Introduction: primary prevention against sudden cardiac death.

P prevention against sudden cardiac death has long been a therapeutic goal. And for a long time a number of investigations, from small studies to large clinical trials, directed toward that end consisted of one or another form of drug therapy, principally in patients with coronary artery disease and a prior myocardial infarction. Clinical trials using b blockers (propranolol, metoprolol, or timolol) in the latter patient population all showed a significant favorable drug effect on all-cause mortality and sudden cardiac death.1 However, subsequent studies with antiarrhythmic drugs, with a few notable exceptions, showed either a neutral effect or, unhappily, an unfavorable effect on all-cause mortality and sudden cardiac death.2 It is in this context that the importance of the outcome of the Multicenter Automatic Defibrillator Implantation Trial (MADIT)3 must be viewed. MADIT was a study of patients with a previous myocardial infarction, nonsustained ventricular tachycardia, and a left ventricular ejection fraction ,36%, in whom sustained ventricular tachycardia induced during electrophysiologic study could not be suppressed by intravenous procainamide therapy.4 Over a 5-year period, 196 such patients were randomized either to placement of an implantable cardioverter defibrillator (ICD) or to treatment with conventional therapy, principally amiodarone.3 The study was terminated by the safety and monitoring committee prior to the completion date, however, because the ICD treatment arm achieved a highly statistically significant decrease in all-cause mortality (54%) compared to the conventional treatment arm (p 5 0.009). There were 2.6-fold more deaths in the conventional treatment arm compared to the ICD treatment arm, and the hazard ratio demonstrating the superiority of the ICD arm was 0.46 (95% confidence limits, 0.26–0.82). In sum, this primary prevention trial demonstrated a very significant benefit with the use of the ICD in MADIT-eligible patients, a subset of patients who have had a prior myocardial infarction. A more complete discussion of the MADIT study is found in this symposium. The fact that an ICD not only is effective treatment of ventricular tachycardia and ventricular fibrillation (well established in previous secondary prevention trials), but also prolongs life significantly compared to conventional antiarrhythmic drug therapy in a population at risk, has enormous implications. It is these implications that are addressed by this symposium. The first presentation by Myerburg et al15 provides a fine discussion of the epidemiology of sudden cardiac death, and places in perspective the risk of sudden cardiac death and the factors that influence efficacy of therapy. It does not specifically focus on many of the questions raised by MADIT. The presentation by Moss6 succinctly discusses the data from the MADIT study, presents data not included in the original report on MADIT, and addresses some of the questions raised after the publication of the original report. However, it does not address all the questions. For From the University Hospitals of Cleveland, Cleveland, Ohio (A.L.W.) and College of Physicians and Surgeons of Columbia University, New York, New York (M.L.W.). Address for reprints: Albert L. Waldo, MD, Case Western Reserve University, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, Ohio 44106-5038.