Contemporary evidence of non-steroidal mineralocorticoid receptor antagonists in cardio-kidney-metabolic syndrome.

Cardiovascular-kidney-metabolic (CKM) syndrome represents a complex interaction between cardiovascular (CV) disease, chronic kidney disease (CKD), and metabolic risk factors. Non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) are an emerging therapy showing promise in improving CKM syndrome outcomes. A recent large randomized trial, the FINEARTS-HF study, demonstrated a 16% reduction in the composite endpoint of worsening heart failure (HF) and CV death in patients with mildly reduced and preserved ejection fraction after a median 32-month follow-up. Additionally, two pivotal randomized studies demonstrated the efficacy of finerenone in CKD with diabetes patients. The FIDELIO-DKD trial showed a reduction in the renal composite outcome, including kidney failure and related death, over 2.6 years. Similarly, the FIGARO-DKD trial demonstrated a reduction in composite CV outcomes, including CV death, myocardial infarction, stroke, or HF hospitalization, after a median follow-up of 3.4 years. Evidence from in vitro and in vivo studies suggests that finerenone attenuates cardiac and kidney injury by reducing fibrosis, apoptotic cell death, oxidative stress, and endothelial dysfunction. Despite these advances, further research is necessary to evaluate the efficacy of ns-MRAs in specific CKM subpopulations, including HF with reduced ejection fraction and CKD without diabetes, to expand their indications and improve outcomes for CKM syndrome patients.