Important Differences in Mode of Death Between Men and Women With Heart Failure Who Would Qualify for a Primary Prevention Implantable Cardioverter-Defibrillator

Background— Whether sex differences in implantable cardioverter-defibrillator (ICD) benefit exist remains unanswered. We evaluated sex differences in mode of death among a large cohort of ambulatory heart failure patients who meet criteria for a primary prevention ICD. Methods and Results— Patients from 5 trials or registries were included if they met American College of Cardiology/American Heart Association/Heart Rhythm Society guideline criteria for implantation of a primary prevention ICD. We investigated the potential sex differences in total deaths and total deaths by mode of death. The relationship between the estimated total mortality and mode of death by percentage of total mortality was also analyzed by sex. The Seattle Heart Failure Model was used to estimate total mortality in this analysis. A total of 8337 patients (1685 [20%] women) met inclusion criteria. One-year mortality was 10.8±0.3%. In women, the age-adjusted all-cause mortality was 24% lower (hazard ratio [HR], 0.76; confidence interval [CI], 0.68–0.85; P<0.0001), the risk of sudden death was 31% lower (HR, 0.69; CI, 0.58–0.83; P<0.0001), but no significant difference in pump failure death was observed. Throughout a range of total mortality risk, women had a 20% lower all-cause mortality (HR, 0.80; CI, 0.71–0.89; P<0.001) and 29% fewer deaths that were sudden (HR, 0.71; CI, 0.59–0.86;P<0.001) compared with men. Conclusions— Women with heart failure have a lower mortality than men, and fewer of those deaths are sudden throughout a spectrum of all-cause mortality risk. These data provide a plausible reason for and thus support the possibility that sex differences in ICD benefit may exist.