Comparison of acebutolol and propranolol for treatment of chronic ventricular arrhythmia: A placebo-controlled, double-blind, randomized crossover study

Abstract

The effects on ventricular arrhythmia of acebutolol were compared with those of propranolol in 31 patients who averaged more than 30 ventricular premature complexes (VPCs) per hour during 72 hours of ambulatory ECG recording during a placebo-controlled baseline period. The study consisted of an initial 2-week placebo-controlled baseline period followed by two 6-week double-blind treatment periods consisting of incremental dose-titration, maintenance and dose-tapering schedules. The treatment during the double-blind period was randomized to either oral acebutolol or propranolol given three times daily. Twenty-four-hour ambulatory ECGs and maximal (symptom-limited) treadmill exercise tests were performed after 1 and 5 weeks of treatment with either acebutolol (1587 ± 397 mg/day) or propranolol (202 ± 63 mg/day) in each patient. The effects of acebutolol and propranolol on the frequency and grade of ventricular arrhythmia during rest and exercise were compared. Acebutolol and propranolol produced comparable levels of adrenergic blockade, as reflected by significant reductions in the mean heart rate during 24-hour ambulatory recording (16% and 18%, respectively) and peak exercise (25% and 24%, respectively) compared with placebo (p < 0.01). Acebutolol and propranolol produced comparable and significant reductions in the VPC frequency during ambulatory ECG recordings (52% and 47%, respectively) and exercise testing (51% and 69%, respectively) compared with placebo (p < 0.001). Each agent produced comparable and significant reductions in the mean VPC grade compared with placebo (using a modified Lown classification) during ambulatory ECG recordings; the approximate reduction was one grade (p < 0.001). During exercise testing acebutolol reduced the VPC grade significantly compared with placebo (p < 0.01); propranolol also reduced the VPC grade, but not significantly. No clinical or laboratory side effects of either agent necessitated drug discontinuance. Acebutolol is a well-tolerated β-blocking agent that compares favorably to propranolol in reducing the frequency and complexity of VPCs at rest and during maximal exercise. The ventricular antiarrhythmic effects of acebutolol are comparable to those of propranolol. Hence, acebutolol represents an important therapeutic addition to β-adrenergic blocking agents.