Finerenone, glycaemic status, and heart failure with mildly reduced or preserved ejection fraction: A prespecified analysis of the FINEARTS-HF trial

Aims: The efficacy and safety of the non-steroidal mineralocorticoid receptor antagonist, finerenone, have not been examined in patients without diabetes. We examined the efficacy and safety of finerenone, compared with placebo, according to glycaemic status in FINEARTS-HF. Methods and results: A total of 6001 patients with heart failure (HF) with New York Heart Association functional class II–IV, left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomized to finerenone or placebo. The effect of finerenone according to glycaemic status (i.e. normoglycaemia [no investigator-reported history of diabetes and glycated haemoglobin (HbA1c) <5.7%], pre-diabetes [no investigator-reported history of diabetes and HbA1c 5.7–6.4%] and diabetes [investigator-reported history of diabetes or HbA1c ≥6.5%]) at baseline were examined. The primary outcome was cardiovascular death and total worsening HF events. At baseline, 1243 (20.8%) patients were normoglycaemic, 1979 (33.1%) had pre-diabetes, and 2764 (46.2%) had diabetes. Compared with patients with normoglycaemia, those with diabetes, but not pre-diabetes, had a higher rate of the primary endpoint (normoglycaemia: reference; pre-diabetes: adjusted rate ratio [RR] 1.02, 95% confidence interval [CI] 0.84–1.23; diabetes: adjusted RR 1.32 [95% CI 1.11–1.58]). The benefit of finerenone on the primary outcome was consistent across glycaemic status (normoglycaemia: RR 0.85 [95% CI 0.63–1.14]; pre-diabetes: RR 0.85 [95% CI 0.66–1.08]; diabetes: RR 0.82 [95% CI 0.69–0.98]; pinteraction = 0.93). The effects of finerenone on the components of the primary outcome, all-cause death, composite kidney endpoints, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score were not modified by glycaemic status. Conclusion: In patients with HF with mildly reduced/preserved ejection fraction, the beneficial effects of finerenone, compared with placebo, on clinical events and symptoms, were consistent, irrespective of glycaemic status at baseline.