The effect of diltiazem and propranolol, alone and in combination, on exercise performance and left ventricular function in patients with stable effort angina: a double-blind, randomized, and placebo-controlled study.

The effects of oral diltiazem and propranolol, alone and in combination, were compared with those of placebo in 12 patients with stable effort angina. Patients performed symptom-limited, multistage, upright bicycle ergometric exercise while undergoing equilibrium-gated radionuclide an- giographic examination after 2 week periods of 90 mg diltiazem four times daily, 60 mg propranolol four times daily, a combination of 90 mg diltiazem and 60 mg propranolol four times daily, and placebo. All drugs were given double blind and in randomized order. Diltiazem, propranolol, and the combination significantly increased exercise duration compared with placebo (562 + 149, 525 + 115, and 549 121, vs 430 + 132 sec); the drugs also increased time to onset of angina pectoris and ischemic ( 1 mm) ST segment depression (all p < .05). Compared with after placebo, heart rate and rate-pressure product at a fixed submaximal workload were decreased after diltiazem (both p < .05), but were unchanged at peak effort. Heart rate and rate-pressure product at both submaximal and peak effort were decreased by propranolol (all p < .001) and were decreased further by the combination of diltiazem and propranolol (all p < .05 vs propranolol). Diltiazem and the combination of diltiazem and propranolol decreased maximal exercise ST segment depression (both p < .01 vs placebo). The mean exercise left ventricular ejection fraction was higher in patients on diltiazem than in those on placebo, propranolol, or the combination of diltiazem and propranolol (all p < .05). Adverse side effects severe enough to require dosage reduction (severe sinus bradycardia or orthostatic hypotension) occurred in four patients on combination therapy. High-dose diltiazem alone appears to be as effective as or more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, myocardial ischemia, and left ventricular function in patients with stable effort angina. Circulation 68, No. 3, 560-567, 1983. CALCIUM-CHANNEL BLOCKERS provide a promising alternative to /8-blockers for the management of patients with exertional angina and fixed coronary ar- tery disease. These drugs can reduce myocardial oxygen demand by decreasing systemic vascular resis- tance, and in some cases cardiac contractility and heart rate, while producing an increase in coronary blood flow through dilation of large coronary vessels. 1 2 The