Finerenone did not significantly reduce death or cause-specific death compared with placebo in patients with HF and EF ≥40%, where 49.6% of the 1013 total deaths were due to cardiovascular causes.
RCT (n=6,001)
randomly assigned
Does finerenone reduce cause-specific mortality in patients with heart failure with mildly reduced or preserved ejection fraction?
In patients with HFmrEF/HFpEF, finerenone did not significantly reduce cause-specific mortality, and cardiovascular death was predominantly due to sudden death in those with EF <50%.
Importance: The mode of death in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) remains poorly understood and may vary by EF. Objective: To evaluate the mode of death according to EF and the treatment effect of finerenone on cause-specific mortality in patients with HFmrEF/HFpEF. Design, Setting, and Participants: This was a prespecified secondary analysis of the Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure (FINEARTS-HF) randomized clinical trial, which evaluated clinical outcomes in 6001 patients with HF and EF greater than or equal to 40% randomly assigned to finerenone or placebo. The mode of death in relation to baseline EF categories (<50%, ≥50-<60%, and ≥60%) was examined, and the effect of randomized treatment on cause-specific death in Cox regression models was assessed. Data analysis was conducted between September 2024 and January 2025. Interventions: Finerenone vs placebo. Main Outcomes and Measures: Mode of death as centrally adjudicated by a clinical end points committee. Results: Of 1013 patients (16.9%; median IQR age, 76 69-82 years; 594 male 58.6%) who died during median (IQR) follow-up of 32 (23-36) months, mode of death was ascribed to cardiovascular causes in 502 (49.6%), noncardiovascular causes in 368 (36.3%), and undetermined cause in 143 (14.1%). Of cardiovascular deaths, 215 (42.8%) were due to sudden death, 163 (32.4%) to HF, 48 (9.6%) to stroke, 25 (5.0%) to myocardial infarction, and 51 (10.2%) to other cardiovascular causes. The proportion of all-cause, cardiovascular, and sudden death was higher in those with EF less than 50%. The proportion of deaths related to HF was similar across EF categories, and the proportion of deaths due to myocardial infarction, stroke, and other cardiovascular causes was low regardless of EF. Randomization to finerenone did not significantly reduce death or cause-specific death compared with placebo in any EF category. Conclusions and Relevance: Among patients with HFmrEF/HFpEF in the FINEARTS-HF randomized clinical trial, higher proportions of cardiovascular and overall mortality in those with EF less than 50% were related principally to higher proportions of sudden death. A clear treatment effect of finerenone on cardiovascular or cause-specific mortality was not identified, although the trial was likely underpowered for these outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04435626.
Desai et al. (Sun,) conducted a rct in heart failure with mildly reduced or preserved ejection fraction (n=6,001). Finerenone vs. placebo was evaluated on Mode of death as centrally adjudicated by a clinical end points committee. Finerenone did not significantly reduce death or cause-specific death compared with placebo in patients with HF and EF ≥40%, where 49.6% of the 1013 total deaths were due to cardiovascular causes.