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.

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Abstract
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 angiographic exaination after 2 wk periods of 90 mg diltiazem 4 times daily, 60 mg propranolol 4 times daily, a combination of 90 mg diltiazem and 60 mg propranolol 4 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 s); the drugs also increased time to onset of angina pectoris and ischemic (.gtoreq. 1 mm) ST segment depression (all P < 0.05). Compared with after placebo, heart rate and rate-pressure product at a fixed submaximal workload were decreased after diltiazem (both P < 0.05), but were unchanged at peak effort. Heart rate and rate-pressure product at both submaximal and peak effort were decreased by propranolol (all P < 0.001) and were decreased further by the combination of diltiazem and propranolol (all P < 0.05 vs. propranolol). Diltiazem and the combination of diltiazem and propranolol decreased maximal exercise ST segment depression (both P < 0.01 vs. placebo). The mean exercise left ventricular ejection fraction was higher in patients on diltiazem than those on placebo, propranolol, or the combination of diltiazem and propranolol (all P < 0.05). Adverse side effects severe enough to require dosage reduction (severe sinus bradycardia or orthostatic hypotension) occurred in 4 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 ischemic and left ventricular function in patients with stable effort angina.