300324,Physical performance is preserved after regression of left ventricular hypertrophy.,Y Lacourcière; L Poirier; J Cléroux,"Reversal of left ventricular hypertrophy has been shown to improve left ventricular diastolic function in elderly patients with hypertension, but little is known about whether this affects physical performance. Left ventricular mass, cardiac function at rest and during submaximal exercise, and physical performance were assessed in 38 elderly patients with hypertension with left ventricular hypertrophy and normal systolic function before and after 8 and 14 months of therapy with amlodipine or hydrochlorothiazide or both. Blood pressure control was achieved with amlodipine in 18 patients, with hydrochlorothiazide in seven, and with the combination of these drugs in 13. Left ventricular mass index was similarly reduced from approximately 150 to approximately 100 g/m2 at 14 months' in each treatment group. Systolic function was maintained with the three treatment regimens, whereas similar decreases in time to peak filling rate and increases in first-third filling fraction occurred both at rest and during submaximal exercise after 8 months and further after 14 months of therapy. Exercise capacity did not significantly change in the group as a whole, but individual changes in peak oxygen uptake at the end of treatment correlated significantly with the decrease in time to peak filling rate during submaximal exercise (r = -0.49; p < 0.01). It is concluded that long-term blood pressure control with amlodipine or hydrochlorothiazide or both is associated with significant reductions in left ventricular mass and improved diastolic function in elderly patients with hypertension with left ventricular hypertrophy. Despite this reduction in left ventricular mass, left ventricular systolic function and physical performance are well preserved during submaximal exercise.",1997.0,0,0
1057,9313601,"Long-term antianginal and antiischemic effects of mibefradil, the novel T-type calcium channel blocker: a multicenter, double-blind, placebo-controlled, randomized comparison with sustained-release diltiazem.",G J Davies; I Kobrin; A Caspi; L H Reisin; D C de Albuquerque; D Armagnijan; O R Coelho; A Schneeweiss,"This study compared the efficacy, safety, and tolerability of mibefradil to sustained-release diltiazem in patients with chronic stable angina pectoris. At week 12, statistically equivalent mean increases in exercise tolerance test (ETT) duration of > 1 minute were observed in both groups. Similar improvements in time to onset of angina and time to persistent 1 mm ST-segment depression were also observed with both drugs. Large reductions in heart rate, blood pressure, and rate-pressure product were observed at each stage of the ETT among patients treated with mibefradil. Each drug was associated with at least a 70% reduction from baseline in anginal frequency and nitroglycerin consumption. Patients maintained on mibefradil during the withdrawal period had significant increases in all three ETT variables at week 16 compared with placebo. The effectiveness of mibefradil is comparable with sustained-release diltiazem in treating chronic stable angina pectoris, although mibefradil provides greater reductions in heart rate and cardiac workload.",1997.0,0,1
1058,9314427,Salt and blood pressure responses to calcium antagonism in hypertensive patients.,M R Weir; P S Hall; M T Behrens; J M Flack,"Since salt intake may affect blood pressure response to antihypertensive drugs, an individual's salt-sensitivity status may be an important consideration in the selection of a medication. The purpose of this single-blind study was to assess the impact of salt sensitivity on the antihypertensive effects of isradipine. A total of 21 evaluable hypertensive patients (10 white, 11 black) 35 to 73 years of age (mean 55.9 years) were randomized to a low-salt diet (mean 24-hour urine sodium 100+/-14 mmol) or a high-salt diet (mean 24-hour urine sodium 210+/-22 mmol) for 7 weeks, followed by crossover to the other diet after a 2-week washout period. On each diet regimen, patients received placebo for 2 weeks, followed by optimal titration of isradipine (2.5 to 10 mg BID) for blood pressure control during the last 5 weeks. On the high-salt diet, salt-sensitive hypertensives (mean arterial blood pressure increase > or = 5 mm Hg, n=5) exhibited a systolic/diastolic blood pressure change of -18.7/-19.6 mm Hg from 157.2/102.9 mm Hg after 5 weeks of isradipine treatment, whereas on a low-salt diet, blood pressure change was -6.9/-12.0 mm Hg from 148.7/97.3 mm Hg. Non-salt-sensitive patients (n=16) exhibited a systolic/diastolic blood pressure change of -12.6/-7.6 mm Hg from 155.3/98.6 mm Hg on the high-salt diet and -19.2/-10.9 mm Hg from 161.0/102.6 mm Hg on the low-salt diet after treatment with isradipine. The absolute blood pressure attained in both salt-sensitive and non-salt-sensitive patients was almost identical with isradipine therapy despite variation in dietary salt, although slightly higher doses of isradipine were required in the salt-sensitive group. Consequently, isradipine, and perhaps calcium antagonists in general, manifests a more robust blood pressure-lowering effect in the setting of high sodium intake. This effect does, however, appear to be largely confined to individuals who are salt sensitive.",1997.0,0,0
1059,9322826,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
1060,9322827,"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
1061,9327716,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
1062,9335410,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
1063,9337374,Prehospital use of intravenous diltiazem (cardizem Lyo-Ject) in the treatment of rapid atrial fibrillation.,N R Abarbanell; M A Marcotte,,1997.0,0,0
1064,9338468,Use of calcium channel blockers and breast carcinoma risk in postmenopausal women.,A L Fitzpatrick; J R Daling; C D Furberg; R A Kronmal; J L Weissfeld,"The use of calcium channel blockers in an elderly population recently was reported to be associated with the incidence of cancer. The Cardiovascular Health Study, a multisite observational cohort study, provided the opportunity to investigate the epidemiologic association between the use of calcium channel blockers and breast carcinoma risk in 3198 women age > or = 65 years. Standard questionnaires and clinical procedures were administered at four study sites annually from 1989-1990 to 1993-1994. Drug usage was assessed by a medication inventory and hospitalizations for 75 incident invasive breast carcinoma cases were identified using International Classification of Diseases-9 Clinical Modification codes. Time-dependent Cox proportional hazards regression models were used to assess associations between incident breast carcinoma and the use of specific antihypertensive medication including calcium channel blockers. In adjusted Cox proportional hazards models, an elevated risk of breast carcinoma was associated with use of calcium channel blockers (hazard ratio [HR]: 2.57; 95% confidence interval [CI], 1.47-4.49). This association persisted when the comparison group was users of other antihypertensive medication. No associations between the use of other antihypertensive medication with incident breast carcinoma were found. Associations were enhanced by assessment of high dose at baseline (HR: 4.42; 95% CI, 1.37-14.27) and when calcium channel blockers were combined with estrogen use (HR: 4.48; 95% CI, 1.58-12.75). The association was found to be strongest for the use of estrogens with immediate release calcium channel blockers (HR: 8.48; 95% CI, 2.99-24.08). Although the number of cases was limited in this observational study, associations found between the use of calcium channel blockers and incident invasive breast carcinoma warrant further investigation. Site specific carcinomas should be included as an outcome of ongoing and planned long term clinical trials using calcium channel blockers.",2000.0,0,1
1065,9352986,"Rationale, design, and baseline characteristics of the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT).",R P Byington; M E Miller; D Herrington; W Riley; B Pitt; C D Furberg; D B Hunninghake; G B Mancini,"The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial is the first angiographic clinical trial to be designed to test whether an agent can slow or even reverse the progression of early coronary atherosclerosis in patients with documented disease. In addition, a subset of patients are undergoing carotid ultrasound examinations, providing a unique opportunity to assess and correlate disease progression in 2 arterial beds.",1997.0,1,1
1066,9355894,,,,,0,1
1067,9355902,Assessment of atrioventricular junction ablation and DDDR mode-switching pacemaker versus pharmacological treatment in patients with severely symptomatic paroxysmal atrial fibrillation: a randomized controlled study.,M Brignole; L Gianfranchi; C Menozzi; P Alboni; G Musso; M G Bongiorni; M Gasparini; A Raviele; G Lolli; N Paparella; S Acquarone,"The purpose of the study was to evaluate the effect of AV junction ablation and pacemaker implantation on quality of life and specific symptoms in patients with paroxysmal atrial fibrillation (AF) not controlled by drugs. We performed a multicenter, randomized, 6-month evaluation of the clinical effects of AV junction ablation and DDDR mode-switching pacemaker (Abl+Pm) versus pharmacological treatment in 43 patients with intolerable, recurrent paroxysmal AF of three or more episodes in the previous 6 months not controlled with three or more antiarrhythmic drugs. Before completion of the study, 3 patients in the drug group withdrew because of the severity of their symptoms and 1 patient assigned to the Abl+Pm group in whom the ablation procedure failed. At the end of the 6 months, the 21 patients of the Abl+Pm group who completed the study showed, in comparison with the 18 of the drug group, lower scores in the Living with Heart Failure Questionnaire (-51%, P=.0006), palpitations (-71%, P=.0000), effort dyspnea (-36%, P=.04), exercise intolerance score (-46%, P=.001), and easy fatigue (-51%, P=.02). The scores for rest dyspnea, chest discomfort, and NYHA functional classification were also lower (-56%, -50%, and -17%, respectively) in the Abl+Pm group, although not significantly. At the end of the study, palpitations were no longer present in 81% of the Abl+Pm group and in 11% of the drug group (P=.0000). AF was documented in 31 of 122 visits (25%) in the Abl+Pm group and in 9 of 107 examinations (8%) in the drug group (P=.0005); chronic AF developed in 5 (24%) and 0 (0%) in the two groups, respectively (P=.04). In patients with paroxysmal AF not controlled by pharmacological therapy, Abl+Pm treatment is highly effective and superior to drug therapy in controlling symptoms and improving quality of life. The discontinuation of drug therapy exposes patients to further recurrences of paroxysmal AF and the risk of developing permanent AF.",1997.0,0,0
1068,9360003,The Hypertension Optimal Treatment (HOT) Study: 24-month data on blood pressure and tolerability.,L Hansson; A Zanchetti,"The Hypertension Optimal Treatment (HOT) Study is an ongoing prospective randomized, multicentre trial conducted in 26 countries. There are two main aims of the study. The first is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and the incidence of cardiovascular morbidity and mortality in hypertensive patients. The second is to determine the effect on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) compared with placebo. Altogether 18,790 patients have been recruited and randomized, and two-year data are now available for all patients. This is a report on the blood pressures achieved, the tolerability, and other available data after 24 months of follow-up of all patients. Special emphasis is given to the subgroup of elderly patients (> or = 65 years, n = 5988) compared with young patients (< 65 years, n = 12 802). On average, patients in the < or = 90 mmHg diastolic blood pressure target group have reached 85 mmHg, in the < or = 85 mmHg target group patients have reached 83 mmHg and in the < or = 80 mmHg target group patients have reached 81 mmHg. The percentage of those achieving target blood pressure in each target group at 24 months of follow-up is 85% in the < or = 90 mmHg target group, 75% in the < or = 85 mmHg target group and 57% in the < or = 80 mmHg target group. In the elderly subgroup (> or = 65 years of age), the percentage of patients achieving target at 24 months is higher for all target groups, namely 89% in the < or = 90 mmHg group, 80% in the 85 mmHg group and 62% in the 80 mmHg group. Antihypertensive treatment was initiated with a calcium antagonist, felodipine, at a dose of 5 mg once daily. If target blood pressure was not reached, additional antihypertensive therapy, with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent, was given. Further dose adjustments were made in accordance with a set protocol. As a fifth, and final, step, a diuretic could be added. There have been relatively few side effects in this large, multinational study of hypertensive patients. Only ankle oedema and coughing exceed a frequency of 0.5% (ankle oedema 1.3% in young and 1.7% in elderly; coughing 0.5% in young and elderly). After two years, 84% of all patients are still taking their baseline therapy, felodipine. The 24-month data presented here indicate that it should be possible to fulfil the primary aims of the HOT Study.",1997.0,0,0
1069,9370387,Calcium antagonism abolishes the antipressor action of vasopressin (V1) receptor antagonism.,G L Bakris; S L Kusmirek; A C Smith; I Gavras; H Gavras,"Previous studies demonstrate that vasopressin (V1) receptor antagonism lowers arterial pressure in blacks. This action of V1 receptor blockade may be mediated through various mechanisms including changes in intracellular calcium fluxes. This study was undertaken to test the hypothesis that inhibition of calcium entry may attenuate the reduction in arterial pressure observed with V1 receptor blockade. Sixteen hypertensive patients, 8 whites and 8 blacks, were examined. Each had their antihypertensive therapy stopped for 1 week. Following three baseline blood pressure measurements, all patients were given an intravenous bolus injection of a V1 receptor antagonist. Blood pressure was monitored every 10 min for a period of 3 h. Subjects were then randomized to either 0.2 mg clonidine twice daily or 300 mg diltiazem CD daily for a period of 3 days and the previous experiments repeated. Patients were then crossed over to the other drug for an additional 3 days and the experiments repeated. There was a significant reduction from baseline in the mean arterial pressure among blacks but not whites (-11 +/- 3 delta mm Hg blacks versus -1 +/- 2 delta mm Hg whites, P < .01). In the presence of clonidine, there were similar reductions in arterial pressure in both groups (P = .026) with a further reduction following V1 receptor blockade only in the blacks (-7 +/- 3 delta mm Hg blacks versus 6 +/- 2 delta mm Hg whites; P < .001). Conversely, in the presence of diltiazem CD, there were no further reductions in arterial pressure in either group following the V1 receptor antagonist. We conclude that calcium channel blockade abolishes the blood pressure lowering response of V1 receptor blockade in blacks.",1997.0,0,0
1070,9373050,Antihypertensive and renal effects of isradipine in essential hypertension: focus on renin system activity.,K Allikmets; T Parik; R Teesalu,"Calcium antagonists are known to exert various effects on the kidney that might modulate their antihypertensive potential. This study evaluated the renal effects, along with the efficacy, of isradipine in two subgroups of patients with mild to moderate essential hypertension (EH), defined according to plasma renin activity (PRA). Twenty-six patients were randomly assigned to receive 12-week treatment with slow-release isradipine (2.5-5 mg) or placebo. Assessment of PRA related to concurrent 24-hour sodium excretion was used to define patients with high/medium (n=16) and low renin profile (n=10). Urinary albumin excretion (UAE), serum creatinine and glomerular filtration rate (GFR, as endogenous creatinine clearance) were measured. Blood pressure (BP) decrease with isradipine was greater in the low PRA group as compared with the high/medium PRA group (P<0.05), and normalization of BP was achieved in all low-renin patients compared with 57% in the high/medium PRA group. BP reduction in the placebo group was statistically not significant. Isradipine, but not placebo, induced significant reduction in UAE (P<0.05); the decrease was similar in both PRA groups. Treatment did not cause any significant changes in GFR, PRA, urinary sodium or creatinine excretion, or serum aldosterone or creatinine concentrations. The decrease of BP in the whole isradipine-treated group was inversely correlated with pretreatment serum creatinine as well as with basal urinary creatinine excretion. In conclusion, the antihypertensive effect of isradipine was more pronounced in low-renin EH patients, despite similar effects on renal function and UAE in both PRA groups.",1997.0,0,0
1071,9374947,Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring.,F H Leenen; T W Wilson; P Bolli; P Larochelle; M Myers; S P Handa; G Boileau; J Tanner,"To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure). Multicentre, nonblinded, parallel group randomized design. Nonacademic primary care practices across Canada. Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects. After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less. During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement. The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments. Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval.",1997.0,0,0
1072,9374948,Efficacy of a low dose nifedipine GITS (20 mg) in patients with mild to moderate hypertension.,C B Toal,"Nifedipine gastrointestinal therapeutic system (GITS) is a once-a-day formulation of nifedipine providing stable plasma concentrations over the entire 24 h dosing interval. The antihypertensive efficacy of a new 24 mg formulation was evaluated in 187 patients in 15 centres across the country. After a two-week placebo washout, mild to moderate hypertensive patients were randomized in a double-blind, parallel design to four weeks of placebo or nifedipine GITS 20 mg once daily treatment. Changes in office blood pressure (BP) were noted for each group. Ambulatory BP was also monitored at baseline and after four weeks of placebo/nifedipine therapy in a subgroup of 66 patients at five centres. After four weeks of treatment, office BP in the placebo group decreased by 5.0 +/- 11.9/5.4 +/- 7.9 mmHg compared with 9.3 +/- 11.2/8.6 +/- 7.4 mmHg in the nifedipine GITS group. Both systolic and diastolic BP were significantly decreased (P = 0.006 and P = 0.001 for systolic and diastolic, respectively) more with nifedipine GITS. Heart rate did not significantly differ between the groups at baseline nor after four weeks of treatment. The percentage of responders--defined as having a sitting diastolic BP less than 90 mmHg or a decrease from baseline of 10 mmHg--was 57% for nifedipine GITS versus 32% for placebo (P < 0.05). Daytime average diastolic blood pressure was 86.4 +/- 6.4 mmHg in the nifedipine GITS 20 mg group compared with 93.7 +/- 8.9 mmHg in the placebo group (P < 0.02). The maximum antihypertensive effect of nifedipine during ambulatory monitoring was similar to the reduction in BP observed in the office at the end of the dosing interval. The frequency of spontaneously reported adverse events was similar for nifedipine GITS (32.3%) and placebo (37.2%). These results indicate that 20 mg of nifedipine GITS is efficacious in decreasing BP, with good 24 h control and an incidence of adverse events similar to that of placebo-treated patients.",1997.0,0,0
1073,9380807,[Comparative study to assess the efficacy and adverse effects of amlodipine and nifedipine retard in patients with stable exertional angina and hypertension].,M Witkowska; W Tracz; G Kubler; M Negrusz-Kawecka; M Hlawaty; M Olszowska; P Salamon,"The purpose of the study was to compare the antianginal and hypotensive efficacy and tolerability of 8 weeks of treatment with amlodipine taken once daily and nifedipine taken twice daily in patients with stable exertional angina pectoris and mild-to-moderate hypertension. Following a 2-week placebo run-in-period 13 patients were randomized to receive amlodipine (5 to 10 mg once daily) and 8 patients to receive nifedipine (20 or 40 mg twice daily) in an 8-week treatment phase. Antianginal efficacy was assessed with angina diares, investigators, and patients global evaluations and with treadmill exercise test during placebo run-in-period and after 8 weeks of the therapy. Amlodipine significantly reduced both weekly anginal attacks and consumption of glyceryl trinitrate tablets. This effect was more pronounced compared to efficacy of nifedipine. Exercise tolerance was also improved more markedly after amlodipine than after nifedipine treatment. Amlodipine treatment resulted in significant increase in total exercise time, increase the exercise time to angina onset, increase time to ST segment depression, decrease in ST segment depression, decrease in total duration of ST segment depression and decrease in duration of pain. In patients treated with nifedipine only favourable effect was significant decrease in total duration of ST segment depression, without significant changes of other examined parameters. Both drugs decreased blood pressure with no significant change in heart rate. No serious adverse events occurred in any patients during therapy with amlodipine as well as with nifedipine. The results of the study demonstrate that amlodipine has markedly better anti-anginal efficacy than nifedipine with respect to the most of the parameters examined. However both drugs showed comparable antihypertensive action and both were well tolerated by angina patients. The good anti-anginal and hypotensive efficacy and safety of amiodipine with once daily dosage regimen makes this drug an excellent choice of treatment for hypertensive patients with severe coronary artery disease.",1998.0,0,0
1074,9383167,Reliable and unbiased assessment of the effects of calcium antagonists: importance of minimizing both systematic and random errors.,S MacMahon; R Collins; J Chalmers,,1997.0,0,0
1075,9383183,Main results of the losartan versus amlodipine (LOA) study on drug tolerability and psychological general well-being. LOA Study Group.,B Dahlöf; L H Lindholm; S Carney; P J Pentikäinen; J Ostergren,"To compare two losartan regimens (with and without hydrochlorothiazide) and amlodipine in treating mild-to-moderate hypertension regarding their blood-pressure-lowering effect, drug tolerability and quality of life. A 12-week, randomized, double-blind, parallel-group, multi-centre study. After 4 weeks of placebo, patients with a diastolic blood pressure (DBP) in the range 95-115 mmHg were allocated randomly to be administered 50 mg losartan (increased to 100 mg if the DBP was 90 mmHg or more after 6 weeks), 50 mg losartan (plus 12.5 mg hydrochlorothiazide under the above conditions), or 5 mg amlodipine (increased to 10 mg under the above condition). The tolerability of the treatment and the quality of life were evaluated by spontaneous reporting, active questioning and the Psychological General Well-Being (PGWB) index. In total 898 hypertensives, mainly referred from primary health care (mean age 57.8 years) of whom 52% were men. Administration of 50 mg losartan (plus 12.5 hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure as well as or better than did 50 mg losartan (or 100 mg if necessary). The incidence of 'any discomfort' and 'swollen ankles' increased with amlodipine but not with losartan treatment. The opposite was found for 'dizziness upon standing'. The incidence of drug-related adverse events and the number of patients withdrawn from therapy were higher with amlodipine than they were with losartan treatment. The PGWB index at week 12 indicated that improvements from baseline had occurred in some domains for the losartan groups whereas it remained unchanged for the amlodipine group. Both losartan and amlodipine were effective in lowering the blood pressure and were tolerated well. Administration of 50 mg losartan (plus 12.5 mg hydrochlorothiazide if necessary) and of 5 mg amlodipine (or 10 mg if necessary) lowered the blood pressure equally well or better than did 50 mg losartan (or 100 mg if necessary). Drug-related adverse effects and withdrawal from the study were more common for the amlodipine group. The clinical significance of the improvements in the PGWB index with losartan needs to be studied further.",1997.0,0,0
1076,9383184,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.",1997.0,0,1
1077,9385481,Nifedipine gastrointestinal therapeutic system (GITS) for hypertensive patients in a primary care setting: results of the Extended Release Adalat Canadian Trial (EXACT).,C B Toal; W A Mahon; C Barnes; D Burelle,"Nifedipine gastrointestinal therapeutic system (GITS) is an extended-release dosage formulation that provides sustained blood concentrations of nifedipine over 24 hours. A 20-week, postmarketing surveillance study of the effectiveness and patient tolerability of nifedipine GITS 30 or 60 mg was conducted in the offices of 187 Canadian general practitioners from September 1992 to March 1994. A total of 1700 patients previously or newly diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure, 95 to 114 mm Hg) were included. The 20-week treatment period was completed by 1326 patients. Patients received nifedipine GITS 30 mg initially; the dose could be titrated upward to 60 mg after 3 and 6 weeks. Of all patients entered, 605 (35.6%) reported one or more adverse events. The three most frequently occurring adverse events were headache (12.2%), peripheral edema (8.1%), and dizziness (2.9%). The frequency of adverse events was highest in the first 3 weeks and decreased subsequently. The overall incidence of adverse events was 29.8% in patients receiving 30 mg of nifedipine GITS and 25.3% in those receiving 60 mg; adverse events were the cause of study discontinuation in 12.3% of patients. The overall health status of patients as measured by the SF-36 questionnaire was comparable to that previously reported for healthy individuals. At baseline, mean (+/- SE) systolic/diastolic blood pressure values for all patients were 160.1 +/- 0.4/97.4 +/- 0.2 mm Hg. Final blood pressure readings after 20 weeks of treatment in the 30-mg group (141.5 +/- 0.4/84.8 +/- 0.2 mm Hg) and the 60-mg group (146.6 +/- 0.8/88.8 +/- 0.4 mm Hg) were significantly decreased from baseline. At week 20, the 30-mg dose was sufficient to maintain blood pressure in 74.5% of patients; 25.5% of patients required 60 mg. Subgroup analysis revealed similar responses in patients who had received blood pressure medication before study initiation and those who had not. Response was also independent of age and type of previous antihypertensive therapy. In general medical practice, the 30-mg and 60-mg doses of nifedipine GITS were both effective and well tolerated and had minimal or no negative effects on the overall health status of treated individuals.",1998.0,0,0
1078,9385483,Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem CD. Mibefradil Hypertension Study Group.,N Bittar,"This multicenter, double-masked, randomized, forced-titration, parallel-group trial was designed to determine whether we could confirm the results of a previous trial that demonstrated a significantly greater antihypertensive effect for mibefradil compared with diltiazem CD. Two hundred thirty-nine patients with uncomplicated mild-to-moderate essential hypertension and a baseline sitting diastolic blood pressure (SDBP) between 95 and 114 mm Hg were randomized to receive once-daily treatment with mibefradil 50 mg (n = 119) or diltiazem CD 180 mg (n = 120). After 4 weeks of treatment, all patients underwent forced titration to mibefradil 100 mg or diltiazem CD 360 mg for an additional 8 weeks. After 12 weeks of active treatment, the mean reduction from baseline in trough SDBP was significantly greater with mibefradil than with diltiazem CD (-14.3 +/- 6.6 mm Hg vs -11.7 +/- 7.4 mm Hg, respectively). In addition, significantly more patients receiving mibefradil had a decrease in SDBP > or = 10 mm Hg or a decrease to < or = 90 mm Hg by week 12 than did patients receiving diltiazem CD (82% vs 72%, respectively). The tolerability of mibefradil and diltiazem CD were comparable, with similar percentages of patients in both groups reporting at least one adverse event (21% vs 22%, respectively) that was considered to be at least remotely related to the study drug. The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 100 mg is significantly more effective than diltiazem CD 360 mg in lowering both diastolic and systolic blood pressure. Both drugs are well tolerated.",1998.0,0,1
1079,9388037,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
1080,9388047,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
1081,9395279,Cardiovascular prognosis in relation to apolipoproteins and other lipid parameters in patients with stable angina pectoris treated with verapamil or metoprolol: results from the Angina Prognosis Study in Stockholm (APSIS).,C Held; P Hjemdahl; N Rehnqvist; I Björkander; L Forslund; U Brodin; L Berglund; B Angelin,"Relationships between apolipoproteins and other lipid parameters and cardiovascular (CV) prognosis were evaluated in the Angina Prognosis Study In Stockholm (APSIS). Out of 809 patients with stable angina pectoris, lipid variables were obtained in 786 patients at baseline, and after one month's double-blind treatment with metoprolol or verapamil, to evaluate treatment effects on these lipid variables. During a median follow-up time of 3.3 years (2663 patient years), 37 patients suffered a CV death, 30 suffered a non-fatal myocardial infarction (MI) and 100 underwent a revascularization. Apolipoprotein (apo) A-I, high-density lipoprotein cholesterol and triglycerides were predictors of CV death or non-fatal MI in univariate analyses, but only apo A-I remained as an independent predictor in multivariate analyses. All lipid variables except low density lipoprotein cholesterol were related to the risk of revascularization in univariate analyses, but only apo A-I and apo B were independent predictors of such events. Triglycerides were weakly, but not independently, associated with prognosis. Verapamil and metoprolol had differential short-term effects on lipids, with a shift towards a more atherogenic profile in metoprolol treated patients. However, there was no significant impact of the treatment given, or of these treatment effects on the risk of CV events. Results of the present study suggest that apolipoprotein levels were better predictors of CV events than other lipid parameters in patients with stable angina pectoris.",1997.0,0,0
1082,9397125,Nifedipine and ritodrine in the management of preterm labor: a randomized multicenter trial.,R B Lewan; C A Flynn,,1997.0,0,0
1083,9397246,Comparison of amlodipine and long-acting diltiazem in the treatment of mild or moderate hypertension.,L D Horwitz; H D Weinberger; L Clegg,"The comparative effects of the once a day calcium channel antagonists amlodipine and long-acting diltiazem were assessed in a parallel design, investigator-blinded, multicenter trial in 123 patients with diastolic blood pressures ranging from 95 to 114 mm Hg before treatment. Patients were randomized to one of the two drugs and titrated at 2-week intervals to 5 or 10 mg of amlodipine or 180, 240, or 360 mg of long-acting diltiazem during a 10-week treatment period. Both drugs significantly reduced resting, sitting, standing, and 24-h ambulatory systolic and diastolic pressures. Amlodipine caused significantly greater reductions in sitting and standing systolic pressures, standing diastolic pressures, and 24-h ambulatory systolic and diastolic pressures versus diltiazem. Sitting systolic pressures were reduced from 151.9 +/- 2.0 (SE) at baseline to 137.9 +/- 1.8 mm Hg with amlodipine treatment and from 149.0 +/- 2.1 to 145.1 +/- 2.5 mm Hg with diltiazem. Sitting diastolic pressures were reduced from 100.2 +/- 0.6 to 87.8 +/- 1.0 mm Hg with amlodipine and from 101.1 +/- 1.0 to 91.9 +/- 1.1 mm Hg with diltiazem. Reductions in standing systolic pressures after treatment were -12.1 +/- 1.5 mm Hg amlodipine v -4.6 +/- 1.5 mm Hg diltiazem (P < .01), and reductions in standing diastolic pressures were -11.8 +/- 0.9 mm Hg amlodipine v -8.6 +/- 0.9 mm Hg diltiazem (P < .02). Heart rates did not change significantly with either drug during the study. Two subjects in each group dropped out because of adverse experiences. Although both agents were well tolerated and reduced blood pressures consistently over the 10-week test period, amlodipine was more effective than diltiazem in reducing systolic and diastolic blood pressures to the target pressures of < 140 mm Hg systolic and < 90 mm Hg diastolic over a range of doses widely used in clinical practice.",1997.0,0,0
1084,9397292,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
1085,9398099,Effects of amlodipine in patients with chronic heart failure.,J T Walsh; R Andrews; S Curtis; A Evans; A J Cowley,"The role of calcium antagonists in patients with ischemic heart failure is currently unclear. We examined the effects of amlodipine on exercise capacity and central and regional hemodynamics in 32 patients with mild to moderate chronic heart failure in a single-center, double-blind, randomized placebo-controlled trial. All were taking at least 40 mg of furosemide daily with an angiotensin-converting enzyme inhibitor. Ischemic heart disease was the most common cause of heart failure, but no patient had symptom-limiting angina. Mean treadmill exercise capacity in patients taking amlodipine increased by 96 seconds (95% confidence interval -23 to 215) and 50 seconds (-34 to 135) in the placebo group; mean difference in change between treatments was 70 seconds (-90 to 233), p = 0.38. Active treatment with amlodipine did not affect self-paced corridor walking times. Similarly, there were no significant effects on cardiac output, oxygen uptake, heart rate, and mean arterial pressure at rest or during exercise. Calf and renal blood flow were also unchanged by treatment. The lack of significant effect demonstrated by these data suggests a limited role for amlodipine in patients with ischemic cardiomyopathy, although it may prove beneficial in those with nonischemic disease. More data are required before amlodipine can be recommended for all patients with chronic heart failure.",1997.0,0,0
1086,9399603,"A systematic review and meta-analysis of the incidence of cancer in randomized, controlled trials of verapamil.",E W Dong; J E Connelly; S P Borden; W Yorzyk; D G Passov; B Kupelnick; D Luo; S D Ross,"We conducted a systematic review of all published randomized, controlled trials to assess the risk of cancer or death in patients receiving verapamil for hypertension, angina pectoris, or cardiac arrhythmias. Meta-analysis comparing the risk of new cancers, cancer deaths, and all deaths was performed. Thirty-nine trials comprising 11,201 patients were eligible. Study durations ranged from 8 days-6 years (mean 29.5 wks). Nine trials (6507 patients) were 24 weeks in duration or longer. For cancer and cancer death, OR was 1.20 (95% CI = 0.60-2.42) for verapamil versus active controls and 0.73 (95% CI = 0.39-1.39) for verapamil versus placebo. For all deaths, OR was 1.13 (95% CI = 0.70-1.82) for verapamil versus active controls and 0.85 (95% CI = 0.71-1.00) for verapamil versus placebo. Sensitivity analysis for the 9 trials 24 weeks' duration or longer gave similar results. There is no statistically significant increased risk of cancer or deaths with verapamil compared with active controls or placebo.",1997.0,0,0
1087,9399606,Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial fibrillation and atrial flutter.,B G Phillips; A J Gandhi; C A Sanoski; V L Just; J L Bauman,"To compare the efficacy and safety of intravenous diltiazem and verapamil in controlling ventricular rate in patients with atrial fibrillation or flutter, and to evaluate the effects of these agents on left ventricular systolic function. Prospective, randomized, double-blind, crossover study. University-affiliated hospital and Veterans Administration hospital. Seventeen men with atrial fibrillation or flutter with a ventricular rate of 120 beats/minute or higher and a systolic blood pressure of 100 mm Hg or greater. Patients received up to two intravenous boluses of either diltiazem or verapamil, followed by an 8-hour continuous infusion if a therapeutic response was achieved (phase I). After a washout period, patients who responded were crossed over to receive the other drug in a similar fashion (phase II). At the end of each infusion, the patient's ejection fraction was assessed by gated angiography. Of the 17 men initially randomized, 8 successfully completed both phases I and II. In these patients, baseline mean (+/- SD) ventricular rates before treatment with intravenous diltiazem and verapamil were 138 +/- 15 and 132 +/- 9 beats/minute, respectively (NS). At 2 minutes after the initial bolus dose, the mean ventricular rate decreased to 100 +/- 13 beats/minute in the diltiazem group compared with 114 +/- 17 beats/minute in those receiving verapamil (p < 0.05). Mean ventricular rates of 96 +/- 11 and 97 +/- 9 beats/minute were maintained during the 8-hour continuous infusion of diltiazem and verapamil, respectively (NS). On completion of the bolus dose(s) and during continuous infusions, there were no significant differences in blood pressures between the groups. Mean ejection fractions were 35.6 +/- 13.6% and 35.5 +/- 15.4% in the diltiazem and verapamil groups, respectively (NS). For the 17 patients, the mean maximum percentage decreases in blood pressure were not significantly different between groups. However, three patients developed symptomatic hypotension, all of whom were randomized to receive verapamil initially. Intravenous diltiazem and verapamil are comparable in terms of efficacy and effect on systolic function in patients with rapid atrial fibrillation and flutter. However, hypotension may limit therapy with verapamil in some patients.",1997.0,0,0
1088,9399608,,,,,0,0
1089,9399710,"Prognostic significance of myocardial ischemia detected by ambulatory electrocardiography, exercise treadmill testing, and electrocardiogram at rest to predict cardiac events by one year (the Asymptomatic Cardiac Ischemia Pilot [ACIP] study)",P H Stone; B R Chaitman; S Forman; T C Andrews; V Bittner; M G Bourassa; R F Davies; J E Deanfield; W Frishman; A D Goldberg; G MacCallum; P Ouyang; C J Pepine; C M Pratt; B Sharaf; R Steingart; G L Knatterud; G Sopko; C R Conti,"Myocardial ischemia identified by ambulatory electrocardiography (AECG), exercising treadmill testing, (ETT), or 12-lead electrocardiogram at rest is associated with an adverse prognosis, but the effect of improving these ischemic manifestations by treatment on outcome is unknown. The Asymptomatic Cardiac Ischemia Pilot (ACIP) study was a National Heart, Lung, and Blood Institute funded study to determine the feasibility of conducting a large-scale prognosis study and to assess the effect of 3 treatment strategies (angina-guided strategy, AECG ischemia-guided strategy, and revascularization strategy) in reducing the manifestations of ischemia as indicated by AECG and ETT. The study cohort for this database study consisted of 496 randomized patients who performed the AECG, ETT, and 12-lead electrocardiogram at rest at both the qualifying and week 12 visits. The effect of modifying ischemia by treatment on the incidence of cardiac events (death, myocardial infarction, coronary revascularization procedure, or hospitalization for an ischemic event) at 1 year was examined. In the 2 medical treatment groups (n = 328) there was an association between the number of ambulatory electrocardiographic ischemic episodes at the qualifying visit and combined cardiac events at 1 year (p = 0.003). In the AECG ischemia-guided patients there was a trend associating greater reduction in the number of ambulatory electrocardiographic ischemia episodes with a reduced incidence of combined cardiac events (r = -0.15, p = 0.06). In the revascularization strategy patients this association was absent. In the medical treatment patients the exercise duration on the baseline ETT was inversely associated with an adverse prognosis (p = 0.02). The medical treatment strategies only slightly improved the exercise time and the exercise duration remained of prognostic significance. In the revascularization group strategy patients this association was absent. Thus, myocardial ischemia detected by AECG and an abnormal ETT are each independently associated with an adverse cardiac outcome in patients subsequently treated medically.",1997.0,0,1
1090,9402450,"Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade. Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study. Working Group on Cardiovascular Research, The Netherlands (WCN).",P Dunselman; A H Liem; G Verdel; H Kragten; A Bosma; P Bernink,"The study aimed to compare the addition of felodipine to metoprolol, and of the replacement of metoprolol by felodipine, with continuation of metoprolol, in patients with angina pectoris despite optimal beta-blockade. The study was double-blind, parallel, randomized and controlled, and comprised 363 patients from 27 outpatient cardiology clinics in the Netherlands. The patients had angina and positive bicycle exercise tests despite optimal beta-blockade (resting heart rate < 65 beats.min-1). Randomization was to three treatment groups: continuation of metoprolol (control), addition of felodipine to metoprolol, and replacement of metoprolol by felodipine. Exercise tests were repeated after 2 and 5 weeks. The main outcome measure was: exercise result after 5 weeks, compared with baseline, between-group comparison of changes vs control. There were no significant differences in exercise duration and onset of chest pain vs control. The addition of felodipine increased time until 1 mm ST depression (43 s, 95% confidence interval 20-65 s), and decreased both ST depression at highest comparable work load (0.46 mm, 95% confidence interval 0.19-0.72), and maximal ST depression (0.49 mm, 95% confidence interval 0.23-0.74). Exercise results after replacement of metoprolol by felodipine were not different from control, apart from a significant increase in rate pressure product. Significantly more patients experienced adverse events in the felodipine monotherapy group. Combination of metoprolol and felodipine is to be preferred to felodipine monotherapy in patients who have signs and symptoms of myocardial ischaemia despite optimal beta-blockade.",1997.0,0,1
1091,9403278,"Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine in elderly patients with mild to moderate hypertension: a randomized, double-blind, cross-over study.",D Bonaduce; V Canonico; M Petretta; L Forgione; A Ianniciello; V Cavallaro; F Bertocchi; F Rengo,"This double-blind, placebo-controlled randomized study was designed to compare the antihypertensive effect and tolerability of extended-release felodipine and slow-release nifedipine retard in elderly hypertensive patients. Thirty patients of both sexes (mean age 71 years) with mild to moderate essential hypertension were recruited from our hypertension outpatient clinic. After a 2-week placebo period, felodipine extended-release (felodipine ER), 10 mg once daily, nifedipine slow-release retard (nifedipine SR), 20 mg twice daily or placebo were administered to each patient for 2 weeks according to a 3 x 3 latin-square design. At the end of each treatment period, the patients underwent 24-h noninvasive blood pressure monitoring. All of the patients completed the trial and no serious adverse experience was reported. In comparison with placebo, felodipine and nifedipine decreased mean 24-h diastolic blood pressure by 6.7 and 4.3 mmHg, respectively, with no significant difference between the two drugs. Mean 24-h systolic blood pressure also decreased after felodipine and nifedipine, with no difference between the two drugs. Both drugs reduced blood pressure variability, lowering the 24-h mean standard deviation of mean hourly blood pressure values. The trough:peak ratio for felodipine was 80% for systolic and 75% for diastolic blood pressure. Felodipine ER once daily lowers blood pressure in elderly hypertensives and is as effective as nifedipine SR twice daily. The high trough:peak ratio suggests that the dose and the between-dose interval of felodipine provides adequate therapeutic coverage.",1997.0,0,0
1092,9403280,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
1093,9404250,Combination treatment with trimetazidine and diltiazem in stable angina pectoris.,S C Manchanda; S Krishnaswami,"To assess antianginal efficacy and possible adverse haemodynamic effects of combination treatment with trimetazidine and diltiazem in patients with stable angina. Double blind, randomised, placebo controlled trial of four weeks duration. Outpatient department of two Indian hospitals. 64 male patients with stable angina, uncontrolled on diltiazem alone. Diltiazem 180 mg and trimetazidine 60 mg, or diltiazem 180 mg and placebo daily. Change in exercise time to 1 mm ST segment depression. 33 patients (55%) had no exercise induced angina at 3 mm ST segment depression at inclusion in the study (silent ischaemia). Intention to treat analysis showed that of 32 patients in each treatment group, the number (%) of patients responding to trimetazidine compared to placebo was: for anginal attacks, 28 (87.5) v 15 (46.9), p < 0.001; for exercise time to 1 mm ST segment depression, 21 (65.6) v 9 (28.1), p < 0.003; for exercise time to angina, 12 (37.5) v 5 (15.6), p < 0.05; and for maximum work at peak exercise, 17 (53.1) v 8 (25), p < 0.02. Compared to placebo, there was net improvement with trimetazidine in mean anginal attacks of 4.8/ week (95% confidence interval (CI) 7.5 to 2.1; p < 0.002); in mean exercise times at 1 mm ST segment depression of 94.2 seconds (95% CI 182.8 to 5.6; p < 0.05), and at onset of angina of 113.1 seconds (95% CI 181.6 to 44.6; p < 0.02); and in mean maximum work at peak exercise of 1.4 metabolic equivalents (95% CI 2.4 to 0.3; p < 0.05). Patients with stable angina uncontrolled with diltiazem had a clinically important improvement after combination treatment with trimetazidine, without adverse haemodynamic events or increased side effects.",1997.0,0,1
1094,9404429,,,,,0,0
1095,9416985,Risk of serious adverse events in hypertensive patients receiving isradipine: a meta-analysis.,S D Ross; B Kupelnick; M Kumashiro; F M Arellano; N Mohanty; I E Allen,"A meta-analysis was performed to compare the risk of serious adverse events associated with the use of all formulations of isradipine, when used as monotherapy in hypertension, to active drug or placebo controls. Eligible studies totalled 65 published and unpublished randomised controlled trials involving 9903 subjects and 10,675 treatment exposures: 4492 to isradipine, 1473 to isradipine sustained release, 2768 to other active drugs, and 1942 to placebo. Mortality, cardiovascular outcomes, other serious incident illnesses, such as cancer, and withdrawals were sought. Seventy-five per cent of the isradipine exposures were to standard-release formulations and 25% were to sustained-release formulations. Overall, isradipine therapy shows no difference in risk of major adverse events or withdrawals compared to other active controls or placebo (odds ratios [OR] 0.9; 95% CI 0.7-1.46 and 0.5; 95% CI 0.2-1.3). These major adverse events included angina, fatal and non-fatal myocardial infarction, stroke and overall mortality. Isradipine sustained release could be compared only to placebo, based on available data, and shows a lower risk of withdrawals (OR 0.5; 95% CI 0.3-0.9), and a similar trend was observed for major adverse events, (OR 0.8; 95% CI 0.3-2.5). Published and unpublished randomised controlled trials were analysed in separate meta-analyses and later combined when this sensitivity analysis of risk showed no differences between the groups. In conclusion, we find no evidence for increased risk of serious adverse events in patients receiving isradipine as monotherapy for hypertension.",1998.0,1,1
1096,9431857,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
1097,9437338,Comparison of treatment of supraventricular tachycardia by Valsalva maneuver and carotid sinus massage.,S H Lim; V Anantharaman; W S Teo; P P Goh; A T Tan,"To compare the efficacy of the Valsalva maneuver with that of carotid sinus massage (CSM) in terminating paroxysmal supraventricular tachycardia (SVT) in the ED. This prospective, randomized case study was performed in the ED of a tertiary care institution. Patients were at least 10 years of age with regular narrow complex tachycardia and had an ECG diagnosis of SVT. Patients with regular narrow complex tachycardia were randomly assigned to undergo either the Valsalva maneuver or CSM. If the tachycardia was not terminated by the method chosen by randomization, then the alternative method of vagal maneuver was used. If the tachycardia was not converted by both methods of vagal stimulation, patients would undergo either synchronized electrical cardioversion or a pharmacologic method of conversion at the discretion of the treating physician, depending on the patient's hemodynamic status. One hundred forty-eight instances of SVT were studied Sixty-two patients underwent Valsalva maneuver first with conversion in 12 (success rate of 19.4%). Eighty-six underwent CSM first with conversion in 9 (success rate 10.5%). Carotid sinus massage was used in the 50 cases of SVT in which conversion was not achieved with the Valsalva maneuver. Conversion occurred in 7 cases (success rate 14.0%). For the 77 cases of SVT in which initial CSM did not achieve conversion, conversion occurred in 13 with the Valsalva maneuver (success rate 16.9%). The Valsalva maneuver and CSM achieved conversion in a total of 41 instances of SVT (success rate 27.7%). Vagal maneuvers are efficacious in terminating about one quarter of spontaneous SVT cases. There is no detectable difference in efficacy between the Valsalva maneuver and CSM.",1998.0,0,0
1098,9440098,Malignant hypertension and hypertensive emergencies.,C Kitiyakara; N J Guzman,"Hypertensive emergencies and urgencies are important causes of morbidity and mortality. Malignant hypertension is a hypertensive urgency characterized by grade III/IV retinopathy and widespread endothelial damage. Control of BP is essential in the treatment of these disorders. The effects of hypertension on target organ function need to be balanced against the risks of excessive BP lowering. In hypertensive emergencies, BP should be lowered within minutes with parenteral agents to prevent critical end-organ damage. In hypertensive urgencies, BP can be lowered more slowly over several hours, often with oral agents, to avoid a detrimental fall in BP. The absolute indications for treatment and the optimal therapy depend on the underlying condition.",1998.0,0,0
1099,9444446,"Comparative efficacy and tolerability of two long-acting calcium antagonists, mibefradil and amlodipine, in essential hypertension. Mibefradil Hypertension Study Group.",F E Karch; R Pordy; J R Benz; A Carr; N M Lunde; T Marbury; J N Tarro,"In a previous forced-titration trial, mibefradil 100 mg QD was as effective as amlodipine 10 mg QD in reducing sitting diastolic blood pressure (SDBP), and it produced significantly less leg edema than did amlodipine 10 mg QD. The present multicenter, double-masked, randomized, parallel-design trial was performed to assess the reproducibility of these results using a flexible-titration design. Following a 4-week, single-masked, placebo run-in period, 296 patients with a trough SDBP of between 95 and 114 mm Hg (21 to 27 hours postdose) were randomized to receive once-daily treatment with mibefradil 50 mg (n = 146) or amlodipine 5 mg (n = 150). In patients whose trough SDBP was greater than 90 mm Hg after 4 or 8 weeks of double-masked therapy, the dosage was titrated upward to mibefradil 100 mg or amlodipine 10 mg for the remainder of the 12-week active treatment period. A greater proportion of amlodipine-treated patients (65%) than of mibefradil-treated patients (54%) required titration to the higher dose. Despite this difference, statistically equivalent reductions in trough SDBP were observed after 12 weeks of treatment with 50 to 100 mg of mibefradil QD (-11.7 +/- 6.4 mm Hg) and 5 to 10 mg of amlodipine QD (-11.9 +/- 6.9 mm Hg). SDBP was normalized to < or = 90 mm Hg at week 12 in 66% of patients treated with mibefradil and 65% of those receiving amlodipine. The tolerability profile of mibefradil was superior to that of amlodipine, with significantly fewer patients (P = 0.009) reporting leg edema after mibefradil treatment (7%) than after amlodipine treatment (17%). The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 50 to 100 mg for 12 weeks was as effective as 12 weeks of once-daily treatment with amlodipine 5 to 10 mg in reducing SDBP and was associated with a significantly lower incidence of leg edema.",1998.0,0,0
1100,9446006,[Effect of diltiazem on concentration of cyclosporin metabolites in Sandimmune and Neoral treated kidney transplant patients].,H Sperschneider; C Wagner; A Korn; U Christians,"Diltiazem reduces the cyclosporine dose required for blood levels in the therapeutic target range by 30 to 40%. The effect of diltiazem on the pharmacokinetic disposition of cyclosporine after oral Neoral application is unknown and it is unclear whether or not the diltiazem-cyclosporine interaction is affected by the galenic cyclosporine formulation. Fifty-one stable renal allograft patients (19 females, 32 males) were enrolled in this prospective, randomized and double-blind study. The patients were assigned to 3 treatment groups: with diltiazem (I, n = 17), with nifedipine (II, n = 17) and without calcium channel blockers (III, n = 17). Nine patients in each group received Sandimmun and 8 patients Neoral. Blood concentrations of cyclosporine and its metabolites AM1 and AM9 were measured using HPLC for 12 weeks. The 3 treatment groups were not different in respect to age, gender distribution and serum creatinine concentration. Cyclosporine doses were adjusted on basis of the blood levels. The cyclosporine doses required to achieve target blood levels were significantly lower in group I compared with group II (-43%) and group III (-33%; p < 0.0001). Although the cyclosporine blood concentrations in all groups were in the therapeutic range, the blood levels in group I showed a much lower variability. The blood concentrations of the metabolite AM1 in group I were significantly higher than those in groups II and III after dose correction (p < 0.0001), those of AM9 were significantly lower in group I than in groups II and III (p < 0.0001). The average dose, and the blood concentration of cyclosporine was not different when patients receiving Neoral were compared with those receiving Sandimmun within the groups. In the patients in group I, the blood concentration of metabolite AM1 was significantly higher after Sandimmun application than after Neoral. No other differences in the metabolite concentrations were detected within the groups comparing patients taking Sandimmun or Neoral. The incidences of acute rejection were lower in group I (17.6%) than in the other groups (II: 52.9%; III: 41%). Diltiazem significantly reduced the necessary dose of cyclosporine. Compared with groups II and III, the blood concentrations were more stable in patients in group I. Diltiazem increased the blood concentration of AM1 in patients treated with Sandimmun to a larger extent than in patients taking Neoral. No additional pharmacokinetic differences of the 2 cyclosporine applications different with Sandimmun or Neoral were found.",2000.0,0,0
1101,9456291,Nifedipine-retard versus nifedipine-capsules for the therapy of hypertensive crisis in black patients.,A Damasceno; E Sevene; S Patel; J Polónia,"In a randomized parallel-group placebo-controlled study, we compared the short-term hypotensive efficacy and the safety of a single administration of nifedipine-retard (20-mg tablets) with that of two administrations 6 h apart of nifedipine capsules (10 mg) in 10 and 11 black patients, respectively, with acute severe hypertension. Both groups had similar pretreatment blood-pressure (BP) values. Blood pressure was recorded at 10-min intervals for 12 h by using an automated device. In the first 3 h of treatment, nifedipine capsules induced a faster and greater hypotensive effect than nifedipine retard, which was associated with an increase in heart rate. At 2 h after treatment, nifedipine capsules decreased BP to levels (159 +/- 5/105 +/- 3 mm Hg) that were significantly lower than those reached by nifedipine-retard (175 +/- 4/118 +/- 4 mm Hg; p < 0.05). Both preparations induced a similar maximal BP decrease of approximately 30% of the placebo values, but the peak decrease of BP occurred significantly later with nifedipine-retard (283 +/- 31 min after administration) than with nifedipine capsules (100 +/- 14 min; p < 0.01). Four hours after administration, the hypotensive effect of nifedipine capsules was blunted, and a second administration was necessary, whereas nifedipine-retard reduced BP slowly and continuously for < or =12 h and more smoothly. Flush and headache were more frequently found with nifedipine capsules. We conclude that in black patients with hypertensive crisis, nifedipine capsules produce an abrupt decrease in BP that may be potentially harmful. Thus for patients suitable for treatment with nifedipine, nifedipine-retard is preferable because it effectively reduces BP for > or =12 h while achieving a rapid enough effect without critical short-term decreases in BP.",1998.0,0,0
1102,9466084,Calcium antagonists and cancer. Is there really a link?,L G Howes; C T Edwards,Recent publications have raised concerns about a possible link between calcium antagonist therapy and the development of cancer. Comparisons of the methodology and results of these studies with other studies where an association between calcium antagonist therapy and cancer has not been apparent suggests that the association is most likely to be due to selection bias or chance. Clinical and biochemical studies have not produced a consistent plausible mechanism for a causative link between calcium antagonists and the development of cancer. Further prospective data that will be available from long-term morbidity and mortality trials of the use of calcium antagonists in cardiovascular diseases will be of value in establishing the safety of these drugs.,1998.0,0,0
1103,9468004,Pro-haemorrhagic effects of calcium antagonists: a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects.,A Smith; J McPherson; M Taylor; A Mason; S Carney; A Gillies,"It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatous effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointestinal bleeding. We identified 43 subjects from general practice with uncomplicated mild to moderate hypertension to compare the effects of the calcium antagonist isradipine with that of the beta-blocker atenolol on platelet function, plasma beta-thromboglobulin levels, fibrinolysis, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenolol produced comparable and clinically significant falls in blood pressure (167 +/- 2/102 +/- 1 to 153 +/- 3/91 +/- 2 mm Hg, and 165 +/- 2/101 +/- 1 to 156 +/- 4/91 +/- 2 mm Hg, respectively), neither drug produced a detectable effect on ex vivo platelet aggregation, platelet retention, or thromboxane generation with adrenaline, collagen, adenosine-di-phosphate, or platelet activating factor. However a decrease in plasma beta-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine but not the atenolol group. A 39% reduction with isradipine compared with 34% following atenolol treatment. Euglobulin clot lysis time was not altered by either drug. Serum cholesterol concentrations were also unaltered by drug treatment. Therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function after several weeks of treatment. However, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.",1998.0,0,0
1104,9468459,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
1105,9469785,"Effects of calcium antagonists on the risks of coronary heart disease, cancer and bleeding. Ad Hoc Subcommittee of the Liaison Committee of the World Health Organisation and the International Society of Hypertension.",,,1998.0,0,1
1106,9482129,Treatment of diastolic dysfunction in hypertensive patients without left ventricular hypertrophy.,E Molinero; N Murga; J D Sagastagoitia; R Fernández; J Garrido,"The aim of this study was to evaluate the influence of verapamil SR 240 mg (V) and the combination amiloride 5 mg + hydrochlorothiazide 50 mg (AH) on diastolic dysfunction of hypertensive patients without left ventricular hypertrophy (LVH). Twenty-six hypertensive patients with diastolic dysfunction, normal systolic function and without LVH were included into a 2-week washout period and then randomised to a 6-month V or AH treatment. One blinded-to-treatment echocardiographist at baseline and at weeks 4, 12 and 24 assessed Doppler-echocardiography. Both V and AH, satisfactorily controlled blood pressure, but only V improved diastolic function shown by a tendency to reduce peak A and to increase peak E/A ratio, and by a significant reduction in deceleration time. After 24 weeks, V significantly reduced wall thickness in comparison with AH. These results need to be confirmed in a larger scale study.",1998.0,0,0
1107,9482142,Antianginal efficacy over 24 hours and exercise hemodynamic effects of once daily sustained-release 300 mg diltiazem and 240 mg verapamil in stable angina pectoris.,M L De Rosa; A Giordano; M Melfi; D Della Guardia; F Ciaburri; F Rengo,"The antianginal efficacy of 240 mg sustained release verapamil once daily doses and 300 mg diltiazem was studied in 20 normotensive patients with chronic stable angina pectoris, using a randomized, double-blind crossover design. Patients received a blinded therapy of verapamil placebo and diltiazem placebo for six weeks than only sustained-release diltiazem (SRD) for a long-term phase of three weeks, after a two-week placebo baseline period. Symptom-limited bicycle exercise was longer with the verapamil (510+/-129.9 s) and diltiazem (540+/-124.6 s) than with placebo at baseline (396+/-152.2 s, P<0.005). Verapamil and diltiazem reduced the weekly rate of anginal attacks from 5.1+/-8.6 during placebo to 4.4+/-4.1 with verapamil and 1.9+/-3.2 with diltiazem (P<0.05). The antianginal effects of the two agents are probably mediated by reduction of myocardial oxygen demand at submaximal exercise. In addition, diltiazem appears to provide more symptomatic relief and reduces the weekly number of anginal attacks significantly more than verapamil. Therefore its once-daily administration simplifies the treatment schedule and should improve patients' compliance.",1998.0,0,1
1108,9485131,"Comparison of effects of controlled onset extended release verapamil at bedtime and nifedipine gastrointestinal therapeutic system on arising on early morning blood pressure, heart rate, and the heart rate-blood pressure product.",W B White; H R Black; M A Weber; W J Elliott; B Bryzinski; T D Fakouhi,"We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.",1998.0,0,0
1109,9486993,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.",1998.0,1,1
1110,9488243,,,,,0,0
1111,9489083,Comparative efficacy and tolerability of nisoldipine coat core and hydrochlorothiazide in mild-to-moderate hypertension.,J G Fodor,"This study compared the efficacy and tolerability of nisoldipine coat core (CC) 10-40 mg o.d. and hydrochlorothiazide (HCTZ) 25-50 mg o.d. Patients with mild-to-moderate essential hypertension received either nisoldipine CC 10 mg o.d. or HCTZ 25 mg o.d. Treatment was titrated at two-weekly intervals as necessary. The primary efficacy endpoint was a defined reduction in diastolic blood pressure (DBP). Response rates were similar for both the nisoldipine CC- and HCTZ-treated groups (74% and 70%, respectively). Secondary efficacy endpoints were reductions in both diastolic and systolic blood pressures (SBP). At treatment endpoint, the change from baseline in SBP was 16.2 mmHg for the nisoldipine CC group and 14.9 mmHg for the HCTZ group. Both drugs were well tolerated, and adverse events were generally minor and typical of these antihypertensive agents. Drug-related adverse events were greater in the nisoldipine CC- than the HCTZ-treated patients (50% and 37%, respectively). Nisoldipine CC was shown to demonstrate antihypertensive efficacy similar to HCTZ in the treatment of mild-to-moderate hypertension.",1998.0,0,0
1112,9501678,[Controversy about using calcium antagonists for treatment of coronary disease and hypertension].,J Głuszek; K Pawlaczyk-Gabriel,"Calcium antagonists are widely used in therapy of hypertension and angina pectoris. Their advantage is good efficacy, relatively few and not dangerous side effects and first of all lack of bad metabolic effects (hypokalemia, hyperuricemia, hyperinsulinemia and hyperlipoproteinemia). In contrast to beta-blockers and diuretics, which decline mortality from myocardial infarctions and strokes there are not similar information concerning calcium antagonists. Two meta-analysis from 1995 unexpectedly suggest, that some preparations of calcium antagonists increase mortality from myocardial infarctions and strokes. In our paper we discuss possible pathogenetic (harmful) mechanisms, pay attention to each class of calcium antagonists and time of action of the particular drugs. Short acting nifedipine formulation should be withdrawn from chronic hypertension and angina pectoris therapy. Ongoing multicenter trials in several European countries and in USA will decide the usefulness of other calcium antagonists preparations.",1998.0,0,0
1113,9504446,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
1114,9504453,Effects of chronic exercise on blood pressure in Dahl salt-sensitive rats.,J M Overton; J M VanNess; H J Takata,"We tested the hypothesis that daily exercise would reduce directly measured arterial blood pressure (BP) and sympathetic nervous system support of BP in conscious, unrestrained, female Dahl salt-sensitive rats consuming 4.0% NaCl. Dahl S/Jr inbred rats were assigned to daily exercise (EX) or sedentary (SED) treatment conditions (n = 12/group) at 4 weeks of age. Rats in the EX group were housed in cages with attached running wheels. After 5 weeks of exercise, rats were running 10.3 +/- 1.7 km/day. After at least 5 wks of treatment, all rats in both groups were placed on a 4.0% NaCl diet for 2 weeks to produce sodium-induced hypertension. Rats continued to either exercise daily or remain sedentary for an additional 2 weeks while consuming the high sodium diet. Carotid and jugular catheters were then implanted for measurements in conscious, resting, unrestrained rats on two separate days. Daily wheel running exercise for 7 to 9 weeks did not alter BP or HR in Dahl S/Jr rats consuming a 4.0% NaCl diet. However, acute arterial depressor responses to ganglionic blockade were less in EX rats. Furthermore, greater alpha-adrenergic (phenylephrine-induced) pressor responses were observed in the EX group while under ganglionic blockade. The findings suggest that overall resting sympathetic neural activity or cardiac beta-adrenergic responsiveness to sympathetic activity is reduced in this model of hypertension by daily wheel running exercise.",1998.0,0,0
1115,9506192,Use of calcium channel blockers in hypertension.,P R Conlin; G H Williams,"During the past 20 years the number of subclasses of calcium channel blockers has increased from one to four. Three classes have only a single clinically approved compound: verapamil, diltiazem, and mibefradil. The fourth class, dihydropyridines, contains numerous compounds. All agents are effective in lowering blood pressure in short-term studies, and side effects that trouble the patient are infrequent. Long-term studies in hypertensive patients are limited. Short-acting agents such as nifedipine have been associated with an increased cardiovascular risk in some, but not all studies. These agents also probably create a compliance problem for hypertensive patients because of the need for multiple daily doses and their unpleasant side effects, e.g., ankle edema, palpitations, and flushing. Therefore, they are not useful or indicated for the treatment of hypertensive patients. No data have suggested that long-acting dihydropyridines or nondihydropyridine calcium channel blockers share the same fate. Indeed, several lines of evidence suggest the opposite: they have a cardioprotective effect. However, definitive information will require the completion of several long-term trials, including ALLHAT, CONVINCE, HOT, INSIGHT and NORDIL. Finally, it is important to reflect on the lessons learned from the controversy associated with the potential risks of calcium channel blockers. First, disagreements are common when one uses case-controlled studies and are reflective of the poor precision of the methods used. What is statistically relevant in one study may not hold true for another and may have no clinical relevance, particularly if the relative risk is less than 2. Investigators need to temper their enthusiasm to reflect this reality. Second, at the cutting edge of science there is probably relatively little agreement about what is correct among equally competent scientists. All have bias in their positions and should both recognize and admit so to themselves and their colleagues. Inferring that those who disagree have an unstated secondary agenda that will bring personal financial rewards or government accolades is inappropriate and counterproductive. Third, the randomized clinical trial, despite all its imperfections, is still the best tool to establish common ground on controversial issues. Finally, what may seem best from the public health perspective may not be in the best interest of the individual patient--a possibility that physicians have to constantly consider. For example, no public health benefit occurs if patients remain hypertensive because they fail to take their medications, no matter what the medication.",1998.0,0,1
1116,9507787,Evaluation of enalapril combined with diltiazem ER in patients with stage 3-4 essential hypertension.,H Gavras; S G Chrysant; A L Niederman; T C Marbury; R Goldstein; E Conradi,"Enalapril combined with an extended-release formulation of diltiazem was evaluated in a 12-week multicenter trial of 112 patients with Stages 3-4 essential hypertension. Patients were randomized to once daily therapy with enalapril 5 mg plus diltiazem ER 120 mg or 180 mg. Dosages could be titrated and other antihypertensive agents added for blood pressure control. Efficacy was assessed with sitting blood pressures at trough (24 hours postdose). Overall, there was a decrease of -21.7/-18.4 mmHg. Patients responding to enalapril/diltiazem ER alone had a reduction of -15.0/-16.3 mmHg. Of all patients, 70% achieved a trough sitting diastolic blood pressure of < 95 mmHg. Common drug-related adverse experiences were headache, dizziness, rash, and asthenia/fatigue. This once daily fixed-combination of enalapril/diltiazem ER was generally well tolerated and effective when given alone or with other antihypertensives in Stage 3-4 hypertension.",1998.0,0,0
1117,9519505,Nifedipine GITS versus diltiazem in chronic stable angina: a randomised multicentre study.,L Zanolla; L Franceschini; L Rossi; M Ochan; S Amigoni; P Zardini,"In order to compare the efficacy of nifedipine gastrointestinal therapeutic system (GITS) with diltiazem, 99 patients with chronic stable angina were studied in a parallel-group randomised trial. According to the results of the two exercise tolerance tests (ETTs) performed during the placebo run-in, patients were divided into a fixed threshold group if the variability in time to 1 mm ST-segment depression was 20%, or a variable threshold group if it was higher. Efficacy was assessed by comparing the time to 1 mm ST-depression on a bicycle ETT after 4 weeks of treatment, adjusting for the baseline value. The adjusted means were 7.44 min for nifedipine GITS and 7.68 min for diltiazem; the difference was -0.24 min, with a lower 90% confidence limit of -0.90, which is within the stated interval for equivalence. The same result was confirmed by the 'intention-to-treat' analysis, and comparable results were obtained both in fixed and in variable threshold groups. The incidence of side effects was 12% with nifedipine GITS and 8.2% with diltiazem. Nifedipine GITS and diltiazem were found to be equally effective in increasing exercise tolerance in chronic stable angina patients.",1998.0,0,0
1118,9525550,Calcium channel blocking agents and risk of cancer in patients with coronary heart disease. Benzafibrate Infarction Prevention (BIP) Study Research Group.,S Braun; V Boyko; S Behar; H Reicher-Reiss; S Laniado; E Kaplinsky; U Goldbourt,"This analysis sought to estimate the risk ratio for cancer incidence and cancer-related mortality associated with the use of calcium channel blocking agents (CCBs) in a large group of patients with chronic coronary heart disease (CHD). Recent publications contend that the use of short-acting CCBs may double the risk of cancer incidence and possibly increase mortality in hypertensive patients. Cancer incidence data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention (BIP) study, one-half of whom were treated at the time of screening with CCBs, over a mean follow-up period of 2.8 years. Cause-specific mortality was available through September 1996 (mean follow-up 5.2 years). The statistical power of detecting an odds ratio > or = 1.5 (given the cancer incidence rate of 2.1 in the nonusers of CCBs) was 0.91. The power declined to 0.77, 0.54 and 0.41, with declining odds ratios of 1.4, 1.3 and 1.25, respectively. Of 246 incident cancer cases, 129 occurred among the users (2.3%) and 117 among nonusers of CCBs (2.1%). After adjustment for age, gender and smoking, the odds ratio estimates for all cancers combined was 1.07 (95% confidence interval [CI] 0.83 to 1.37) for CCB users relative to nonusers. The adjusted risk ratio for all-cause mortality for age, gender and smoking and pertinent prognostic clinical characteristics was estimated at 0.94 (95% CI 0.85 to 1.04). The adjusted risk ratio for cancer-related mortality was 1.03 (95% CI 0.75 to 1.41). Patients with CHD treated with CCBs exhibited a similar risk of cancer incidence and total and cancer-related mortality compared with nonusers of CCBs. This analysis provides a certain assurance that CCB use in middle-aged and elderly patients with CHD is not associated with a meaningful difference in cancer incidence and related mortality.",1998.0,1,1
1119,9533424,Evaluation of changes in sympathetic nerve activity and heart rate in essential hypertensive patients induced by amlodipine and nifedipine.,T Hamada; M Watanabe; T Kaneda; A Ohtahara; T Kinugawa; I Hisatome; Y Fujimoto; A Yoshida; C Shigemasa,"To compare the effects of amlodipine and nifedipine on heart rate and parameters of sympathetic nerve activity during the acute and chronic treatment periods in order to elucidate their influence on cardiovascular outcome. A randomized and single-blind study. We performed 24 h ambulatory electrocardiography and blood pressure monitoring of 45 essential hypertensive inpatients. Plasma and urinary catecholamine levels were measured during the control (pretreatment) period, on the first day (acute period) and after 4 weeks (chronic period) of administration of amlodipine and of short-acting nifedipine or its slow-releasing formulation. The low-frequency and high-frequency power spectral densities and low-frequency: high-frequency ratio were obtained by heart rate power spectral analysis. Blood pressure was significantly and similarly reduced by administrations of amlodipine, short-acting nifedipine and slow-releasing nifedipine during the chronic period. The total QRS count per 24 h, which remained constant during the chronic period of administration of slow-releasing nifedipine and was increased by administration of nifedipine, was decreased by 2.8% by administration of amlodipine. Administration of amlodipine decreased the plasma and urinary norepinephrine levels during the chronic period, whereas the levels were significantly increased by administration of short-acting nifedipine and not changed by administration of slow-release nifedipine. Although low-frequency: high-frequency ratio was increased significantly by administration of short-acting nifedipine and slightly by administration of slow-releasing nifedipine, administration of amlodipine reduced it during the acute and chronic periods. Administration of amlodipine did not induce an increase in sympathetic nerve activity in essential hypertensive patients during the chronic period, suggesting that beneficial effects on essential hypertension can be expected after its long-term administration. Administration of slow-releasing nifedipine induces milder reflex sympathetic activation than does that of short-acting nifedipine.",1998.0,0,0
1120,9533498,Calcium channel blockers and the risk of cancer.,L Rosenberg; R S Rao; J R Palmer; B L Strom; P D Stolley; A G Zauber; M E Warshauer; S Shapiro,"Recent epidemiologic studies have raised the concern that calcium channel blocker use may increase the risk of cancer overall and of several specific cancers. To assess whether calcium channel blocker use increases the risk of cancer overall and of specific cancers. Case-control drug surveillance study based on data collected from 1983 to 1996. Hospitals in Baltimore, Md, New York, NY, and Philadelphia, Pa. A total of 9513 patients aged 40 to 69 years with incident cancer of various sites and 6492 controls aged 40 to 69 years admitted for nonmalignant conditions. Incident cancer overall and 23 specific cancers. Calcium channel blocker use was unrelated to the risk of cancer overall (relative risk [RR], 1.1; 95% confidence interval [CI], 0.9-1.3). Use was not significantly associated with increased risks of individual cancers, including those previously implicated, except cancer of the kidney (RR, 1.8; 95% CI, 1.1 -2.7). Recent use, use for 5 or more years, and use of individual calcium channel blocker drugs were also not associated with cancer incidence. Use of beta-blockers and angiotensin-converting enzyme inhibitors was generally unrelated to cancer overall or individual cancers, but both were associated with kidney cancer (RR, 1.8; 95% CI, 1.3-2.5; and RR, 1.9; 95% CI, 1.2-3.0, respectively). The present study suggests that the use of calcium channel blockers is unrelated to an increase in the overall risk of cancer or of individual cancers, except kidney cancer, which has been associated with hypertension or drugs to treat hypertension in previous studies.",2001.0,1,1
1121,9535429,Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects.,S E Kjeldsen; T Hedner; K Jamerson; S Julius; W E Haley; M Zabalgoitia; A R Butt; S N Rahman; L Hansson,"The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus < or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69; ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.",1998.0,0,0
1122,9536505,Amlodipine in patients with stable angina pectoris treated with beta-blockers. Double-blind comparison with placebo.,J Rossinen; J Partanen; M S Nieminen,"In order to assess additional anti-ischaemic effects of amlodipine (AML) on coronary artery disease (CAD) treated with beta-blockers, 32 patients with CAD, verified on angiograms, and stable angina were randomized to receive 5 mg/day of AML or placebo, increasing to 10 mg/day after 2 weeks. Baseline recording of 24-h ambulatory ECG and blood pressure, echocardiography and bicycle exercise test was repeated after treatment for 2 weeks and for 6 weeks. Reduction of ambulatory ischaemia was not significantly greater with AML than with placebo. In exercise tests the time to 0.1 mV ST segment depression and the total exercise time remained unaltered. Blood pressure was reduced by 10 mg AML. The total variability and the very low frequency component of heart rate were reduced after both doses. The clinical significance of the possible unfavourable change in autonomic modulation of the heart in CAD patients is not known.",1998.0,0,0
1123,9538375,[Comparison of anti-ischemic effect of bepridil and diltiazem evaluated by exercise test in patients with coronary disease. A multicenter study. Groupe d'Investigateurs].,P Sellier; L Quilliet,"Bepridil (Cordium) is a calcium channel blocker which has been demonstrated to be effective in the preventive treatment of angina. Few controlled trials have compared bepridil to diltiazem (Tildiem), the reference calcium channel blocker. The objective of this study was to evaluate the efficacy and safety of bepridil in stable coronary patients. 148 patients (139 M, 9 F, mean age: 58 +/- 8.6 years), with documented coronary artery disease and positive stress test after 5 days of placebo were included. After double-blind randomization, they received bepridil (300 mg/day ion 3 doses), or diltiazem (180 mg+/day in 3 doses) for 15 days. A stress test was then performed under the same conditions as on inclusion. The anti-ischaemic efficacy of the two drugs was comparable. Total work increased from 4,552.4 +/- 2,179.4 Kpm a 6,103.2 +/- 2,849.2 Kpm with bepridil (p < or = 0.0001) and from 4,524.8 +/- 2,160.5 Kpm a 5,848.3 +/- 2,800.3 Kpm (p < or = 0.0001) with diltiazem, with no intergroup difference. Duration of effort was significantly prolonged: from 10.5 +/- 3.0 min to 12.5 +/- 3.3 min with bepridil (p < or = 0.0001) and from 10.5 +/- 2.9 min to 12.1 +/- 3.4 min with diltiazem (p < or = 0.0001), with no intergroup difference. The time to onset of 1 min of ST depression increased significantly between the two stress tests, from 8.36 +/- 2.7 min to 10.82 +/- 3.4 min with bepridil (p < or = 0.001) and from 8.02 +/- 3.0 min to 10.53 +/- 3.6 min with diltiazem (p < or = 0.001), with no significant difference between the two groups. The clinical safety of the two products was comparable. On the electrocardiogram, the QT interval was significantly prolonged with bepridil, from 368.6 +/- 37.5 msec to 393.6 +/- 38.7 msec (p < or = 0.0001), reflecting cellular impregnation of the drug.",1998.0,0,0
1124,9538979,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
1125,9539602,Epidural verapamil reduces analgesic consumption after lower abdominal surgery.,H Choe; J S Kim; S H Ko; D C Kim; Y J Han; H S Song,"In this double-blind study, we administered lumbar epidural bupivacaine or bupivacaine plus verapamil to investigate the possible role of the calcium channel blocker, verapamil, in postoperative pain. One hundred patients (ASA physical class I or II) scheduled for lower abdominal surgery were randomly assigned to one of four groups. Group 1 received 10 mL of 0.5% epidural bupivacaine injected 15 min before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 2 received 10 mL of epidural normal saline injected before incision, followed by 10 mL of 0.5% epidural bupivacaine 30 min after incision. Group 3 received 10 mL of 0.5% epidural bupivacaine plus 5 mg of verapamil injected before incision, followed by 10 mL of epidural normal saline 30 min after incision. Group 4 received the same drugs as Group 3, in the reverse order. Pain and mood numeric rating scores, sedation scores, Prince Henry scores, patient-controlled cumulative postoperative analgesic consumption, and the incidence of side effects were assessed 2, 6, 12, 24, and 48 h after the operation in each group. Cumulative postoperative analgesic consumption in Groups 3 and 4 was significantly lower (P < 0.05) than that in Groups 1 and 2 24 and 48 h after surgery. There were no differences in the pain, mood, and sedation scores and the incidence of side effects among the four groups. We conclude that epidural verapamil decreases postoperative pain, possibly by interfering with normal sensory processing and by preventing the establishment of central sensitization. Calcium plays an important role in pain physiology at the spinal cord level. We examined the effect of bupivacaine plus verapamil (calcium channel blocker) and of bupivacaine alone. We demonstrated that the combination, administered epidurally, resulted in less postoperative analgesic consumption than bupivacaine alone.",1998.0,0,0
1126,9543597,A comparison of the safety and efficacy of mibefradil and nifedipine SR in patients with renal disease and hypertension.,A J Woittiez; F T Huysmans; R Bailey; R A Robson; D Mion Júnior; G Villa; I Kobrin,"The antihypertensive efficacy and safety of mibefradil and nifedipine SR were compared in 143 patients with chronic renal failure and mild-to-moderate hypertension in a multicenter, double-blind, randomized, parallel-design study. At treatment week 12, a significantly greater decrease in sitting diastolic blood pressure (SDBP) was seen with mibefradil than with nifedipine SR (12.8 mmHg vs 8.1 mmHg, respectively; p = 0.014). A significantly greater number of mibefradil-treated patients achieved normalization of SDBP by week 12 (62% vs 37%; p < 0.01). The changes in renal function parameters and the incidence of adverse events were similar in both groups. In this population, 12 weeks of treatment with mibefradil were more effective than nifedipine SR for lowering blood pressure and had similar effects on renal function parameters.",1998.0,0,0
1127,9544873,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
1128,9551874,A placebo-controlled comparison of diltiazem and amlodipine monotherapy in essential hypertension using 24-h ambulatory monitoring.,R W Watts; L M Wing,"Thirty patients (17 females, median age 55 years) with mild/moderate hypertension (sitting diastolic blood pressure 95-110 mmHg over 2 consecutive weeks) participated in a study of the efficacy and tolerability of once-daily diltiazem ""controlled delivery"" 180 mg-360 mg and amlodipine 5-10 mg compared with placebo (using clinic and 24-h ambulatory blood pressure measurement (Accutraker II). The study was conducted in a general practice setting using a randomized double-blind crossover design with Latin square allocation of treatment order within subjects. During each phase, doses were titrated to achieve a predose clinic sitting diastolic blood pressure of 90 mmHg. Three patients withdrew while taking amlodipine and 3 while taking placebo. The numbers of patients receiving the higher dose in each phase were as follows: placebo 22, diltiazem 12 and amlodipine 19. End-of-phase mean clinic sitting blood pressures were as follows: placebo 152/100, diltiazem 146/95 and amlodipine 140/93. End-of-phase mean 24-h ambulatory blood pressures were as follows: placebo 151/93, diltiazem 143/86 and amlodipine 137/84. Both clinic and ambulatory blood pressures were therefore significantly reduced (p < 0.01) in both active phases compared with placebo, and systolic blood pressure was also significantly lower with amlodipine compared with diltiazem. Heart rate was increased with amlodipine. Both drugs were well tolerated, and adverse events were predictable for each agent, with amlodipine causing more vasodilator side effects. Thus both amlodipine and diltiazem once-daily are effective in reducing blood pressure. While amlodipine is more potent than diltiazem in reducing systolic blood pressure, it causes more vasodilator side effects.",1998.0,0,0
1129,9556644,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
1130,9568234,Study poses new questions about calcium-channel blockers.,E R Jeffers,,1998.0,0,0
1131,9570428,Calcium channel blockers in heart failure.,U Elkayam,"A considerable effort has been made in the last 15 years to evaluate the safety and efficacy of calcium channel blockers (CCBs) in the treatment of patients with chronic congestive heart failure (CHF). Available studies have provided strong evidence for a potential detrimental effect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in patients with significant depression of left ventricular systolic function. A number of second-generation CCB have demonstrated a strong vasodilatory effect and favorable hemodynamic action but failed to show a similar improvement in exercise capacity, morbidity and mortality. Moreover, drugs such as nicardipine and nisoldipine have resulted in a detrimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Available information from the V-HeFT III study demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both the felodipine and the placebo group, because of the relatively small number of patients in this study, no clear conclusion can be drawn regarding the effect of felodipine on mortality in patients with CHF. An encouraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRAISE study. This prospective large-scale study demonstrated the safety of amlodipine, a long-acting dihydropyridine derivative, when used in patients with heart failure due to coronary artery disease. Furthermore, this study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population. No clear explanation is available at the present time regarding the reason for the deleterious effect demonstrated with some of the dihydropyridines and the contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become available in the next year. The PRAISE II study is ongoing and will provide further information regarding the therapeutic role of amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study is evaluating the effect of mibefradil, a predominant T-type channel blocker with an ideal activity profile, on morbidity and mortality in patients with chronic CHF.",2000.0,0,0
1132,9571349,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.",1998.0,1,1
1133,9579813,Interventional study of diltiazem in dilated cardiomyopathy: a report of multiple centre clinical trial in China. Chinese Cooperative Group of Diltiazem Intervention Trial in Dilated Cardiomyopathy.,Y H Liao,"The aim of this study was to determine the interventional effects of diltiazem on autoantibody mediated myocardial damage in dilated cardiomyopathy (DCM). 221 patients with DCM in 16 hospitals were included in the multiple centre clinical trial from January 1995 to November 1996, using the diltiazem or placebo based on the background therapy for heart failure. Patients were randomly divided into groups for a single blind trial, followed by observation for an average of 7.4 months. After treatment, the heart function of 84% of patients in the diltiazem group recovered to grade I or II, but this occurred for 64% of patients in the placebo group. Heart-thorax ratio was decreased from 0.59+/-0.07 to 0.56+/-0.07 and the left ventricular end-diastolic dimension (LVEDd) from 65.40+/-8.60 mm to 61.12+/-9.86 mm, the left ventricular ejection fraction (EF) was increased from 35.75+/-10.78% to 42.52%+/-11.41% (P<0.01) in the diltiazem group (n=114). The above parameters were not significantly changed in the placebo group (n=107). Mortality was 3.5% in the diltiazem group and 11.2% in the placebo group (P<0.05). Further analysis also shows that LVEDd were reduced and EF were obviously elevated in patients with DCM of LVEDd <70 mm, but the above parameters weren't improved in patients of LVEDd >70 mm. The study suggests that diltiazem is safe and effective in the treatment of DCM, the action mechanism might be intervention in antibody-mediated myocardial damage and protection of myocardium. Diltiazem is suitable for the treatment of the early stage in DCM.",1998.0,0,0
1134,9588123,A clinical and histological comparative study of the effect of nifedipine and phenytion on human gingiva.,M A Shoieb; L M Fathy; O Abu-el-Dahab; M M el-Sherbiny,"Ten patients manifesting gingival enlargement were chosen for this study. Five patients had been treated with 4 mg nifedipine per day as a treatment for angina pectoris, while the other five patients treated with phenytion as an anticonvulsant drug. Clinical and histological data showed that nefidipine induced gingival hyperplasia which is of close similarity to that induced by phenytion despite the differences in target tissue.",1998.0,0,0
1135,9588402,"A randomized, double-blind comparison of intravenous diltiazem and digoxin for atrial fibrillation after coronary artery bypass surgery.",J E Tisdale; I D Padhi; A D Goldberg; N A Silverman; C R Webb; R S Higgins; G Paone; D M Frank; S Borzak,"Atrial fibrillation (AF) after coronary bypass graft surgery may result in hypotension, heart failure symptoms, embolic complications, and prolongation in length of hospital stay (LOHS). The purpose of this study was to determine whether intravenous diltiazem is more effective than digoxin for ventricular rate control in AF after coronary artery bypass graft surgery. A secondary end point was to determine whether ventricular rate control with diltiazem reduces postoperative LOHS compared with digoxin. Patients with AF and ventricular rate > 100 beats/min within 7 days after coronary artery bypass graft surgery were randomly assigned to receive intravenous therapy with diltiazem (n = 20) or digoxin (n = 20). Efficacy was measured with ambulatory electrocardiography (Holter monitoring). Safety was assessed by clinical monitoring and electrocardiographic recording. LOHS was measured from the day of surgery. Data were analyzed with the intention-to-treat principle in all randomly assigned patients. In addition, a separate intention-to-treat analysis was performed excluding patients who spontaneously converted to sinus rhythm. In the analysis of all randomly assigned patients, those who received diltiazem achieved ventricular rate control (> or = 20% decrease in pretreatment ventricular rate) in a mean of 10 +/- 20 (median 2) minutes compared with 352 +/- 312 (median 228) minutes for patients who received digoxin (p < 0.0001). At 2 hours, the proportion of patients who achieved rate control was significantly higher in patients treated with diltiazem (75% vs 35%, p = 0.03). Similarly, at 6 hours, the response rate associated with diltiazem was higher than that in the digoxin group (85% vs 45%, p = 0.02). However, response rates associated with diltiazem and digoxin at 12 and 24 hours were not significantly different. At 24 hours, conversion to sinus rhythm had occurred in 11 of 20 (55%) patients receiving diltiazem and 13 of 20 (65%) patients receiving digoxin (p = 0.75). Results of the analysis of only those patients who remained in AF were similar to those presented above. There was no difference between the diltiazem-treated and digoxin-treated groups in postoperative LOHS (8.6 +/- 2.2 vs 7.7 +/- 2.0 days, respectively, p = 0.43). Ventricular rate control occurs more rapidly with intravenous diltiazem than digoxin in AF after coronary artery bypass graft surgery. However, 12- and 24-hour response rates and duration of postoperative hospital stay associated with the two drugs are similar.",1998.0,0,1
1136,9591892,Value of the addition of amlodipine to atenolol in patients with angina pectoris despite adequate beta blockade.,P H Dunselman; L H van Kempen; L H Bouwens; K J Holwerda; A H Herweijer; P J Bernink,"Anginal patients who remain symptomatic despite optimally dosed beta blockade may also be given dihydropyridine calcium antagonists. This treatment regimen was examined in a double-blind parallel, randomized, controlled study in 147 patients with angina and positive bicycle exercise tests despite optimal beta blockade with atenolol (heart rate at rest <60 beats/min). Patients were randomized to atenolol and/or placebo (control), and atenolol and/or amlodipine. The main outcome measurement was exercise tolerance after 8 weeks compared with baseline. After 8 weeks, no significant differences in time to 0.1-mV ST-segment depression, time to chest pain, and time to end of exercise were observed. The number of patients with chest pain during exercise decreased significantly in the amlodipine group (p = 0.04 vs controls). The subgroup of patients with an early (<6 minutes) onset of chest pain at baseline showed a significant increase in time to chest pain after amlodipine (p = 0.0001 vs controls). In the amlodipine group, ST depression and rate-pressure product at submaximum comparable workload decreased to 0.4 mm (0.56) (p = 0.03 vs controls) and 1.223 (2.652) beats/ min x mm Hg (p = 0.01 vs controls). The number of patients in each group with adverse events was not different. The addition of amlodipine to the treatment of patients with myocardial ischemia, despite optimal beta blockade, is well tolerated and may lead to improvement in symptomatic anginal patients, who have a rapid onset of exercise-induced ischemia.",1998.0,1,1
1137,9591893,Amlodipine versus diltiazem as additional antianginal treatment to atenolol. Centralised European Studies in Angina Research (CESAR) Investigators.,C J Knight; K M Fox,"The antianginal efficacy and tolerability of amlodipine and diltiazem were compared in a double-blind randomized trial of 97 patients with angina resistant to atenolol alone. Both amlodipine and diltiazem significantly reduced the frequency of angina attacks (p <0.001) and glyceryl trinitrate consumption (p <0.05 to p <0.01). During Holter monitoring, both treatments reduced the overall frequency of ambulatory myocardial ischemia, although changes did not reach statistical significance. Exercise test parameters (total exercise time, time to angina, time to ST depression, and maximum ST depression) tended to improve with both treatments, but changes did not achieve statistical significance relative to baseline or to each other. Both drugs were generally well tolerated. Adverse events occurred in 15 patients in the amlodipine group (30%) and in 17 patients in the diltiazem group (36%), but patients taking diltiazem reported almost twice as many adverse events (30) patients taking amlodipine (18). Quality of life, as assessed by total Nottingham Health Profile Scores, was not significantly different between treatments. The addition of either once-daily amlodipine or twice-daily sustained release diltiazem improved symptoms in patients with angina resistant to atenolol alone, but diltiazem was associated with more frequent and more serious adverse events.",1998.0,1,1
1138,9591899,Safety of long-acting dihydropyridine calcium channel blockers in hypertensive patients.,R A Kloner; G W Vetrovec; B J Materson; M Levenstein,"Issues raised recently concerning the safety of calcium channel blockers (CCBs) prompted an analysis of the occurrence of cardiovascular events and death in the Pfizer Inc. hypertension clinical trial databases for amlodipine (Norvasc) and nifedipine in the gastrointestinal therapeutic system (GITS) formulation (Procardia XL). Prospectively defined analyses of data from comparative and noncomparative trials of amlodipine and nifedipine GITS were conducted. Outcome measures included cardiovascular and noncardiovascular deaths, and adverse cardiovascular events including new/worsened angina, myocardial infarction (MI), serious arrhythmia, stroke, congestive heart failure, and bleeding. Among all amlodipine-treated patients (n = 32,920), the incidence rates for all-cause death, MI, and new/worsened angina were 3.0, 3.3, and 1.6/1,000 patient-years of exposure, respectively. Among those in comparative trials alone (n = 4,126), the all-cause death rate was 4.1/1,000 patient-years, which was comparable to that of other non-CCB agents and significantly less than that of other CCBs (23.8/1,000 patient-years, p = 0.015), although the difference in rates represents only 2 deaths. Among all nifedipine-GITS-treated patients (n = 2,645), the rate of all-cause death was 4.1/1,000 patient-years, of MI 6.5/1,000 patient-years, and of new/ worsened angina 5.7/1,000 patient-years. The incidence rates for MI and other cardiac events were low in these hypertension trials, and did not differ among treatment groups in either the amlodipine or nifedipine GITS comparative analyses. In the clinical trial databases analyzed, there is no signal suggesting excessive risk of death or cardiovascular events for hypertensive patients treated with amlodipine or nifedipine GITS.",1998.0,0,0
1139,9594859,Intravenous diltiazem and acute renal failure after cardiac operations.,E W Young; A Diab; M M Kirsh,"Perioperative administration of intravenous diltiazem to patients undergoing cardiac procedures has been shown to decrease the incidence of ischemia and arrhythmias. However, after adopting this practice in our cardiac surgery program, we perceived an increased incidence of postoperative renal dysfunction. A directed record review of postoperative renal function was conducted for consecutive patients undergoing cardiac operation for the time periods before and after adoption of prophylactic intravenous diltiazem (0.1 mg.kg-1.h-1 for 24 hours). The two groups were compared using chi 2 and two-sample t tests. The risk of development of postoperative renal failure was modeled with logistic regression. Diltiazem-treated patients (n = 271) were similar to the control patients (n = 143) in terms of age (64 versus 61 years; p = 0.14), ejection fraction (0.46 versus 0.47; p = 0.61), baseline serum creatinine level (1.2 versus 1.1 mg/dL; p = 0.27), prevalence of comorbid conditions, and surgical characteristics. The prevalence of left main coronary artery disease was lower in the diltiazem group than the control group (39% versus 52%; p = 0.01). During the 7-day postoperative period, the average peak serum creatinine level was higher in the diltiazem group (1.7 +/- 0.9 mg/dL; mean +/- 1 standard deviation) than the control group (1.5 +/- 0.5 mg/dL; p = 0.003). The incidence of acute renal failure requiring dialysis was 4.4% in the diltiazem group versus 0.7% in the control group (p = 0.04). There was no difference in length of hospitalization or mortality. The risk of acute renal failure was strongly associated with intravenous diltiazem (adjusted odds ratio [AOR] 6.3; p = 0.08), age (AOR 2.5 per 10 years; p = 0.07), baseline serum creatinine (AOR 4.8 per 1 mg/dL; p = 0.02), the presence of left main coronary disease (AOR 5.3; p = 0.02), and the presence of cerebrovascular disease (AOR 4.5; p = 0.05). Our retrospective analysis suggests that prophylactic use of intravenous diltiazem in patients undergoing cardiac operations was associated with increased renal dysfunction. Further studies of the risk and benefits of intravenous diltiazem in this setting should be undertaken.",1998.0,0,1
1140,9595376,"Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension.",P S Snyder,"The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo-controlled, randomized, blinded clinical trial. Five cats were randomized to receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily. The average systolic blood pressure (SBP) recorded by the Doppler method on day 0 was 212 +/- 21 mm Hg in the AML group and 216 +/- 32 mm Hg in the PLA group. On day 7, the cats receiving AML had a significantly lower average daily SBP (160 +/- 30 mm Hg) but SBP in the PLA group was unchanged (207 +/- 31 mm Hg). On day 7, all cats receiving PLA and one cat receiving AML were crossed over to the other group because of inadequate response. Blood pressure did not decrease adequately in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats requiring 1.25 mg AML once daily (6.1 kg +/- 0.7 kg) weighed significantly more than cats that responded to 0.625 mg AML once daily (4.1 +/- 0.7 kg). The average daily SBP recorded in the 6 cats that completed the study was significantly lower after 16 weeks of treatment (152 +/- 14 mm Hg) compared to day 0 (221 +/- 24 mm Hg). Three cats were euthanized before completion of the study. All 3 cats were responders to AML on day 7. SBPs measured 24 hours after AML administration were similar to the average daily SBP, suggesting that AML effectively controlled SBP for a 24-hour period. AML was shown to be an effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg sid.",1998.0,0,0
1141,9605051,Direct medical costs of coronary artery disease in the United States.,M W Russell; D M Huse; S Drowns; E C Hamel; S C Hartz,"To generate current incidence-based estimates of the direct medical costs of coronary artery disease (CAD) in the United States, a Markov model of the economic costs of CAD-related medical care was developed. Risks of initial and subsequent CAD events (sudden CAD death, fatal/nonfatal acute myocardial infarction [AMI], unstable angina, and stable angina) were estimated using new Framingham Heart Study risk equations and population risk profiles derived from national survey data. Costs were assumed to be those related to treatment of initial and subsequent CAD events (""event-related"") and follow-up care (""nonevent-related""), respectively. Cost estimates were derived primarily from national public-use databases. First-year direct medical costs of treating CAD events are estimated to be $17,532 for fatal AMI, $15,540 for nonfatal AMI, $2,569 for stable angina, $12,058 for unstable angina, and $713 for sudden CAD death. Nonevent-related direct costs of CAD treatment are estimated to be $1,051 annually. The annual incidence of CAD in the United States is estimated at 616,900 cases, with first-year costs of treatment totaling $5.54 billion. Five- and 10-year cumulative costs in 1995 dollars for patients who are initially free of CAD are estimated at $9.2 billion and $16.5 billion, respectively; for all patients with CAD, these costs are estimated to be $71.5 billion and $126.6 billion, respectively. The direct medical costs of CAD create a large economic burden for the United States health-care system.",1998.0,0,0
1142,9607386,Replacing short-acting nifedipine with alternative medications at a large health maintenance organization.,R C Kaplan; B M Psaty; D Kriesel; S R Heckbert; N L Smith; C Gillett; A G Golston,"In response to recent evidence about the safety of calcium channel blockers, Group Health Cooperative of Puget Sound (GHC), a large health maintenance organization, implemented a plan in April 1996 to reevaluate the medications of 1349 patients who were taking short-acting nifedipine. Following the intervention, 79.8% of patients taking short-acting nifedipine discontinued use, and 45.6% switched to once-daily felodipine. By presenting physicians and patients with recent evidence about the safety of short-acting nifedipine, a large health maintenance organization was able to motivate broad-scale changes to safer alternative drug therapies.",1998.0,0,0
1143,9607387,Compliance and antihypertensive efficacy of amlodipine compared with nifedipine slow-release.,C Mounier-Vehier; C Bernaud; A Carré; B Lequeuche; J M Hotton; J C Charpentier,"Poor compliance is a principal cause of treatment failure in hypertensive patients. Once-daily dosing improves compliance, but 24-h antihypertensive activity should be provided. The compliance, efficacy, and safety of amlodipine and nifedipine slow-release (SR) were compared in patients with mild-to-moderate essential hypertension recruited among 24 centers in France. After a 2-week washout period, 103 patients were randomized to 12 weeks of 5 to 10 amlodipine mg once daily (n = 55) or 20 mg nifedipine SR twice daily (n = 48). Compliance was calculated by electronic drug monitoring. Efficacy was measured by ambulatory and casual BP recordings. Patients receiving amlodipine demonstrated better compliance than patients receiving nifedipine SR with respect to compliance index (the total number of doses taken divided by the total number of doses prescribed, expressed as a percentage; 98.3% v 87%; P < .0001), days on which the correct number of doses were taken (92.5% v 74.8%; P < .0001), and prescribed doses taken on schedule (88.7% v 71.6%; P < .0001). Absolute and relative therapeutic coverage were higher in patients receiving amlodipine than nifedipine SR (P < .0001). Mean SBP and DBP decreased equally in both groups, although amlodipine offered better BP control compared with nifedipine SR at specific times of day. Fewer patients had high nocturnal SBP with amlodipine (39.3%) than nifedipine SR (71.4%; P = .042). Adverse events and treatment withdrawals occurred less frequently in amlodipine-treated patients than in nifedipine SR-treated patients. Amlodipine (5 to 10 mg) once daily provides improved compliance, better 24-h BP control, and fewer adverse events than 20 mg nifedipine SR twice daily in patients with mild-to-moderate hypertension.",1998.0,0,0
1144,9610546,Potassium channel-blocking actions of nifedipine: a cause for morbidity at high doses?,X Zhang; D Fedida,,1998.0,0,1
1145,9613736,Cinnarizine-induced parkinsonism: ten years later.,J F Martí-Massó; J J Poza,"A retrospective study was carried out to investigate the evolution of patients diagnosed with cinnarizine-induced parkinsonism (CIP) over the past 15 years. A total of 74 cases of CIP were found among 172 patients with drug-induced parkinsonism (DIP). Both CIP and other DIP were significantly more frequent in women. No clinical differences between CIP and other DIP were found. Most of the patients (66 of 74) completely recovered after cinnarizine withdrawal in 1-16 months. Eleven patients later developed Parkinson's disease; four of them had previously recovered. Five patients had tardive dyskinesia. CIP accounts for a high proportion of DIP referred to neurologists in populations in which cinnarizine is widely prescribed. The symptoms typically resolve after drug withdrawal, although complete recovery may take more than 1 year.",1998.0,0,0
1146,9627524,,,,,0,0
1147,9635947,Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group.,L Hansson; A Zanchetti; S G Carruthers; B Dahlöf; D Elmfeldt; S Julius; J Ménard; K H Rahn; H Wedel; S Westerling,"Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.",2000.0,0,0
1148,9638316,"[Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test].",G Fröhlich; S Burmeister; A Wiedemann; M Bulitta,"Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.",1998.0,0,0
1149,9639942,"Calcium antagonists, is there a real concern about safety?",D A Duprez; M L De Buyzere; D L Clement,"Calcium antagonists are widely used in the treatment of arterial hypertension and, or in ischemic heart disease. During the last 3 years, controversial articles and editorials have been published concerning the potential risk of calcium antagonists in regard to mortality, cancer and haemorrhage. The information has been mainly derived from case-control studies. The major concern about such observational studies of treatment outcome is the large potential for systematic error to affect the results. However, overviews of controlled trials with calcium antagonists do not provide clear evidence of an effect of calcium antagonists on mortality, risk of cancer and risk of bleeding.",1998.0,0,0
1150,9652872,Nifedipine after acute myocardial infarction--sola dosis facit venenum: only the dose determines the harm.,F H Messerli,,1998.0,0,0
1151,9657538,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
1152,9657628,Effect of amlodipine versus felodipine extended release on 24-hour ambulatory blood pressure in hypertension.,J Ostergren; H Isaksson; U Brodin; A Schwan; K P Ohman,"Amlodipine and felodipine are calcium antagonists of the dihydropyridine type. The elimination half-life of amlodipine is longer than that of felodipine. To study whether the different elimination rates of the drugs were reflected in different duration of blood pressure (BP) control, we compared amlodipine and felodipine extended release (ER) by both conventional clinic BP 24 h after drug intake and 24 h ambulatory BP monitoring (ABPM), with special reference to nighttime and morning blood pressure. Two hundred and sixteen patients with primary hypertension (supine diastolic BP, 95 to 115 mm Hg) were randomized to receive amlodipine or felodipine ER in a multicenter study. The starting dose of both drugs was 5 mg. If the target clinic diastolic BP (90 mm Hg) had not been achieved after 4 weeks the dose was increased to 10 mg. Twenty-four-hour ABPM was performed with the subjects taking placebo medication before randomization and after 4 and 8 weeks undergoing active treatment. Significantly more patients responded after 4 weeks of treatment with amlodipine (50%) as compared with felodipine (33%) (P = .013). ABPM during daytime (07:00 to 23:00) was similar during both treatments, but nighttime systolic (P = .026) and diastolic (P = .019) BP was more effectively reduced by amlodipine than by felodipine. After 8 weeks 82% achieved the target pressure with amlodipine and 69% with felodipine (P = .036 for the difference). Amlodipine seems to be more effective than felodipine when the drugs are compared in the same dose, with regard to the effect on clinic BP 24 h after dosing and to ambulatory BP during the night. The longer elimination half-life of amlodipine as compared to felodipine is the probable reason for this finding.",1998.0,0,0
1153,9660521,"Distinct vasodilation, without reflex neurohormonal activation, induced by barnidipine in hypertensive patients.",L Argenziano; R Izzo; G Iovino; N De Luca; L Parrella; C Morisco; B Trimarco,"Barnidipine is a new 1,4-dihydropyridine calcium antagonist with a strong and long-lasting vasodilatory effect. In order to assess the haemodynamic profile of the antihypertensive effect of barnidipine, a randomized, double-blind study of barnidipine vs nitrendipine was performed in 24 patients with mild to moderate essential hypertension. Following an initial 4-week placebo period, patients whose sitting diastolic blood pressure (SiDBP) was between 95 and 114 mm Hg, and whose sitting systolic blood pressure was between 150 and 219 mm Hg, were randomized (2:1 ratio) to receive either barnidipine (10 mg) or nitrendipine (10 mg) once daily, for a 6-week double-blind period. Subsequently, patients with an SiDBP of less than 90 mm Hg continued for a second 6-week period with the same monotherapy, while patients with an SiDBP of 90 mm Hg or above received double the dose of antihypertensive treatment for the next 6 weeks. Two-dimensional M- and B-mode echocardiography with Doppler flowmetry was performed at the end of both the placebo and active treatment phases. Barnidipine and nitrendipine reduced blood pressure by the same degree (barnidipine: from 165 +/- 2/100 +/- 1 to 145 +/- 2/89 +/- 1 mm Hg, p < 0.01; nitrendipine: from 163 +/- 3/100 +/- 2 to 143 +/- 7/90 +/- 3 mm Hg, p < 0.01) as a result of peripheral vasodilation. This was not accompanied by reflex neurohormonal activation. Moreover, only in the group receiving barnidipine was a significant decrease in plasma noradrenaline observed, both when the patients were in the supine position (from 298 +/- 27 to 214 +/- 21 pg/ml, p < 0.05) and when they were upright (from 472 +/- 37 to 348 +/- 38 pg/ml, p < 0.05).",1998.0,0,0
1154,9660524,Diversity and intensity of adverse events in the treatment of hypertension with barnidipine.,J W van der Velden; H J Beudeker; M Nishi,"Calcium antagonists (CaAs) are divided into three structural classes, typically represented by verapamil, diltiazem and nifedipine. As a group, the principal (type I) adverse effects of these drugs relate to the pharmacological action of calcium channel blockade, namely vasodilation, and include dizziness, flushing, palpitations and peripheral oedema. The clinical safety of the new dihydropyridine CaA, barnidipine, has been assessed in more than 12 clinical trials, including 2041 patients who have been treated with one or more doses of barnidipine (dose of up to 50 mg). Adverse events with barnidipine are of mild to moderate intensity, most commonly of type I, occurring in the early phase of treatment. The incidence of serious adverse events and the rate of withdrawals are low. Hence, barnidipine is likely to be well tolerated in general clinical use.",1998.0,0,0
1155,9669789,Life-threatening interaction of mibefradil and beta-blockers with dihydropyridine calcium channel blockers.,M E Mullins; B Z Horowitz; D H Linden; G W Smith; R L Norton; J Stump,"Mibefradil is a T-type and L-type calcium channel blocker (CCB) released in the United States in 1997 for management of hypertension and chronic stable angina. Postmarketing surveillance revealed a potential serious interaction between mibefradil and beta-blockers, digoxin, verapamil, and diltiazem, especially in elderly patients. The manufacturer voluntarily withdrew mibefradil on June 8, 1998. We describe 4 cases of cardiogenic shock in patients taking mibefradil and beta-blockers who began taking dihydropyridine CCBs. One case resulted in death; the other 3 survived episodes of cardiogenic shock with intensive support of heart rate and blood pressure. Physicians who are preparing to switch patients' medications from mibefradil to other antihypertensive agents should be aware of these potentially life-threatening drug-drug interactions.",2001.0,0,0
1156,9674632,"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
1157,9679720,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
1158,9683312,Rationale and design for the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial.,H R Black; W J Elliott; J D Neaton; G Grandits; P Grambsch; R H Grimm; L Hansson; Y Lacoucière; J Muller; P Sleight; M A Weber; W B White; G Williams; J Wittes; A Zanchetti; T D Fakouhi,"The Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Trial is a randomized, prospective, double-blind, parallel-group, two-arm, actively controlled, multicenter, international 5-year clinical trial involving 15,000 patients. CONVINCE will compare the incidence of fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, or cardiovascular-disease-related death in two antihypertensive treatment regimens. One treatment arm begins with controlled onset-extended release (COER)-verapamil, which has its major antihypertensive effect 6-12 hours after administration. The other arm (standard of care (SOC)) begins with either hydrochlorothiazide (HCTZ) or atenolol, one of which is preselected by the investigator for an individual patient prior to randomization. Secondary objectives include comparisons of the regimens for each of the components of the primary endpoint (separately), death or hospitalization related to cardiovascular disease, efficacy in lowering blood pressure to goal, primary events occurring between 6 am and noon, all-cause mortality, withdrawals from blinded therapy, cancer, and hospitalizations due to bleeding. Patients may be enrolled if they are hypertensive and at least 55 years of age and have an established second risk factor for cardiovascular disease. Initial medications include COER-verapamil (180 mg/d), HCTZ (12.5 mg/d), or atenolol (50 mg/d). Initial doses are doubled if blood pressure (BP) does not reach goal (systolic BP < 140 mm and diastolic BP < 90 mm Hg). If BP is not controlled by the higher dose of the initial medication, HCTZ is added to COER-verapamil, or the SOC choice not initially selected is added in the SOC arm. An ACE-inhibitor is recommended (although nearly any open-label medication is allowed) as the third step for patients whose BP is not adequately controlled or who have a contraindication to one of the two SOC medications. Patients take two sets of tablets daily, one in the morning and one in the evening. Although most patients switch from an established antihypertensive medication to randomized treatment, untreated patients with stages I-III hypertension (SBP between 140 and 190 or DBP between 90 and 110 mm Hg) are eligible. Outcomes are monitored by an independent Data and Safety Monitoring Board. Enrollment began during the third quarter of 1996, and follow-up is to be completed in the third quarter of 2002.",2001.0,1,1
1159,9684422,Managing migraine.,,"There have been important advances in the management of migraine headache since we last reviewed the subject in 1981. Formal diagnostic criteria, which were introduced in 1988, have led to more reliable assessment of the prevalence of migraine and how it affects attendance and efficiency at work. In addition, the use of the 5HT1 agonists has become established. In this article, we discuss how these changes have altered the management of migraine in adults.",1998.0,0,0
1160,9688432,Withdrawal effects of antianginal therapy: comparison of isosorbide dinitrate and nifedipine.,; N Koutishenko; V I Metelitsa,"We compared the effects of abrupt cessation of nifedipine and isosorbide dinitrate therapy in patients with stable angina pectoris. Eighteen males were studied. Each patient received isosorbide dinitrate and nifedipine continuously for 5 weeks by randomised cross-over technique. Exercise treadmill tests were performed before each treatment period, at the beginning of treatment, 4 weeks after initiation of treatment and on the first and eighth days of drug withdrawal. At the end of treatment the antianginal effect of both agents attenuated (versus acute administration). Abrupt cessation of isosorbide dinitrate caused only a tendency towards decrease in exercise tolerance versus pre-treatment level. Alternatively, abrupt cessation of nifedipine resulted in substantial deterioration in exercise tolerance, which was statistically significant 21 and 24 h after the last dose administration. The number of anginal attacks increased >25% in two patients after cessation of isosorbide dinitrate and in eight patients after cessation of nifedipine. In no patient rest angina episodes appeared after stopping of isosorbide dinitrate, however, after stopping of nifedipine rest angina episodes appeared in three patients. We conclude that withdrawal phenomenon of nifedipine is much more pronounced than that of isosorbide dinitrate and may emerge on the first day of drug cessation. Such a phenomenon may be evident even in patients in whom nifedipine effect have attenuated due to the development of tolerance.",1998.0,0,1
1161,9688484,"A prospective, randomized trial of nifedipine vs. ritodrine in threatened preterm labor.",J A García-Velasco; A González González,"To compare the tocolytic efficacy and maternal tolerance of nifedipine with ritodrine in the management of threatened preterm labor. Prospective randomized study of 52 singleton pregnancies with preterm labor between 26 and 34 week's gestation. The capacity to delay delivery 48 h, 7 days, until week 36 or until fetal weight reached 2500 g were the outcome variables assessed. Doppler ultrasound studies were performed on the fetal umbilical artery as control. No significant differences were found in the delay of delivery, but significantly fewer maternal side-effects were found in the nifedipine group. Doppler ultrasound results were similar in both groups. Nifedipine is a valid and well-tolerated alternative among the tocolytic drugs, and apparently does not significantly alter fetal vascular blood flow.",1998.0,0,0
1162,9696952,A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine.,T Risler; R Bohm; D Wetzchewald; H P Nast; H H Koch; G Stein; C M Erley,"A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage. Equally high blood pressure without symptoms is called a hypertensive crisis. Patients with hypertensive crisis or emergency need prompt, effective, and specific therapy and a controlled reduction of blood pressure. We performed a randomized, double-blind multi-centre study, to compare the safety, efficacy and tolerability of an intravenous (i.v.) infusion of two dihydropyridine calcium channel blockers (either nifedipine or felodipine) in 122 patients, of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis, who had not reacted adequately (diastolic blood pressure <115 mmHg) to 5 mg of nifedipine PO. Both drugs lowered blood pressure adequately in more than 90% of the patients and were well tolerated. Only one patient had to be withdrawn, because of an excessive decrease in blood pressure. Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV. Felodipine is easier to handle because of its lack of light sensitivity.",1998.0,0,0
1163,9700998,"Comparison of 24-hour blood pressure, heart rate, and autonomic nerve activity in hypertensive patients treated with cilnidipine or nifedipine retard.",J Minami; T Ishimitsu; Y Kawano; A Numabe; H Matsuoka,"We compared the effects of cilnidipine and nifedipine retard on 24-h blood pressure (BP), heart rate (HR), and autonomic nerve activity in patients with essential hypertension. Cilnidipine is a novel and unique 1,4-dihydropyridine calcium antagonist that has the L-type and N-type voltage-dependent calcium channel-blocking action. Fourteen hypertensive outpatients (four men and 10 women; aged 64 +/- 2 years, mean +/- SEM) were enrolled in this study. Their ambulatory BP and electrocardiogram were monitored for 24 h at intervals of 30 min with a portable recorder after a 4-week drug-free period, after a 4-week treatment period with cilnidipine (5 or 10 mg once daily), and after a 4-week treatment period with nifedipine retard (10 or 20 mg twice daily). The order of the three periods was randomized. Autonomic nerve activity was evaluated by a power spectral analysis of HR variability, by using the high-frequency (HF) component as an index of parasympathetic nerve activity and the ratio of the low-frequency (LF) component to the HF component (LF/HF) as an index of sympathovagal balance. Cilnidipine and nifedipine retard significantly reduced the 24-h BP of these patients to similar extents (cilnidipine, -11 +/- 3/-6 +/- 1 mm Hg; nifedipine retard, -15 +/- 3/-6 +/- 2 mm Hg). Cilnidipine did not change the 24-h average HR, whereas nifedipine retard significantly increased it (+3.3 +/- 1.4 beats/min; p < 0.05). Nifedipine retard significantly increased the LF/HF ratio in the daytime and the nighttime. Such changes were limited to the daytime in the treatment period with cilnidipine. These results suggest that cilnidipine is effective as a once-daily antihypertensive agent and had less influence on autonomic nervous system and HR than did nifedipine retard.",1998.0,0,1
1164,9705044,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
1165,9706857,Surgical treatment of cyclosporine A- and nifedipine-induced gingival enlargement: gingivectomy versus periodontal flap.,A Pilloni; P M Camargo; M Carere; F A Carranza,"The purpose of this study was to compare probing depth resolution achieved by gingivectomy and periodontal flap techniques in the treatment of cyclosporine A- and nifedipine-induced gingival enlargement. Ten kidney transplant patients who were receiving cyclosporine A and nifedipine for at least 6 months participated in the study. Five patients were randomly assigned to the gingivectomy group and 5 patients to the periodontal flap group. Only anterior segments of the oral cavity (canine to canine) were surgically treated. Clinical measurements, including probing depths, plaque index, and gingival sulcus index, were taken at baseline, 6 weeks, 6 months, and 1 year. Results showed that probing depths, while similar for both groups in the first 6 weeks of the study, were significantly shallower for the periodontal flap group when compared to the gingivectomy group at 6 months (2.48 +/- 0.34 mm versus 4.87 +/- 0.79 mm, respectively) and 1 year (322 +/- 0.65 mm versus 6.40 +/- 1.02 mm, respectively). Within its limitations, this study suggests that the pocket reduction achieved by the periodontal flap may be sustained for longer periods of time than by the gingivectomy technique in the treatment of cyclosporine A- and nifedipine-induced gingival enlargement.",2001.0,0,0
1166,9717598,Calcium channel blockers attenuate cardiovascular responses to tracheal extubation in hypertensive patients.,Y Fujii; S Kihara; S Takahashi; H Tanaka; H Toyooka,"Hypertensive patients exhibit exaggerated cardiovascular responses to tracheal extubation. This study was undertaken to examine the inhibitory effects of calcium channel blockers, nicardipine and diltiazem, on haemodynamic changes after tracheal extubation. Sixty hypertensive patients (ASA physical status II) undergoing elective orthopaedic (upper and lower extremity) surgery received, in a randomized, double-blind manner, 30 micrograms.kg-1 nicardipine, 0.2 mg.kg-1 diltiazem or saline (as a control) (n = 20 of each) i.v. before tracheal extubation. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and after tracheal extubation. The HR, MAP and RPP increased after tracheal extubation in the control group (P < 0.05). The increases in these haemodynamic variables were attenuated with nicardipine or diltiazem. The inhibitory effects of diltiazem on these cardiovascular responses to tracheal extubation were greater than those of nicardipine (HR; 86 +/- 7 vs 101 +/- 10, RPP; 11,437 +/- 1,575 vs 14,675 +/- 2,874, mean +/- SD, P < 0.05). Compared with nicardipine, administration of diltiazem produced greater attenuating the circulatory responses to tracheal extubation in hypertensive patients.",1998.0,0,0
1167,9727544,,,,,0,1
1168,9727772,Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension.,O Sitbon; M Humbert; J L Jagot; O Taravella; M Fartoukh; F Parent; P Herve; G Simonneau,"In a subset of patients with primary pulmonary hypertension (PPH), high doses of oral calcium-channel blockers (CCB) produce a sustained clinical and haemodynamic improvement. However, significant side-effects have been reported during acute testing with CCB. Therefore, to identify accurately patients who may benefit from long-term CCB therapy, there is a need for a safe, potent and short-acting vasodilator. The aim of this study was to compare the acute response to inhaled nitric oxide (NO) and oral high doses of CCB in 33 consecutive patients with PPH. A significant acute vasodilator response was defined by a fall in both mean pulmonary artery pressure and total pulmonary resistance by >20%. Ten patients responded acutely to NO, nine of whom responded acutely to CCB, without any complications. The 23 other patients failed to respond to NO and CCB. In these nonresponders, nine serious adverse events were observed with CCB (38%). There was no clinical or baseline haemodynamic feature predicting acute vasodilator response. Long-term oral treatment with CCB was restricted to the nine acute responders and a sustained clinical and haemodynamic improvement was observed in only six patients. In primary pulmonary hypertension, the acute response rate to high doses of calcium-channel blockers is low (27%). Serious adverse reactions to high doses of calcium-channel blockers during acute testing are frequently observed in nonresponders. It is concluded that nitric oxide may be used as a screening agent for safely identifying patients with primary pulmonary hypertension who respond acutely to calcium-channel blockers and may benefit from long-term treatment with these agents.",1998.0,0,0
1169,9727842,Amlodipine once-daily in systemic hypertension.,J P Pfammatter; C Clericetti-Affolter; A C Truttmann; K Busch; R Laux-End; M G Bianchetti,"The calcium channel blocker nifedipine is widely used in children with systemic hypertension: however, because of the short duration of action, three to four daily doses of the standard preparation are required. Amlodipine once-daily, a calcium channel blocker structurally related to nifedipine with an excellent bioavailability and a long elimination half-time, has been shown to reduce blood pressure in adults. No information is available on the use of amlodipine in childhood. The effects of amlodipine once-daily (5 to 10 mg) were therefore assessed in 28 paediatric patients with hypertension. Amlodipine was withdrawn in five patients who experienced oedema and flushing. In the remaining 23 patients blood pressure was significantly reduced 3 weeks after amlodipine (on average by 7/5 mm Hg) and further decreased at 12 weeks (by 21/12 mm Hg). Heart rate and body weight were unchanged. In eight patients concomitantly treated with cyclosporine, the blood level of this agent was stable throughout the study, thus not requiring any dose adjustment. The study illustrates the antihypertensive properties of amlodipine once-daily in paediatric hypertension. Amlodipine appears particularly indicated in patients concomitantly treated with cyclosporine.",1998.0,0,0
1170,9732337,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
1171,9732338,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
1172,9737514,"Assessment of atrioventricular junction ablation and VVIR pacemaker versus pharmacological treatment in patients with heart failure and chronic atrial fibrillation: a randomized, controlled study.",M Brignole; C Menozzi; L Gianfranchi; G Musso; R Mureddu; N Bottoni; G Lolli,"Uncontrolled studies have suggested that atrioventricular junction ablation and pacemaker implantation have beneficial effects on quality of life in patients with chronic atrial fibrillation (AF). We performed a multicenter, controlled, randomized, 12-month evaluation of the clinical effects of atrioventricular junction ablation and VVIR pacemaker (Abl+Pm) versus pharmacological (drug) treatment in 66 patients with chronic (lasting >6 months) AF who had clinically manifest heart failure and heart rate >90 bpm on 3 standard ECGs recorded at rest during stable clinical conditions on different days. Before completion of the study, withdrawals occurred in 8 patients of the drug group and in 4 patients of the Abl+Pm group. At the end of the 12 months, the 28 Abl+Pm patients who completed the study showed lower scores in palpitations (-78%; P=0.000) and effort dyspnea (-22%; P=0.05) than the 26 of the drug group. Lower scores, although not significant, were also observed for exercise intolerance (-20%), easy fatigue (-17%), chest discomfort (-50%), Living with Heart Failure Questionnaire (-14%), New York Heart Association functional classification (-4%), and Activity scale (-12%). The intrapatient comparison between enrollment and month 12 showed that in the Abl+Pm group, all variables except easy fatigue improved significantly from 14% to 82%. However, because an improvement was also observed in the drug group, the difference between the 2 groups was significant only for palpitations (P=0.000), effort dyspnea (P=0.01), exercise intolerance (P=0.005), easy fatigue (P=0.02), and chest discomfort (P=0.02). Cardiac performance, evaluated by means of standard echocardiogram and exercise test, did not differ significantly between the 2 groups and remained stable over time. In patients with heart failure and chronic AF, Abl+Pm treatment is effective and superior to drug therapy in controlling symptoms, although its efficacy appears to be less than that observed in uncontrolled studies because some improvement can also be expected in medically treated patients. Cardiac performance is not modified by the treatment.",1998.0,0,0
1173,9739499,Is the use of some calcium antagonists linked to cancer? Evidence from recent observational studies.,M Pahor; C D Furberg,"In animal and in vitro studies, several calcium antagonists have been shown to block apoptosis (programmed cell death), a natural cellular defence against cancer. On the basis of these studies, it has been hypothesised that calcium antagonists may function as cancer promoters and that they might cause cancer in humans. The association between the use of calcium antagonists and cancer has been addressed recently in 6 independent epidemiological studies. Four of these studies--2 cohort and 2 case-control--found a significantly higher risk of cancer among users of certain calcium antagonists as compared with either non-users or with users of other antihypertensive agents. The other 2 studies failed to find support for this association. All studies had limitations of varying types and significance. The emerging pattern from these investigations includes the following features: (i) the strength of the association appears to be dependent on daily dosage, ranging from no association in users of low dosages to a 2-fold (or possibly higher) increased risk in users of higher dosages; (ii) the time lag to the appearance of this association appears to be at least 2 to 3 years; (iii) an association with a higher risk of cancer has been found primarily for verapamil, while no such relationship has been reported for diltiazem; and (iv) no highly consistent associations have been shown with specific cancer sites or histological types. More data, preferably from long-term randomised clinical trials, are required before firm conclusions can be drawn.",1998.0,0,1
1174,9739779,Ventricular arrhythmias in the elderly.,D D Tresch; R K Thakur,"Sudden cardiac death (SCD) remains a significant medical problem in the United States. The incidence of SCD increases with advancing age because cardiovascular disease is more prevalent in the elderly. Management of ventricular arrhythmias in the elderly patient is especially challenging because of increased risk of interventional and pharmacologic therapies, altered pharmacokinetics of drugs, and sometimes unclear long-term benefits.",1998.0,0,0
1175,9740342,Long-term follow-up after early intervention with intravenous diltiazem or intravenous nitroglycerin for unstable angina pectoris.,E J Göbel; W H van Gilst; P J de Kam; M G ter Napel; G P Molhoek; K I Lie,"In a double-blind randomized trial in unstable angina it was shown that intravenous diltiazem reduced ischaemic events in the first 48 h after inclusion better than intravenous nitroglycerin. The present study was performed to establish the long-term prognosis of the randomized patients, with respect to their initial treatment assignment. One year follow-up data on ischaemic end-points and anti-ischaemic medication were recorded. Results were available for all of the 121 randomized patients. One hundred and sixty-seven primary endpoint events were recorded, of which 54 occurred in the first 48 h and 113 during the follow-up. Survival analysis showed that event-free survival was significantly better in the diltiazem group (45.0%) than in the nitroglycerin group (34.4%), P=0.04. The incidence rate after 48 h and one year for cardiac death are, respectively, 0% and 4.1%. The trend in anti-ischaemic medication was higher in the nitroglycerin group. For beta-blockers, this trend became significant after 12 months (P=0.03). These results show that the initial benefit obtained by early treatment with intravenous diltiazem was preserved during the first year after the initial hospitalization, and that, despite the high risk of cardiac events in our population, the overall mortality 12 months after inclusion was low.",1998.0,0,0
1176,9741502,,,,,0,0
1177,9744143,A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension.,C Hoglund; H G Hutchinson,"The efficacy and safety of nisoldipine CC and felodipine were compared in a multicentre, randomised, double-blind, trial in patients with mild-to-moderate hypertension (n = 229). Following a two-week placebo run-in period, patients were randomised to 16 weeks' active treatment with nisoldipine coat core (CC) 20-40 mg or felodipine 5-10 mg once daily. At week 16, a higher proportion of patients in the nisoldipine CC group were on low-dose therapy (51% vs 36%, p = 0.07). The proportion of treatment responders was 77.8% with nisoldipine CC and 66.5% with felodipine. The mean change from baseline in systolic/diastolic blood pressure was -18.8/-13.6 mmHg with nisoldipine CC and -17.4/-11.3 mmHg with felodipine. The most common adverse events included peripheral oedema and headache; neither treatment affected heart rate. Thus, nisoldipine CC and felodipine provide comparable antihypertensive efficacy. The adverse effects of both drugs are related to their vasodilator properties and are common to the class.",1998.0,0,0
1178,9746025,Fatal aplastic anaemia associated with nifedipine.,J R Laporte; L Ibáñez; E Ballarín; E Pérez; X Vidal,,1998.0,0,0
1179,9752892,"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
1180,9758086,Reduction of cardiovascular structural changes by nifedipine GITS in essential hypertensive patients.,E Agabiti-Rosei; R Zulli; M L Muiesan; M Salvetti; D Rizzoni; C Corbellini; C Monteduro,"The aim of this study was to evaluate the effect of the calcium antagonist Nifedipine GITS in a double-blind, randomized comparison with the diuretic hydrochlorothiazide (HCTZ) on reduction of left ventricular (LV) mass and minimal vascular resistance in a group of essential hypertensives with left ventricular hypertrophy (LVH). The effects on blood pressure and on echocardiographic LV functional parameters were also analysed. After two months of randomized treatment with Nifedipine GITS or HCTZ, if diastolic blood pressure was > 90 mmHg, a combination of the two drugs was given and was continued for 24 weeks. M-mode, 2D-guided echocardiography was used to measure LV mass index (LVMI) according to the ""Penn convention"". Minimal vascular resistance was measured in the forearm, from arterial pressure and maximal blood flow, using a strain gauge plethysmography. All examinations were performed before and after 8 and 24 weeks of treatment. Changes in LVMI were analysed at 8 weeks and at 24 weeks in patients receiving monotherapy (""according to protocol"" analysis), and also at the end of treatment in patients taking Nifedipine or HCTZ monotherapy or the combination of the two drugs (""intention to treat"" analysis). Both Nifedipine and HCTZ significantly reduced systolic and diastolic blood pressure (p < 0.001), without any significant difference between the two drug treatments. Heart rate was not significantly modified by either treatment. A progressive decrease in LVMI was observed after 8 and 24 weeks of treatment with Nifedipine monotherapy (ANOVA, p = 0.03), while the decrease in LVMI during HCTZ treatment did not progress further at 24 weeks (ANOVA, p = 0.49). A significant reduction of minimal vascular resistance was observed in patients treated with Nifedipine GITS monotherapy (ANOVA, p = 0.001), but not in the HCTZ group (ANOVA, p = 0.06). Comparison of changes of forearm minimal vascular resistance, considering baseline values, could demonstrate a greater effect during Nifedipine monotherapy as compared to HCTZ monotherapy. In conclusion, in a group of hypertensive patients with LVH, treatment for 24 weeks with Nifedipine GITS alone or in combination with HCTZ induced a significant reduction in LVMI and of forearm vascular structural changes, as evaluated by minimal vascular resistance. The decrease of minimal vascular resistance was significantly greater in patients treated with Nifedipine monotherapy, as compared to those given HCTZ.",1998.0,0,0
1181,9758088,The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design.,J Mann; S Julius,"Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.",1998.0,0,0
1182,9758323,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
1183,9764967,Constipation as an adverse effect of drug use in nursing home patients: an overestimated risk.,K N van Dijk; C S de Vries; P B van den Berg; A M Dijkema; J R Brouwers; L T de Jong-van den Berg,"To investigate whether results from case control and cross sectional studies which suggest an association between laxative use and other drug use could be confirmed in a cohort study of nursing home patients. A prospective cohort study of 2355 nursing home patients aged 65 years and over was performed to estimate the incidence relative risk of constipation associated with drug use. The study was conducted with prescription sequence analysis of each resident's detailed pharmacy records and data on morbidity and mobility. Use of drugs, which according to the summaries of product characteristics (SPC) and the literature on adverse drug effects have moderately to strongly constipating properties, was associated with a relative risk of 1.59 (95% CI 1.24-2.04) for the occurrence of constipation during exposure time. Use of drugs with mildly to moderately constipating effects was not associated with laxative use (RR 1.13; 95% CI 0.93-1.38). Stratification on the level of age, gender, type of nursing (psychogeriatric or somatic), morbidity, number of medications taken and mobility showed no confounding effects of these variables on outcome measurements. These variables all acted as effect modifiers. Effect of age and number of medications taken on the relative risk was nonlinear. Although an association between drugs that exhibit moderately to strongly constipating effects and occurrence of constipation was found, the risk was not as high as seen in previous studies. The high prevalence of constipation in nursing home patients is only partly due to adverse drug effects.",1998.0,0,0
1184,9775988,,,,,0,0
1185,9778203,Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks.,W D Hall; J W Reed; J M Flack; C Yunis; J Preisser,"Hypertension is a prevalent disease among African Americans, and successful treatment rates are low. Since calcium channel blockers are well-tolerated and efficacious in African Americans, we undertook this study to compare the efficacy, safety, and tolerability of 3 commonly prescribed calcium channel blockers: amlodipine besylate (Norvasc), nifedipine coat core (CC) (Adalat CC), and nifedipine gastrointestinal therapeutic system (GITS) (Procardia XL). One hundred ninety-two hypertensive patients across 10 study centers were randomly assigned to double-blind monotherapy with amlodipine besylate (5 mg/d), nifedipine CC (30 mg/d), or nifedipine GITS (30 mg/d) for 8 weeks. Patients not achieving therapeutic response after 4 weeks had their dose doubled for the next 4 weeks. The primary end point was a comparison of the average reduction (week 8 minus baseline) in 24-hour ambulatory diastolic blood pressure (DBP). Secondary end points included a comparison of average 24-hour ambulatory systolic blood pressure (SBP), office SBP or DBP reduction, responder rates, safety, and tolerability. One hundred sixty-three patients were evaluable for efficacy after 8 weeks. There was no significant difference in the average 24-hour ambulatory DBP (-8.5, -9.0, and -6.1 mm Hg, respectively) or SBP (-14.3, -15.7, and -11.8 mm Hg, respectively) reduction. Average office SBP and DBP were reduced to a comparable degree (19-22 mm Hg [P =.50] and 12-14 mm Hg [P =.51], respectively). Responder rates (DBP <90 or reduced by > or = 10 mm Hg) were similar (P = .38). Discontinuation rates and adverse event frequency were distributed similarly across the 3 treatment groups. The efficacy, safety, and tolerability of the 3 dihydropyridine calcium channel blockers are equivalent in African Americans with stages 1 and 2 hypertension.",1998.0,0,0
1186,9781971,Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.,C M O'Connor; P E Carson; A B Miller; M L Pressler; R N Belkin; G W Neuberg; D J Frid; A B Cropp; S Anderson; J H Wertheimer; D L DeMets,"Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.",1998.0,1,1
1187,9785750,Calcium channel blockers for prevention of noise trauma in otologic surgery.,J Maurer; W J Mann; R G Amedee,"One hundred patients were tested prior to otologic ear surgery in a prospective, randomized, double-blind study to assess the perioperative efficiacy of a calcium channel blocker (diltiazem) in preventing acoustical trauma during middle ear surgery. The patients were randomly divided into a therapy group (diltiazem), and a control group (placebo). Bone conduction hearing thresholds were examined preoperatively and followed at 1 day and 3 months postoperatively. Frequency-dependent changes in postoperative bone conduction and the number of patients with various degrees of postoperative hearing loss in both groups were statistically analyzed. The results indicated only a small postoperative hearing loss after ear surgery in both groups. There was a tendency for better results in the therapy group but this was not found to be statistically significant. Despite favorable results in animal trials utilizing different kinds of noise with the prophylactic application of diltiazem, further studies in humans will be needed to determine the role of calcium antagonist drugs in the prophylaxis or treatment of acoustical trauma.",1998.0,0,0
1188,9790159,Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness.,P J Pazzaglia; R M Post; T A Ketter; A M Callahan; L B Marangell; M A Frye; M S George; T A Kimbrell; G S Leverich; G Cora-Locatelli; D Luckenbaugh,"Of 30 patients with treatment-refractory affective illness, 10 showed a moderate to marked response to blind nimodipine monotherapy compared with placebo on the Clinical Global Impressions Scale. Fourteen inadequately responsive patients (3 unipolar [UP], 11 bipolar [BP]) were treated with the blind addition of carbamazepine. Carbamazepine augmentation of nimodipine converted four (29%) of the partial responders to more robust responders. Patients who showed an excellent response to the nimodipine-carbamazepine combination included individual patients with patterns of rapid cycling, ultradian cycling, UP recurrent brief depression, and one with BP type II depression. When verapamil was blindly substituted for nimodipine, two BP patients failed to maintain improvement but responded again to nimodipine and remained well with a blind transition to another dihydropyridine L-type calcium channel blocker (CCB), isradipine. Mechanistic implications of the response to the dihydropyridine L-type CCB nimodipine alone and in combination with carbamazepine are discussed.",1998.0,0,0
1189,9794714,Quality of life of elderly patients with isolated systolic hypertension: baseline data from the Syst-Eur trial. Syst-Eur Trial Investigators.,A E Fletcher; C J Bulpitt; J Tuomilehto; J Browne; A Bossini; K Kawecka-Jaszcz; P Kivinen; E O'Brien; J Staessen; L Thijs; O Vänskä; H Vanhanen,"To describe measures of quality of life of elderly patients with isolated systolic hypertension at entry to a placebo-controlled randomized trial of antihypertensive treatment and to investigate factors associated with these. Cross-sectional analyses at entry to a randomized controlled trial. Patients attending hypertension clinics or general practitioners' surgeries at 30 centres in 10 European countries. Six hundred and thirty-one patients aged 60 years or more, with a sitting systolic blood pressure during the run-in phase of 160-219 mmHg, a sitting diastolic blood pressure below 95 mmHg and a standing systolic blood pressure of 140 mmHg or more. Cognitive function tests (Reitan Trail Making 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 Housework). Poor quality of life was generally associated with increasing age, previous treatment with antihypertensive drugs, presence of cardiovascular complications and, among women, high diastolic blood pressure, higher consumption of alcohol and high body mass index. At entry to the trial there was considerable heterogeneity of patients in terms of measures of quality of life and cognitive performance. It remains to be determined whether these influence subsequent quality of life during randomized treatment.",1998.0,0,1
1190,9794736,Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst-Eur Vascular Dementia Project.,M L Seux; L Thijs; F Forette; J A Staessen; W H Birkenhäger; C J Bulpitt; X Girerd; M Jääskivi; H Vanhanen; P Kivinen; Y Yodfat; O Vänskä; R Antikainen; T Laks; J R Webster; T Hakamäki; E Lehtomäki; E Lilov; M Grigorov; K Janculova; K Halonen; P Kohonen-Jalonen; R Kermowa; C Nachev; J Tuomilehto,"To assess cognitive functions and their correlates for a dementia-free cohort of old patients with isolated systolic hypertension. Cross-sectional data from the randomization period of the European Trial in Elderly with Systolic Hypertension (Syst-Eur Vascular Dementia Project). Sixteen European countries and Israel. We studied 2252 patients aged 60-100 years (mean 70). Mini Mental State Examination (MMSE) and Spearman correlation of MMSE scores to demographic data or blood pressure. The MMSE was successfully completed for 1474 women and 751 men. The baseline blood pressure averaged 173 +/- 10/86 +/- 6 mmHg (means +/- SD). Median age at which education of patients at school had stopped was 15 years. Men and women who consumed alcohol (28%) had median intakes of 8 and 3 g/day, respectively. The median MMSE score was 29 (range 15-30). The maximum score of 30 was attained by 609 (30%) subjects. Fifty-nine (3%) patients had a MMSE score of 23 or less. The MMSE score decreased with advancing age (r = -0.21, P < 0.001). Both for men and for women, it was positively correlated to the level of education (r = 0.30 and r = 0.32, P < 0.001). For women after adjustment for age and the level of education, the score was correlated negatively to systolic blood pressure (r = -0.07, P < 0.05) but positively to intake of alcohol (r = 0.06, P < 0.05). In a cohort of elderly patients with isolated systolic hypertension, baseline cognitive function measured in terms of the MMSE score was high, probably due to selective recruitment of patients who were not clinically demented. Blood pressure was a weak contributor to cognitive status compared with age and level of education. Baseline cognitive function of women was negatively and independently correlated to systolic blood pressure.",1998.0,0,1
1191,9795483,Antihypertensive effect of amlodipine compared with nifedipine retard in patients with mild and moderate essential hypertension.,Z Kalina; B Okopień; A Madej; D Tokarz; A Maślankiewicz; Z Szwed; V Gross-Furek; Z S Herman,"The present study was undertaken to evaluate the efficacy and safety of amlodipine for hypertension treatment in comparison with nifedipine retard. We examined 31 patients with arterial blood pressure approximately 155-165 mmHg/100-105 mm Hg at the beginning of the trial. It was a randomized double-blind, parallel-group trial including two groups of patients. Patients of the first group were given active amlodipine and nifedipine retard placebo during 6 weeks, while the second group was given active nifedipine retard and amlodipine placebo. Statistical analysis was made using the paired Student's t-test, chi-square test and ANOVA test. At end point we observed significant decrease in arterial blood pressure after treatment of both drugs. The treatment with nifedipine retard increased the mean heart rate of patients. Amlodipine therapy in comparison to nifedipine retard did not change the heart rate in treated patients. Safety parameters: SGOT, SGTP, creatinine and others were in laboratory norms ranges. Amlodipine proved to be an effective, more safe and better-tolerated therapeutical alternative for hypertension management than nifedipine retard.",1998.0,0,0
1192,9806660,"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.",2000.0,0,1
1193,9808599,"Intensive medical therapy versus coronary angioplasty for suppression of myocardial ischemia in survivors of acute myocardial infarction: a prospective, randomized pilot study.",H A Dakik; N S Kleiman; J A Farmer; Z X He; J A Wendt; C M Pratt; M S Verani; J J Mahmarian,"Patients who have inducible ischemia after acute myocardial infarction (AMI) generally undergo coronary angiography with the intent to revascularize. Whether this approach is superior to intensive treatment with anti-ischemic medications is unknown. We performed a prospective, randomized pilot study comparing intensive medical therapy with coronary angioplasty (PTCA) for suppression of myocardial ischemia in 44 stable survivors of AMI. Myocardial ischemia was quantified with adenosine 201Tl tomography (SPECT) performed 4.5+/-2.9 days after AMI. All patients at baseline had a large total (>/=20%) and ischemic (>/=10%) left ventricular perfusion defect size (PDS). SPECT was repeated at 43+/-26 days after therapy was optimized. The total stress-induced PDS was comparably reduced with medical therapy (from 38+/-13% to 26+/-16%; P<0.0001) and PTCA (from 35+/-12% to 20+/-16%; P<0.0001). The reduction in ischemic PDS was also similar (P=NS) in both groups. Cardiac events occurred in 7 of 44 patients over 12+/-5 months. Patients who remained clinically stable had a greater reduction in ischemic PDS (-13+/-9%) than those who had a recurrent cardiac event (-5+/-7%; P<0.02). Event-free survival was superior in the 24 patients who had a significant (>/=9%) reduction in PDS (96%) compared with those who did not (65%; P=0.009). In this small pilot study, intensive medical therapy and PTCA were comparable at suppressing ischemia in stable patients after AMI. Sequential imaging with adenosine SPECT can track changes in PDS after anti-ischemic therapies and thereby predict subsequent outcome. Corroboration of these preliminary findings in a larger cardiac-event trial is warranted.",1998.0,0,0
1194,9809930,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.",1998.0,1,1
1195,9819017,"A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension.",P R Conlin; M Elkins; C Liss; A J Vrecenak; E Barr; J M Edelman,"We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.",1998.0,0,0
1196,9820054,[The TEAM study--a study of the effectiveness and tolerance of treatment of essential hypertension with a fixed combination of trandolapril and verapamil].,J Widimský; R Dzúrik,"The TEAM trial investigated the effectiveness and tolerance of a fixed combination of the ACE inhibitor and calcium channel blocker (2 mg trandolapril and 180 mg verapamil retard) (preparation Tarka) in an open multicentre prospective study of treatment of moderately severe hypertension (diastolic pressure at the end of the two-week wash-out period 100-115 mm Hg). The trial comprised 163 patients who were treated first for four weeks by a monotherapy with 2 mg trandolapril. After these four weeks patients who attained normal blood pressure proceeded with trandolapril treatment. Hypertensive patients who did not attain normal diastolic pressure levels were treated for another four weeks by a fixed combination of trandolapril and verapamil SR. After four weeks of treatment with trandolapril 62 patients of 163 (37%) had a diastolic blood pressure of less than 90 mm Hg. The fixed combination of trandolapril and verapamil SR reduced the diastolic blood pressure to less than 90 mm Hg in 71.6% of the patients resistant to treatment with 2 mg trandolapril and in another 15.6% of patients it reduced the diastolic blood pressure by 10 mm Hg or more. After two months of treatment 60 patients had a normal blood pressure due to trandolapril (37%) and another 73 patients (45%) treated by a combination of trandolapril and verapamil SR, i.e. a total of 133 patients (82%) who originally suffered from moderately severe hypertension, attained a normal diastolic blood pressure. The mean decrease of diastolic pressure after two months of treatment was 19.5 mm Hg in ""non-respondents"" to trandolapril monotherapy and 23.6 mm Hg in ""respondents"". The mean decrease of systolic pressure in ""non-respondents"" and ""respondents"" after trandolapril treatment was 19.5 mm Hg and 35.0 mm Hg resp. The fixed combination of trandolapril and verapamil was not only effective but was associated with a minimum of undesirable effects. The incidence of headaches declined significantly. The combination of the above preparations is useful also because both preparations have a cardio- and nephroprotective effect and do not affect the lipid and carbohydrate metabolism. Treatment with a fixed combination of trandolapril and verapamil SR is indicated in moderately severe hypertension not responding to monotherapy, in particular when associated with diabetes, hyperlipoproteinaemia, ischaemic heart disease or left ventricular hypertrophy.",1998.0,0,0
1197,9821992,Beta-adrenergic blockade accelerates conversion of postoperative supraventricular tachyarrhythmias.,J R Balser; E A Martinez; B D Winters; P W Perdue; A W Clarke; W Huang; G F Tomaselli; T Dorman; K Campbell; P Lipsett; M J Breslow; B A Rosenfeld,"Postoperative supraventricular tachyarrhythmia is a common complication of surgery. Because chemical cardioversion is often ineffective, ventricular rate control remains a principal goal of therapy. The authors hypothesized that patients with supraventricular tachyarrhythmia after major noncardiac surgery who receive intravenous beta-adrenergic blockade for ventricular rate control would experience conversion to sinus rhythm at a rate that differs from those receiving intravenous calcium channel blockade. The rate of conversion to sinus rhythm at 2 and 12 h after treatment was examined in 64 cases of postoperative supraventricular tachyarrhythmia. After adenosine administration, patients who remained in supraventricular tachyarrhythmia were prospectively randomized to receive either intravenous diltiazem or intravenous esmolol for ventricular rate control (unblinded). Loading and infusion rates were adjusted to achieve equivalent degrees of ventricular rate control. Patients were similar with regard to age and Apache III score. Most patients in both groups had atrial fibrillation (esmolol, 79%; diltiazem, 81%), and none experienced stable conversion with adenosine. Patients randomized to receive esmolol experienced a 59% rate of conversion to sinus rhythm within 2 h of treatment, compared with only 33% for patients randomized to receive diltiazem (intention to treat, P = 0.049; odds ratio, 2.9; 95% confidence interval, 1.046 to 7.8). After 12 h of therapy, the number of patients converting to sinus rhythm increased in both groups (esmolol, 85%; diltiazem, 62%), and the rates of conversion no longer differed significantly. Ventricular rates when supraventricular tachyarrhythmia began and after 2 and 12 h of rate control therapy were similar in the two treatment groups. The in-hospital mortality rate and length of stay in the intensive care unit were not significantly influenced by treatment group. Among adenosine-resistant patients in the intensive care unit with atrial fibrillation after noncardiac surgery, intravenous esmolol produced a more rapid (2-h) conversion to sinus rhythm than did intravenous diltiazem.",1998.0,0,0
1198,9825197,"Modulation of ventricular rate in permanent atrial fibrillation: randomized, crossover study of the effects of slow-release formulations of gallopamil, diltiazem, or verapamil.",G L Botto; W Bonini; T Broffoni,"The management of permanent atrial fibrillation (PAF) consists primarily of long-term anticoagulation with either aspirin or warfarin to prevent systemic embolization, and modulation of ventricular rate (VR) to improve cardiac function by prolonging the ventricular diastolic filling time. The effects of slow-release formulations of gallopamil (100 mg b.i.d.), diltiazem (120 mg b.i.d.), or verapamil (120 mg b.i.d.) on VR were evaluated in 18 patients with PAF without organic heart disease. In all patients, each treatment was administered randomly, was compared with oral digoxin, and was assessed by 24-h Holter monitoring during daily life and by a 6-min walking test. There were no significant differences in mean and minimum VR recorded during 24-h Holter monitoring among the four treatments. Peak heart rates recorded during the 6-min walking test with digoxin treatment was 167 +/- 12 beats/min. This was significantly reduced by gallopamil (149 +/- 23 beats/min, p = 0.01), diltiazem (142 +/- 24 beats/min, p < 0.001), and verapamil (137 +/- 30 beats/min, p < 0.001). There were no significant differences in peak VR during the walking test among the three calcium antagonists. Pauses of > 3 s were observed in 3 of 18 (17%) patients who received digoxin (max 3.4 s) and in 5 of 18 (28%) patients who received diltiazem (max 3.4 s); p = NS. Periods of bradycardia < 30 beats/min were observed in 5 of 18 (28%) patients during digoxin treatment, and in 3 of 18 (17%) patients during treatment with gallopamil, diltiazem, and verapamil; p = NS. Gallopamil, diltiazem, or verapamil are superior to digoxin in controlling VR during mild exercise in patients with PAF without organic heart disease. The reduction of peak VR is obtainable without further slowing of resting VR. However, gallopamil appears to be the least effective calcium blocker at controlling resting and exercise VR; thus, there are no advantages over the other calcium blockers in its use in the clinical setting.",1998.0,1,1
1199,9836028,Diltiazem-lidocaine combination for the attenuation of cardiovascular responses to tracheal intubation in hypertensive patients.,Y Fujii; Y Saitoh; S Takahashi; H Toyooka,"Hypertensive patients are prone to haemodynamic changes after laryngoscopy and tracheal intubation. This study was undertaken to compare the efficacy of a combination of diltiazem and lidocaine with that of each drug alone for suppressing the cardiovascular responses to tracheal intubation. Sixty hypertensive patients (ASA II), defined as systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 95 mmHg (World Health Organization), undergoing elective surgery received, in a randomized, double-blind manner, 0.3 mg.kg-1 diltiazem, 1.5 mg.kg-1 lidocaine, or 0.3 mg.kg-1 diltiazem plus 1.5 mg.kg-1 lidocaine i.v. (n = 20 of each) before the initiation of laryngoscopy. Anaesthesia was induced with 5 mg.kg-1 thiopentone i.v., and tracheal intubation was facilitated with 2 mg.kg-1 succinylcholine i.v. after precurarization with 0.02 mg.kg-1 vecuronium i.v. Changes in heart rate (HR), mean arterial pressure (MAP) and rate-pressure product (RPP) were measured before and at immediate, 1, 2, 3, 5 and 10 min after tracheal intubation. The inhibitory effects of diltiazem-lidocaine combination on cardiovascular responses to tracheal intubation was greater than those of diltiazem or lidocaine as a sole medicine (RPP; 10,602 +/- 1448 (combination) vs 11,787 +/- 1345 (diltiazem), 15,428 +/- 1756 (lidocaine), mean +/- SD, P < 0.05). Prophylactic therapy with diltiazem-lidocaine combination is more effective than diltiazem or lidocaine alone for attenuating the cardiovascular changes associated with tracheal intubation in hypertensive patients.",1998.0,0,0
1200,9839057,Do calcium channel blockers increase the risk of myocardial infarction in hypertensive patients with diabetes mellitus?,L Park; C P Por; M F Evans,,1998.0,0,1
1201,9839101,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
1202,9856368,The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.,A Zanchetti; E A Rosei; C Dal Palù; G Leonetti; B Magnani; A Pessina,"It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.",1998.0,0,1
1203,9865094,[Recommended article of the month: Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial].,J Maldonado,,1998.0,0,0
1204,9869019,Quality of life and calcium channel blockade with nifedipine GITS versus amlodipine in hypertensive patients in Spain. Gastrointestinal Therapeutic System.,M A Testa; R R Turner; D C Simonson; M B Krafcik; C Calvo; M Luque-Otero,"Compliance with hypertension treatment is affected by treatment-related factors (complexity, side effects), efficacy and compound-specific effects that impact on quality of life. This study examined the differences in quality of life produced by two once-daily calcium channel blockers using different delivery systems: nifedipine gastrointestinal therapeutic system (GITS) and amlodipine. This was a double-blind, double-dummy, randomized clinical trial comparing nifedipine GITS (30 mg) and amlodipine (5 mg) for 24 weeks following a placebo run-in. Clinical, laboratory evaluations and quality-of-life data were assessed at screening, baseline randomization and three times during active therapy. The study was conducted in 13 medical clinics in Spain. The sample comprised 430 screened and 356 randomized patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg). Change in systolic and diastolic blood pressure and in health-related quality of life were the main outcome measures. There were no significant differences between active treatment groups in the blood pressure changes (systolic blood pressure: nifedipine GITS -15.5 mmHg; amlodipine -15.7 mmHg). Spontaneous adverse events consistent with calcium channel blockage were not different. The nifedipine GITS group improved in all quality-of-life measures except Sexual Symptom Distress and showed a significantly greater improvement than amlodipine in overall Quality of Life (P< 0.05), General Perceived Health (P < 0.026) and its subscale Vitality (P < 0.019). The amlodipine group declined in overall Quality of Life, General Perceived Health, Vitality and Sleep Disturbance, and significantly in Sexual Symptom Distress (P < 0.045). However, this group improved in self-reported Cognitive Functioning (P=0.036), Mental Acuity (P < 0.005) and Detachment/disorientation (P=0.01). These results suggest compound-specific effects on quality of life that may be due to differences in the delivery system. Nifedipine GITS is short-acting (2 h half-life) and is delivered continuously over a 24 h period, while amlodipine has a half-life of 40 h, which may produce more sustained low-level effects. While a more beneficial profile was observed for nifedipine, amlodipine demonstrated potential positive effects on cognitive functioning.",1998.0,1,1
1205,9880123,Calcium channel blocker use and the risk of prostate cancer.,R M Vezina; S M Lesko; L Rosenberg; S Shapiro,"A recent study suggested that the risk of all cancers, including prostate cancer, is increased by the use of calcium channel blockers. The objective of this study was to determine whether prostate cancer is associated with calcium channel blocker use. A case-control study was conducted in Massachusetts using cases diagnosed from December 1992 through February 1995. Cases were men identified by tumor registrars who were less than 70 years old with newly diagnosed prostate cancer. Controls were men with no history of prostate cancer or symptoms of undiagnosed prostate cancer, and were matched to the cases on precinct of residence and half-decade of age. A total of 1217 cases of prostate cancer and 1400 community controls are included in this analysis. Data were collected by telephone interview. Multiple logistic regression was used to estimate relative risks for calcium channel blockers use while controlling for confounding. The relative risk for prostate cancer for any use of calcium channel blockers relative to nonuse was 1.2 (95% confidence interval [CI], 0.9-1.5). There was no evidence of a trend according to duration of use. When the analysis was confined to symptomatic men, the relative risk estimate was 1.1 (0.8-1.4) overall and 1.2 (0.8-1.7) among those aged 65 to 69 years. Relative risk estimates for the use of other classes of antihypertensive drugs among symptomatic men were close to 1.0; the corresponding estimates among asymptomatic men were generally further from 1.0. These findings suggest that calcium channel blockers do not increase the risk of prostate cancer. The differences in the relative risk estimates between symptomatic and asymptomatic men are compatible with detection bias. Because of the widespread use of Prostate-Specific Antigen testing for early detection of prostate cancer, potential detection bias needs to be considered in future studies of prostate cancer.",1999.0,0,1
1206,9885099,Outpatient management of congestive heart failure.,E K Massin,,1999.0,0,0
1207,9886905,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
1208,9889429,Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis.,J Nakayama; T Koga; M Furue,"Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.",1999.0,0,1
1209,9890408,Analysis of arrhythmias in the Circadian Antiischemia Program in Europe (CAPE) study.,P R Lichtlen; L D Fisher,"The aim of this study was to analyze whether, in patients with long-standing (>4 years) coronary artery disease (CAD), the addition of the long-acting calcium channel blocker (CCB) amlodipine to conventional treatment [beta-blockers (BBLs) and nitrates] during anginal attacks would have a proarrhythmic effect. This was tested by analyzing data from patients who had taken part in the Circadian Anti-ischemia Program in Europe (CAPE) trial. After a 2-week, single-blind, run-in period (Phase 1), patients were randomized to amlodipine, 5 mg/day (first 4 weeks) and 10 mg/day (second 4 weeks), or placebo for 8 weeks (Phase 2). The 48-h Holter data were analyzed for 167 amlodipine-treated patients and 83 placebo patients based on a 2:1 randomization scheme. Sixty-three per cent of amlodipine patients and 67% of placebo patients were receiving concomitant BBLs, and >90% had taken sublingual nitrates during anginal attacks, as basic antiischemic therapy. After 7 weeks of therapy, when 48-h Holter monitoring was repeated, there were no significant changes in the frequency of ventricular arrhythmias in the placebo or amlodipine groups for all patients or subgroups of patients with or without BBLs. Also, between-group comparisons showed no significant differences in arrhythmias between amlodipine and placebo patients. In summary, amlodipine (5-10 mg/day) given to patients with severe, chronic CAD receiving conventional antiischemic therapy, did not produce any proarrhythmic effects.",1999.0,0,0
1210,9893735,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
1211,9894374,"Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group.",R M Schaefer; P M Aldons; E D Burgess; R Tilvis; X Girerd; G P Singh; L Rehn; T O Morgan,"The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was > 160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p = 0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.",1999.0,0,0
1212,9917082,Comparison of 24-hour ambulatory blood pressure data in hypertensive patients switched from nifedipine-GITS to nifedipine-CC.,R L Wurdeman; A N Mooss; S M Mohiuddin; B D Lucas; K L Ryschon; D E Hilleman,"To evaluate 24-hour blood pressure control and frequency of adverse effects in patients with mild to moderate hypertension switched from nifedipine gastrointestinal therapeutic system (Nif-GITS) to nifedipine coat core (Nif-CC). Open-label, prospective, switch study University-affiliated outpatient cardiology clinic. Twenty patients with mild to moderate essential hypertension, who were taking Nif-GITS 30, 60, or 90 mg/day for 8 weeks or longer. Patients stabilized with Nif-GITS 30, 60, or 90 mg were monitored over 24 hours with an ambulatory blood pressure monitor and were then switched to an equivalent dosage of Nif-CC. After 8 weeks+/-1 week taking Nif-CC, they were again monitored with a 24-hour blood pressure monitor. The 24-hour blood pressure load (percentage of values > 135/85 mm Hg for 24 hrs), daytime blood pressure load (percentage of values > 140/90 mm Hg from 7:00 A.M.-10:00 P.M.), nighttime blood pressure load (percentage of values > 120/80 mm Hg from 10:00 P.M.-7:00 A.M.), diurnal blood pressure variation, average 24-hour blood pressure, daytime blood pressure, nighttime blood pressure, mean blood pressure for the first 4 hours, and last 8 hours of the dosing interval were measured. Adverse effects such as headache, dizziness, and edema were also reported. No differences in average 24 hour-blood pressure readings were observed but significant differences in blood pressure control during the first 4 and last 8 hours of the dosing interval were seen. Systolic and diastolic blood pressures were higher after approximately 16 hours in patients switched from Nif-GITS to Nif-CC. Although Nif-CC caused a greater initial response, it was less effective than Nif-GITS after 16 hours. This could explain the lack of differences in average 24-hour blood pressure values between formulations. Of the 20 patients, 20% experienced increased headaches, 20% showed signs of increased peripheral edema, and 10% reported occasional dizziness after switching agents. Three patients discontinued Nif-CC, two as ordered by their primary care physician and one on his own due to headache. This study suggests that patients switched from Nif-GITS to Nif-CC could experience increased blood pressure during the night or toward the end of the dosing interval. They could also experience adverse effects such as headache, edema, and dizziness, which could result in more physician visits and put patients with other disease states such as coronary heart disease at increased risk.",2001.0,0,0
1213,9919418,,,,,0,0
1214,9928753,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
1215,9928754,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
1216,9928755,A randomised double-blind study comparing nifedipine GITS 20 mg and bendrofluazide 2.5 mg administered once daily in mild-to-moderate hypertension.,C G Isles; N R Kitchin,"A multicentre, randomised, double-blind, parallel group comparison of nifedipine GITS 20 mg (Adalat LA) once daily and bendrofluazide 2.5 mg once daily in patients with mild-to-moderate hypertension was conducted. Two hundred patients with a diastolic blood pressure (BP) in the range 95 to 109 mm Hg were randomised to active treatment for 6 weeks. For the per-protocol efficacy population, both treatments resulted in clinically significant mean reductions of trough diastolic BP (nifedipine GITS -8.9 mm Hg, bendrofluazide -7.9 mm Hg) and systolic BP (nifedipine GITS -10.4 mm Hg, bendrofluazide -10.5 mm Hg). The study demonstrated that nifedipine GITS was 'at least equivalent' to bendrofluazide in the reduction of trough diastolic BP (one-sided upper 95% confidence limit, 0.5 mm Hg), where inequivalence had been pre-defined as a difference in mean diastolic BP of > or =5 mm Hg. Both drugs were well tolerated, the overall incidence of adverse events in the nifedipine GITS treatment group being 34.0% (34/100) and in the bendrofluazide treatment group being 29.0% (29/100). The commonest events (incidence > or =5%) were headache, constipation, 'flu syndrome and vasodilatation with nifedipine GITS and headache and nausea with bendrofluazide. An increased incidence of elevations of plasma urea and glucose was observed in patients treated with bendrofluazide (9.6% and 30.4% respectively) compared to those treated with nifedipine GITS (3.1% and 18.8% respectively). Nifedipine GITS 20 mg once daily is 'at least equivalent' to bendrofluazide 2.5 mg once daily in reduction of blood pressure in patients with mild-to-moderate hypertension.",1999.0,0,0
1217,9931077,Safety of nifedipine in angina pectoris: a meta-analysis.,W B Stason; C H Schmid; D Niedzwiecki; G W Whiting; J F Caubet; D Cory; D Luo; S D Ross; T C Chalmers,"-Our objective was to compare cardiovascular event rates in patients with stable angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. A MEDLARS search of published articles from 1966 to 1995 in English, French, German, Italian, or Spanish, supplemented by a manual search of bibliographies, identified 60 randomized controlled trials that met protocol criteria. Blinded articles were extracted by 2 physicians. The pooled risks of death, withdrawal, and cardiovascular event were computed and expressed as odds ratios (ORs) for all nifedipine formulations and relative to same study control drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine exposures (1.14%) and 19 events in 2655 other active drug exposures (0.72%). Unadjusted ORs for nifedipine versus controls were 1.40 (95% CI, 0.56 to 3.49) for major events (death, nonfatal myocardial infarction, stroke, revascularization procedure), 1.75 (95% CI, 0.83 to 3.67) for increased angina, and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased angina). Episodes of increased angina were more frequent on immediate-release nifedipine (OR, 4.19 [95% CI, 1.41 to 12.49]) and on nifedipine monotherapy (OR, 2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was significantly higher than that for sustained-release/extended-release nifedipine (P=0.001), and the OR for nifedipine monotherapy was higher than that for nifedipine combination therapy (P=0.03). Increased risks of cardiovascular events in patients with stable angina on nifedipine were due primarily to more episodes of increased angina, confined to the immediate-release formulation and to nifedipine monotherapy.",1999.0,1,1
1218,9973007,Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens.,R Farshi; D Kistner; J S Sarma; J A Longmate; B N Singh,"We compared the effects of five pharmacologic regimens on the circadian rhythm and exercise-induced changes of ventricular rate (VR) in patients with chronic atrial fibrillation (CAF). Systematic comparison of standardized drug regimens on 24 h VR control in CAF have not been reported. In 12 patients (11 male, 69+/-6 yr) with CAF, the effects on VR by 5 standardized daily regimens: 1) 0.25 mg digoxin, 2) 240 mg diltiazem-CD, 3) 50 mg atenolol, 4) 0.25 mg digoxin + 240 mg diltiazem-CD, and 5) 0.25 mg digoxin + 50 mg atenolol; were studied after 2 week treatment assigned in random order. The VR data were analyzed by ANOVA with repeated measures. The circadian phase differences were evaluated by cosinor analysis. The 24-h mean (+/-SD) values of VR (bpm) were - digoxin: 78.9 +/- 16.3, diltiazem: 80.0+/-15.5, atenolol: 75.9+/-11.7, digoxin + diltiazem: 67.3+/-14.1 and digoxin + atenolol: 65.0+/-9.4. Circadian patterns were significant in each treatment group (p < 0.001). The VR on digoxin + atenolol was significantly lower than that on digoxin (p < 0.0001), diltiazem (p < 0.0002) and atenolol (p < 0.001). The time of peak VR on Holter was significantly delayed with regimens 3 and 5 which included atenolol (p < 0.03). During exercise, digoxin and digoxin + atenolol treatments resulted in the highest and lowest mean VR respectively. The exercise Time-VR plots of all groups were nearly parallel (p = ns). The exercise duration was similar in all treatment groups (p = ns). This study indicates that digoxin and diltiazem, as single agents at the doses tested, are least effective for controlling ventricular rate in atrial fibrillation during daily activity. Digoxin + atenolol produced the most effective rate control reflecting a synergistic effect on the AV node. The data provides a basis for testing the effects of chronic suppression of diurnal fluctuations of VR on left atrial and ventricular function in CAF.",1999.0,1,1