Implantable Cardioverter-Defibrillator And Frailty In Non-ischemic Heart Failure With Reduced Ejection Fraction: Extended Follow-Up Of The DANISH Trial

Patients with frailty are often perceived to have a less favorable risk/benefit profile for pharmacological and device-based therapies. We examined the long-term effects of a primary prevention implantable cardioverter-defibrillator (ICD), compared with usual care, according to frailty status in an extended follow-up study of the Danish Study to Assess the Efficacy of ICDs in Patients with nonischemic Systolic Heart failure on Mortality (DANISH) trial. The DANISH trial randomized 1,116 patients with nonischemic heart failure with reduced ejection fraction (HFrEF) to ICD implantation or usual care. Frailty was measured using the Rockwood cumulative deficit approach. The primary outcome was all-cause death, and secondary outcomes were cardiovascular death and sudden cardiovascular death. A frailty index (FI) was calculable in 1,109 patients. In total, 618 (55.7%) patients were in frailty class 1 (FI <0.210, i.e., not frail), 361 (32.6%) in frailty class 2 (FI 0.211 to 0.310, i.e., more frail), and 130 (11.7%) in frailty class 3 (FI >0.311, i.e., most frail). Compared with patients in FI class 1, those in FI class 2 and 3 had a higher rate of all outcomes. The effect of ICD implantation on all-cause death did not vary significantly by frailty class (class 1, HR 0.92 [95% CI, 0.68 to 1.24]; class 2 to 3, 0.93 [0.73 to 1.19]; Pinteraction = 0.99). Consistent effects were observed for cardiovascular death (Pinteraction = 0.94), but not for sudden cardiovascular death (Pinteraction = 0.03); the beneficial effect of ICD implantation on this outcome appeared to be greater in patients who were more frail. However, when the FI was analyzed as a continuous variable, frailty no longer significantly modified the effects of ICD implantation on any outcome. In conclusion, in patients with nonischemic HFrEF, frailty did not significantly modify the effects of ICD implantation compared with usual care. However, the need for a primary prevention ICD in frail patients with HFrEF receiving contemporary guideline-directed medical therapy remains uncertain. Clinical Trial Registration Number: NCT00542945.