Diltiazem and Propranolol Combination for the Treatment of Chronic Stable Angina Pectoris

To examine the benefits and risks of combined diltiazem and propranolol therapy, 23 patients who had completed a double-blind placebo-controlled cross-over comparison between diltiazem and propranolol and who continued to develop angina despite treatment were studied. The patients received the previous dose of diltiazem (180 or 360 mg/day) combined with propranolol 120 mg daily for 4 weeks and if they still developed angina on exercise testing, they went on to propranolol 240 mg daily for a further 4 weeks. Efficacy and safety were evaluated by computer-assisted maximal treadmill tests, ambulatory heart rate monitoring, and resting systolic time intervals at the end of each 4-week treatment period. Low-dose combination therapy abolished treadmill angina in 6 patients, but 2 patients had to be withdrawn. The high-dose combination abolished treadmill angina in 5 of 15 patients. The exercise time and 1-mm ST depression time increased with each increment of combination therapy in patients on both doses of diltiazem. The resting, maximal, and ambulatory heart rates progressively decreased with each increment of combined therapy. Left ventricular function, as evaluated clinically and by the systolic time intervals, was not impaired, but severe sinus bradycardia (heart rate less than 40 beats/min) appeared in 3 patients. Two died during 6 months of follow-up. Only 11 of the 23 patients completed 6 months of combined therapy without an adverse reaction. Although combined diltiazem and propranolol therapy relieved angina and increased exercise tolerance in patients refractory to single drug therapy, it should be used with caution in such patients, since bradycardia can pose serious problems.