Current Problems in Cardiology · Mar 24, 2026

Comparative effectiveness of mineralocorticoid receptor antagonists in cardiovascular, renal and metabolic disease

By Filippatos C, Kourek C, Boutsikos I et al.

PURPOSE: Mineralocorticoid receptor antagonists (MRAs) are pivotal in managing cardiorenal disease, yet head-to-head comparisons across distinct phenotypes remain limited. This real-world study aims to compare their effectiveness and safety profiles in the context of cardio-renal-metabolic disease. METHODS: Using the TriNetX global health research network, adult patients initiating spironolactone, eplerenone, or finerenone (concurrent with SGLT2 inhibitors) were identified. Stratification included five cohorts: HFrEF, HFpEF, CKD, DM and non-DM. Pairwise 1:1 propensity score matching was performed. RESULTS: In patients with heart failure, finerenone was associated with a significant reduction in HF events compared to steroidal MRAs (HFrEF: HR 0.75; HFpEF: HR 0.62; p < 0.001 for both), though no significant differences were observed in overall survival or in other cardiovascular outcomes. However, it also seemed to be associated with trend of increased risk of hyperkalemia (HFrEF: HR 1.42, p = 0.103; HFpEF: HR 1.41, p = 0.057), compared to steroidal MRAs. On the other hand, in the CKD, DM, and non-DM cohorts, finerenone exhibited comprehensive superiority, significantly reducing the risk of death and the risk of cardiovascular events, compared to steroidal MRAs. Regarding safety, the non-steroidal MRA was associated with a lower risk of acute kidney injury (AKI) across CKD, DM, and non-DM phenotypes and a significantly reduced risk of hyperkalemia in CKD and non-DM patients. CONCLUSION: Finerenone appears superior for cardiorenal protection in CKD and metabolic phenotypes, whereas steroidal MRAs offer a favorable efficacy-safety balance in HF. These observations are hypothesis-generating and support phenotype-specific, individualized selection of MRAs pending validation in further prospective research.

doi.org/10.1016/j.cpcardiol.2026.103335PubMed 41887307Interventions