Expanding Indications for the Use of Class III Agents in Patients at High Risk for Sudden Death

The evidence that antiarrhythmic compounds that act by slowing conduction velocity increase mortality in patients with cardiac disease is now compelling. Emphasis is now shifting to agents that act by lengthening repolarization and have additional antiadrenergic properties. There is preliminary evidence that pure Class III agents devoid of antisympathetic activity may also increase rather than decrease mortality in certain patients. Thus, in recent years, sotalol and amiodarone have emerged as the preferred agents for the control of most ventricular arrhythmias occurring in the setting of significant heart disease. Sotalol has not been widely studied in postinfarct patients; one trial indicated that the drug did reduce total mortality but the difference did not reach statistical significance. A number of studies with amiodarone in the postmyocardial infarction patients have revealed benefit, but these were from nonblinded studies. Two blinded, placebo-controlled studies are currently ongoing. A potential new indication of amiodarone is in patients with arrhythmias in heart failure in whom amiodarone markedly increased left ventricular ejection fraction, with a pronounced suppressant effect on premature ventricular complexes and nonsustained ventricular tachycardia and a trend for a decrease in mortality in patients with nonischemic cardiomyopathy. The most promising indication of amiodarone in low doses is in the maintenance of sinus rhythm in patients with atrial flutter and fibrillation. For the present, amiodarone appears to be the best prototype of a desirable complex antiarrhythmic compound, if its variegated side effect profile can be favorably modified from knowledge of structure-activity relationships.