Superiority of combined diltiazem and propranolol therapy for angina pectoris

Twenty-four patients with stable angina were evaluated in a 14 week crossover trial. A single-blind placebo period (baseline 1) was followed by two double-blind periods evaluating maximum tolerated doses of diltiazem (up to 360 mg daily) vs placebo. Over the next 1 to 4 weeks, propranolol was started and increased until clinically documented beta-blockade was achieved (baseline 2). The final phase consisted of a pair of evaluation periods comparing propranolol plus the maximum tolerated dose of diltiazem to propranolol and placebo. The daily rate of angina attack was 1.6 during baseline, was unchanged during placebo therapy, but fell during treatment with diltiazem to 0.6 (p less than .005). With the addition of diltiazem to propranolol, the angina rate was improved (0.3) compared with that with either propranolol alone (0.6) or propranolol and placebo (0.5) (p less than .01). Total exercise duration during baseline 1 was 360 sec and increased to 497 sec with diltiazem, 481 sec with propranolol, and 527 sec with the combination of diltiazem and propranolol. Two patients with reduced ejection fractions developed congestive heart failure with propranolol. The combination of diltiazem and propranolol similarly resulted in congestive heart failure in one patient who had tolerated both drugs alone.