764 Amiodarone and Post - MI Patients

Survivors of acute myocardial infarction (MI) remain at risk of sudden cardiac death after being discharged from the hospital. In these patients, frequent premature ventricular contractions (PVCs) and depressed ventricular function herald sudden cardiac death.1-3 These observations triggered the idea that if PVCs were suppressed by antiarrhythmic agents, then sudden cardiac death could be averted.3,4 That belief led to an explosion in the use of antiarrhythmic drugs 20 years ago, and the pharmaceutical industry mounted a massive development campaign to find more effective antiarrhythmic agents for ventricular arrhythmia suppression, which, it was hoped, would prevent sudden cardiac death. To this end, throughout the 1980s, about two new antiarrhythmic compounds were developed every year.5 As the number of antiarrhythmic drug prescriptions rose dramatically,6 soon came troubling reports that class 1 antiarrhythmic agents failed to reduce the sudden cardiac death rate: Indeed, many class I compounds had proarrhythmic and negative inotropic effects.7-9 CAST I and II dealt what many considered the fatal blow to the use of class lc antiarrhythmic drugs in post-MI patients10"'1: Encainide and flecainide increased the mortality rate of these patients, whereas moricizine, a class la agent, significantly increased the risk of sudden cardiac death during the first 2 weeks of therapy and was not effective over the long term.'1 Given the results of CAST and other studies, many physicians were skeptical about whether antiarrhythmic agents played any role in sudden cardiac death prophylaxis. By the 1990s, physicians were in a quandary: How should one treat potentially life-threatening ventricular tachyarrhythmias in MI survivors? As many antiarrhythmic agents were falling from favor, amiodarone -an antiarrhythmic compound that had been viewed since its approval in 1984 by the Food and Drug Administration as a "last resort" drug-was gaining hard-won acceptance on the basis of several studies showing that the drug effectively controlled life-threatening ventricular tachyarrhythmias.12-19 Data from several trials20-24 suggesting that amiodarone might effectively control and prevent arrhythmias in MI survivors also called for a reevaluation of the "lastresort" status of the drug.