Comparative efficacy of mineralocorticoid receptor antagonists in prevention of adverse cardiovascular events: a network meta-analysis.

Abstract

Mineralocorticoid receptor antagonists (MRAs) potentially reduce adverse cardiovascular events by modulating proinflammatory signaling pathways. However, their efficacy varies across agents and clinical populations. We compared the efficacy of different MRAs in reducing composite adverse cardiovascular events. We systematically searched MEDLINE, Embase, Web of Science, and the Cochrane Central up to 13 May 2025 for randomized controlled trials (RCTs) or cohort studies reporting hazard ratios (HRs) for composite adverse cardiovascular events comparing MRAs with placebo, another MRA, or non-MRA users. A frequentist random-effects network meta-analysis with P-score rankings was conducted, including subgroup analyses by clinical condition. Twenty-five study analyses (from 16 RCTs and 6 observational cohorts; 54,964 patients; mean age 66.1 ± 10.7 years; 65.1% male) with 4–44 months follow-up were included. All MRAs were effective in preventing composite adverse cardiovascular events. Eplerenone was most effective compared to control (HR: 0.75; 95% CI: 0.64–0.88), with consistent effects in subgroups with chronic kidney disease (HR: 0.62) and diabetes mellitus (HR: 0.54). Spironolactone was most effective in patients with heart failure (HF, HR: 0.70), HF with reduced ejection fraction (HR: 0.66), HF with preserved ejection fraction (HR: 0.73), and without HF (HR: 0.40). Head-to-head comparisons indicated eplerenone’s superiority over finerenone in the overall population and finerenone’s inferiority in non-HF patients. Sensitivity analyses yielded consistent results, except for HFpEF, where finerenone showed greatest efficacy. MRAs reduce composite adverse cardiovascular events across populations. Eplerenone and spironolactone appear most effective, while finerenone offers comparable benefits in select contexts, warranting future direct head-to-head trials to optimize agent selection.