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)

中文翻译：

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飞利酮、肥胖和射血分数轻度降低/保留的心力衰竭：FINEARTS-HF 的预先指定分析

 背景

肥胖与脂肪细胞来源的醛固酮分泌过多有关，与经典的肾素-血管紧张素-醛固酮级联反应无关，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。

 目标

本研究旨在根据 FINEARTS-HF 中的体重指数 （BMI） 检查非甾体盐皮质激素受体拮抗剂 finerenone 与安慰剂相比的效果（FINerenone 试验，以调查 paTientS 心力衰竭患者的疗效和 sAfety 优于安慰剂）。

 方法

共有 6,001 例 NYHA 功能分级为 II、III 和 IV、左心室射血分数为 ≥40%、结构性心脏病证据和利钠肽水平升高的 HF 患者被随机分配到非奈利酮组或安慰剂组。BMI （kg/m²） 使用世界卫生组织类别进行检查，即体重不足/正常体重（x3C25.0 kg/m²;n = 1,306）;超重（25.0-29.9 kg/m²;n = 1,990）;肥胖 I 级 （30.0-34.9 kg/m²;n = 1,546）;肥胖 II 级 （35.0-39.9 kg/m²;n = 751）;和肥胖 III 级 （≥40 kg/m²;n = 395）。主要结局是心血管死亡和总恶化的 HF 事件。

 结果

有 5,988 名患者的基线 BMI 数据（中位数：29.2 kg/m²;Q1-Q3： 25.5-33.6 kg/m²）.与体重不足/体重正常的患者相比，II 级或 III 级肥胖患者发生主要结局的风险更高（体重不足/正常体重，参考;超重，未经调整的比率：0.96 [95% CI：0.81-1.15];肥胖 I 级：1.04 [95% CI：0.86-1.26];肥胖 II-III 级：1.26 [95% CI：1.03-1.54]）。非奈利酮对主要结局的影响不因基线 BMI 而异（体重不足/正常体重，比率比：0.80 [95% CI：0.62-1.04];超重：0.91 [95% CI：0.72-1.15];肥胖 I 级：0.92 [95% CI：0.72-1.19];肥胖 II-III 级：0.67 [95% CI：0.50-0.89];P_交互作用 = 0.32）。然而，当 BMI 作为一个连续变量进行检查时，finerenone 的有益影响似乎在 BMI 较高的患者中更大 （P_交互作用 = 0.005）。对于总恶化的 HF 事件，也观察到类似的模式。观察到心血管和全因死亡的基线 BMI 影响一致，堪萨斯城心肌病问卷评分也有所改善。

 结论

在射血分数轻度降低/保留的 HF 患者中，无论基线时的 BMI 如何，finerenone 对临床事件和症状的有益影响是一致的，对于基线时的 BMI，可能对 BMI 较高的患者的主要结局影响更大。（FINEARTS-HF [FINerenone 试验研究 paTientS 心力衰竭患者的疗效和优于安慰剂的 sAfety 试验];NCT04435626）