Nadolol versus diltiazem and combination for preventing exercise-induced ischemia in severe angina pectoris

Combination beta-blocker and calcium antagonist therapy has been shown to be superior to monotherapy with either class of drugs in the treatment of patients with severe angina pectoris. Some combinations of these agents have resulted in an increased frequency of adverse effects. Although nadolol and diltiazem have low incidences of side effects as monotherapy, little is known about their combination. Thus, 18 patients with angina pectoris despite medical therapy were randomly assigned to 3-week periods of nadolol (160 mg/day), diltiazem (240 mg/day) or their combination. At the end of each treatment period, treadmill exercise testing and rest and peak bicycle exercise 2-dimensional echocardiography were performed. The heart rate-systolic blood pressure product was decreased most at peak treadmill exercise with the combination therapy versus monotherapy with either nadolol or diltiazem (12 vs 14 vs 22 x 10(3), respectively, p less than 0.05). Exercise duration did not differ with any of the 3 regimens, but the number of patients without angina during exercise was lowest with the combination therapy versus nadolol or diltiazem alone (5, 10 and 11, respectively, p less than 0.05); similar results were noted with the number of patients developing 1-mm ST depression on the exercise electrocardiogram (6, 10 and 13, respectively, p less than 0.05). The left ventricular ejection fraction at rest and during peak exercise was similar among the 3 treatments. The therapeutic combination of nadolol and diltiazem is well tolerated and results in less evidence of myocardial ischemia during exercise than monotherapy with either agent.