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Abstract
CAST, which was preceded by a well-designed feasibility study, the Cardiac Arrhythmia Pilot Study,1 is the first long-term, multicenter, multidrug, placebo-controlled trial of the safety and efficacy of antiarrhythmic drug therapy in reducing the risk of sudden death.2 The preliminary results, as presented in the media and in expanded form in this issue of the Journal ,2 have astounded most observers and challenge much of the conventional wisdom about antiarrhythmic drugs and some of the arrhythmias they have been used to treat. Both encainide and flecainide are associated with inefficient suppression of the sustained ventricular arrhythmias induced by programmed electrical stimulation.7 In addition, encainide and other sodium-channel blockers have been shown to raise the energy requirements for ventricular defibrillation in experimental models.8 Which of these mechanisms, if any, contribute to the occurrence of sudden death in patients treated with encainide and flecainide after myocardial infarction is unknown. Beta-adrenergic-blocking agents should be administered after infarction to all patients who tolerate them, since they are the only class of drugs of established benefit in reducing the risk of sudden cardiac death in ischemic heart disease.9 The use of encainide and flecainide to treat patients with symptomatic sustained ventricular arrhythmias remains an approved indication if their efficacy is established with the use of objective end points. If treatment with moricizine reduces the risk of sudden death, however, or results in rates of fatal arrhythmia and total mortality no different from those in the placebo group, there will be strong support for the hypothesis that the adverse outcomes observed with encainide and flecainide represent a Class IC proarrhythmic effect rather than a universal property of antiarrhythmic drugs.