Combination antiarrhythmic drug therapy for ventricular tachyarrhythmias

Abstract

New antiarrhythmic drug regimens are constantly being sought because of the relatively low efficacy rates of standard antiarrhythmic agents in preventing induction of ventricular tachyarrhythmias; the application of these agents is also limited due to serious or debilitating side-effects. The combination of two antiarrhythmic agents with complimentary electrophysiologic activities and differing toxicities might offer significant advantages in overcoming the drawbacks of standard antiarrhythmic drug therapy. A knowledge of the pharmacodynamics of the major classes of antiarrhythmic agents will allow informed choices of drugs for use in combination therapy. Judging antiarrhythmic drug efficacy is a complex problem, requiring an understanding of the influence of the arrhythmia monitoring technique, arrhythmia morphology and the response to previous drugs on drug efficacy rates, so that accurate comparisons of drug effectiveness can be made among different agents or combinations. A number of combination therapies have been tested for suppression of complex ventricular ectopy, nonsustained ventricular tachycardia and sustained ventricular tachycardia and ventricular fibrillation. The most successful combinations have been those using class IA and IB agents and class IA and II agents. In general, these combinations tend to show higher efficacy rates in suppressing all forms of ventricular ectopy and ventricular tachyarrhythmias, and usually have a lower incidence of toxic side-effects compared with individual agents alone. On the basis of these initial results, it seems warranted to perform further studies to explore these combinations in larger populations and to test new combinations developed on the basis of pharmacodynamic principles.