Sex Differences in Device Therapies for Ventricular Arrhythmias or Death in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Trial

Sex Differences in VT/VF or Death in MADIT‐CRT Introduction Studies suggest that women with ischemic heart disease are less likely to experience appropriate ICD therapies for ventricular arrhythmias (VT/VF). We evaluated the influence of sex on arrhythmic events or death in subjects enrolled in MADIT‐CRT. Methods and Results Arrhythmic event rates, defined as VT/VF treated with defibrillator therapy or all‐cause death, were determined among 1,790 subjects enrolled in MADIT‐CRT with documented 3‐year follow‐up. Predictors of VT/VF/death were identified using multivariate analysis. Ninety‐one (21%) women and 466 (35%) men experienced VT/VF/death over the follow‐up period. The overall probability of VT/VF/death was significantly lower in women versus men (HR 0.62; P < 0.001). The probability of VT/VF/death was the lowest in women with ischemic heart disease (HR 0.51; P = 0.003). In ICD subjects, the 3‐year risk of VT/VF was lower in ischemic women versus men (P = 0.021), and in nonischemic women versus men (P = 0.049). The probability of VT/VF/death was significantly lower in women (HR 0.52; P = 0.007) and men (HR 0.74; P = 0.018) with LBBB who received CRT‐D. Appropriate shock therapy strongly correlated with increased risk of death during postshock follow‐up in women (HR 5.18; P = 0.001) and men (HR 1.63; P = 0.033); interaction P value of 0.034. Conclusion In this substudy of MADIT‐CRT, sex, etiology of heart disease and type of device implanted significantly influenced subsequent risk for VT/VF or death. Women with ischemic heart disease and women with LBBB who received CRT‐D had the lowest incidence of VT/VF or death when compared to men. Appropriate shock therapy was a strong predictor of death, particularly in women.