Background The Digitalis Investigation Group trial reportedthat treatment with digoxin did not decrease overall mortalityamong patients with heart failure and depressed left ventricularsystolic function, although it did reduce hospitalizations slightly.Even though the epidemiologic features, causes, and prognosisof heart failure vary between men and women, sex-based differencesin the effect of digoxin were not evaluated.
Methods We conducted a post hoc subgroup analysis to assesswhether there were sex-based differences in the effect of digoxintherapy among the 6800 patients in the Digitalis InvestigationGroup study. The presence of an interaction between sex anddigoxin therapy with respect to the primary end point of deathfrom any cause was evaluated with the use of Mantel–Haenszeltests of heterogeneity and a multivariable Cox proportional-hazardsmodel, adjusted for demographic and clinical variables.
Results There was an absolute difference of 5.8 percent (95percent confidence interval, 0.5 to 11.1) between men and womenin the effect of digoxin on the rate of death from any cause(P=0.034 for the interaction). Specifically, women who wererandomly assigned to digoxin had a higher rate of death thanwomen who were randomly assigned to placebo (33.1 percent vs.28.9 percent; absolute difference, 4.2 percent, 95 percent confidenceinterval, –0.5 to 8.8). In contrast, the rate of deathwas similar among men randomly assigned to digoxin and men randomlyassigned to placebo (35.2 percent vs. 36.9 percent; absolutedifference, –1.6 percent; 95 percent confidence interval,–4.2 to 1.0). In the multivariable analysis, digoxin wasassociated with a significantly higher risk of death among women(adjusted hazard ratio for the comparison with placebo, 1.23;95 percent confidence interval, 1.02 to 1.47), but it had nosignificant effect among men (adjusted hazard ratio, 0.93; 95percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction).
Conclusions The effect of digoxin therapy differs between menand women. Digoxin therapy is associated with an increased riskof death from any cause among women, but not men, with heartfailure and depressed left ventricular systolic function.
Source Information
From the Section of Cardiovascular Medicine, Department of Internal Medicine (S.S.R., Y.W., H.M.K.), and the Section of Health Policy and Administration, Department of Epidemiology and Public Health (H.M.K.), Yale University School of Medicine; and the Center for Outcomes Research and Evaluation, Yale–New Haven Hospital (H.M.K.) — both in New Haven, Conn.
Digoxin for the Treatment of Heart Failure
Moulias S., Tigoulet F., Meaume S., Hudson M., Pilote L., Hallberg P., Michaëlsson K., Melhus H., Rathore S. S., Krumholz H. M.
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N Engl J Med 2003;
348:661-663, Feb 13, 2003.
Correspondence
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