The efficacy of finerenone on hierarchical composite endpoint analysed using win statistics in patients with heart failure and mildly reduced or preserved ejection fraction: A prespecified analysis of FINEARTS-HF

Aims: FINEARTS-HF demonstrated the efficacy of finerenone in reducing total worsening heart failure (HF) events (first and recurrent) and cardiovascular death, compared to placebo, in patients with HF and mildly reduced or preserved ejection fraction. We examined the effect of finerenone on these events according to their clinical importance using win statistics. Methods and results: We developed a prespecified hierarchical composite endpoint including the components of the original primary outcome: cardiovascular death (tier 1), total HF hospitalizations (tier 2), and total urgent HF visits (tier 3). For tiers 2 and 3, the number of events was analysed first, followed by the time-to-first event. Because win statistics are affected by the censoring distribution, we assessed the hierarchical composite outcome over a fixed period of 24 months. The 6001 participants analysed were randomized equally to finerenone (n = 3003) or placebo (n = 2998). At 24 months, a total of 825 cardiovascular deaths and worsening HF events were observed in the finerenone group, compared with 1012 events in the placebo group. The win ratio was 1.17 (95% confidence interval [CI] 1.04–1.32) (p = 0.010), demonstrating more wins than losses in the finerenone group. The win odds, corresponding to the treatment effect, was 1.05 (95% CI 1.01–1.09), and the net benefit, corresponding to the absolute risk difference, was 2.6% (95% CI 0.6–4.5%). The win ratio remained above 1.0 from 60 days after randomization and reached a plateau after approximately 12 months. HF hospitalizations contributed more to the overall results than cardiovascular death. The win odds at 12 months was 1.04 (95% CI 1.01–1.08), and when adding the Kansas City Cardiomyopathy Questionnaire total symptom score to the hierarchical endpoint as a continuous variable, that increased to 1.07, which is almost identical to the win ratio due to the decrease in ties. Conclusion: Finerenone treatment led to a significant improvement in a composite hierarchical outcome that incorporated cardiovascular death, total HF hospitalizations, and total urgent HF visits, with early onset of benefit. Clinical Trial Registration: ClinicalTrials.gov ID NCT04435626.