Shokri Kasra, Mohammadi Abbas, Karimian Azin, Adeel Muhammad Yasir, Mozaffari Mohammad Ali, Frishman William H, Aronow Wilbert S
From the Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Medicine, Valley Health System, Las Vegas, NV.
Cardiol Rev. 2025 May 27. doi: 10.1097/CRD.0000000000000958.
The mineralocorticoid receptor (MR) plays a pivotal role in cardiorenal disease progression, but steroidal MR antagonists (MRAs) are limited by hyperkalemia, hormonal side effects, and uncertain efficacy in heart failure with preserved ejection fraction (HFpEF). Finerenone, a first-in-class nonsteroidal MRA, offers selective MR blockade with balanced tissue distribution, mitigating off-target effects while demonstrating cardiorenal benefits. Phase 3 trials (FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF) show significant reductions in renal (18-21%) and cardiovascular (13-16%) composite endpoints, including HFpEF, where it reduced worsening heart failure events by 16%. Unlike steroidal MRAs, finerenone reduces off-target effects while maintaining efficacy in HFpEF, a population with limited therapeutic options. This review synthesizes finerenone's pharmacological innovations, clinical evidence, and practical challenges, highlighting its potential as a transformative therapy in cardiorenal disease.
盐皮质激素受体（MR）在心脏和肾脏疾病进展中起关键作用，但甾体类MR拮抗剂（MRA）受到高钾血症、激素副作用以及射血分数保留的心力衰竭（HFpEF）中疗效不确定的限制。非奈利酮是首个非甾体类MRA，具有选择性MR阻断作用，组织分布均衡，可减轻脱靶效应，同时显示出心脏和肾脏保护作用。3期试验（FIDELIO-DKD、FIGARO-DKD和FINEARTS-HF）表明，肾脏（18-21%）和心血管（13-16%）复合终点显著降低，包括HFpEF，在HFpEF中，非奈利酮可使心力衰竭恶化事件减少16%。与甾体类MRA不同，非奈利酮在HFpEF中减少了脱靶效应，同时保持疗效，而HFpEF患者的治疗选择有限。本综述综合了非奈利酮的药理学创新、临床证据和实际挑战，突出了其作为心脏和肾脏疾病变革性治疗方法的潜力。
