Mexiletine and Disopyramide Suppress Ventricular Premature Contractions(VPC) Irrespective of the Relationship between the VPC and the Underlying Heart Rate.

The effects of mexiletine (300 mg/day, 24 patients) and disopyramide (300 mg/day, 20 patients) on ventricular premature contractions (VPCs) were studied using a 24-hour ambulatory electrocardiogram. The VPC frequency was evaluated as a function of the underlying heart rate (HR). The VPC-HR correlation was classified into 2 major types, depending on whether the frequency of the VPC increased with the increased HR (positive type) or not (nonpositive type). The effects of the drugs were assessed based on the VPC-HR correlation and on the percent reduction of the VPC frequency. Mexiletine and disopyramide significantly decreased the frequency of the VPCs of both the positive and nonpositive types. Each drug was assumed to be effective when the percent reduction of the VPC frequency exceeded 70%. Mexiletine (300 mg/day) was 58.5% effective in positive type patients and 33.3% effective in nonpositive type patients, with a total efficacy of 45.8%. Disopyramide was effective in 50% of total cases with 44.4% in positive type patients and 54.5% in nonpositive type patients. However, the efficacy of these drugs on the 2 different types of VPCs was the same statistically. The findings strikingly contrasted those obtained with diltiazem and atenolol, which predominantly suppressed VPCs of the positive type which share similar characteristics with a triggered activity in vitro. We conclude that the mode of action of class I antiarrhythmics on the VPCs differs from that of class II or IV antiarrhythmics, as viewed from the VPC-HR relationship, and that the difference probably comes from the different arrhythmogenesis for positive and nonpositive types of VPCs, in addition to the different electrophysiological actions of mexiletine and disopyramide.