Butt Jawad H, Henderson Alasdair D, Jhund Pardeep S, Claggett Brian L, Desai Akshay S, Lay-Flurrie James, Viswanathan Prabhakar, Lage Andrea, Scheerer Markus F, Lam Carolyn S P, Senni Michele, Shah Sanjiv J, Voors Adriaan A, Bauersachs Johann, Fonseca Cândida, Kosiborod Mikhail N, Linssen Gerard C M, Petrie Mark C, Schou Morten, Verma Subodh, Zannad Faiez, Pitt Bertram, Vaduganathan Muthiah, Solomon Scott D, McMurray John J V
British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Am Coll Cardiol. 2025 Jan 21;85(2):140-155. doi: 10.1016/j.jacc.2024.10.111. Epub 2024 Dec 10.
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.
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).
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/m) was examined using World Health Organization categories, namely, underweight/normal weight (<25.0 kg/m; n = 1,306); overweight (25.0-29.9 kg/m; n = 1,990); obesity class I (30.0-34.9 kg/m; n = 1,546); obesity class II (35.0-39.9 kg/m; n = 751); and obesity class III (≥40 kg/m; n = 395). The primary outcome was cardiovascular death and total worsening HF events.
Data on baseline BMI were available for 5,988 patients (median: 29.2 kg/m; Q1-Q3: 25.5-33.6 kg/m). 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 = 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 = 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.
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).
肥胖与脂肪细胞衍生的醛固酮分泌过多有关，独立于经典的肾素 - 血管紧张素 - 醛固酮级联反应，盐皮质激素受体拮抗剂可能对心力衰竭（HF）和肥胖患者更有效。
本研究旨在根据体重指数（BMI），比较非甾体盐皮质激素受体拮抗剂非奈利酮与安慰剂在FINEARTS - HF（非奈利酮研究心力衰竭患者疗效和安全性优于安慰剂的试验）中的效果。
共有6001例纽约心脏病协会（NYHA）功能分级为II、III和IV级、左心室射血分数≥40%、有结构性心脏病证据且利钠肽水平升高的HF患者被随机分为非奈利酮组或安慰剂组。使用世界卫生组织的分类标准检查BMI（kg/m²），即体重过轻/正常体重（<25.0 kg/m²；n = 1306）；超重（25.0 - 29.9 kg/m²；n = 1990）；I级肥胖（30.0 - 34.9 kg/m²；n = 1546）；II级肥胖（35.0 - 39.9 kg/m²；n = 751）；III级肥胖（≥40 kg/m²；n = 395）。主要结局是心血管死亡和总的HF恶化事件。
5988例患者有基线BMI数据（中位数：29.2 kg/m²；第一四分位数 - 第三四分位数：25.5 - 33.
