Effect of antiarrhythmic drugs on mortality after myocardial infarction

Abstract

The theoretical potential for a preventive or prophylactic effect of antiarrhythmic drugs (excluding beta blockers) in the treatment of coronary patients with ventricular arrhythmias has not been realized. Randomized controlled clinical trials conducted during the early hospital phase after an acute myocardial infarction as well as after discharge have not demonstrated an effect on patient survival.

Three possible explanations exist. First, treatment of ventricular arrhythmias does not improve prognosis. Although this explanation is supported by the overall trial results, it is contrary to massive evidence from animal, clinical and epidemiologic studies. Second, treatment of ventricular arrhythmias does prolong life but benefit has not been observed in the trials. Limitations in applied methods, including insufficient sample sizes, may have obscured a true favorable intervention effect. Third, control of ventricular arrhythmias helps some patients but harms others. Concomitant treatment with digitalis and diuretics and, possibly, arrhythmogenic properties of the investigational drugs themselves might have confounded the overall results.

The second in particular, but also the third explanation, are the most plausible. Only 1 of the 20 controlled clinical trials considered for this review required presence of ventricular arrhythmias as an entry criterion. All trials were small; the largest number of patients enrolled in a single trial was 610 and the highest number of deaths in a trial was 49.

To resolve the uncertainty, increased attention to methodologic issues, such as selection of appropriate study populations, intervention strategies and larger sample sizes, is required. Only then will it be possible to determine whether antiarrhythmic drugs exert a life-prolonging effect.