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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Diltiazem and propranolol alone and in combination as antianginal agents were compared with placebo in 12 patients with stable exertional angina at Stanford University Medical Center. The patients performed symptom-limited, multi-stage upright bicycle ergometric exercise while undergoing radionuclide angiographic studies every two weeks while being treated with 90 mg of diltiazem four times daily, 60 mg of propranolol four times daily, a combination of 90 mg of diltiazem and 60 mg of propranolol four times daily, and placebo. Diltiazem, propranolol and a combination all significantly increased exercise duration compared to placebo (526 +/- 149, 525 +/- 115, and 549 +/- 129 vs 430 +/- 132 sec.). Although rate pressure product and heart rate decreased with diltiazem therapy at submaximal workloads, these values were unchanged at peak exercise in contrast to propranolol or the combination of propranolol or diltiazem. Diltiazem decreased the sub-maximal and maximal degree of exercise-induced ST segment depression by over 50% compared to placebo (P less than 0.01 vs placebo). Diltiazem resulted in a higher exercise left ventricular ejection fraction compared to placebo, propranolol or the combination of diltiazem or propranolol (all less than P less than 0.05). Sinus bradycardia or orthostatic hypertension occurred in four patients on the high-dose combination therapy and required dose reduction. We concluded that high-dose diltiazem, appeared to be even more effective than moderate-dose propranolol or the combination of diltiazem and propranolol in improving exercise tolerance, electrocardiographic evidence of myocardial ischaemia and left ventricular function in patients with stable effort angina due to occlusive coronary artery disease.
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