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]; Pinteraction = 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 (Pinteraction = 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).
| Discipline Area | Score |
|---|---|
| Family Medicine (FM)/General Practice (GP) |  |
| General Internal Medicine-Primary Care(US) | |
| Cardiology | |
| Endocrine | |
| Internal Medicine | |
| Special Interest - Obesity -- Physician |  |
As a family physician in a primary care unit, I have never used finerenone in my patients. Most patients with heart failure are referred to a cardiologist and receive continuous treatment at the hospital.
This is a further analysis of the FINEARTS-HF trial. Finerenone in heart failure with preserved ejection fraction (HFpEF) appears to reduce cardiovascular deaths and heart failure events with more beneficial effects noted in patients with higher levels of obesity as measured by BMI. Patient characteristics and medication side effects may ultimately determine the optimal regimen in HFpEF patients with SGLT2I and GLP1RA showing reduced hospitalizations and improved quality-of-life.