Mineralocorticoid receptor antagonists and mortality in hypertension: a systematic review and meta-analysis

International guidelines differ in their recommendations for mineralocorticoid receptor antagonist (MRA) use in hypertension, as the effect on mortality is unclear. We meta-analyzed trial-level data to determine the association of MRA use with all-cause mortality in hypertension.

MEDLINE and EMBASE were searched for randomized clinical trials published from database inception through March 14, 2025, evaluating MRA use in trial populations with at least 85% prevalence of hypertension. The control groups consisted of placebo or usual care. Two reviewers independently screened and extracted data. Pooled estimates were calculated using random-effects and inverse variance models. The primary outcome was all-cause mortality.

Seventeen randomized clinical trials were eligible for inclusion ( n   =  25 498), of which 12 trials reported mortality events ( n   =  24 426). The mean (±SD) baseline prevalence of hypertension was 95.0% (±5.0), mean baseline SBP was 134.8 (±9.0) mmHg, mean age was 64.1 (±5.3) years and 43.3% ( n   =  11 047) were female. The median duration of follow-up was 12 months (interquartile range 9-32 months). MRA use versus control was significantly associated with lower odds of all-cause mortality (12 trials, n   =  24 426) (10.7 versus 11.6% over a median follow-up of 20.5 months; odds ratio (OR), 0.91 [95% confidence interval, 95% CI, 0.84-0.99]; absolute risk reduction, 0.88% [95% CI, 0.1-1.7]; I2   =  0.0%).

In this meta-analysis of randomized clinical trials in predominantly hypertensive populations with substantial comorbidity, MRA use was significantly associated with lower all-cause mortality. Further dedicated trials in hypertensive populations, with longer follow-up and mortality as primary outcome, are warranted to confirm these findings. (PROSPERO; CRD420250601811).