Key result
Frailty status fails to modify primary prevention ICD mortality benefits in non-ischemic HFrEF.
Why the study?
Patients with frailty are often perceived to have a less favorable risk/benefit profile for pharmacological and device-based therapies, leaving the long-term effects of primary prevention ICDs across frailty status uncertain.
Does primary prevention ICD implantation reduce all-cause death in patients with non-ischemic HFrEF across different frailty statuses?
RCT (n=1,116)
unblinded
randomized 1,116 patients with non-ischemic HFrEF to ICD implantation or usual care
Yes
Does primary prevention ICD implantation reduce all-cause death in patients with non-ischemic HFrEF across different frailty statuses?
Frailty does not significantly modify the long-term effects of primary prevention ICD implantation on all-cause death in patients with non-ischemic HFrEF.
Frailty does not modify the neutral effect of primary prevention ICD on all-cause death in non-ischemic HFrEF; extends DANISH results to frail patients.
ABSTRACT 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 trial. The DANISH trial randomized 1,116 patients with non-ischemic 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 0.211-0.310, 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, 0.68-1.24]; class 2-3, 0.93 [0.73-1.19]; 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 non-ischemic 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.
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Butt et al. (2025) conducted an RCT in non-ischemic HFrEF (n=1,116). Implantable cardioverter-defibrillator (ICD) vs. Usual clinical care was evaluated on All-cause death (HR 0.89, 95% CI 0.74-1.08). In patients with non-ischemic HFrEF, frailty did not significantly modify the effects of primary prevention ICD implantation on all-cause death compared with usual care.
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