Overview of Completed Sudden Death Trials: US Experience

Abstract

Ventricular arrhythmias are the major cause of death in patients with coronary heart disease. By suppressing the arrhythmias, antiarrhythmic agents have the theoretical potential of preventing sudden arrhythmic deaths. A large number of randomized, controlled clinical trials of these agents have been conducted during the early hospital phase after an acute myocardial infarction as well as after discharge. Included in this review are approximately 20 mortality trials of antiarrhythmic drugs, including beta blockers, which have been conducted in the United States and Australia. Results of the trials of antiarrhythmics reported to date have not demonstrated an effect on patient survival or risk of sudden death. Three possible explanations exist. First, these agents do not improve prognosis, which is contrary to massive evidence from animal, clinical, and epidemiologic studies. Second, drug treatment prolongs life, but benefit has not been observed in the trials. This explanation is plausible, since the completed trials have methodologic limitations. Third, control of ventricular arrhythmias helps some patients but harms others. Larger, properly designed trials are needed to resolve the uncertainty about the value of antiarrhythmics in the prevention of sudden death. The short- and long-term trials of beta blockers have documented an effect on survival. The benefit seems to be explained primarily through a reduction in sudden or instantaneous death. Whether this effect is mediated through a reduction in ventricular ectopies or an elevation of the fibrillation threshold is debated, as is the effect, if any, of beta-2 blockade on the incidence of ventricular fibrillation.