Propranolol-verapamil versus propranolol-nifedipine in severe angina pectoris of effort: A randomized, double-blind, crossover study

Michael D. Winniford, Kay L. Fulton, James R. Corbett, Charles H. Croft, L. David Hillis

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26 Scopus citations


To compare a propranolol-verapamil with a propranolol-nifedipine combination in patients with severe angina of effort, 16 patients (11 men and 5 women, aged 56 ± 8 years [mean ± standard deviation]) with more than 5 episodes/week of angina and a positive exercise tolerance test despite propranolol (229 ± 44 mg/day [range 180 to 360]) were maintained on this dose of propranolol and, in addition, received verapamil (360 mg/day) and nifedipine (60 mg/day) for 3 weeks each in a double-blind, randomized fashion. In comparison with propranolol alone, anginal frequency and nitroglycerin usage were reduced by propranolol-verapamil but not by propranolol-nifedipine. Exercise time (standard Bruce protocol) was similar for the 2 combinations (6.4 ± 2.0 minutes with propranol-olverapamil, 6.6 ± 2.1 minutes with propranolol-nifedipine, difference not significant), but the magnitude of ST-segment depression at peak exercise was less (p < 0.05) during propranolol-verapamil (0.03 ± 0.06 mV) than during propranolol alone (0.18 ± 0.07 mV) and propranolol-nifedipine (0.08 ± 0.07 mV). Left ventricular ejection fraction at rest was higher (p < 0.05) with propranolol-nifedipine (0.62 ± 0.10) than with propranolol-verapamil (0.58 ± 0.10), but neither differed from ejection fraction at rest with propranolol alone (0.59 ± 0.08). Ejection fraction at peak exercise was similar during all 3 periods. In 2 patients, verapamil caused weakness, lightheadedness, and severe sinus bradycardia (40 to 48 beats/min), and the dosage was reduced (blindly) to 240 mg/day, with the alleviation of bradycardia and associated symptoms. Thus, in patients with severe angina of effort with propranolol alone, the addition of verapamil is more effective than the addition of nifedipine in reducing anginal frequency, nitroglycerin usage, and the magnitude of the electrocardiographic response to exercise. Although both combinations are generally safe and well-tolerated, in an occasional patient symptomatic sinus bradycardia develops during therapy with propranolol-verapamil; therefore, this combination must be given carefully.

Original languageEnglish (US)
Pages (from-to)281-285
Number of pages5
JournalThe American journal of cardiology
Issue number4
StatePublished - Feb 1 1985
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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