Finerenone: A Non-Steroidal Mineralocorticoid Receptor Antagonist and Its Emerging Role in Cardiovascular-Kidney-Metabolic Syndrome.

Abstract

Cardiovascular-kidney-metabolic (CKM) syndrome represents the interconnected pathophysiology of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease, leading to multiorgan dysfunction and elevated adverse outcomes. Overactivation of the mineralocorticoid receptor (MR), via aldosterone-dependent and ligand-independent pathways, drives inflammation, fibrosis, and oxidative stress and facilitates CKM progression. Finerenone is a selective non-steroidal MR antagonist (nsMRA) that exhibits high MR affinity, has balanced cardiac and renal distribution, and minimal off-target steroidal effects, which make it mechanistically different from steroidal MRAs. Large phase 3 trials such as FIDELIO-DKD and FIGARO-DKD in type 2 diabetes with CKD, and FINEARTS-HF in heart failure (HF) with a left ventricular ejection fraction (LVEF) > 40%, demonstrated consistent cardiorenal benefits. The prespecified FINE-HEART pooled analysis showed finerenone reduced all-cause mortality (HR 0.91, 95% CI 0.84-0.99), HF hospitalizations (HR 0.83, 95% CI 0.75-0.92), and the kidney composite outcome (HR 0.80, 95% CI 0.72-0.90), with benefits consistent across CKM components and background therapies including sodium-glucose cotransporter 2 (SGLT2) inhibitors. Recent data from FIND-CKD extend utility to non-diabetic CKD. Various guidelines incorporate finerenone as an additive therapy for patients with persistent albuminuria on maximal renin-angiotensin system inhibition (RASi) + SGLT2i. This review summarizes the MR pathophysiology in CKM syndrome, compares the mechanisms of non-steroidal versus steroidal MRAs, synthesizes clinical trial evidence, safety, and guideline-directed place in therapy, addresses implementation barriers, including cost, and outlines future research directions. Finerenone may fill a critical gap in multimodal CKM management, enabling comprehensive pillar-based therapy to mitigate residual cardiorenal risk.