Biochem Pharmacol. 2026 Jun 27:118201. doi: 10.1016/j.bcp.2026.118201. Online ahead of print.
ABSTRACT
Cardiovascular diseases (CVDs) remain a leading cause of global mortality, necessitating novel therapeutic strategies. Mineralocorticoid receptor (MR) overactivation drives pathological inflammation, fibrosis, and oxidative stress in cardiovascular and renal tissues. Traditional steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, are limited by adverse effects including hyperkalemia and endocrine disturbances. Finerenone, a novel nonsteroidal MRA, offers enhanced MR selectivity and an improved safety profile. This review provides a comprehensive overview of finerenone's pharmacology, preclinical evidence, and clinical applications. Finerenone exerts potent anti-inflammatory, anti-fibrotic, and antioxidant effects, conferring cardiorenal protection in diabetic kidney disease (DKD), heart failure with preserved ejection fraction (HFpEF), hypertension, myocardial infarction, atrial fibrillation, and left ventricular hypertrophy. Key clinical trials (FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF) demonstrate that finerenone reduces composite cardiovascular and renal outcomes with a lower risk of hyperkalemia compared to steroidal agents. Emerging evidence supports its expanding role in diabetic cardiomyopathy and heart failure with reduced ejection fraction. However, challenges remain, including the need for long-term safety data, personalized treatment strategies, and elucidation of non-genomic MR signaling mechanisms. This review concludes that finerenone represents a promising therapeutic advancement, and ongoing research will further optimize its clinical use to improve patient outcomes in cardiorenal diseases.
PMID:42364820 | DOI:10.1016/j.bcp.2026.118201