Sex Differences in Outcome After ICD Implantation
Sex Differences in Outcome After ICD Implantation
Background: Women have been underrepresented in randomized trials of implantable cardioverter defibrillator (ICD) therapy, and limited data suggest that women may not benefit from prophylactic ICD implantation to the same extent as men. In the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a reduction in all-cause mortality was seen in men (P = .018) but not for women (P = .76).
Methods: Sex-specific cumulative probabilities of event-free survival from total, arrhythmic, and noncardiac mortality as well as appropriate shocks were calculated, and log-rank tests were performed. Interaction terms in multivariable Cox proportional hazards models were used to test the hypothesis that the effectiveness of the ICD differed between men and women.
Results: Among 458 patients (326 men and 132 women) with nonischemic cardiomyopathy enrolled in the DEFINITE trial, the test for an interaction between sex and ICD treatment on total mortality was not significant in unadjusted (P = .11) or in multivariable adjusted (P = .18) analyses. When we examined cause-specific mortality, we found no sex difference in the incidence of arrhythmic death. Instead, we documented a relative excess of noncardiac death among women randomized to the ICD (P = .02) as compared with women randomized to standard medical therapy. With respect to device use, there was a trend for women to have fewer appropriate ICD shocks after multivariable adjustment (P = .06).
Conclusion: Among patients with nonischemic cardiomyopathy enrolled in DEFINITE, we found no conclusive evidence for a sex difference in the effectiveness of the ICD; however, the trial was not adequately powered to detect such interaction effects. Larger studies are required to definitively address whether the benefit of ICD therapy differs between men and women.
Randomized clinical trials have demonstrated convincing survival benefits conferred by implantable cardioverter defibrillator (ICD) therapy in selected patients with a history of clinically recognized left ventricular dysfunction. As has been seen in other randomized trials in heart failure populations, women comprised a minority of participants in these trials (10%-29%). Therefore, as is the case in other trials where women are underrepresented, there is always the concern that extrapolation of results to women based upon trials composed primarily of men may not be appropriate. Subgroup analyses from 2 of these trials, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), raised the concern that women may not benefit to the same degree as men enrolled in these trials. However, formal tests for interaction were not performed in either of the main studies. Because it has been documented that women have a lower risk of SCD, and women with congestive heart failure have lower mortality and SCD rates in several series, it is plausible that women may not benefit to the same degree as men.
In the present study, we further explore the possible sex difference in outcome observed in one of these randomized trials, the DEFINITE trial, which enrolled 458 patients (326 men and 132 women) with New York Heart Association (NYHA) class I to III heart failure and left ventricular dysfunction secondary to nonischemic cardiomyopathy (NISCM).
Background: Women have been underrepresented in randomized trials of implantable cardioverter defibrillator (ICD) therapy, and limited data suggest that women may not benefit from prophylactic ICD implantation to the same extent as men. In the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) trial, a reduction in all-cause mortality was seen in men (P = .018) but not for women (P = .76).
Methods: Sex-specific cumulative probabilities of event-free survival from total, arrhythmic, and noncardiac mortality as well as appropriate shocks were calculated, and log-rank tests were performed. Interaction terms in multivariable Cox proportional hazards models were used to test the hypothesis that the effectiveness of the ICD differed between men and women.
Results: Among 458 patients (326 men and 132 women) with nonischemic cardiomyopathy enrolled in the DEFINITE trial, the test for an interaction between sex and ICD treatment on total mortality was not significant in unadjusted (P = .11) or in multivariable adjusted (P = .18) analyses. When we examined cause-specific mortality, we found no sex difference in the incidence of arrhythmic death. Instead, we documented a relative excess of noncardiac death among women randomized to the ICD (P = .02) as compared with women randomized to standard medical therapy. With respect to device use, there was a trend for women to have fewer appropriate ICD shocks after multivariable adjustment (P = .06).
Conclusion: Among patients with nonischemic cardiomyopathy enrolled in DEFINITE, we found no conclusive evidence for a sex difference in the effectiveness of the ICD; however, the trial was not adequately powered to detect such interaction effects. Larger studies are required to definitively address whether the benefit of ICD therapy differs between men and women.
Randomized clinical trials have demonstrated convincing survival benefits conferred by implantable cardioverter defibrillator (ICD) therapy in selected patients with a history of clinically recognized left ventricular dysfunction. As has been seen in other randomized trials in heart failure populations, women comprised a minority of participants in these trials (10%-29%). Therefore, as is the case in other trials where women are underrepresented, there is always the concern that extrapolation of results to women based upon trials composed primarily of men may not be appropriate. Subgroup analyses from 2 of these trials, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), raised the concern that women may not benefit to the same degree as men enrolled in these trials. However, formal tests for interaction were not performed in either of the main studies. Because it has been documented that women have a lower risk of SCD, and women with congestive heart failure have lower mortality and SCD rates in several series, it is plausible that women may not benefit to the same degree as men.
In the present study, we further explore the possible sex difference in outcome observed in one of these randomized trials, the DEFINITE trial, which enrolled 458 patients (326 men and 132 women) with New York Heart Association (NYHA) class I to III heart failure and left ventricular dysfunction secondary to nonischemic cardiomyopathy (NISCM).
