MORTALITY IN THE SURVIVAL WITH ORAL D-SOTALOL (SWORD) TRIAL - WHY DIDPATIENTS DIE

The Survival With ORal D-sotalol (SWORD) trial tested the hypothesis t hat the prophylactic administration of oral d-sotalol would reduce tot al mortality in patients surviving myocardial infarction (MI) with a l eft ventricular ejection fraction (LVEF) of less than or equal to 40%, Two index MI groups were included: recent (6 to 42 days) and remote ( >42 days) with clinical heart failure (n = 915 and 2,206, respectively ), The trial was discontinued when the statistical boundary for harm w as crossed (RR 1.65; p = 0.006), All baseline variables known to be as sociated with mortality risk (e.g., LVEF, heart failure class, age) as well as variables related to torsades de pointes (e.g., time from beg inning of therapy, QT(c), gender, potassium, renal function, dose of d -sotalol) were assessed for interaction of each variable with treatmen t assignment, computing RR and 95% confidence interval (CI) from Cox r egression models. The d-sotalol-associated mortality was greatest in t he group with remote MI and LVEFs of 31% to 40% (RR = 7.9; 95% CI 2.4 to 26.2), Most variables known to be associated with torsades de point es were not differentially predictive of d-sotalol-associated risk, ex cept female gender (RR = 4.7; 95% CI 1.4 to 16.5), These findings sugg est that (1) most of the d-sotalol-associated risk was in patients rem ote from MI with a LVEF of 31% to 40%; comparable placebo patients had a very low mortality (0.5%); and (2) very little objective data suppo rts torsades de pointes or any specific proarrhythmic mechanism as an explanation for d-sotalol-associated mortality risk. (C) 1998 by Excer pta Medica, Inc.