Efficacy of Implantable Cardioverter Defibrillator in Nonischemic Systolic Heart Failure According to Sex: Extended Follow-Up Study of the DANISH Trial

Abstract

Background: Men and women may respond differently to certain therapies for heart failure with reduced ejection fraction, including implantable cardioverter defibrillators (ICD). In an extended follow-up study of the DANISH trial (Danish Study to Assess the Efficacy of ICDs in Patients With Non-Ischemic Systolic Heart Failure on Mortality), adding 4 years of additional follow-up, we examined the effect of ICD implantation according to sex. Methods: In the DANISH trial, 1116 patients with nonischemic systolic heart failure were randomized to receive an ICD (N=556) or usual clinical care (N=550). The primary outcome was all-cause mortality. Results: Of the 1116 patients randomized in the DANISH trial, 307 (27.5%) were women. During a median follow-up of 9.5 years, women had a lower associated rate of all-cause mortality (hazard ratio [HR], 0.60 [95% CI, 0.47–0.78]) cardiovascular death (HR, 0.62 [95% CI, 0.46–0.84]), nonsudden cardiovascular death (HR, 0.59 [95% CI, 0.42–0.85]), and a numerically lower rate of sudden cardiovascular death (HR, 0.70 [95% CI, 0.40–1.25]), compared with men. Compared with usual clinical care, ICD implantation did not reduce the rate of all-cause mortality, irrespective of sex (men, HR, 0.85 [95% CI, 0.69–1.06]; women, HR, 0.98 [95% CI, 0.64–1.50]; P interaction=0.51). In addition, sex did not modify the effect of ICD implantation on sudden cardiovascular death (men, HR, 0.57 [95% CI, 0.36–0.92]; women, HR, 0.68 [95% CI, 0.26–1.77]; P interaction=0.76). Conclusions: In patients with nonischemic systolic heart failure, ICD implantation did not provide an overall survival benefit, but reduced sudden cardiovascular death, irrespective of sex. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00542945.