Comparative effect of disopyramide and ethmozine in suppressing complex ventricular arrhythmias by use of a double-blind, placebo-controlled, longitudinal crossover design.

Abstract

This placebo-controlled, double-blind, longitudinal crossover study compares the efficacy of disopyramide and ethmozine, a new investigational drug, in suppressing frequent (40 or more/h) ventricular premature depolarizations (VPD) in 27 patients completing a 37 day protocol. Although both drugs significantly reduced VPD relative to placebo, ethmozine was a superior antiarrhythmic drug in achieving near-total abolition of VPD (30% of patients), which was never observed during disopyramide dosing (P < 0.05). At the 80% VPD reduction level, ethmozine was effective in 56% of all patients compared with an effectiveness in only 22% of patients during disopyramide therapy (P < 0.05). The mean peak plasma level of ethmozine was 0.66 .+-. 0.8 .mu.g/ml, which significantly fell to a trough level of 0.1 .+-. 0.08 .mu.g/ml (P < 0.001). Mean peak and trough plasma levels of disopyramide exhibited less fluctuation (2.6 .+-. 0.9 .mu.g/ml vs. 2.2 .+-. 0.9 .mu.g/ml). Ethmozine had no effect on the QTc interval, whereas disopyramide prolonged it significantly. Importantly, while dispyramide produced serious side effects in 30% of patients, ethmozine was well tolerated with no statistically significant side effects compared with placebo.