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A new calcium ion antagonist, gallopamil, 150 mg/day, was compared with propranolol, 240 mg/day, in 20 patients with stable chronic angina. The patients were studied in a randomized, placebo-controlled, double-blind, crossover trial. Multistage treadmill exercise with computer-assisted electrocardiographic analysis was performed after 2 weeks of placebo therapy and at the end of each 4-week active treatment period. The mean (+/- standard error of the mean) exercise time to development of angina was 5.4 +/- 0.3 minutes with placebo; this increased to 9.4 +/- 0.7 minutes with propranolol (p less than 0.001) and 10.1 +/- 0.7 minutes with gallopamil (p less than 0.001 vs placebo; difference not significant vs propranolol). Both drugs significantly prolonged the time to development of 1 mm of ST depression. Five patients became free of angina during treadmill testing with gallopamil therapy and 2 with propranolol. Both drugs decreased the heart rate at rest; propranolol also decreased the maximal exercise heart rate, which was slightly increased with gallopamil. With the exception of 1 patient in whom raised liver enzymes developed, gallopamil was well tolerated. Thus, gallopamil is an effective antianginal agent that has few of the unwanted effects associated with other calcium channel-blocking drugs.

The comparative efficacy of verapamil (360 mg daily) and propranolol (240 mg daily) was evaluated with computerized treadmill exercise in 22 patients with chronic stable angina in a placebo-controlled double-blind crossover study with 4 weeks on each active phase. Fourteen of these patients still had angina despite active drug therapy and they were further treated with a combination of verapamil (360 mg) and propranolol (120 mg) for 4 weeks. The mean exercise time for these patients taking placebo was 4.8 +/- 0.22 minutes (mean +/- standard error of the mean) and this increased to 6.8 +/- 0.64 minutes with propranolol and 8.0 +/- 0.5 minutes with verapamil. A further increase to 10.1 +/- 0.88 minutes was observed with the combination of both drugs and seven patients became symptom-free. S-T segment criteria improved with both drugs, and combination therapy produced a further reduction in peak S-T depression. Electrocardiographic ambulatory monitoring showed no evidence of conduction defects and mean hourly heart rates were similar to those seen with propranolol alone. Left ventricular function indexes were not significantly different from those obtained with propranolol. Combination therapy with verapamil and propranolol appears to be efficacious in the treatment of selected patients with severe chronic stable angina. The patients need to be carefully monitored for adverse effects.

Two dose levels of diltiazem with propranolol were compared in the management of chronic stable angina. Two groups of patients were treated for alternate periods of 4 weeks with each drug in a double-blind crossover with computer-assisted maximal treadmill tests and ambulatory ST-segment monitoring for evaluation of efficacy and safety. In 12 patients who received diltiazem, 180 mg/day, the time to development of angina increased from 5.9 +/- 0.7 minutes (+/- standard error of the mean) during placebo treatment to 8.3 +/- 0.8 minutes during diltiazem treatment and to 9.2 +/- 0.8 minutes with propranolol, 240 mg/day. Three patients became angina-free when they were treated with both drugs. Among 12 patients who received diltiazem, 360 mg/day, 1 patient became angina-free during treatment with both drugs and 1 became angina-free with diltiazem only. The mean exercise time increased from 5.8 +/- 0.7 minutes with placebo to 8.6 +/- 1.0 minutes with diltiazem, 360 mg/day, and to 8.2 +/- 0.6 minutes with propranolol, 240 mg/day. Analysis of variance showed no difference in efficacy between the 2 doses of diltiazem or between the 2 drugs. Ambulatory heart rate was reduced both during the day and at night with both drugs and significantly more with propranolol than with diltiazem treatment. Except for 1 patient in whom a rash developed when given diltiazem, 180 mg/day, and another who had both a rash and first-degree heart block with diltiazem, 360 mg/day, both drugs were well tolerated. Thus, diltiazem in a daily dose of 180 or 360 mg/day is as effective as propranolol for the treatment of chronic stable angina.

The effectiveness and safety of verapamil, nifedipine, and placebo in patients with chronic stable angina pectoris were evaluated and compared in two double-blind randomized crossover trials. In the first study, nifedipine (10 mg 3 times daily) was compared with placebo in 24 patients with chronic effort-related angina pectoris; no significant differences in exercise performance were observed with nifedipine compared with placebo. In the second study, the effects of verapamil (120 mg 3 times daily), nifedipine (20 mg 3 times daily), and placebo were compared in 32 patients with chronic stable angina using a double-blind crossover study design. Compared with placebo, both nifedipine and verapamil prolonged exercise duration (5.7 +/- 0.3 minutes with placebo, 7.9 +/- 0.5 minutes with nifedipine [p less than 0.001], and 10.0 +/- 0.7 minutes with verapamil [p less than 0.001]), but the improvement with verapamil was greater than that seen with nifedipine (p less than 0.01). Seven patients had increasing angina with nifedipine, none did with verapamil; the exacerbation of angina during nifedipine therapy appeared related to our observation that, compared with placebo, patients receiving nifedipine had higher heart rates, while patients receiving verapamil had slower heart rates. This study indicates that, at the doses used, verapamil was more effective and better tolerated than nifedipine in patients with chronic stable angina pectoris.

The effectiveness and safety of the beta-adrenergic blocking agent propranolol and the calcium channel antagonist verapamil were compared in 22 patients with chronic stable angina pectoris using a double-blind randomized placebo-controlled crossover protocol. The double-blind phase was preceded by a 2 week single-blind placebo period, followed by randomization to either 4 weeks' therapy with verapamil, 360 mg/day, or propranolol, 240 mg/day, followed by crossover to the other drug. Both verapamil and propranolol increased exercise tolerance (5.5 +/- 0.4 minutes with placebo, 7.8 +/- 0.5 minutes with propranolol [p less than 0.001], and 9.1 +/- 0.5 minutes with verapamil [p less than 0.001]), but the increase with verapamil was significantly greater (p less than 0.01). Both drugs prolonged the exercise duration to 1 mm S-T depression (3.3 +/- 0.4 minutes with placebo, 5.7 +/- 0.5 minutes with propranolol [p less than 0.001] and 5.5 +/- 0.6 minutes with verapamil [p less than 0.001]); the degree of improvement was similar with both active drugs. Both drugs decreased the resting heart rate (76 +/- 3 beats/min with placebo, 56 +/- 2 beats/min with propranolol [p less than 0.001], and 71 +/- 3 beats/min with verapamil [p less than 0.01]), but the heart rate decreased more with propranolol than with verapamil (p less than 0.001). Neither drug produced significant adverse reactions. This study, along with 8 similar double-blind placebo-controlled randomized investigations which have compared verapamil with propranolol, indicate that verapamil is as effective and safe as propranolol in relieving symptoms and improving exercise tolerance in patients with chronic stable angina pectoris and may be considered a first-line therapeutic agent in patients with ischemic heart disease.

A randomized double-blind crossover trial was performed in 32 patients with chronic stable angina to compare the antianginal actions of verapamil (120 mg 3 times daily) and nifedipine (20 mg 3 times daily). Efficacy was assessed using objective end points obtained by computer-assisted exercise testing and 24 hour ambulatory monitoring for S-T segment shift. Twenty-eight patients completed the trial. The mean exercise time to produce angina improved from 5.7 +/- 0.3 minutes (mean +/- standard error of the mean) in patients on placebo, to 7.9 +/- 0.5 minutes in those on nifedipine and 10.0 +/- 0.7 minutes in those on verapamil. Similar improvement was seen in all other objective variables. Generally verapamil produced mild bradycardia and nifedipine mild tachycardia. Four patients complained of palpitations and angina after ingestion of nifedipine and were identified by ambulatory monitoring to have tachycardia and persistent S-T depression. These opposite effects on heart rate may explain the differences in efficacy between these 2 potent calcium ion antagonists.

An objective assessment of the efficacy of bevantolol was performed in 21 patients with chronic, stable angina using computer-assisted exercise testing and ambulatory ST-segment monitoring. Given once daily, 200 mg of bevantolol was compared with 200 mg of bevantolol given twice daily and with placebo, using a double-blind crossover technique. The mean exercise time with placebo was 7.4 +/- 0.6 minutes; this increased to 10.6 +/- 0.9 minutes (p less than 0.001) with once-daily bevantolol and to 9.4 +/- 0.9 minutes (p less than 0.001) with twice-daily bevantolol. The mean heart rate at rest was 80 +/- 3 beats/min with placebo; it decreased to 63 +/- 2 beats/min (p less than 0.001) with once-daily bevantolol and to 66 +/- 2 beats/min (p less than 0.001) with twice-daily bevantolol. The maximum exercise heart rate of 118 +/- 6 beats/min with placebo was reduced to 99 +/- 4 beats/min (p less than 0.001) on once-daily and 101 +/- 4 beats/min (p less than 0.001) on twice-daily bevantolol. There was a corresponding decrease in the rate-pressure product. The corrected maximum ST-segment depression was reduced from 0.3 +/- 0.06 mm min-1 with placebo to 0.2 +/- 0.03 mm min-1 (p less than 0.02) with once-daily and 0.2 +/- 0.04 mm min-1 (p less than 0.05) with twice-daily bevantolol. The mean hourly ambulatory heart rate was significantly reduced for 21 hours with once-daily and 22 hours with twice-daily bevantolol. The lowest mean minimum heart rate was 55 beats/min during twice-daily treatment. The mean number of episodes of ST depression over 24 hours in lead CM5 was decreased from 6.89 +/- 1.7 with placebo to 2.50 +/- 0.6 (p less than 0.001) with once-daily and to 3.72 +/- 1.3 (p less than 0.001) with twice-daily bevantolol. Three patients were withdrawn during the once-daily bevantolol regimen due to adverse experiences, and another patient was admitted for coronary artery bypass surgery after 25 days.(ABSTRACT TRUNCATED AT 250 WORDS)

The long-term efficacy of diltiazem, 360 mg/day, in patients with grade II or III stable exertional angina pectoris (Canadian Cardiovascular Society criteria) was assessed by multistage graded exercise tests. Seventeen patients undertook a placebo-controlled, double-blind, dose-titration protocol and all received long-term therapy. Exercise tests were performed at the end of 2 weeks of placebo treatment and after 6, 18, 26, 40 and 52 weeks of diltiazem, 360 mg/day. All patients had angina during treadmill testing with placebo and the mean (+/- standard error of the mean) exercise time was 5.8 +/- 0.7 minutes. This increased to 10.8 +/- 1.0 minutes after 6 weeks, 11.3 +/- 1.1 minutes after 18 weeks, 11.4 +/- 1.1 minutes after 26 weeks, 12.9 +/- 1.2 minutes after 40 weeks and 11.6 +/- 1.3 minutes after 52 weeks of continuous diltiazem therapy (p less than 0.001 vs placebo at all stages). Four patients were withdrawn after 26 weeks of treatment; one patient underwent coronary artery bypass surgery and 3 patients required the addition of beta-adrenoreceptor blocking agents. In 1 patient an irritant rash developed on the torso, legs and arms after 39 weeks of diltiazem and disappeared after discontinuing the drug. One patient complained of swelling and stiffness of the fingers and 3 patients complained of shoulder and elbow pain. Another patient had a myocardial infarction after 8 weeks of diltiazem treatment and died. No other adverse effects were observed during this study.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of placebo were studied in 150 patients (135 men, 15 women) aged 42 to 75 years with stable exertional angina pectoris, using multistage graded exercise testing. Treadmill exercise, using on-line computer analysis of the electrocardiogram, was performed after a basal period, during which time the patients had no treatment for 2 weeks, and after 2 weeks of placebo therapy. Mean exercise time during no treatment was 6.0 +/- 0.2 minutes and during placebo was 6.1 +/- 0.2 minutes (difference not significant). Similarly, time to development of 1 mm of ST-segment depression of 4.0 +/- 0.2 minutes without treatment was 4.1 +/- 0.2 minutes after 2 weeks of placebo therapy (difference not significant). Placebo failed to show any effect on rest or maximal heart rate or on maximal ST-segment depression. It also failed to increase exercise tolerance or to improve other objective indexes of effort-induced myocardial ischemia in both single-and double-blind protocols in patients with stable exertional angina pectoris. Therefore, placebo control of antianginal drug trials that use exercise testing for evaluation of effect is unnecessary and can be omitted.