The Addition of a Defibrillator to Resynchronization Therapy Decreases Mortality in Patients With Nonischemic Cardiomyopathy

Objectives: The aim of this study was to determine whether patients with heart failure with reduced ejection fraction (HFrEF) due to nonischemic etiology eligible for cardiac resynchronization therapy (CRT) benefit from an implantable cardioverter-defibrillator (ICD).

Background: It is uncertain whether CRT with an ICD (CRT-D) compared to without an ICD (CRT-P) is associated with a survival benefit in patients with nonischemic etiologies of HFrEF.

Methods: Analyses of the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure) trial were performed, using Cox proportional hazards modeling stratified by HFrEF etiology of nonischemic cardiomyopathy (NICM) or ischemic cardiomyopathy (ICM). The primary outcome was all-cause mortality (ACM), and secondary outcomes were the combination of cardiovascular mortality or heart failure hospitalization and sudden cardiac death.

Results: Among patients randomized to CRT (n = 1,212), 236 (19.5%) died, 131 and 105 in the CRT-P and CRT-D arms, respectively. The unadjusted and adjusted hazard ratios (HRs) for CRT-D versus CRT-P were both 0.84 (95% confidence interval [CI]: 0.65 to 1.09) for ACM, with a significant device-etiology interaction (p_interaction = 0.015 adjusted; p_interaction = 0.040 unadjusted). In patients with NICM (n = 555), CRT-D versus CRT-P was associated with reduced ACM (adjusted HR: 0.54; 95% CI: 0.34 to 0.86), while patients with ICM (n = 657) did not exhibit a between-device reduction in ACM (adjusted HR: 1.05; 95% CI: 0.77 to 1.44). The effects of CRT-D versus CRT-P on sudden cardiac death (advantage CRT-D) and cardiovascular mortality or heart failure hospitalization (no difference between CRT-P and CRT-D) were similar between the 2 HFrEF etiologies.

Conclusions: COMPANION patients with NICM exhibited a decrease in ACM associated with CRT-D but not CRT-P treatment, whereas patients with ICM did not.