Mineralocorticoid Receptor Antagonists and Aldosterone Synthase Inhibitors: Agent Comparison With Implications for Clinical Practice and Trial Design

Abstract

Steroidal (s) and nonsteroidal (ns) mineralocorticoid receptor antagonists (MRAs) and aldosterone synthase inhibitors (ASis) are either available for clinical use or are being tested in clinical trials in cardiovascular, kidney and metabolic (CKM) conditions. All agents block the actions of aldosterone, but they present important differences in terms of modes of action, pharmacokinetics and dynamics and side-effect profiles. Such differences may have clinical implications. To ascertain such potential differences, we performed a description and indirect comparison of MRA and ASi trial results in hypertension, chronic kidney disease and heart failure. Whenever possible, we used data from head-to-head comparisons. We then used this information to provide clinical guidance and to suggest how to improve clinical trials in the future. Notably, by performing more head-to-head comparison trials and trials with dual or triple combination therapies with sodium glucose co-transporter 2 inhibitors (SGLT2is) and/or oral glucagon-like peptide 1 receptor agonists (GLP1ras). In short, this article focuses on the similarities and potential differences among MRAs, nsMRAs and ASis, with implications for both clinical use and clinical trial design.

Keywords: Mineralocorticoid receptor antagonists; aldosterone synthase inhibitors; clinical trials.