Finerenone’s Effects in HFmrEF/HFpEF and Obesity
Summary: Finerenone’s Effects in HFmrEF/HFpEF and Obesity
Source: Butt JH, Henderson AD, Jhund PS, et al. J Am Coll Cardiol. 2025, j.jacc. (AHA highlited in 12 March2025.)
1. Study Background:
• Obesity is associated with increased aldosterone secretion, which may influence heart failure (HF) progression.
• Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA), was shown to reduce cardiovascular (CV) death and worsening HF events in HF with mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) in the FINEARTS-HF trial.
2. Study Design & Methods:
• Phase 3, international, double-blind, placebo-controlled RCT.
• 6,001 HFmrEF/HFpEF patients with LVEF ≥40%, NYHA class II–IV, and elevated NT-proBNP randomized to finerenone or placebo.
• Median follow-up: 32 months.
• Patients stratified by BMI categories: underweight/normal weight (<25 kg/m²), overweight (25.0–29.9 kg/m²), obesity class I (30.0–34.9 kg/m²), and obesity class II/III (≥35.0 kg/m²).
3. Clinical Outcomes by BMI:
• Obesity class II/III patients had higher risks of CV death or worsening HF events (WHFEs) compared to underweight/normal-weight individuals.
• Overweight and obesity class I patients had no significant difference in primary endpoint risk but had a lower risk of all-cause mortality.
• In fully adjusted models, BMI ≥30 kg/m² was associated with a higher primary endpoint risk, while the mortality benefit disappeared.
4. Efficacy of Finerenone:
• Finerenone reduced the risk of CV death or WHFEs regardless of BMI.
• Patients with higher BMI seemed to derive a greater benefit.
• No significant interaction was observed between BMI and the treatment effect on secondary endpoints.
5. Conclusion:
• Finerenone effectively reduced CV death and WHFEs in HFmrEF/HFpEF patients, irrespective of BMI.
• Higher BMI patients may experience greater benefits.
• The study found no consistent evidence supporting the “obesity-survival paradox” in HF.