Finerenone, Obesity, and Heart Failure With Mildly Reduced/Preserved Ejection Fraction: Prespecified Analysis of FINEARTS-HF

Background: Obesity is associated with excessive adipocyte-derived aldosterone secretion, independent of the classical renin-angiotensin-aldosterone cascade, and mineralocorticoid receptor antagonists may be more effective in patients with heart failure (HF) and obesity.

Objectives: This study sought to examine the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone compared with placebo, according to body mass index (BMI) in FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure).

Methods: A total of 6,001 patients with HF with NYHA functional class II, III, and IV, a left ventricular ejection fraction of ≥40%, evidence of structural heart disease, and elevated natriuretic peptide levels were randomized to finerenone or placebo. BMI (kg/m²) was examined using World Health Organization categories, namely, underweight/normal weight (<25.0 kg/m²; n = 1,306); overweight (25.0-29.9 kg/m²; n = 1,990); obesity class I (30.0-34.9 kg/m²; n = 1,546); obesity class II (35.0-39.9 kg/m²; n = 751); and obesity class III (≥40 kg/m²; n = 395). The primary outcome was cardiovascular death and total worsening HF events.

Results: Data on baseline BMI were available for 5,988 patients (median: 29.2 kg/m²; Q1-Q3: 25.5-33.6 kg/m²). Compared with patients who were underweight/normal weight, those with obesity class II or III had a higher risk of the primary outcome (underweight/normal weight, reference; overweight, unadjusted rate ratio: 0.96 [95% CI: 0.81-1.15]; obesity class I: 1.04 [95% CI: 0.86-1.26]; obesity class II-III: 1.26 [95% CI: 1.03-1.54]). The effect of finerenone on the primary outcome did not vary by baseline BMI (underweight/normal weight, rate ratio: 0.80 [95% CI: 0.62-1.04]; overweight: 0.91 [95% CI: 0.72-1.15]; obesity class I: 0.92 [95% CI: 0.72-1.19]; obesity class II-III: 0.67 [95% CI: 0.50-0.89]; P_interaction = 0.32). However, when BMI was examined as a continuous variable, the beneficial effect of finerenone seemed to be greater in those with a higher BMI (P_interaction = 0.005). A similar pattern was observed for total worsening HF events. Consistent effects across baseline BMI were observed for cardiovascular and all-cause death and improvement in the Kansas City Cardiomyopathy Questionnaire scores.

Conclusions: In patients with HF with mildly reduced/preserved ejection fraction, the beneficial effects of finerenone on clinical events and symptoms were consistent, irrespective of BMI at baseline, possibly with a greater effect on the primary outcome in patients with higher BMI. (FINEARTS-HF [FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure]; NCT04435626).