TY - JOUR
T1 - Mortality in the survival with oral D-sotalol (SWORD) trial
T2 - Why did patients die?
AU - Pratt, Craig M.
AU - Camm, A. John
AU - Cooper, William
AU - Friedman, Peter L.
AU - MacNeil, Daniel J.
AU - Moulton, Kathleen M.
AU - Pitt, Bertram
AU - Schwartz, Peter J.
AU - Veltri, Enrico P.
AU - Waldo, Albert L.
N1 - Funding Information:
This work was supported by a grant from Bristol-Myers Squibb, Princeton, New Jersey.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - The Survival With Oral D-sotalol (SWORD) trial tested the hypothesis that the prophylactic administration of oral d-sotalol would reduce total mortality in patients surviving myocardial infarction (MI) with a left ventricular ejection fraction (LVEF) of ≤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 was crossed (RR = 1.65; p = 0.006). All baseline variables known to be associated with mortality risk (e.g., LVEF, heart failure class, age) as well as variables related to torsades de pointes (e.g., time from beginning of therapy QT(c), gender, potassium, renal function, dose of d-sotalol) were assessed for interaction of each variable with treatment assignment, computing RR and 95% confidence interval (CI) from Cox regression models. The d-sotalol-associated mortality was greatest in the 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 pointes were not differentially predictive of d-sotalol-associated risk, except female gender (RR = 4.7; 95% CI 1.4 to 16.5). These findings suggest that (1) most of the d-sotalol-associated risk was in patients remote 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 supports torsades de pointes or any specific proarrhythmic mechanism as an explanation for d-sotalol-associated mortality risk.
AB - The Survival With Oral D-sotalol (SWORD) trial tested the hypothesis that the prophylactic administration of oral d-sotalol would reduce total mortality in patients surviving myocardial infarction (MI) with a left ventricular ejection fraction (LVEF) of ≤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 was crossed (RR = 1.65; p = 0.006). All baseline variables known to be associated with mortality risk (e.g., LVEF, heart failure class, age) as well as variables related to torsades de pointes (e.g., time from beginning of therapy QT(c), gender, potassium, renal function, dose of d-sotalol) were assessed for interaction of each variable with treatment assignment, computing RR and 95% confidence interval (CI) from Cox regression models. The d-sotalol-associated mortality was greatest in the 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 pointes were not differentially predictive of d-sotalol-associated risk, except female gender (RR = 4.7; 95% CI 1.4 to 16.5). These findings suggest that (1) most of the d-sotalol-associated risk was in patients remote 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 supports torsades de pointes or any specific proarrhythmic mechanism as an explanation for d-sotalol-associated mortality risk.
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U2 - 10.1016/S0002-9149(98)00006-X
DO - 10.1016/S0002-9149(98)00006-X
M3 - Article
C2 - 9555777
AN - SCOPUS:0032053864
SN - 0002-9149
VL - 81
SP - 869
EP - 876
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 7
ER -