Combination of verapamil and beta blockers in systemic hypertension

Abstract

The efficacy and safety of verapamil and propranolol were examined in 14 hypertensive patients (mean age 51.2, range 30 to 65) in a double-blind, randomized, crossover study of verapamil, 360 mg, propranolol, 240 mg, these 2 formulations in combination and placebo, each given for 4 weeks. Supine blood pressure, heart rate, atrioventricular conduction (PR interval) and left ventricular function were measured. All treatments reduced diastolic blood pressure (mean +/- standard deviation) (p less than 0.001): placebo to 106.6 +/- 8.1 mm Hg; propranolol to 93.8 +/- 7.7; verapamil to 89.8 +/- 7.8; the combination to 84.1 +/- 6.1, but the effect of the combination was significantly greater than that of either drug alone (p less than 0.05). Heart rate at rest (placebo, 80.2 +/- 12.2 beats/min) was reduced by propranolol (63.3 +/- 9.4, p less than 0.001), but not by verapamil (79.0 +/- 8.9). However, the addition of verapamil to propranolol led to a further reduction in heart rate (56.9 +/- 8.4, p less than 0.005). PR interval was prolonged significantly by the combination (185.5 +/- 35.3 ms) when compared with placebo (154.0 +/- 22.7); propranolol (159.1 +/- 21.2) and verapamil (165.5 +/- 32.4) (p less than 0.005 for each). The active drugs increased end-diastolic dimension and end-systolic dimension. For each variable, the effect of the combination was statistically significant (p less than 0.01). Fractional shortening was not altered significantly by any of the treatments. Thus verapamil plus propranolol is a very effective antihypertensive combination but heart rate, atrioventricular conduction and left ventricular function may be affected adversely, necessitating careful monitoring of therapy.