Superiority of verapamil to propranolol in stable angina pectoris: A double-blind, randomized crossover trial

W. H. Frishman, N. A. Klein, J. A. Strom, H. Willens, T. H. LeJemtel, J. Jentzer, L. Siegel, N. Kirschen, R. Silverman, S. Pollack, R. Doyle, E. Kirsten, E. H. Sonnenblick

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Abstract

The effects of oral verapamil and oral propranolol were compared in 20 patients with stable angina pectoris using a placebo-control, double-blind, randomized crossover protocol. All patients received placebo for 2 weeks and were then randomized to initial propranolol (n = 10) and verapamil (n = 10) treatment groups. Increasing doses of propranolol (60, 160 and 320 mg) or verapamil (240, 360 and 480 mg) were administered in divided doses over 3 weeks. Patients were then weaned onto placebo for 1 week, followed by crossover to the other treatment schedule and a second 1-week withdrawal period. Frequency of anginal attacks, nitroglycerin consumption and exercise tolerance (Bruce protocol) were assessed weekly during the placebo baseline, drug treatment and withdrawal phases; plasma drug were also measured. Compared with placebo, the frequency of anginal attacks and the amount of nitroglycerin consumed were reduced with verapamil, 480 mg/day (p <0.05), but not propranolol, 320 mg/day. Exercise duration increased significantly from baseline with both propranolol and verapamil (p <0.001); however, the improvement with verapamil was greater (p <0.04). Compared with placebo, only verapamil reduced the degree of ECG ST-segment depression at the end point of exercise. Verapamil caused a significant reduction in resting systolic and diastolic blood pressure (p <0.001); there was no reduction with propranolol. Both drugs reduced the resting heart rate (p <0.001 compared with placebo); however, the effect was greater with propranolol. Both drugs blunted the blood pressure response to exercise (p <0.05); however, the reduction in exercise tachycardia was significantly greater with propranolol (p <0.001). The resting and exercise rate-pressure products were reduced with both drugs, but significantly more so with propranolol (p <0.05). The levels of propranolol and verapamil in the blood were within the therapeutic range. Both drugs were well tolerated, and there were no rebound effects seen with withdrawal of verapamil treatment; two of 20 patients developed a severe exacerbation of angina pectoris after propranolol withdrawal. Verapamil appears to be a safe and effective treatment alternative to propranolol in patients with stable angina pectoris.

Original languageEnglish (US)
Pages (from-to)I-51-I59
JournalCirculation
Volume65
Issue number1 II
StatePublished - Feb 6 1982

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Frishman, W. H., Klein, N. A., Strom, J. A., Willens, H., LeJemtel, T. H., Jentzer, J., Siegel, L., Kirschen, N., Silverman, R., Pollack, S., Doyle, R., Kirsten, E., & Sonnenblick, E. H. (1982). Superiority of verapamil to propranolol in stable angina pectoris: A double-blind, randomized crossover trial. Circulation, 65(1 II), I-51-I59.