Evolving Mineralocorticoid Receptor Antagonism: a Narrative Review on Differences between Steroidal MRAs, Non-Steroidal MRAs and Aldosterone Synthase Inhibitors in Cardiorenal Disease.

PURPOSE OF REVIEW: This review explores the evolution of mineralocorticoid receptor antagonists (MRAs) in cardiorenal disease, comparing steroidal MRAs with newer non-steroidal MRAs and emerging aldosterone synthase inhibitors (ASIs). It examines their efficacy, safety, and positioning in heart failure (HF) and chronic kidney disease (CKD), aiming to guide optimal treatment across cardiorenal diseases.

RECENT FINDINGS: Steroidal MRAs remain foundational in HF with reduced ejection fraction, but are underused due to hyperkalemia, worsening renal function, and hormonal side effects. Non-steroidal MRAs have demonstrated cardiorenal benefits in high-risk populations (e.g. diabetic kidney disease) while mitigating some safety concerns. Emerging ASIs directly inhibit aldosterone synthase, reducing aldosterone levels and potentially preventing breakthrough. Ongoing trials are further defining their roles as standalone or combination therapies. Non-steroidal MRAs expand the use of mineralocorticoid receptor blockade into populations underserved by steroidal agents. Ongoing studies will establish the role of direct aldosterone synthase inhibition.