A Comparison of Seven Antiarrhythmic Drugs in Patients with Ventricular Tachyarrhythmias

BACKGROUND: The relative efficacies of various antiarrhythmic drugs in the treatment of ventricular tachyarrhythmias are not well known. This study examined the effectiveness of imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial. METHODS: Patients were randomly assigned to undergo serial testing of the efficacy of the seven antiarrhythmic drugs by one of two strategies: electrophysiologic study or Holter monitoring together with exercise testing. The seven drugs were then tested for efficacy in random order in patients who were eligible to receive them. The frequencies of predictions of drug efficacy and of adverse drug effects during the initial drug titration were tabulated for all 486 randomized subjects. Patients received long-term treatment with the first antiarrhythmic drug that was predicted to be effective on the basis of drug testing. Recurrences of arrhythmia, deaths, and adverse drug effects during long-term follow-up were recorded for the 296 patients in whom an antiarrhythmic drug was predicted to be effective. RESULTS: In the electrophysiologic-study group, the percentage of patients who had predictions of drug efficacy was higher with sotalol (35 percent) than with the other drugs (16 percent, P < 0.001). There was no significant difference among the drugs in the Holter-monitoring group. The percentage of patients with adverse drug effects was lowest among those receiving sotalol. The actuarial probability of a recurrence of arrhythmia after a prediction of drug efficacy by either strategy was significantly lower for patients treated with sotalol than for patients treated with the other drugs (risk ratio, 0.43; 95 percent confidence interval, 0.29 to 0.62; P < 0.001). With sotalol, as compared with the other drugs combined, there were lower risks of death from any cause (risk ratio, 0.50; 95 percent confidence interval, 0.30 to 0.80; P = 0.004), death from cardiac causes, (0.50; P = 0.02), and death from arrhythmia (0.50; P = 0.04). The cumulative percentage of patients in whom a drug was predicted to be effective and in whom it remained effective and tolerated was higher for sotalol than for the other drugs (P < 0.001). CONCLUSIONS: Sotalol was more effective than the other six antiarrhythmic drugs in preventing death and recurrences of arrhythmia. In patients similar to those in this study, if antiarrhythmic-drug therapy is to be used to prevent recurrences of ventricular tachyarrhythmias, treatment with sotalol and assessment of its potential efficacy by Holter monitoring are a reasonable initial strategy.