Randomized, double-blind comparison of propranolol alone and a propranolol-verapamil combination in patients with severe angina of effort

This study compared propranolol alone with a combination of propranolol and verapamil in patients with severe, limiting angina of effort. Accordingly, 13 men (average age 57 years) with severe angina were enrolled in a study of 7 weeks' duration. Throughout the study, a stable dose of propranolol (295 ± 83 [mean ± standard deviation] mg/day) was administered. In addition to propranolol therapy, each patient was given 2 weeks of up-titration of open label verapamil, 1 week of verapamil down-titration and two 2 week periods of randomized, double-blind therapy, one of placebo and the other of verapamil (431 ± 77 mg/day). A propranolol-verapamil combination caused a decline in anginal episodes/ week (7.3 ± 6.9/week during propranolol-placebo, 4.7 ± 5.0/week during propranolol-verapamil, p = 0.03) and nitroglycerin tablets used/week (7.6 ± 6.6/week during propranolol-placebo, 4.4 ± 4.2/week during propranolol-verapamil, p = 0.008). With propranolol-placebo, all 13 patients had angina after 4.6 ±2.1 minutes of supine bicycle exercise. With propranolol-verapamil, five had no angina with exercise even though their duration of exercise increased; in the other eight, time to angina increased (from 4.0 ±1.5 minutes with propranolol-placebo to 5.3 ± 1.6 minutes with propranolol-verapamil, p = 0.01).A propranolol-verapamil combination induced no change in rest or peak exercise left ventricular volumes or ejection fraction (assessed by equilibrium gated blood pool scintigraphy). With propranolol-verapamil, four patients had PR interval prolongation, and two had fatigue and dyspnea. In addition, two had marked sinus bradycardia with junctional escape rhythm that was resolved with a reduction of verapamil dosage. No patient developed congestive heart failure or high degree atrioventricular block. Thus, a combination of propranolol and verapamil is superior to propranolol alone in patients with severe, limiting angina, but such a combination must be used cautiously because of potentially serious adverse effects