Which strategy is "best" after myocardial infarction? The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator Trial: Rationale and study design

The Beta-blocker Strategy plus Implantable Cardioverter Defibrillator (BEST -ICD) Trial is a multicenter prospective randomized trial that started in J une 1998, in 95 centers in Italy and Germany. The trial will test the hypot hesis whether, in high-risk post myocardial infarction (MI) patients alread y created with beta blockers, electrophysiologic study (EPS)-guided therapy (including the prophylactic implantation of implantable cardioverter defib rillator [ICD] in inducible patients) will improve survival compared with c onventional therapy. patients eligible for the study are survivors of recen t MI (greater than or equal to 5 and less than or equal to 21 days), aged l ess than or equal to 80 years, with left ventricular ejection fraction less than or equal to 35% and greater than or equal to 1 of the following addit ional risk factors: (1) ventricular premature bats greater than or equal to 10/hour; (2) decreased heart rate variability (standard deviation of unusu al RR intervals <70 msec); and (3) presence of ventricular late potentials. Furthermore, all enrolled patients must be able to tolerate at least 25 mg of metoprolol per day. These patients constitute about 9% of all patients with recent Mi and are expected to have a 2-year all-cause mortality >25% o f which 50% is anticipated to be from sudden death. The main criteria of ex clusion from the study are (1) a history of sustained ventricular arrhythmi a; (2) documentation of nonsustained ventricular tachycardia during the scr eening phase; and (3) the need for myocardial revascularization and contrai ndications or intolerance to beta-blocker therapy. Eligible patients will b e randomized to 2 differ ent therapeutic strategies: conventional strategy or EPS/ ICD strategy. Patients allocated to the EPS/ICD strategy will under go further risk stratification, and electrophysiologically inducible patien ts (similar to 35%) will receive prophylactic ICDs, in addition to the conv entional therapy, whereas noninducible patients will be only conventionally treated. The primary endpoint of the study will be death from all causes. By hypothesizing a 30% reduction in the 2-year mortality (from 20% to 14%) in the EPS/ICD group compared with conventionally treated patients, 1,200 p atients will have to be included. A triangular, 2-sided sequential design w ith preset boundaries, for a 5% significance level and 90% power to detect a reduction in 2-year mortality from 20% to 14%, will be used to permit ear ly termination of the trial if the strategy is found to be efficacious, no difference, or inefficacious. (C) 1999 by Excerpta Medico, Inc.